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Conserved domains on  [gi|1050394579|gb|OCT96769|]
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hypothetical protein XELAEV_18008984mg [Xenopus laevis]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1007-1186 5.48e-79

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


:

Pssm-ID: 239850  Cd Length: 184  Bit Score: 258.39  E-value: 5.48e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1007 DGNALQDQQLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKHQLEDVTDVLKYFF 1086
Cdd:cd04385      1 DGPALEDQQLTDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1087 YEIDDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLF 1166
Cdd:cd04385     81 RDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLF 160
                          170       180
                   ....*....|....*....|....
gi 1050394579 1167 QT----NGENEQEVAVLEDLISNY 1186
Cdd:cd04385    161 QTdehsVGQTSHEVKVIEDLIDNY 184
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
575-695 2.31e-75

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP2 localizes to the cell periphery and on focal adhesions composed of paxillin and vinculin, and functions downstream of RhoA to regulate focal adhesion dynamics. ARAP2 is a PI(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RhoGAP domain and does not have RhoGAP activity. ARAP2 reduces Rac1oGTP levels by reducing Arf6oGTP levels through GAP activity. AGAP2 also binds to and regulates focal adhesion kinase (FAK). Thus, ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology.


:

Pssm-ID: 350081 [Multi-domain]  Cd Length: 121  Bit Score: 245.20  E-value: 2.31e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  575 ETLADYEVAEKIWFNEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTTIWSNELVELFIVVG 654
Cdd:cd08856      1 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVVG 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1050394579  655 NEKVNNIWEANLLPENMLHMDSDVSQRRLFITQKYKEGRFK 695
Cdd:cd08856     81 NKPANLFWAANLFSEEDLHMDSDVEQRTPFITQKYKEGKFR 121
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
1329-1430 8.99e-51

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13259:

Pssm-ID: 450165  Cd Length: 121  Bit Score: 174.93  E-value: 8.99e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1329 SGYMKFKEDPSKLLSGNKFQERYFVLHERKLLLYKDIKSIKHEKELPVKSCKVYAGVKKKMKPPTRWGFTIYSEKSQWHL 1408
Cdd:cd13259     16 HGMLKFREEPSKLLSGNKFQDRYFILNDECLLLYKDVKSSKPEKEWPLKSLKVYLGIKKKLKPPTSWGFTVLLEKQQWYL 95
                           90       100
                   ....*....|....*....|..
gi 1050394579 1409 CCDTQESQKEWLGSLFSAQHPG 1430
Cdd:cd13259     96 CCDSQMEQREWMATILSAQHDG 117
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
783-895 6.56e-38

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13256:

Pssm-ID: 450165  Cd Length: 110  Bit Score: 137.97  E-value: 6.56e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  783 SLFYCGFLHKASSStSKMTINRKSKEvpEMKRWWCTIENNFLKYYENETAPVADGVIDLSEVLCLVVHPSDCSSNGMAAF 862
Cdd:cd13256      1 SVFHSGFLYKSPSA-AKPTLERRARE--EFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEIVCLAVSPPDTHPGDGFPF 77
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1050394579  863 TFEIYFLSERMFLFGAENVESRREWTRAIAKNF 895
Cdd:cd13256     78 TFELYLESERLYLFGLETAEALHEWVKAIAKAF 110
Ubl1_cv_Nsp3_N-like super family cl28922
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ...
1218-1309 4.13e-37

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.


The actual alignment was detected with superfamily member cd17227:

Pssm-ID: 452900  Cd Length: 98  Bit Score: 135.02  E-value: 4.13e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1218 SGDLLIEVYVERKDPDMCVIIRVPPTMETAELTNCAMGIKNITLTEEIPWATFEVIENGELERLMHDAEKVLETVLYWSS 1297
Cdd:cd17227      1 AGDLLIEVYLEKKEPDCSIIIRVSPTMEAEELTNDVLEIKNIIPDKKDIWATFEVIENGELERPLHYKENVLEQVLQWSS 80
                           90
                   ....*....|..
gi 1050394579 1298 LSDPGAAHLLVK 1309
Cdd:cd17227     81 LSEPGSAYLIVK 92
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
384-471 1.29e-35

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13253:

Pssm-ID: 450165  Cd Length: 94  Bit Score: 130.59  E-value: 1.29e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  384 TKTGWLEKLSPHRSC-MFQKRWVKVDGMHLSYYSNNRDMFSKGKISLSAIITLNKMGENKFEVVTIQRTFVFRAEKEEDR 462
Cdd:cd13253      1 IKSGYLDKQGGQGNNkGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNKFELVTTNRTFVFRAESDDER 80

                   ....*....
gi 1050394579  463 DDWIGTLQS 471
Cdd:cd13253     81 NLWCSTLQA 89
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
481-570 7.05e-34

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13254:

Pssm-ID: 450165  Cd Length: 90  Bit Score: 125.61  E-value: 7.05e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  481 PGLSMTEKNGYLELKGYKNKIFTVINGSKLWFSKNKQDASTGITITDLTLTMASVKNIDRKSFELSTPFRNFSLTAESER 560
Cdd:cd13254      1 PRKPNPDKCGYLELRGYKAKVYAALMGDEVWLYKNEQDFRLGIGITVIEMNGANVKDVDRRSFDLTTPYRSFSFTAESEH 80
                           90
                   ....*....|
gi 1050394579  561 EKQEWTEAIQ 570
Cdd:cd13254     81 EKQEWIEAVQ 90
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
908-1003 2.17e-26

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13257:

Pssm-ID: 450165  Cd Length: 91  Bit Score: 104.16  E-value: 2.17e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  908 FTLLGYLYYKNSYSLNQWKKAWFALDKACLH-YWNTEDCGkaDTIQLKKLQELTANSSMLNgekgNILLLVENGRTFYIH 986
Cdd:cd13257      1 FERLGRLFYKDGLALDRAREGWFALDKSSLHaCLQMQEVE--ERMHLRKLQELSIQGDVQL----DVLVLVERRRTLYIQ 74
                           90
                   ....*....|....*..
gi 1050394579  987 GHTMLDFTVWHLAIEKA 1003
Cdd:cd13257     75 GERKLDFTGWHTAIQKA 91
SAM_superfamily super family cl15755
SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of ...
6-67 1.92e-19

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.


The actual alignment was detected with superfamily member cd09490:

Pssm-ID: 449586  Cd Length: 63  Bit Score: 83.50  E-value: 1.92e-19
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1050394579    6 EQISDIVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSI 67
Cdd:cd09490      1 EADLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLPII 62
PRK08581 super family cl35718
amidase domain-containing protein;
121-333 4.59e-04

amidase domain-containing protein;


The actual alignment was detected with superfamily member PRK08581:

Pssm-ID: 236304 [Multi-domain]  Cd Length: 619  Bit Score: 44.78  E-value: 4.59e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  121 SSVSKEVDHNATSQYQQTEDPNDQNKKSLEIKDHSVKHFSLDTETQLDSQNSSFFafqgpmvendIYDK-SQDDGHKSLL 199
Cdd:PRK08581    40 SHDSKKSNDDETSKDTSSKDTDKADNNNTSNQDNNDKKFSTIDSSTSDSNNIIDF----------IYKNlPQTNINQLLT 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  200 KSPPTKSFILRNRPVPKLPFSVSNTFPKCCCQERHLDNKAAQESSASKPQNQESEEQNINLISpyeetffSNSEFTKETS 279
Cdd:PRK08581   110 KNKYDDNYSLTTLIQNLFNLNSDISDYEQPRNSEKSTNDSNKNSDSSIKNDTDTQSSKQDKAD-------NQKAPSSNNT 182
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1050394579  280 GDKLNFSPNSEHNEKSLERNASTSCGSVPANNGSSPSLGDHISEESIYSTMEEY 333
Cdd:PRK08581   183 KPSTSNKQPNSPKPTQPNQSNSQPASDDTANQKSSSKDNQSMSDSALDSILDQY 236
 
Name Accession Description Interval E-value
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1007-1186 5.48e-79

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239850  Cd Length: 184  Bit Score: 258.39  E-value: 5.48e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1007 DGNALQDQQLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKHQLEDVTDVLKYFF 1086
Cdd:cd04385      1 DGPALEDQQLTDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1087 YEIDDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLF 1166
Cdd:cd04385     81 RDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLF 160
                          170       180
                   ....*....|....*....|....
gi 1050394579 1167 QT----NGENEQEVAVLEDLISNY 1186
Cdd:cd04385    161 QTdehsVGQTSHEVKVIEDLIDNY 184
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
575-695 2.31e-75

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP2 localizes to the cell periphery and on focal adhesions composed of paxillin and vinculin, and functions downstream of RhoA to regulate focal adhesion dynamics. ARAP2 is a PI(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RhoGAP domain and does not have RhoGAP activity. ARAP2 reduces Rac1oGTP levels by reducing Arf6oGTP levels through GAP activity. AGAP2 also binds to and regulates focal adhesion kinase (FAK). Thus, ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology.


Pssm-ID: 350081 [Multi-domain]  Cd Length: 121  Bit Score: 245.20  E-value: 2.31e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  575 ETLADYEVAEKIWFNEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTTIWSNELVELFIVVG 654
Cdd:cd08856      1 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVVG 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1050394579  655 NEKVNNIWEANLLPENMLHMDSDVSQRRLFITQKYKEGRFK 695
Cdd:cd08856     81 NKPANLFWAANLFSEEDLHMDSDVEQRTPFITQKYKEGKFR 121
PH5_ARAP cd13259
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
1329-1430 8.99e-51

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 5; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the five PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270079  Cd Length: 121  Bit Score: 174.93  E-value: 8.99e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1329 SGYMKFKEDPSKLLSGNKFQERYFVLHERKLLLYKDIKSIKHEKELPVKSCKVYAGVKKKMKPPTRWGFTIYSEKSQWHL 1408
Cdd:cd13259     16 HGMLKFREEPSKLLSGNKFQDRYFILNDECLLLYKDVKSSKPEKEWPLKSLKVYLGIKKKLKPPTSWGFTVLLEKQQWYL 95
                           90       100
                   ....*....|....*....|..
gi 1050394579 1409 CCDTQESQKEWLGSLFSAQHPG 1430
Cdd:cd13259     96 CCDSQMEQREWMATILSAQHDG 117
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
580-696 2.50e-41

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 426250 [Multi-domain]  Cd Length: 117  Bit Score: 147.77  E-value: 2.50e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  580 YEVAEKIWFNEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVN 659
Cdd:pfam01412    1 KRVLRELLKLPGNKVCADCGAPNPTWASLNLGIFICIDCSGVHRSLGVHISKVRSLTLDT--WTDEQLEFMKAGGNDRAN 78
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1050394579  660 NIWEANLLPENMLHMDSDVSQRRLFITQKYKEGRFKK 696
Cdd:pfam01412   79 EFWEANLPPSYKPPPSSDDEKRESFIRAKYVEKKFAK 115
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
783-895 6.56e-38

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 3; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the third PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270076  Cd Length: 110  Bit Score: 137.97  E-value: 6.56e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  783 SLFYCGFLHKASSStSKMTINRKSKEvpEMKRWWCTIENNFLKYYENETAPVADGVIDLSEVLCLVVHPSDCSSNGMAAF 862
Cdd:cd13256      1 SVFHSGFLYKSPSA-AKPTLERRARE--EFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEIVCLAVSPPDTHPGDGFPF 77
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1050394579  863 TFEIYFLSERMFLFGAENVESRREWTRAIAKNF 895
Cdd:cd13256     78 TFELYLESERLYLFGLETAEALHEWVKAIAKAF 110
RA_ARAP2 cd17227
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1218-1309 4.13e-37

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2); ARAP2, also termed Centaurin-delta-1 (Cnt-d1), or Protein PARX, is a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating protein (GAP), which promotes GLUT1-mediated basal glucose uptake by modifying sphingolipid metabolism through glucosylceramide synthase (GCS). ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology. ARAP2 contains multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340747  Cd Length: 98  Bit Score: 135.02  E-value: 4.13e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1218 SGDLLIEVYVERKDPDMCVIIRVPPTMETAELTNCAMGIKNITLTEEIPWATFEVIENGELERLMHDAEKVLETVLYWSS 1297
Cdd:cd17227      1 AGDLLIEVYLEKKEPDCSIIIRVSPTMEAEELTNDVLEIKNIIPDKKDIWATFEVIENGELERPLHYKENVLEQVLQWSS 80
                           90
                   ....*....|..
gi 1050394579 1298 LSDPGAAHLLVK 1309
Cdd:cd17227     81 LSEPGSAYLIVK 92
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
384-471 1.29e-35

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 130.59  E-value: 1.29e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  384 TKTGWLEKLSPHRSC-MFQKRWVKVDGMHLSYYSNNRDMFSKGKISLSAIITLNKMGENKFEVVTIQRTFVFRAEKEEDR 462
Cdd:cd13253      1 IKSGYLDKQGGQGNNkGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNKFELVTTNRTFVFRAESDDER 80

                   ....*....
gi 1050394579  463 DDWIGTLQS 471
Cdd:cd13253     81 NLWCSTLQA 89
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
1022-1168 1.62e-35

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 425782  Cd Length: 152  Bit Score: 132.70  E-value: 1.62e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1022 PIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIkLKVGKHQLEDVTDVLKYFFYEIDDALLTKELYPY 1101
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDSGEDVD-LDLEEEDVHDVASLLKLFLRELPEPLLTFELYEE 79
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050394579 1102 WISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQT 1168
Cdd:pfam00620   80 FIEAAKSEDEEERIEALRELLEKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRP 146
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
1020-1186 3.25e-35

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 132.39  E-value: 3.25e-35
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  1020 NIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLkVGKHQLEDVTDVLKYFFYEIDDALLTKELY 1099
Cdd:smart00324    2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLD-LSEYDVHDVAGLLKLFLRELPEPLITYELY 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  1100 PYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQTNGENEQEVA-- 1177
Cdd:smart00324   81 EEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKdi 160
                           170
                    ....*....|....
gi 1050394579  1178 -----VLEDLISNY 1186
Cdd:smart00324  161 rhqntVIEFLIENA 174
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
481-570 7.05e-34

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 2; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the second PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270074  Cd Length: 90  Bit Score: 125.61  E-value: 7.05e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  481 PGLSMTEKNGYLELKGYKNKIFTVINGSKLWFSKNKQDASTGITITDLTLTMASVKNIDRKSFELSTPFRNFSLTAESER 560
Cdd:cd13254      1 PRKPNPDKCGYLELRGYKAKVYAALMGDEVWLYKNEQDFRLGIGITVIEMNGANVKDVDRRSFDLTTPYRSFSFTAESEH 80
                           90
                   ....*....|
gi 1050394579  561 EKQEWTEAIQ 570
Cdd:cd13254     81 EKQEWIEAVQ 90
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
592-694 2.41e-31

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 119.37  E-value: 2.41e-31
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:smart00105   10 NKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDT--WTEEELRLLQKGGNENANSIWESNLDDFSL 87
                            90       100
                    ....*....|....*....|....
gi 1050394579   672 LHMDSDVSQRRL-FITQKYKEGRF 694
Cdd:smart00105   88 KPPDDDDQQKYEsFIAAKYEEKLF 111
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
589-701 6.82e-30

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 121.81  E-value: 6.82e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  589 NEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLP 668
Cdd:COG5347     17 DSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDN--WTEEELRRMEVGGNSNANRFYEKNLLD 94
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1050394579  669 ENMLHMD--SDVSQRRLFITQKYKEGRFKKICFPG 701
Cdd:COG5347     95 QLLLPIKakYDSSVAKKYIRKKYELKKFIDDSSSP 129
PH4_ARAP cd13257
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
908-1003 2.17e-26

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 4; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the fourth PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270077  Cd Length: 91  Bit Score: 104.16  E-value: 2.17e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  908 FTLLGYLYYKNSYSLNQWKKAWFALDKACLH-YWNTEDCGkaDTIQLKKLQELTANSSMLNgekgNILLLVENGRTFYIH 986
Cdd:cd13257      1 FERLGRLFYKDGLALDRAREGWFALDKSSLHaCLQMQEVE--ERMHLRKLQELSIQGDVQL----DVLVLVERRRTLYIQ 74
                           90
                   ....*....|....*..
gi 1050394579  987 GHTMLDFTVWHLAIEKA 1003
Cdd:cd13257     75 GERKLDFTGWHTAIQKA 91
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
6-67 1.92e-19

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.


Pssm-ID: 188889  Cd Length: 63  Bit Score: 83.50  E-value: 1.92e-19
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1050394579    6 EQISDIVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSI 67
Cdd:cd09490      1 EADLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLPII 62
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
1328-1428 2.75e-13

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 67.19  E-value: 2.75e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  1328 MSGYMKFKEDPSKllsgNKFQERYFVLHERKLLLYKDIK---SIKHEKELPVKSCKVYAGVKKKMKpPTRWGFTI-YSEK 1403
Cdd:smart00233    3 KEGWLYKKSGGGK----KSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSS-KKPHCFEIkTSDR 77
                            90       100
                    ....*....|....*....|....*
gi 1050394579  1404 SQWHLCCDTQESQKEWLGSLFSAQH 1428
Cdd:smart00233   78 KTLLLQAESEEEREKWVEALRKAIA 102
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
574-657 1.34e-10

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 65.26  E-value: 1.34e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  574 AETLAD-YEVAEKIWFNEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIV 652
Cdd:PLN03114     3 SENLNDkISVFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDS--WSSEQLKMMIY 80

                   ....*
gi 1050394579  653 VGNEK 657
Cdd:PLN03114    81 GGNNR 85
PH pfam00169
PH domain; PH stands for pleckstrin homology.
383-471 1.80e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 59.50  E-value: 1.80e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  383 PTKTGWLEKLSPHRSCMFQKRWVKVDGMHLSYYSNNRDMFS---KGKISLSAI----ITLNKMGENK--FEVVTIQ---- 449
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSKKSkepKGSISLSGCevveVVASDSPKRKfcFELRTGErtgk 80
                           90       100
                   ....*....|....*....|..
gi 1050394579  450 RTFVFRAEKEEDRDDWIGTLQS 471
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQS 102
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
784-891 2.75e-10

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 58.71  E-value: 2.75e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   784 LFYCGFLHKASSSTSKmtinrkskevpEMKRWWCTIENNFLKYYENETAP---VADGVIDLSEvlCLVVHPSDCSSNGMA 860
Cdd:smart00233    1 VIKEGWLYKKSGGGKK-----------SWKKRYFVLFNSTLLYYKSKKDKksyKPKGSIDLSG--CTVREAPDPDSSKKP 67
                            90       100       110
                    ....*....|....*....|....*....|.
gi 1050394579   861 aFTFEIYFLSERMFLFGAENVESRREWTRAI 891
Cdd:smart00233   68 -HCFEIKTSDRKTLLLQAESEEEREKWVEAL 97
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
383-471 5.24e-10

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 57.94  E-value: 5.24e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   383 PTKTGWLEKLSPHRSCMFQKRWVKVDGMHLSYYSNNRDMFS---KGKISLSAII------TLNKMGENKFEVVTIQR-TF 452
Cdd:smart00233    1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTvreapdPDSSKKPHCFEIKTSDRkTL 80
                            90
                    ....*....|....*....
gi 1050394579   453 VFRAEKEEDRDDWIGTLQS 471
Cdd:smart00233   81 LLQAESEEEREKWVEALRK 99
PH pfam00169
PH domain; PH stands for pleckstrin homology.
1327-1428 5.95e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 57.96  E-value: 5.95e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1327 MMSGYMKFKEDPSKllsgNKFQERYFVLHERKLLLYKDIKSIKHEK---ELPVKSCKVYAGVKKKMkPPTRWGFTIY--- 1400
Cdd:pfam00169    2 VKEGWLLKKGGGKK----KSWKKRYFVLFDGSLLYYKDDKSKKSKEpkgSISLSGCEVVEVVASDS-PKRKFCFELRtge 76
                           90       100
                   ....*....|....*....|....*....
gi 1050394579 1401 -SEKSQWHLCCDTQESQKEWLGSLFSAQH 1428
Cdd:pfam00169   77 rTGKRTYLLQAESEEERKDWIKAIQSAIR 105
SAM_2 pfam07647
SAM domain (Sterile alpha motif);
9-68 6.33e-09

SAM domain (Sterile alpha motif);


Pssm-ID: 429573  Cd Length: 66  Bit Score: 53.81  E-value: 6.33e-09
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579    9 SDIVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIK 68
Cdd:pfam07647    7 ESVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
9-70 3.26e-08

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 51.53  E-value: 3.26e-08
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1050394579     9 SDIVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIKEQ 70
Cdd:smart00454    7 ESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
912-1004 8.81e-07

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 48.70  E-value: 8.81e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   912 GYLYYKNSYSLNQWKKAWFALDKACLHYWNTEDCGKADT----IQLKKLQELTANSSMLNGEKGNILLLVENGRTFYIHG 987
Cdd:smart00233    5 GWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKpkgsIDLSGCTVREAPDPDSSKKPHCFEIKTSDRKTLLLQA 84
                            90
                    ....*....|....*..
gi 1050394579   988 HTMLDFTVWHLAIEKAA 1004
Cdd:smart00233   85 ESEEEREKWVEALRKAI 101
PH pfam00169
PH domain; PH stands for pleckstrin homology.
784-891 7.47e-06

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 46.40  E-value: 7.47e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  784 LFYCGFLHKASSSTSKMTINRkskevpemkrwWCTIENNFLKYYENETAPVAD---GVIDLSEvlCLVVHPSDCSSNGmA 860
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKSWKKR-----------YFVLFDGSLLYYKDDKSKKSKepkGSISLSG--CEVVEVVASDSPK-R 66
                           90       100       110
                   ....*....|....*....|....*....|....
gi 1050394579  861 AFTFEIYFLS---ERMFLFGAENVESRREWTRAI 891
Cdd:pfam00169   67 KFCFELRTGErtgKRTYLLQAESEEERKDWIKAI 100
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
486-574 3.97e-05

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 44.08  E-value: 3.97e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   486 TEKNGYLELKGYKN-----KIFTVINGSKLWFSKNKQDASTG-----ITITDLTLTMASVKNIDRK--SFELSTPFRN-F 552
Cdd:smart00233    1 VIKEGWLYKKSGGGkkswkKRYFVLFNSTLLYYKSKKDKKSYkpkgsIDLSGCTVREAPDPDSSKKphCFEIKTSDRKtL 80
                            90       100
                    ....*....|....*....|..
gi 1050394579   553 SLTAESEREKQEWTEAIQQSIA 574
Cdd:smart00233   81 LLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
912-1003 2.86e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 41.78  E-value: 2.86e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  912 GYLYYKNSYSLNQWKKAWFALDKACLHYWNTEDCGKAD----TIQLKKLQ-ELTANSSMLNGEKGNILLLVE--NGRTFY 984
Cdd:pfam00169    5 GWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSKKSKepkgSISLSGCEvVEVVASDSPKRKFCFELRTGErtGKRTYL 84
                           90
                   ....*....|....*....
gi 1050394579  985 IHGHTMLDFTVWHLAIEKA 1003
Cdd:pfam00169   85 LQAESEEERKDWIKAIQSA 103
PRK08581 PRK08581
amidase domain-containing protein;
121-333 4.59e-04

amidase domain-containing protein;


Pssm-ID: 236304 [Multi-domain]  Cd Length: 619  Bit Score: 44.78  E-value: 4.59e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  121 SSVSKEVDHNATSQYQQTEDPNDQNKKSLEIKDHSVKHFSLDTETQLDSQNSSFFafqgpmvendIYDK-SQDDGHKSLL 199
Cdd:PRK08581    40 SHDSKKSNDDETSKDTSSKDTDKADNNNTSNQDNNDKKFSTIDSSTSDSNNIIDF----------IYKNlPQTNINQLLT 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  200 KSPPTKSFILRNRPVPKLPFSVSNTFPKCCCQERHLDNKAAQESSASKPQNQESEEQNINLISpyeetffSNSEFTKETS 279
Cdd:PRK08581   110 KNKYDDNYSLTTLIQNLFNLNSDISDYEQPRNSEKSTNDSNKNSDSSIKNDTDTQSSKQDKAD-------NQKAPSSNNT 182
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1050394579  280 GDKLNFSPNSEHNEKSLERNASTSCGSVPANNGSSPSLGDHISEESIYSTMEEY 333
Cdd:PRK08581   183 KPSTSNKQPNSPKPTQPNQSNSQPASDDTANQKSSSKDNQSMSDSALDSILDQY 236
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
1223-1309 6.99e-04

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 40.39  E-value: 6.99e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1223 IEVYVERKDPDM-CVIIRVPPTMETAELTNCAMGIKNITLTEEiPWATFEVIENGELERLMHDAEKVLETVLYWSslSDP 1301
Cdd:pfam00788    5 LKVYTEDGKPGTtYKTILVSSSTTAEEVIEALLEKFGLEDDPR-DYVLVEVLERGGGERRLPDDECPLQIQLQWP--RDA 81

                   ....*...
gi 1050394579 1302 GAAHLLVK 1309
Cdd:pfam00788   82 SDSRFLLR 89
PH pfam00169
PH domain; PH stands for pleckstrin homology.
486-574 6.60e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 37.93  E-value: 6.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  486 TEKNGYLELKGYKNKI-----FTVINGSKLWFSKNKQDASTG-----ITITDLTLT--MASVKNIDRKSFELST----PF 549
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKswkkrYFVLFDGSLLYYKDDKSKKSKepkgsISLSGCEVVevVASDSPKRKFCFELRTgertGK 80
                           90       100
                   ....*....|....*....|....*
gi 1050394579  550 RNFSLTAESEREKQEWTEAIQQSIA 574
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1007-1186 5.48e-79

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239850  Cd Length: 184  Bit Score: 258.39  E-value: 5.48e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1007 DGNALQDQQLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKHQLEDVTDVLKYFF 1086
Cdd:cd04385      1 DGPALEDQQLTDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1087 YEIDDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLF 1166
Cdd:cd04385     81 RDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLF 160
                          170       180
                   ....*....|....*....|....
gi 1050394579 1167 QT----NGENEQEVAVLEDLISNY 1186
Cdd:cd04385    161 QTdehsVGQTSHEVKVIEDLIDNY 184
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
575-695 2.31e-75

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP2 localizes to the cell periphery and on focal adhesions composed of paxillin and vinculin, and functions downstream of RhoA to regulate focal adhesion dynamics. ARAP2 is a PI(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RhoGAP domain and does not have RhoGAP activity. ARAP2 reduces Rac1oGTP levels by reducing Arf6oGTP levels through GAP activity. AGAP2 also binds to and regulates focal adhesion kinase (FAK). Thus, ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology.


Pssm-ID: 350081 [Multi-domain]  Cd Length: 121  Bit Score: 245.20  E-value: 2.31e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  575 ETLADYEVAEKIWFNEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTTIWSNELVELFIVVG 654
Cdd:cd08856      1 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVVG 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1050394579  655 NEKVNNIWEANLLPENMLHMDSDVSQRRLFITQKYKEGRFK 695
Cdd:cd08856     81 NKPANLFWAANLFSEEDLHMDSDVEQRTPFITQKYKEGKFR 121
ArfGap_ARAP cd08837
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily ...
580-695 1.54e-63

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics.


Pssm-ID: 350066 [Multi-domain]  Cd Length: 116  Bit Score: 211.47  E-value: 1.54e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  580 YEVAEKIWFNEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTTIWSNELVELFIVVGNEKVN 659
Cdd:cd08837      1 YEVAEKIWSNPANRFCADCGAPDPDWASINLCVVICKQCAGEHRSLGSNISKVRSLKMDTKVWTEELVELFLKLGNDRAN 80
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1050394579  660 NIWEANLLPENMLHMDSDVSQRRLFITQKYKEGRFK 695
Cdd:cd08837     81 RFWAANLPPSEALHPDADSEQRREFITAKYREGKYR 116
ArfGap_ARAP3 cd17902
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily ...
580-695 5.01e-56

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP3 possesses a unique dual-specificity GAP activity for Arf6 and RhoA regulated by PI(3,4,5)P3 and a small GTPase Rap1-GTP. The RhoGAP activity of ARAP3 is enhanced by direct binding of Rap1-GTP to the Ras-association (RA) domain. ARAP3 is involved in regulation of cell shape and adhesion.


Pssm-ID: 350089 [Multi-domain]  Cd Length: 116  Bit Score: 189.73  E-value: 5.01e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  580 YEVAEKIWFNEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTTIWSNELVELFIVVGNEKVN 659
Cdd:cd17902      1 YEVAEKIWSNKANRFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKLDTSVWSNEIVQLFIVLGNDRAN 80
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1050394579  660 NIWEANLLPENMLHMDSDVSQRRLFITQKYKEGRFK 695
Cdd:cd17902     81 RFWAARLPASEALHPDATPEQRREFISRKYREGRFR 116
PH5_ARAP cd13259
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
1329-1430 8.99e-51

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 5; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the five PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270079  Cd Length: 121  Bit Score: 174.93  E-value: 8.99e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1329 SGYMKFKEDPSKLLSGNKFQERYFVLHERKLLLYKDIKSIKHEKELPVKSCKVYAGVKKKMKPPTRWGFTIYSEKSQWHL 1408
Cdd:cd13259     16 HGMLKFREEPSKLLSGNKFQDRYFILNDECLLLYKDVKSSKPEKEWPLKSLKVYLGIKKKLKPPTSWGFTVLLEKQQWYL 95
                           90       100
                   ....*....|....*....|..
gi 1050394579 1409 CCDTQESQKEWLGSLFSAQHPG 1430
Cdd:cd13259     96 CCDSQMEQREWMATILSAQHDG 117
ArfGap_ARAP1 cd17901
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily ...
581-695 6.60e-47

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP1 localizes to the plasma membrane, the Golgi complex, and endosomal compartments. It displays PI(3,4,5)P3-dependent ArfGAP activity that regulates Arf-, RhoA-, and Cdc42-dependent cellular events. For example, ARAP1 inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome.


Pssm-ID: 350088 [Multi-domain]  Cd Length: 116  Bit Score: 163.83  E-value: 6.60e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  581 EVAEKIWFNEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTTIWSNELVELFIVVGNEKVNN 660
Cdd:cd17901      2 EVAEKIWSVESNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKMDRKVWTEELIELFLLLGNGKANQ 81
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1050394579  661 IWEANLLPENMLHMDSDVSQRRLFITQKYKEGRFK 695
Cdd:cd17901     82 FWAANVPPSEALCPSSSSEERRHFITAKYKEGKYR 116
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
580-696 2.50e-41

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 426250 [Multi-domain]  Cd Length: 117  Bit Score: 147.77  E-value: 2.50e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  580 YEVAEKIWFNEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVN 659
Cdd:pfam01412    1 KRVLRELLKLPGNKVCADCGAPNPTWASLNLGIFICIDCSGVHRSLGVHISKVRSLTLDT--WTDEQLEFMKAGGNDRAN 78
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1050394579  660 NIWEANLLPENMLHMDSDVSQRRLFITQKYKEGRFKK 696
Cdd:pfam01412   79 EFWEANLPPSYKPPPSSDDEKRESFIRAKYVEKKFAK 115
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
592-689 9.81e-41

GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family of proteins containing an ArfGAP catalytic domain that induces the hydrolysis of GTP bound to the small guanine nucleotide-binding protein Arf, a member of the Ras superfamily of GTPases. Like all GTP-binding proteins, Arf proteins function as molecular switches, cycling between GTP (active-membrane bound) and GDP (inactive-cytosolic) form. Conversion to the GTP-bound form requires a guanine nucleotide exchange factor (GEF), whereas conversion to the GDP-bound form is catalyzed by a GTPase activating protein (GAP). In that sense, ArfGAPs were originally proposed to function as terminators of Arf signaling, which is mediated by regulating Arf family GTP-binding proteins. However, recent studies suggest that ArfGAPs can also function as Arf effectors, independently of their GAP enzymatic activity to transduce signals in cells. The ArfGAP domain contains a C4-type zinc finger motif and a conserved arginine that is required for activity, within a specific spacing (CX2CX16CX2CX4R). ArfGAPs, which have multiple functional domains, regulate the membrane trafficking and actin cytoskeleton remodeling via specific interactions with signaling lipids such as phosphoinositides and trafficking proteins, which consequently affect cellular events such as cell growth, migration, and cancer invasion. The ArfGAP family, which includes 31 human ArfGAP-domain containing proteins, is divided into 10 subfamilies based on domain structure and sequence similarity. The ArfGAP nomenclature is mainly based on the protein domain structure. For example, ASAP1 contains ArfGAP, SH3, ANK repeat and PH domains; ARAPs contain ArfGAP, Rho GAP, ANK repeat and PH domains; ACAPs contain ArfGAP, BAR (coiled coil), ANK repeat and PH domains; and AGAPs contain Arf GAP, GTP-binding protein-like, ANK repeat and PH domains. Furthermore, the ArfGAPs can be classified into two major types of subfamilies, according to the overall domain structure: the ArfGAP1 type includes 6 subfamilies (ArfGAP1, ArfGAP2/3, ADAP, SMAP, AGFG, and GIT), which contain the ArfGAP domain at the N-terminus of the protein; and the AZAP type includes 4 subfamilies (ASAP, ACAP, AGAP, and ARAP), which contain an ArfGAP domain between the PH and ANK repeat domains.


Pssm-ID: 350058 [Multi-domain]  Cd Length: 106  Bit Score: 145.72  E-value: 9.81e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08204     10 NKVCADCGAPDPRWASINLGVFICIRCSGIHRSLGVHISKVRSLTLDS--WTPEQVELMKAIGNARANAYYEANLPPGFK 87
                           90
                   ....*....|....*....
gi 1050394579  672 L-HMDSDVSQRRLFITQKY 689
Cdd:cd08204     88 KpTPDSSDEEREQFIRAKY 106
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
783-895 6.56e-38

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 3; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the third PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270076  Cd Length: 110  Bit Score: 137.97  E-value: 6.56e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  783 SLFYCGFLHKASSStSKMTINRKSKEvpEMKRWWCTIENNFLKYYENETAPVADGVIDLSEVLCLVVHPSDCSSNGMAAF 862
Cdd:cd13256      1 SVFHSGFLYKSPSA-AKPTLERRARE--EFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEIVCLAVSPPDTHPGDGFPF 77
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1050394579  863 TFEIYFLSERMFLFGAENVESRREWTRAIAKNF 895
Cdd:cd13256     78 TFELYLESERLYLFGLETAEALHEWVKAIAKAF 110
RA_ARAP2 cd17227
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1218-1309 4.13e-37

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2); ARAP2, also termed Centaurin-delta-1 (Cnt-d1), or Protein PARX, is a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating protein (GAP), which promotes GLUT1-mediated basal glucose uptake by modifying sphingolipid metabolism through glucosylceramide synthase (GCS). ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology. ARAP2 contains multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340747  Cd Length: 98  Bit Score: 135.02  E-value: 4.13e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1218 SGDLLIEVYVERKDPDMCVIIRVPPTMETAELTNCAMGIKNITLTEEIPWATFEVIENGELERLMHDAEKVLETVLYWSS 1297
Cdd:cd17227      1 AGDLLIEVYLEKKEPDCSIIIRVSPTMEAEELTNDVLEIKNIIPDKKDIWATFEVIENGELERPLHYKENVLEQVLQWSS 80
                           90
                   ....*....|..
gi 1050394579 1298 LSDPGAAHLLVK 1309
Cdd:cd17227     81 LSEPGSAYLIVK 92
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
384-471 1.29e-35

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 130.59  E-value: 1.29e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  384 TKTGWLEKLSPHRSC-MFQKRWVKVDGMHLSYYSNNRDMFSKGKISLSAIITLNKMGENKFEVVTIQRTFVFRAEKEEDR 462
Cdd:cd13253      1 IKSGYLDKQGGQGNNkGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNKFELVTTNRTFVFRAESDDER 80

                   ....*....
gi 1050394579  463 DDWIGTLQS 471
Cdd:cd13253     81 NLWCSTLQA 89
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
1022-1168 1.62e-35

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 425782  Cd Length: 152  Bit Score: 132.70  E-value: 1.62e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1022 PIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIkLKVGKHQLEDVTDVLKYFFYEIDDALLTKELYPY 1101
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDSGEDVD-LDLEEEDVHDVASLLKLFLRELPEPLLTFELYEE 79
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050394579 1102 WISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQT 1168
Cdd:pfam00620   80 FIEAAKSEDEEERIEALRELLEKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRP 146
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
1020-1186 3.25e-35

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 132.39  E-value: 3.25e-35
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  1020 NIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLkVGKHQLEDVTDVLKYFFYEIDDALLTKELY 1099
Cdd:smart00324    2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLD-LSEYDVHDVAGLLKLFLRELPEPLITYELY 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  1100 PYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQTNGENEQEVA-- 1177
Cdd:smart00324   81 EEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKdi 160
                           170
                    ....*....|....
gi 1050394579  1178 -----VLEDLISNY 1186
Cdd:smart00324  161 rhqntVIEFLIENA 174
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
481-570 7.05e-34

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 2; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the second PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270074  Cd Length: 90  Bit Score: 125.61  E-value: 7.05e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  481 PGLSMTEKNGYLELKGYKNKIFTVINGSKLWFSKNKQDASTGITITDLTLTMASVKNIDRKSFELSTPFRNFSLTAESER 560
Cdd:cd13254      1 PRKPNPDKCGYLELRGYKAKVYAALMGDEVWLYKNEQDFRLGIGITVIEMNGANVKDVDRRSFDLTTPYRSFSFTAESEH 80
                           90
                   ....*....|
gi 1050394579  561 EKQEWTEAIQ 570
Cdd:cd13254     81 EKQEWIEAVQ 90
ArfGap_ACAP cd08835
ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP ...
592-694 2.35e-31

ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP domain is an essential part of ACAP proteins that play important role in endocytosis, actin remodeling and receptor tyrosine kinase-dependent cell movement. ACAP subfamily of ArfGAPs are composed of coiled coils (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. In addition, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350064 [Multi-domain]  Cd Length: 116  Bit Score: 119.29  E-value: 2.35e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLlpENM 671
Cdd:cd08835     13 NAQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDS--WEPELLKVMLELGNDVVNRIYEANV--PDD 88
                           90       100
                   ....*....|....*....|....*..
gi 1050394579  672 LHM----DSDVSQRRLFITQKYKEGRF 694
Cdd:cd08835     89 GSVkptpDSSRQEREAWIRAKYVEKKF 115
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
592-694 2.41e-31

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 119.37  E-value: 2.41e-31
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:smart00105   10 NKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDT--WTEEELRLLQKGGNENANSIWESNLDDFSL 87
                            90       100
                    ....*....|....*....|....
gi 1050394579   672 LHMDSDVSQRRL-FITQKYKEGRF 694
Cdd:smart00105   88 KPPDDDDQQKYEsFIAAKYEEKLF 111
RA_ARAP3 cd17228
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1218-1309 1.01e-30

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3 (ARAP3); ARAP3, also termed Centaurin-delta-3 (Cnt-d3), is a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating protein (GAP) that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members, ADP-ribosylation factor 6 (Arf6) and Ras homolog gene family member A (RhoA). It is regulated by phosphatidylinositol 3,4,5-trisphosphate and a small GTPase Rap1-GTP, and has been implicated in the regulation of cell shape and adhesion. ARAP3 contains multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340748  Cd Length: 99  Bit Score: 116.90  E-value: 1.01e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1218 SGDLLIEVYVERKDPDMCVIIRVPPTMETAELTNCAMGIKNITLTEEIPWATFEVIENGELERLMHDAEKVLETVLYWSS 1297
Cdd:cd17228      1 AGDLIIEVYLEQKLPDCCVTLKVSPTMTAEELTNQVLDMRNIAAASKDVWLTFEVIENGELERPLHPKEKVLEQALQWCK 80
                           90
                   ....*....|..
gi 1050394579 1298 LSDPGAAHLLVK 1309
Cdd:cd17228     81 LPEPSSAYLLVK 92
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
589-701 6.82e-30

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 121.81  E-value: 6.82e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  589 NEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLP 668
Cdd:COG5347     17 DSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDN--WTEEELRRMEVGGNSNANRFYEKNLLD 94
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1050394579  669 ENMLHMD--SDVSQRRLFITQKYKEGRFKKICFPG 701
Cdd:COG5347     95 QLLLPIKakYDSSVAKKYIRKKYELKKFIDDSSSP 129
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
592-694 2.14e-29

ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation factor GTPase-activating proteins; The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. Both ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350063 [Multi-domain]  Cd Length: 117  Bit Score: 113.85  E-value: 2.14e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08834     15 NDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDN--LGTSELLLARNLGNEGFNEIMEANLPPGYK 92
                           90       100
                   ....*....|....*....|...
gi 1050394579  672 LHMDSDVSQRRLFITQKYKEGRF 694
Cdd:cd08834     93 PTPNSDMEERKDFIRAKYVEKKF 115
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
592-689 2.59e-29

ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350065 [Multi-domain]  Cd Length: 108  Bit Score: 113.15  E-value: 2.59e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08836     12 NDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDD--WPVELLKVMSAIGNDLANSVWEGNTQGRTK 89
                           90
                   ....*....|....*...
gi 1050394579  672 LHMDSDVSQRRLFITQKY 689
Cdd:cd08836     90 PTPDSSREEKERWIRAKY 107
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1020-1190 8.93e-29

RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239863  Cd Length: 192  Bit Score: 114.81  E-value: 8.93e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1020 NIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKHQLED---VTDVLKYFFYEIDDALLTK 1096
Cdd:cd04398     15 NVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLISPEDYESDihsVASLLKLFFRELPEPLLTK 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1097 ELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQTNGENEQEV 1176
Cdd:cd04398     95 ALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLMNAAPDNAADM 174
                          170
                   ....*....|....*...
gi 1050394579 1177 A----VLEDLISNYVNIF 1190
Cdd:cd04398    175 SfqsrVIETLLDNAYQIF 192
RA_ARAPs cd17113
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1218-1315 1.97e-28

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing proteins ARAP1, ARAP2, ARAP3, and similar proteins; ARAPs are phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating proteins (GAPs). They contain multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340633  Cd Length: 95  Bit Score: 110.03  E-value: 1.97e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1218 SGDLLIEVYVERKDpDMCVIIRVPPTMETAELTNCAMGIKNITLTEEiPWATFEVIENGELERLMHDAEKVLETVLYWSS 1297
Cdd:cd17113      1 SGDFLIPVYIEEKE-GTSVNIKVTPTMTAEEVVEQALNKKNLGGPEG-NWALFEVIEDGGLERPLHESEKVLDVVLRWSQ 78
                           90
                   ....*....|....*...
gi 1050394579 1298 LSDPGaAHLLVKPQNTRD 1315
Cdd:cd17113     79 WPRKS-NYLCVKKNPLLE 95
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
592-666 3.02e-28

ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350061 [Multi-domain]  Cd Length: 113  Bit Score: 110.43  E-value: 3.02e-28
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANL 666
Cdd:cd08832     17 NNTCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDN--WDDSQVEFMEENGNEKAKAKYEAHV 89
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
1022-1185 3.78e-28

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.


Pssm-ID: 238090  Cd Length: 169  Bit Score: 112.01  E-value: 3.78e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1022 PIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKvgKHQLEDVTDVLKYFFYEIDDALLTKELYPY 1101
Cdd:cd00159      1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLE--DYDVHDVASLLKLYLRELPEPLIPFELYDE 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1102 WISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQTNGENEQE------ 1175
Cdd:cd00159     79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELledikk 158
                          170
                   ....*....|.
gi 1050394579 1176 -VAVLEDLISN 1185
Cdd:cd00159    159 lNEIVEFLIEN 169
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
590-689 1.13e-27

Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350068 [Multi-domain]  Cd Length: 103  Bit Score: 108.13  E-value: 1.13e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  590 EYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANlLPE 669
Cdd:cd08839      8 EDNKYCADCGAKGPRWASWNLGVFICIRCAGIHRNLGVHISKVKSVNLDS--WTPEQVQSMQEMGNARANAYYEAN-LPD 84
                           90       100
                   ....*....|....*....|
gi 1050394579  670 NMLHMDSDVSQRRlFITQKY 689
Cdd:cd08839     85 GFRRPQTDSALEN-FIRDKY 103
PH4_ARAP cd13257
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
908-1003 2.17e-26

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 4; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the fourth PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270077  Cd Length: 91  Bit Score: 104.16  E-value: 2.17e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  908 FTLLGYLYYKNSYSLNQWKKAWFALDKACLH-YWNTEDCGkaDTIQLKKLQELTANSSMLNgekgNILLLVENGRTFYIH 986
Cdd:cd13257      1 FERLGRLFYKDGLALDRAREGWFALDKSSLHaCLQMQEVE--ERMHLRKLQELSIQGDVQL----DVLVLVERRRTLYIQ 74
                           90
                   ....*....|....*..
gi 1050394579  987 GHTMLDFTVWHLAIEKA 1003
Cdd:cd13257     75 GERKLDFTGWHTAIQKA 91
ArfGap_ACAP1 cd08852
ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs ...
592-694 2.64e-25

ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350077 [Multi-domain]  Cd Length: 120  Bit Score: 102.34  E-value: 2.64e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLlpENM 671
Cdd:cd08852     13 NAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLGVHFSKVRSLTLDS--WEPELVKLMCELGNVIINQIYEARI--EAM 88
                           90       100
                   ....*....|....*....|....*..
gi 1050394579  672 L----HMDSDVSQRRLFITQKYKEGRF 694
Cdd:cd08852     89 AikkpGPSSSRQEKEAWIRAKYVEKKF 115
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
592-689 5.91e-24

The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350062 [Multi-domain]  Cd Length: 109  Bit Score: 97.76  E-value: 5.91e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDttIWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08833      8 ARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKD--QWPPSLLEMVQTLGNNGANSIWEHSLLDPSQ 85
                           90       100
                   ....*....|....*....|....
gi 1050394579  672 LHM------DSDVSQRRLFITQKY 689
Cdd:cd08833     86 SGKrkpippDPVHPTKEEFIKAKY 109
ArfGap_AGAP1 cd08854
ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation ...
592-690 1.19e-22

ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350079 [Multi-domain]  Cd Length: 109  Bit Score: 94.31  E-value: 1.19e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDttIWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08854     13 NSLCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLD--DWPRELTLVLTAIGNHMANSIWESCTQGRTK 90
                           90
                   ....*....|....*....
gi 1050394579  672 LHMDSDVSQRRLFITQKYK 690
Cdd:cd08854     91 PAPDSSREERESWIRAKYE 109
ArfGap_ArfGap1 cd08830
Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
592-671 1.48e-22

Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350059 [Multi-domain]  Cd Length: 115  Bit Score: 94.10  E-value: 1.48e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08830     14 NNRCFDCGAPNPQWASVSYGIFICLECSGVHRGLGVHISFVRSITMDS--WSEKQLKKMELGGNAKLREFFESYGISPDL 91
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
592-690 1.85e-22

ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion.


Pssm-ID: 350080 [Multi-domain]  Cd Length: 110  Bit Score: 93.58  E-value: 1.85e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08855     14 NSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDD--WPVELSMVMTAIGNAMANSVWEGALDGYSK 91
                           90
                   ....*....|....*....
gi 1050394579  672 LHMDSDVSQRRLFITQKYK 690
Cdd:cd08855     92 PGPDSTREEKERWIRAKYE 110
ArfGap_AGAP2 cd08853
ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation ...
592-690 1.35e-21

ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350078 [Multi-domain]  Cd Length: 109  Bit Score: 91.23  E-value: 1.35e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08853     13 NSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDD--WPVELRKVMSSIGNELANSIWEGSSQGQTK 90
                           90
                   ....*....|....*....
gi 1050394579  672 LHMDSDVSQRRLFITQKYK 690
Cdd:cd08853     91 PSSDSTREEKERWIRAKYE 109
ArfGap_SMAP2 cd08859
Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of ...
590-693 1.84e-21

Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350083 [Multi-domain]  Cd Length: 107  Bit Score: 90.82  E-value: 1.84e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  590 EYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEAnLLPE 669
Cdd:cd08859      8 EENKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHISRVKSVNLDQ--WTQEQIQCMQEMGNGKANRLYEA-FLPE 84
                           90       100
                   ....*....|....*....|....
gi 1050394579  670 NMLHMDSDVSQrRLFITQKYKEGR 693
Cdd:cd08859     85 NFRRPQTDQAV-EGFIRDKYEKKK 107
ArfGap_ASAP1 cd08848
ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); ...
592-698 4.89e-21

ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350073 [Multi-domain]  Cd Length: 122  Bit Score: 90.09  E-value: 4.89e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDtTIWSNELVeLFIVVGNEKVNNIWEANLL-PEN 670
Cdd:cd08848     15 NEVCCDCGSPDPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELD-KLGTSELL-LAKNVGNNSFNDIMEGNLPsPSP 92
                           90       100
                   ....*....|....*....|....*....
gi 1050394579  671 MLHMDSDVSQRRLFITQKYKEGRF-KKIC 698
Cdd:cd08848     93 KPSPSSDMTARKEYITAKYVEHRFsRKTC 121
ArfGap_ACAP3 cd08850
ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs ...
592-694 5.01e-21

ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. It has been shown that ACAP3 positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) also have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages.


Pssm-ID: 350075 [Multi-domain]  Cd Length: 116  Bit Score: 90.00  E-value: 5.01e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08850     13 NDQCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDS--WEPELLKLMCELGNSTVNQIYEAQCEELGL 90
                           90       100
                   ....*....|....*....|....*
gi 1050394579  672 LHMDSDVSQ--RRLFITQKYKEGRF 694
Cdd:cd08850     91 KKPTASSSRqdKEAWIKAKYVEKKF 115
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
592-694 1.26e-20

ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350076 [Multi-domain]  Cd Length: 116  Bit Score: 88.89  E-value: 1.26e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLlpENM 671
Cdd:cd08851     13 NASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDT--WEPELLKLMCELGNDVINRIYEARV--EKM 88
                           90       100
                   ....*....|....*....|....*..
gi 1050394579  672 -LHMDSDVSQRR---LFITQKYKEGRF 694
Cdd:cd08851     89 gAKKPQPGGQRQekeAYIRAKYVERKF 115
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1006-1172 2.11e-20

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239860  Cd Length: 196  Bit Score: 90.92  E-value: 2.11e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1006 TDGNALQDQQLSKNN--IPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKHQ-LEDVTDVL 1082
Cdd:cd04395      1 TFGVPLDDCPPSSENpyVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRdVNVVSSLL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1083 KYFFYEIDDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFS 1162
Cdd:cd04395     81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160
                          170
                   ....*....|
gi 1050394579 1163 SCLFQTNGEN 1172
Cdd:cd04395    161 PTLVRTSDDN 170
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
6-67 1.92e-19

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.


Pssm-ID: 188889  Cd Length: 63  Bit Score: 83.50  E-value: 1.92e-19
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1050394579    6 EQISDIVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSI 67
Cdd:cd09490      1 EADLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLPII 62
ArfGap_ASAP3 cd17900
ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ...
592-694 2.12e-19

ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP1 and ASAP2, ASAP3 do not have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350087 [Multi-domain]  Cd Length: 124  Bit Score: 85.67  E-value: 2.12e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDtTIWSNELVeLFIVVGNEKVNNIWEANL----- 666
Cdd:cd17900     15 NSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYSRIQSLTLD-LLSTSELL-LAVSMGNTRFNEVMEATLpahgg 92
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1050394579  667 ---LPEnmlhmdSDVSQRRLFITQKYKEGRF 694
Cdd:cd17900     93 pkpSAE------SDMGTRKDYIMAKYVEHRF 117
ArfGap_ArfGap2_3_like cd08831
Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
592-671 4.45e-19

Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350060 [Multi-domain]  Cd Length: 116  Bit Score: 84.13  E-value: 4.45e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08831     15 NKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLGVHISFVRSTNLDS--WTPEQLRRMKVGGNAKAREFFKQHGGLLSG 92
ArfGap_ArfGap1_like cd08959
ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
592-671 5.86e-19

ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350084 [Multi-domain]  Cd Length: 115  Bit Score: 83.72  E-value: 5.86e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08959     14 NKVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGVHISFVRSTTMDK--WTEEQLRKMKVGGNANAREFFKQHGIYDSM 91
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
592-668 8.35e-19

ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350070 [Multi-domain]  Cd Length: 112  Bit Score: 83.28  E-value: 8.35e-19
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLgSNISKVHSLILDttIWSNELVELFIVVGNEKVNNIWEANLLP 668
Cdd:cd08844     17 NSVCADCGAPDPDWASYTLGIFICLNCSGVHRNL-PDISRVKSIRLD--FWEDELVEFMKENGNLKAKAKFEAFVPP 90
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1018-1169 2.92e-18

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239842  Cd Length: 186  Bit Score: 84.41  E-value: 2.92e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1018 KNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKvgKHQLEDVTDVLKYFFYEIDDALLTKE 1097
Cdd:cd04377     12 DRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLE--DYPIHVITSVLKQWLRELPEPLMTFE 89
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1050394579 1098 LYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQTN 1169
Cdd:cd04377     90 LYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRCP 161
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
592-696 1.73e-17

ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2); The Arf GAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf , thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport.


Pssm-ID: 350074 [Multi-domain]  Cd Length: 123  Bit Score: 80.02  E-value: 1.73e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDtTIWSNELVeLFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd08849     15 NDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLD-VLGTSELL-LAKNIGNAGFNEIMEACLPAEDV 92
                           90       100
                   ....*....|....*....|....*..
gi 1050394579  672 LHMD--SDVSQRRLFITQKYKEGRFKK 696
Cdd:cd08849     93 VKPNpgSDMNARKDYITAKYIERRYAR 119
ArfGap_GIT2 cd08847
GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
595-689 4.57e-16

GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350072 [Multi-domain]  Cd Length: 111  Bit Score: 75.44  E-value: 4.57e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  595 CADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSliLDTTIWSNELVELFIVVGNEKVNNIWEANLL-PENML- 672
Cdd:cd08847     11 CADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRH--LKHTSWPPTLLQMVQTLYNNGANSIWEHSLLdPASIMs 88
                           90       100
                   ....*....|....*....|...
gi 1050394579  673 ------HMDSDVSQRRLFITQKY 689
Cdd:cd08847     89 gkrkanPQDKVHPNKAEFIRAKY 111
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1017-1190 5.25e-16

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239849 [Multi-domain]  Cd Length: 195  Bit Score: 77.93  E-value: 5.25e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1017 SKNNIPIIVNSCIAFVTQYGLgSKSLYLKNGNPSPVRELLEEFKRDAR-SIKLKVGKHQLEDVTDVLKYFFYEIDDALLT 1095
Cdd:cd04384     14 SGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIpDLTKDVYIQDIHSVSSLCKLYFRELPNPLLT 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1096 KELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQT----NGE 1171
Cdd:cd04384     93 YQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRSkqieSAC 172
                          170
                   ....*....|....*....
gi 1050394579 1172 NEQEVAVLEDLISNYVNIF 1190
Cdd:cd04384    173 FSGTAAFMEVRIQSVVVEF 191
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1018-1167 9.91e-16

RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239872 [Multi-domain]  Cd Length: 186  Bit Score: 76.95  E-value: 9.91e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1018 KNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKvgKHQLEDVTDVLKYFFYEIDDALLTKE 1097
Cdd:cd04407     12 KTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLE--NYPIHAITGLLKQWLRELPEPLMTFA 89
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1098 LYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQ 1167
Cdd:cd04407     90 QYNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLR 159
ArfGap_ADAP1 cd08843
ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
592-668 1.24e-15

ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350069 [Multi-domain]  Cd Length: 112  Bit Score: 74.27  E-value: 1.24e-15
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLgSNISKVHSLILDTtiWSNELVELFIVVGNEKVNNIWEANLLP 668
Cdd:cd08843     17 NARCADCGAPDPDWASYTLGVFICLSCSGIHRNI-PQVSKVKSVRLDA--WEEAQVEFMASHGNDAARARFESKVPS 90
ArfGap_AGFG cd08838
ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ...
590-694 3.03e-15

ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350067 [Multi-domain]  Cd Length: 113  Bit Score: 73.38  E-value: 3.03e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  590 EYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGsniSKVHSliLDTTIWSNELVELFIVVGNEKVNNIWEANLLPE 669
Cdd:cd08838     11 PENKRCFDCGQRGPTYVNLTFGTFVCTTCSGIHREFN---HRVKS--ISMSTFTPEEVEFLQAGGNEVARKIWLAKWDPR 85
                           90       100
                   ....*....|....*....|....*.
gi 1050394579  670 NMLHMDS-DVSQRRLFITQKYKEGRF 694
Cdd:cd08838     86 TDPEPDSgDDQKIREFIRLKYVDKRW 111
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1011-1161 1.05e-14

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239869  Cd Length: 195  Bit Score: 74.30  E-value: 1.05e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1011 LQDQQLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDarsikLKVGKHQLEDV---TDVLKYFFY 1087
Cdd:cd04404     13 LKEKNPEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMG-----EPVDFDQYEDVhlpAVILKTFLR 87
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1050394579 1088 EIDDALLTKELYPYWISALDIRNDqERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAF 1161
Cdd:cd04404     88 ELPEPLLTFDLYDDIVGFLNVDKE-ERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
385-471 1.59e-14

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 70.70  E-value: 1.59e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPHRSCMFQKRWVKVDGMHLSYYSNNRDMFSKGKISL-----------SAIITLNKMGENKFEVVTIQRTFV 453
Cdd:cd01251      4 KEGYLEKTGPKQTDGFRKRWFTLDDRRLMYFKDPLDAFPKGEIFIgskeegysvreGLPPGIKGHWGFGFTLVTPDRTFL 83
                           90
                   ....*....|....*...
gi 1050394579  454 FRAEKEEDRDDWIGTLQS 471
Cdd:cd01251     84 LSAETEEERREWITAIQK 101
ArfGap_GIT1 cd08846
GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
595-667 2.93e-14

GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350071 [Multi-domain]  Cd Length: 111  Bit Score: 70.52  E-value: 2.93e-14
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1050394579  595 CADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSliLDTTIWSNELVELFIVVGNEKVNNIWEANLL 667
Cdd:cd08846     11 CADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKH--LRHSAWPPTLLQMVHTLASNGANSIWEHSLL 81
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1008-1166 2.98e-14

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239838  Cd Length: 185  Bit Score: 72.49  E-value: 2.98e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1008 GNALQDQQLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDaRSIKLKVGKHQLEDVTDVLKYFFY 1087
Cdd:cd04373      2 GVPLANVVTSEKPIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQD-HNLDLVSKDFTVNAVAGALKSFFS 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1050394579 1088 EIDDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLF 1166
Cdd:cd04373     81 ELPDPLIPYSMHLELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLM 159
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
1015-1175 4.55e-14

RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239868 [Multi-domain]  Cd Length: 187  Bit Score: 72.04  E-value: 4.55e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1015 QLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELleEFKRDaRSIKLKVGKHQLED---VTDVLKYFFYEIDD 1091
Cdd:cd04403     10 QRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKL--RFAVD-HDEKLDLDDSKWEDihvITGALKLFFRELPE 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1092 ALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQtnge 1171
Cdd:cd04403     87 PLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLR---- 162

                   ....
gi 1050394579 1172 NEQE 1175
Cdd:cd04403    163 PEQE 166
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1008-1152 7.93e-14

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239848  Cd Length: 188  Bit Score: 71.68  E-value: 7.93e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1008 GNALQDQQLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKHQLEDVTDVLKYFFY 1087
Cdd:cd04383      5 GSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLKLYFR 84
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1050394579 1088 EIDDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPdlnkATLAALMEHLFRIqkcfdINHL 1152
Cdd:cd04383     85 GLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLP----RSVIIVMRYLFAF-----LNHL 140
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
1021-1167 1.26e-13

RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239873  Cd Length: 200  Bit Score: 71.39  E-value: 1.26e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1021 IPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKvgKHQLEDVTDVLKYFFYEIDDALLTKELYP 1100
Cdd:cd04408     16 VPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDLS--GHSPHDITSVLKHFLKELPEPVLPFQLYD 93
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1050394579 1101 YWIS-ALDIRNDQER-----------VRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQ 1167
Cdd:cd04408     94 DFIAlAKELQRDSEKaaespsiveniIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIVFGPTLLR 172
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1021-1195 1.61e-13

RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239841  Cd Length: 206  Bit Score: 70.93  E-value: 1.61e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1021 IPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRdARSIKLkVGKHQLEDVTDVLKYFFYEIDDALLTKELYP 1100
Cdd:cd04376      9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDR-GIDVVL-DENHSVHDVAALLKEFFRDMPDPLLPRELYT 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1101 YWISALDIRNDqERVRKYKNIIGTLPDLNKATLAALMEHLFRIQ-----------KCFDINHLDTLTLAKAFSSCLFQ-- 1167
Cdd:cd04376     87 AFIGTALLEPD-EQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAehaadsidedgQEVSGNKMTSLNLATIFGPNLLHkq 165
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1050394579 1168 ------------TNGENEQEVAVLEDLISNYVNIFNVSED 1195
Cdd:cd04376    166 ksgerefvqaslRIEESTAIINVVQTMIDNYEELFMVSPE 205
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
1328-1428 2.75e-13

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 67.19  E-value: 2.75e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  1328 MSGYMKFKEDPSKllsgNKFQERYFVLHERKLLLYKDIK---SIKHEKELPVKSCKVYAGVKKKMKpPTRWGFTI-YSEK 1403
Cdd:smart00233    3 KEGWLYKKSGGGK----KSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSS-KKPHCFEIkTSDR 77
                            90       100
                    ....*....|....*....|....*
gi 1050394579  1404 SQWHLCCDTQESQKEWLGSLFSAQH 1428
Cdd:smart00233   78 KTLLLQAESEEEREKWVEALRKAIA 102
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1011-1185 3.50e-13

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by up several orders of magnitude.


Pssm-ID: 239858 [Multi-domain]  Cd Length: 189  Bit Score: 69.80  E-value: 3.50e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1011 LQDQQLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEefkrdarsiKLKVGKHQ-LEDVTDV------LK 1083
Cdd:cd04393     10 LQQAGQPENGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQ---------RLDSGEEVdLSKEADVcsaaslLR 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1084 YFFYEIDDALLTKELYPYWISAL-DIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFS 1162
Cdd:cd04393     81 LFLQELPEGLIPASLQIRLMQLYqDYNGEDEFGRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFG 160
                          170       180
                   ....*....|....*....|....*....
gi 1050394579 1163 SCLFQT----NGENEQE--VAVLEDLISN 1185
Cdd:cd04393    161 PDVFHVytdvEDMKEQEicSRIMAKLLEN 189
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1021-1150 3.75e-13

RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239843  Cd Length: 203  Bit Score: 69.76  E-value: 3.75e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1021 IPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRdarsiklkvGKHQLE-------DVTDVLKYFFYEIDDAL 1093
Cdd:cd04378     16 VPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFEN---------GKDLVElselsphDISSVLKLFLRQLPEPL 86
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050394579 1094 LTKELYPYWIS-ALDIRNDQER-------------VRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDIN 1150
Cdd:cd04378     87 ILFRLYNDFIAlAKEIQRDTEEdkapntpievnriIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEEN 157
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
385-469 5.47e-13

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 66.03  E-value: 5.47e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPHRSCMFQKRWVKVDGMHLSYYSNNRDMFS--KGKISLSAIITL----NKMGENKFEVVT-IQRTFVFRAE 457
Cdd:cd00821      1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYkpKGSIPLSGILEVeevsPKERPHCFELVTpDGRTYYLQAD 80
                           90
                   ....*....|..
gi 1050394579  458 KEEDRDDWIGTL 469
Cdd:cd00821     81 SEEERQEWLKAL 92
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1008-1190 6.23e-13

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239867  Cd Length: 192  Bit Score: 68.86  E-value: 6.23e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1008 GNALQDQqLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEefkrdarsiKLKVGKHQLED------VTDV 1081
Cdd:cd04402      3 GQPLSNI-CEDDNLPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKE---------KLNSGVEVDLKaepvllLASV 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1082 LKYFFYEIDDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAF 1161
Cdd:cd04402     73 LKDFLRNIPGSLLSSDLYEEWMSALDQENEEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCI 152
                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1050394579 1162 SSCLFQTNGENEQEVAVLED-------LISNYVNIF 1190
Cdd:cd04402    153 APSLLWPPASSELQNEDLKKvtslvqfLIENCQEIF 188
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
1021-1167 4.36e-12

RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239852 [Multi-domain]  Cd Length: 196  Bit Score: 66.88  E-value: 4.36e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1021 IPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKHQLEDVTDVLKYFFYEIDDALLTKELYP 1100
Cdd:cd04387     16 VPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLYFRELPEPLFTDELYP 95
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050394579 1101 YWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQ 1167
Cdd:cd04387     96 NFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLR 162
RhoGAP_myosin_IXA cd04406
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1021-1167 4.58e-12

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239871  Cd Length: 186  Bit Score: 66.56  E-value: 4.58e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1021 IPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKvgKHQLEDVTDVLKYFFYEIDDALLTKELYP 1100
Cdd:cd04406     15 VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVNLD--DYNIHVIASVFKQWLRDLPNPLMTFELYE 92
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050394579 1101 YWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQ 1167
Cdd:cd04406     93 EFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILR 159
ArfGap_ArfGap2 cd09029
Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
592-643 1.11e-11

Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350086 [Multi-domain]  Cd Length: 120  Bit Score: 63.16  E-value: 1.11e-11
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTTiWS 643
Cdd:cd09029     19 NKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHLSFIRSTELDSN-WN 69
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1008-1191 1.15e-11

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239851  Cd Length: 203  Bit Score: 65.56  E-value: 1.15e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1008 GNALQDQ-QLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFkrDARSIKLKVgKHQLED---VTDVLK 1083
Cdd:cd04386      6 GTPLEEHlKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAAL--DAGTFSLPL-DEFYSDphaVASALK 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1084 YFFYEIDDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSS 1163
Cdd:cd04386     83 SYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAP 162
                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1050394579 1164 CLFQTNGENEQE----------VAVLEDLISNYVNIFN 1191
Cdd:cd04386    163 NLLWAKNEGSLAemaagtsvhvVAIVELIISHADWFFP 200
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
385-471 1.72e-11

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 61.93  E-value: 1.72e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSpHRSCMFQKRWVKVDGMHLSYYSNNRDMFSK--GKISLSAIITLNKM-GENKFEVVTIQRTFVFRAEKEED 461
Cdd:cd13282      1 KAGYLTKLG-GKVKTWKRRWFVLKNGELFYYKSPNDVIRKpqGQIALDGSCEIARAeGAQTFEIVTEKRTYYLTADSEND 79
                           90
                   ....*....|
gi 1050394579  462 RDDWIGTLQS 471
Cdd:cd13282     80 LDEWIRVIQN 89
ArfGap_ArfGap3 cd09028
Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
592-643 2.91e-11

Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350085 [Multi-domain]  Cd Length: 120  Bit Score: 62.01  E-value: 2.91e-11
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTTiWS 643
Cdd:cd09028     19 NKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIRSTELDSN-WS 69
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1015-1190 5.18e-11

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239837  Cd Length: 194  Bit Score: 63.30  E-value: 5.18e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1015 QLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKH-QLEDVTDVLKYFFYEIDDAL 1093
Cdd:cd04372     10 KAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYpDINVITGALKLYFRDLPIPV 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1094 LTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQTNGENE 1173
Cdd:cd04372     90 ITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPEDSA 169
                          170       180
                   ....*....|....*....|....*
gi 1050394579 1174 --------QEVAVLEDLISNYVNIF 1190
Cdd:cd04372    170 lttlndmrYQILIVQLLITNEDVLF 194
RA_ARAP1 cd17226
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1218-1311 6.66e-11

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1); ARAP1, also termed Centaurin-delta-2 (Cnt-d2), is a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating protein (GAP) that inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome. It associates with the Cbl-interacting protein of 85 kDa (CIN85), regulates endocytic trafficking of the EGFR, and thus affects ubiquitination of EGFR. It also regulates the ring size of circular dorsal ruffles through Arf1 and Arf5. ARAP1 contains multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340746  Cd Length: 93  Bit Score: 60.25  E-value: 6.66e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1218 SGDLLIEVYVERKDPDMCVIIRVPPTMETAELTNCAMGIKNITLTEEIPWATFEVIENGELERLMHDAEKVLEtvLYWSS 1297
Cdd:cd17226      1 SPDFICTVYLEEKKEGSEQHVQVPASMTAEELTFEILDRRNIHTREKDYWSCFEVNEREEAERPLHFSEKVLP--IFHSL 78
                           90
                   ....*....|....
gi 1050394579 1298 LSDpgaAHLLVKPQ 1311
Cdd:cd17226     79 GSD---SHLVVKKH 89
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
574-657 1.34e-10

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 65.26  E-value: 1.34e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  574 AETLAD-YEVAEKIWFNEYNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVHSLILDTtiWSNELVELFIV 652
Cdd:PLN03114     3 SENLNDkISVFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDS--WSSEQLKMMIY 80

                   ....*
gi 1050394579  653 VGNEK 657
Cdd:PLN03114    81 GGNNR 85
PH pfam00169
PH domain; PH stands for pleckstrin homology.
383-471 1.80e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 59.50  E-value: 1.80e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  383 PTKTGWLEKLSPHRSCMFQKRWVKVDGMHLSYYSNNRDMFS---KGKISLSAI----ITLNKMGENK--FEVVTIQ---- 449
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSKKSkepKGSISLSGCevveVVASDSPKRKfcFELRTGErtgk 80
                           90       100
                   ....*....|....*....|..
gi 1050394579  450 RTFVFRAEKEEDRDDWIGTLQS 471
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQS 102
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
784-891 2.75e-10

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 58.71  E-value: 2.75e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   784 LFYCGFLHKASSSTSKmtinrkskevpEMKRWWCTIENNFLKYYENETAP---VADGVIDLSEvlCLVVHPSDCSSNGMA 860
Cdd:smart00233    1 VIKEGWLYKKSGGGKK-----------SWKKRYFVLFNSTLLYYKSKKDKksyKPKGSIDLSG--CTVREAPDPDSSKKP 67
                            90       100       110
                    ....*....|....*....|....*....|.
gi 1050394579   861 aFTFEIYFLSERMFLFGAENVESRREWTRAI 891
Cdd:smart00233   68 -HCFEIKTSDRKTLLLQAESEEEREKWVEAL 97
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
383-471 5.24e-10

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 57.94  E-value: 5.24e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   383 PTKTGWLEKLSPHRSCMFQKRWVKVDGMHLSYYSNNRDMFS---KGKISLSAII------TLNKMGENKFEVVTIQR-TF 452
Cdd:smart00233    1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTvreapdPDSSKKPHCFEIKTSDRkTL 80
                            90
                    ....*....|....*....
gi 1050394579   453 VFRAEKEEDRDDWIGTLQS 471
Cdd:smart00233   81 LLQAESEEEREKWVEALRK 99
PH pfam00169
PH domain; PH stands for pleckstrin homology.
1327-1428 5.95e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 57.96  E-value: 5.95e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1327 MMSGYMKFKEDPSKllsgNKFQERYFVLHERKLLLYKDIKSIKHEK---ELPVKSCKVYAGVKKKMkPPTRWGFTIY--- 1400
Cdd:pfam00169    2 VKEGWLLKKGGGKK----KSWKKRYFVLFDGSLLYYKDDKSKKSKEpkgSISLSGCEVVEVVASDS-PKRKFCFELRtge 76
                           90       100
                   ....*....|....*....|....*....
gi 1050394579 1401 -SEKSQWHLCCDTQESQKEWLGSLFSAQH 1428
Cdd:pfam00169   77 rTGKRTYLLQAESEEERKDWIKAIQSAIR 105
SAM_2 pfam07647
SAM domain (Sterile alpha motif);
9-68 6.33e-09

SAM domain (Sterile alpha motif);


Pssm-ID: 429573  Cd Length: 66  Bit Score: 53.81  E-value: 6.33e-09
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579    9 SDIVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIK 68
Cdd:pfam07647    7 ESVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
1328-1423 7.57e-09

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 54.47  E-value: 7.57e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1328 MSGYMKFKEDPSKllsgNKFQERYFVLHERKLLLYKDIK--SIKHEKELPV-KSCKVYAGVKKKMKPptrwGFTIYSEKS 1404
Cdd:cd00821      1 KEGYLLKRGGGGL----KSWKKRWFVLFEGVLLYYKSKKdsSYKPKGSIPLsGILEVEEVSPKERPH----CFELVTPDG 72
                           90       100
                   ....*....|....*....|
gi 1050394579 1405 Q-WHLCCDTQESQKEWLGSL 1423
Cdd:cd00821     73 RtYYLQADSEEERQEWLKAL 92
RhoGap_RalBP1 cd04381
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
997-1140 7.81e-09

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239846 [Multi-domain]  Cd Length: 182  Bit Score: 56.67  E-value: 7.81e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  997 HLAIEKAAGTDGNalqdqqlsknNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSiklKVGKHQLE 1076
Cdd:cd04381      6 SLAVERSRCHDGI----------DLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESP---NLEEYEPP 72
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1050394579 1077 DVTDVLKYFFYEIDDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHL 1140
Cdd:cd04381     73 TVASLLKQYLRELPEPLLTKELMPRFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHM 136
RhoGAP_fRGD2 cd04399
RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1053-1190 9.14e-09

RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD2-like proteins. Yeast Rgd2 is a GAP protein for Cdc42 and Rho5. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239864  Cd Length: 212  Bit Score: 57.34  E-value: 9.14e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1053 RELLEE-FKRDARSIKLKvgKHQLEDVTDVLKYFFYEIDDALLT-------KELYPYWiSALDIRNDQERVRKYKNIIGT 1124
Cdd:cd04399     57 RNLLNKpKKPDKEVIILK--KFEPSTVASVLKLYLLELPDSLIPhdiydliRSLYSAY-PPSQEDSDTARIQGLQSTLSQ 133
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1050394579 1125 LPDLNKATLAALMEHLFR---IQKCFDINHLDTLTLAKA----FSSCLFQTNG--ENEQEVAVLEDLISNYVNIF 1190
Cdd:cd04399    134 LPKSHIATLDAIITHFYRlieITKMGESEEEYADKLATSlsreILRPIIESLLtiGDKHGYKFFRDLLTHKDQIF 208
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
784-893 1.81e-08

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275402  Cd Length: 116  Bit Score: 53.78  E-value: 1.81e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  784 LFYcGFLHKASSSTSKM-TINRKSKEVPEMKRWWCTIENNFLKYYENETAP-VADGVIDLSEVLCLVVhpsdCSSNGMAA 861
Cdd:cd13215      9 CFF-AYLPKRSGAVIKSgYLSKRSKRTLRYTRYWFVLKGDTLSWYNSSTDLyFPAGTIDLRYATSIEL----SKSNGEAT 83
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1050394579  862 FTFEIyFLSERMFLFGAENVESRREWTRAIAK 893
Cdd:cd13215     84 TSFKI-VTNSRTYKFKADSETSADEWVKALKK 114
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
488-574 1.95e-08

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 53.38  E-value: 1.95e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  488 KNGYLeLKGYKNKIFT------VINGSKLWFSKNKQDASTGITITDLTL-TMASVKNIDRK-SFELSTPFRNFSLTAESE 559
Cdd:cd13250      1 KEGYL-FKRSSNAFKTwkrrwfSLQNGQLYYQKRDKKDEPTVMVEDLRLcTVKPTEDSDRRfCFEVISPTKSYMLQAESE 79
                           90
                   ....*....|....*
gi 1050394579  560 REKQEWTEAIQQSIA 574
Cdd:cd13250     80 EDRQAWIQAIQSAIA 94
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
385-466 2.71e-08

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 53.19  E-value: 2.71e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPHRScMFQKRWVKVDGMHLSYYSNNRDMFSKGKISLSAIITLN----KMGENKFEVVTIQRTFVFRAEKEE 460
Cdd:cd13255      8 KAGYLEKKGERRK-TWKKRWFVLRPTKLAYYKNDKEYRLLRLIDLTDIHTCTevqlKKHDNTFGIVTPARTFYVQADSKA 86

                   ....*.
gi 1050394579  461 DRDDWI 466
Cdd:cd13255     87 EMESWI 92
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1021-1166 2.81e-08

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239844  Cd Length: 207  Bit Score: 55.94  E-value: 2.81e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1021 IPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLkvGKHQLEDV---TDVLKYFFYEIDDALLTKE 1097
Cdd:cd04379     18 VPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVEL--SEELYPDInviTGVLKDYLRELPEPLITPQ 95
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1050394579 1098 LYPYWISALDIR--NDQERVRKY-KNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLF 1166
Cdd:cd04379     96 LYEMVLEALAVAlpNDVQTNTHLtLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAVCFGPVLM 167
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
9-70 3.26e-08

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 51.53  E-value: 3.26e-08
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1050394579     9 SDIVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIKEQ 70
Cdd:smart00454    7 ESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1011-1150 6.01e-08

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239856  Cd Length: 216  Bit Score: 55.04  E-value: 6.01e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1011 LQDQQLSKN-NIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKHQLEDVTDVLKYFFYEI 1089
Cdd:cd04391     11 ERDQKKVPGsKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAKFYEGTFLWDQVKQHDAASLLKLFIREL 90
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050394579 1090 DDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDIN 1150
Cdd:cd04391     91 PQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKN 151
RhoGAP_fLRG1 cd04397
RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1017-1142 6.18e-08

RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal LRG1-like proteins. Yeast Lrg1p is required for efficient cell fusion, and mother-daughter cell separation, possibly through acting as a RhoGAP specifically regulating 1,3-beta-glucan synthesis. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239862  Cd Length: 213  Bit Score: 54.68  E-value: 6.18e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1017 SKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKHQLEdVTDVLKYFFYEIDDALLTK 1096
Cdd:cd04397     23 GKLRIPALIDDIISAMRQMDMSVEGVFRKNGNIRRLKELTEEIDKNPTEVPDLSKENPVQ-LAALLKKFLRELPDPLLTF 101
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1050394579 1097 ELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATlaalMEHLFR 1142
Cdd:cd04397    102 KLYRLWISSQKIEDEEERKRVLHLVYCLLPKYHRDT----MEVLFS 143
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
401-471 1.02e-07

Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called Collagen type IV alpha-3-binding protein/hCERT; START domain-containing protein 11/StARD11; StAR-related lipid transfer protein 11) is a kinase that phosphorylates an N-terminal region of the alpha 3 chain of type IV collagen, which is commonly known as the goodpasture antigen. Its splice variant the ceramide transporter (CERT) mediates the cytosolic transport of ceramide. There have been additional splice variants identified, but all of them function as ceramide transport proteins. GPBP and CERT both contain an N-terminal PH domain, followed by a serine rich domain, and a C-terminal START domain. However, GPBP has an additional serine rich domain just upstream of its START domain. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270100 [Multi-domain]  Cd Length: 100  Bit Score: 51.52  E-value: 1.02e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1050394579  401 QKRWVKVDGMHLSYY--SNNRDMFSKGKISLS-AIITLNKMGENKFEVVTIQRTFVFRAEKEEDRDDWIGTLQS 471
Cdd:cd13283     16 QDRYFVLKDGTLSYYksESEKEYGCRGSISLSkAVIKPHEFDECRFDVSVNDSVWYLRAESPEERQRWIDALES 89
SAM_EPH-B4 cd09554
SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
15-70 1.40e-07

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.


Pssm-ID: 188953  Cd Length: 67  Bit Score: 49.86  E-value: 1.40e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1050394579   15 LADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIKEQ 70
Cdd:cd09554     10 LRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLRMGVTLAGHQKKILSSIQAMGIQ 65
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
786-891 1.86e-07

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 50.23  E-value: 1.86e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  786 YCGFLHKassstskmtinrksKEVPEMKRW---WCTIENNFLKYYENETAP--VADGVIDLSEVLCLVVHPSDCSSNgma 860
Cdd:cd00821      1 KEGYLLK--------------RGGGGLKSWkkrWFVLFEGVLLYYKSKKDSsyKPKGSIPLSGILEVEEVSPKERPH--- 63
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1050394579  861 afTFEIYFLSERMFLFGAENVESRREWTRAI 891
Cdd:cd00821     64 --CFELVTPDGRTYYLQADSEEERQEWLKAL 92
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
371-470 2.76e-07

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275402  Cd Length: 116  Bit Score: 50.70  E-value: 2.76e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  371 SPYACFYgpSSMPT------KTGWLEKLSPHRScMFQKRWVKVDGMHLSYYSNNRDM-FSKGKISLSAII---TLNKMGE 440
Cdd:cd13215      5 SKHLCFF--AYLPKrsgaviKSGYLSKRSKRTL-RYTRYWFVLKGDTLSWYNSSTDLyFPAGTIDLRYATsieLSKSNGE 81
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1050394579  441 N--KFEVVTIQRTFVFRAEKEEDRDDWIGTLQ 470
Cdd:cd13215     82 AttSFKIVTNSRTYKFKADSETSADEWVKALK 113
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
386-471 4.46e-07

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269966  Cd Length: 102  Bit Score: 49.63  E-value: 4.46e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  386 TGWLEKLSPHRSCM--FQKRWVKVD--GMHLSYYSNNRDMFSKGKISLS-AIITLN-KMGENKFEVVTIQRTFVFRAEKE 459
Cdd:cd01265      3 CGYLNKLETRGLGLkgWKRRWFVLDesKCQLYYYRSPQDATPLGSIDLSgAAFSYDpEAEPGQFEIHTPGRVHILKASTR 82
                           90
                   ....*....|..
gi 1050394579  460 EDRDDWIGTLQS 471
Cdd:cd01265     83 QAMLYWLQALQS 94
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
912-1004 8.81e-07

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 48.70  E-value: 8.81e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   912 GYLYYKNSYSLNQWKKAWFALDKACLHYWNTEDCGKADT----IQLKKLQELTANSSMLNGEKGNILLLVENGRTFYIHG 987
Cdd:smart00233    5 GWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKpkgsIDLSGCTVREAPDPDSSKKPHCFEIKTSDRKTLLLQA 84
                            90
                    ....*....|....*..
gi 1050394579   988 HTMLDFTVWHLAIEKAA 1004
Cdd:smart00233   85 ESEEEREKWVEALRKAI 101
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
500-572 9.81e-07

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270093  Cd Length: 97  Bit Score: 48.55  E-value: 9.81e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1050394579  500 KIFTVINGSKLWFSKNKQDAS-TGITITDLTLTMASVKNIDRkSFELSTPFRNFSLTAESEREKQEWTEAIQQS 572
Cdd:cd13274     18 RRYFKLKGRKLYYAKDSKSLIfEEIDLSDASVAECSTKNVNN-SFTVITPFRKLILCAESRKEMEEWISALKTV 90
SAM_EPH-A5 cd09546
SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
15-71 1.22e-06

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.


Pssm-ID: 188945  Cd Length: 66  Bit Score: 47.23  E-value: 1.22e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1050394579   15 LADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIKEQM 71
Cdd:cd09546     10 LEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSIQEMRVQL 66
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
385-479 1.45e-06

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 48.39  E-value: 1.45e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPHRScMFQKRWVKVDGMHLSYYSNNRDMFSKGKISLSAIITL----NKMGENKFEVVTIQRTFVFRAEKEE 460
Cdd:cd13298      8 KSGYLLKRSRKTK-NWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSELLAVaplkDKKRKNVFGIYTPSKNLHFRATSEK 86
                           90
                   ....*....|....*....
gi 1050394579  461 DRDDWIGTLQSDSKSEPYE 479
Cdd:cd13298     87 DANEWVEALREEFRLDDEE 105
SAM_EPH-R cd09488
SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH ...
15-67 1.70e-06

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.


Pssm-ID: 188887  Cd Length: 61  Bit Score: 46.45  E-value: 1.70e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1050394579   15 LADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSI 67
Cdd:cd09488      9 LESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKILNSIQAL 61
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
385-471 2.63e-06

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 47.46  E-value: 2.63e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPHRSCM----FQKRWVKVDGMHLSYYSNNRDMF-SKGKISLSAIITL--NKMGENKFEVVTIQRTFVFRAE 457
Cdd:cd13296      1 KSGWLTKKGGGSSTLsrrnWKSRWFVLRDTVLKYYENDQEGEkLLGTIDIRSAKEIvdNDPKENRLSITTEERTYHLVAE 80
                           90
                   ....*....|....
gi 1050394579  458 KEEDRDDWIGTLQS 471
Cdd:cd13296     81 SPEDASQWVNVLTR 94
SAM_EPH-A4 cd09545
SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
7-76 3.09e-06

SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A4 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of EPH-A4 receptors can form homodimers. EPH-A4 receptors bind ligands such as erphirin A1, A4, A5. They are known to interact with a number of different proteins, including meltrin beta metalloprotease, Cdk5, and EFS2alpha, however SAM domain doesn't participate in these interactions. EPH-A4 receptors are involved in regulation of corticospinal tract formation, in pathway controlling voluntary movements, in formation of motor neurons, and in axon guidance (SAM domain is not required for axon guidance or for EPH-A4 kinase signaling). In Xenopus embryos EPH-A4 induces loss of cell adhesion, ventro-lateral protrusions, and severely expanded posterior structures. Mutations in SAM domain conserved tyrosine (Y928F) enhance the ability of EPH-A4 to induce these phenotypes, thus supporting the idea that the SAM domain may negatively regulate some aspects of EPH-A4 activity. EphA4 gene was found overexpressed in a number of different cancers including human gastric cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. It is likely to be a promising molecular target for the cancer therapy.


Pssm-ID: 188944  Cd Length: 71  Bit Score: 46.10  E-value: 3.09e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579    7 QISDIVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIKEQMTKEYG 76
Cdd:cd09545      2 AVASVDDWLQAIKMERYKDNFTAAGYTTLEAVVHMNQDDLARIGISAIAHQNKILSSVQGMRSQMQQMQG 71
SAM_superfamily cd09487
SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of ...
10-65 6.60e-06

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.


Pssm-ID: 188886 [Multi-domain]  Cd Length: 56  Bit Score: 44.92  E-value: 6.60e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1050394579   10 DIVQLLADINLDTYLSIFlKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQ 65
Cdd:cd09487      1 DVAEWLESLGLEQYADLF-RKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAIQ 55
PH pfam00169
PH domain; PH stands for pleckstrin homology.
784-891 7.47e-06

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 46.40  E-value: 7.47e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  784 LFYCGFLHKASSSTSKMTINRkskevpemkrwWCTIENNFLKYYENETAPVAD---GVIDLSEvlCLVVHPSDCSSNGmA 860
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKSWKKR-----------YFVLFDGSLLYYKDDKSKKSKepkGSISLSG--CEVVEVVASDSPK-R 66
                           90       100       110
                   ....*....|....*....|....*....|....
gi 1050394579  861 AFTFEIYFLS---ERMFLFGAENVESRREWTRAI 891
Cdd:pfam00169   67 KFCFELRTGErtgKRTYLLQAESEEERKDWIKAI 100
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
378-470 8.43e-06

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 2; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the second PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270074  Cd Length: 90  Bit Score: 45.48  E-value: 8.43e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  378 GPSSMPTKTGWLEkLSPHRScmfqKRWVKVDGMHLSYYSNNRDmFSKGkISLsAIITLN----KMGENK-FEVVTIQRTF 452
Cdd:cd13254      1 PRKPNPDKCGYLE-LRGYKA----KVYAALMGDEVWLYKNEQD-FRLG-IGI-TVIEMNganvKDVDRRsFDLTTPYRSF 72
                           90
                   ....*....|....*...
gi 1050394579  453 VFRAEKEEDRDDWIGTLQ 470
Cdd:cd13254     73 SFTAESEHEKQEWIEAVQ 90
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
385-469 1.10e-05

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 45.77  E-value: 1.10e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPH-RScmFQKRW-VKVDGMHLSYYSNNRDMFSK--GKISLSAIIT-------LNKmgENKFEVVTIQRTFV 453
Cdd:cd13276      1 KAGWLEKQGEFiKT--WRRRWfVLKQGKLFWFKEPDVTPYSKprGVIDLSKCLTvksaedaTNK--ENAFELSTPEETFY 76
                           90
                   ....*....|....*.
gi 1050394579  454 FRAEKEEDRDDWIGTL 469
Cdd:cd13276     77 FIADNEKEKEEWIGAI 92
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
912-1001 1.14e-05

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 45.37  E-value: 1.14e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  912 GYLYyKNSYSLNQWKKAWFALDKACLHYWNTEDcgkaDTIqlKKLQ---ELTANSSMLNGEKGNILLLVENGRTFYIHGH 988
Cdd:cd13282      3 GYLT-KLGGKVKTWKRRWFVLKNGELFYYKSPN----DVI--RKPQgqiALDGSCEIARAEGAQTFEIVTEKRTYYLTAD 75
                           90
                   ....*....|...
gi 1050394579  989 TMLDFTVWHLAIE 1001
Cdd:cd13282     76 SENDLDEWIRVIQ 88
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
379-466 1.47e-05

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269939  Cd Length: 103  Bit Score: 45.28  E-value: 1.47e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  379 PSSMPTKTGWLEKLSPHRScMFQKRWVKVDGMHLSYYSNNRDMFSKGKISLSAI---------ITLNKMgeNKFEVVTIQ 449
Cdd:cd01233      2 KSPVVSKRGYLLFLEDATD-GWVRRWVVLRRPYLHIYSSEKDGDERGVINLSTArveyspdqeALLGRP--NVFAVYTPT 78
                           90
                   ....*....|....*..
gi 1050394579  450 RTFVFRAEKEEDRDDWI 466
Cdd:cd01233     79 NSYLLQARSEKEMQDWL 95
SAM_AIDA1AB-like_repeat2 cd09500
SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of ...
3-64 1.86e-05

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.


Pssm-ID: 188899  Cd Length: 65  Bit Score: 43.83  E-value: 1.86e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1050394579    3 SSPEQISdivQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQK-MGISLTGHRKRIIAKL 64
Cdd:cd09500      3 NSPASVS---EWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTNvLEINKLGHRKRILASL 62
ArfGap_AGFG1 cd08857
ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain ...
591-694 2.22e-05

ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG1 is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG1 plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG1 promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350082 [Multi-domain]  Cd Length: 116  Bit Score: 45.03  E-value: 2.22e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  591 YNRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNiSKVHSLILdtTIWSNELVELFIVVGNEKVNNIWEANLLPEN 670
Cdd:cd08857     13 HNRKCFDCDQRGPTYANMTVGSFVCTSCSGILRGLNPP-HRVKSISM--TTFTQQEIEFLQKHGNEVCKQIWLGLFDDRS 89
                           90       100
                   ....*....|....*....|....*
gi 1050394579  671 MLHMD-SDVSQRRLFITQKYKEGRF 694
Cdd:cd08857     90 SAIPDfRDPQKVKEFLQEKYEKKRW 114
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
379-471 2.34e-05

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 45.40  E-value: 2.34e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  379 PSSMPTKTGWLEKlSPHRSCM---------FQKRWVK----VDGMH-LSYYSNNRDMFSKGKISL---SAIITLNKMGEN 441
Cdd:cd13267      2 GESGITKEGYLYK-GPENSSDsfislamksFKRRFFHlkqlVDGSYiLEFYKDEKKKEAKGTIFLdscTGVVQNSKRRKF 80
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1050394579  442 KFEV-VTIQRTFVFRAEKEEDRDDWIGTLQS 471
Cdd:cd13267     81 CFELrMQDKKSYVLAAESEAEMDEWISKLNK 111
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
1021-1165 2.84e-05

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239865 [Multi-domain]  Cd Length: 190  Bit Score: 46.58  E-value: 2.84e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1021 IPIIVNSCIAFV-TQYGLGSKSLYLKNGNPSPVRELLEEFKR----DARSIKLKVGKHQledVTDVLKYFFYEIDDALLT 1095
Cdd:cd04400     22 LPSVVYRCIEYLdKNRAIYEEGIFRLSGSASVIKQLKERFNTeydvDLFSSSLYPDVHT---VAGLLKLYLRELPTLILG 98
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050394579 1096 KELYPYWISALDIRNDQ-ERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCL 1165
Cdd:cd04400     99 GELHNDFKRLVEENHDRsQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRNVCIVFSPTL 169
ArfGap_AGFG2 cd17903
ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain ...
592-694 3.66e-05

ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG2 is a member of the HIV-1 Rev binding protein (HRB) family and contains one Arf-GAP zinc finger domain, several Phe-Gly (FG) motifs, and four Asn-Pro-Phe (NPF) motifs. AGFG2 interacts with Eps15 homology (EH) domains and plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350090 [Multi-domain]  Cd Length: 116  Bit Score: 44.59  E-value: 3.66e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNiSKVHSLILdtTIWSNELVELFIVVGNEKVNNIWEANLLPENM 671
Cdd:cd17903     14 NRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISM--TTFTEPEVLFLQARGNEVCRKIWLGLFDARTS 90
                           90       100
                   ....*....|....*....|....
gi 1050394579  672 LHMDS-DVSQRRLFITQKYKEGRF 694
Cdd:cd17903     91 LIPDSrDPQKVKEFLQEKYEKKRW 114
SAM_EPH-A2 cd09543
SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of ...
11-71 3.67e-05

SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A2 subfamily of receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A2 receptors and appears to mediate cell-cell initiated signal transduction. For example, SAM domain of EPH-A2 receptors interacts with SAM domain of Ship2 proteins (SH2 containing phosphoinositide 5-phosphotase-2) forming heterodimers; such recruitment of Ship2 by EPH-A2 attenuates the positive signal for receptor endocytosis. Eph-A2 is found overexpressed in many types of human cancer, including breast, prostate, lung and colon cancer. High level of expression could induce cancer progression by a variety of mechanisms and could be used as a novel tag for cancer immunotherapy. EPH-A2 receptors are attractive targets for drag design.


Pssm-ID: 188942  Cd Length: 70  Bit Score: 43.29  E-value: 3.67e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050394579   11 IVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIKEQM 71
Cdd:cd09543      8 VAEWLESIKMQQYTEHFMAAGYNSIDKVLQMTQEDIKHIGVRLPGHQKRIAYSILGLKEQV 68
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
486-574 3.97e-05

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 44.08  E-value: 3.97e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   486 TEKNGYLELKGYKN-----KIFTVINGSKLWFSKNKQDASTG-----ITITDLTLTMASVKNIDRK--SFELSTPFRN-F 552
Cdd:smart00233    1 VIKEGWLYKKSGGGkkswkKRYFVLFNSTLLYYKSKKDKKSYkpkgsIDLSGCTVREAPDPDSSKKphCFEIKTSDRKtL 80
                            90       100
                    ....*....|....*....|..
gi 1050394579   553 SLTAESEREKQEWTEAIQQSIA 574
Cdd:smart00233   81 LLQAESEEEREKWVEALRKAIA 102
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
488-574 5.53e-05

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 43.85  E-value: 5.53e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  488 KNGYLE-----LKGYKNKIFtVINGSKL-WFSKNK-QDASTGITITDLTLTMaSVKNIDRK-----SFELSTPFRNFSLT 555
Cdd:cd13276      1 KAGWLEkqgefIKTWRRRWF-VLKQGKLfWFKEPDvTPYSKPRGVIDLSKCL-TVKSAEDAtnkenAFELSTPEETFYFI 78
                           90
                   ....*....|....*....
gi 1050394579  556 AESEREKQEWTEAIQQSIA 574
Cdd:cd13276     79 ADNEKEKEEWIGAIGRAIV 97
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
385-471 5.78e-05

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 43.36  E-value: 5.78e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPHRSCMFQKRWVKVDGMHLSYYSNNRDMFSKGK---ISLSAIitlnKMGENK-----FEVVTIQRTFVFRA 456
Cdd:cd13250      1 KEGYLFKRSSNAFKTWKRRWFSLQNGQLYYQKRDKKDEPTVMvedLRLCTV----KPTEDSdrrfcFEVISPTKSYMLQA 76
                           90
                   ....*....|....*
gi 1050394579  457 EKEEDRDDWIGTLQS 471
Cdd:cd13250     77 ESEEDRQAWIQAIQS 91
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
1350-1423 6.18e-05

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 43.77  E-value: 6.18e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1050394579 1350 RYFVLHERKLLLYKDIKSIKHEKELPVKSCKVYAGVKKKMKPPTrwgFTIYSEKSQWHLCCDTQESQKEWLGSL 1423
Cdd:cd13298     25 RWVVLRPCQLSYYKDEKEYKLRRVINLSELLAVAPLKDKKRKNV---FGIYTPSKNLHFRATSEKDANEWVEAL 95
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
813-892 6.34e-05

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 43.77  E-value: 6.34e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  813 KRWWCTIENNFLKYYENETA--PVadGVIDLSevlCLVVHPSDCSSNgmaaFTFEIYFLSE--RMFLFGAENVESRREWT 888
Cdd:cd13288     25 QKRWFVLKGNLLFYFEKKGDrePL--GVIVLE---GCTVELAEDAEP----YAFAIRFDGPgaRSYVLAAENQEDMESWM 95

                   ....
gi 1050394579  889 RAIA 892
Cdd:cd13288     96 KALS 99
PH3_MyoX-like cd13297
Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a ...
1329-1423 6.59e-05

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270109  Cd Length: 126  Bit Score: 43.96  E-value: 6.59e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1329 SGYMkFKEDPSKLLSGNKF-QERYFVLHERKLLLYKDIksikhEKE------LPVKS-CKVYAGVKKKMKPPTRWGFTIY 1400
Cdd:cd13297     16 RGWL-YKEGGKGGARGNLTkKKRWFVLTGNSLDYYKSS-----EKNslklgtLVLNSlCSVVPPDEKMAKETGYWTFTVH 89
                           90       100
                   ....*....|....*....|...
gi 1050394579 1401 SEKSQWHLCCDTQESQKEWLGSL 1423
Cdd:cd13297     90 GRKHSFRLYTKLQEEAMRWVNAI 112
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
9-68 6.91e-05

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerize with other SAM domains.


Pssm-ID: 425739  Cd Length: 64  Bit Score: 42.26  E-value: 6.91e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579    9 SDIVQLLADINLDTYLSIFLKsGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIK 68
Cdd:pfam00536    6 EDVGEWLESIGLGQYIDSFRA-GYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRLK 64
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1036-1188 7.02e-05

RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239853  Cd Length: 200  Bit Score: 45.64  E-value: 7.02e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1036 GLGSKSLYlKNGNPSPVRELLEEFKRDARSIKLKvgKHQLEDVTDVLKYFFYEIDDALLTKELYPYWIS-ALDIRNDQER 1114
Cdd:cd04388     30 GLESSTLY-RTQSSSSLTELRQILDCDAASVDLE--QFDVAALADALKRYLLDLPNPVIPAPVYSEMISrAQEVQSSDEY 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1115 VRKYKNII--GTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQ----TNGENEQEVAVLEDLISNYVN 1188
Cdd:cd04388    107 AQLLRKLIrsPNLPHQYWLTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFRfqpaSSDSPEFHIRIIEVLITSEWN 186
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
1325-1420 8.62e-05

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 42.96  E-value: 8.62e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1325 HYMMSGYMKfKEDPSKllsGNKFQERYFVLHERKLLLYKDIKSiKHEK-ELPVKSC----KVYAGVKKKMKPPTRWGFTI 1399
Cdd:cd01251      1 DFLKEGYLE-KTGPKQ---TDGFRKRWFTLDDRRLMYFKDPLD-AFPKgEIFIGSKeegySVREGLPPGIKGHWGFGFTL 75
                           90       100
                   ....*....|....*....|.
gi 1050394579 1400 YSEKSQWHLCCDTQESQKEWL 1420
Cdd:cd01251     76 VTPDRTFLLSAETEEERREWI 96
SAM_EPH-B6 cd09555
SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
15-71 8.95e-05

SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B6 receptors and appears to mediate cell-cell initiated signal transduction. Receptors of this type are highly expressed in embryo and adult nervous system, in thymus and also in T-cells. They are involved in regulation of cell adhesion and migration. (EPH-B6 receptor is unusual; it fails to show catalytic activity due to alteration in kinase domain). EPH-B6 may be considered as a biomarker in some types of tumors; EPH-B6 activates MAP kinase signaling in lung adenocarcinoma, suppresses metastasis formation in non-small cell lung cancer, and slows invasiveness in some breast cancer cell lines.


Pssm-ID: 188954  Cd Length: 69  Bit Score: 42.22  E-value: 8.95e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1050394579   15 LADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIKEQM 71
Cdd:cd09555     13 LSAIGLECYQDNFSKFGLCTFSDVAQLSLEDLPALGITLAGHQKKLLHHIQLLQQHL 69
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
488-574 9.25e-05

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 43.05  E-value: 9.25e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  488 KNGYLELKGYKNKIFTvingsKLWF-----------SKNKQDASTGITITDLTLTMASVKNIDRKS-FELSTPFRNFSLT 555
Cdd:cd13273     10 KKGYLWKKGHLLPTWT-----ERWFvlkpnslsyykSEDLKEKKGEIALDSNCCVESLPDREGKKCrFLVKTPDKTYELS 84
                           90
                   ....*....|....*....
gi 1050394579  556 AESEREKQEWTEAIQQSIA 574
Cdd:cd13273     85 ASDHKTRQEWIAAIQTAIR 103
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
1327-1423 9.91e-05

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 43.16  E-value: 9.91e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1327 MMSGYMKFKEDPSKLLSgnKFQERYFVLHERKLLLYKDIKSikhekelpvKSCK---VYAGVKKKMKPPTR----WGFTI 1399
Cdd:cd13308     10 IHSGTLTKKGGSQKTLQ--NWQLRYVIIHQGCVYYYKNDQS---------AKPKgvfSLNGYNRRAAEERTsklkFVFKI 78
                           90       100
                   ....*....|....*....|....*..
gi 1050394579 1400 Y---SEKSQWHLCCDTQESQKEWLGSL 1423
Cdd:cd13308     79 IhlsPDHRTWYFAAKSEDEMSEWMEYI 105
SAM_EPH-A1 cd09542
SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
11-65 1.07e-04

SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A1 subfamily of the receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A1 receptors and appears to mediate cell-cell initiated signal transduction. Activation of these receptors leads to inhibition of cell spreading and migration in a RhoA-ROCK-dependent manner. EPH-A1 receptors are known to bind ILK (integrin-linked kinase) which is the mediator of interactions between integrin and the actin cytoskeleton. However SAM is not sufficient for this interaction; it rather plays an ancillary role. SAM domains of Eph-A1 receptors do not form homo/hetero dimers/oligomers. EphA1 gene was found expressed widely in differentiated epithelial cells. In a number of different malignant tumors EphA1 genes are downregulated. In breast carcinoma the downregulation is associated with invasive behavior of the cell.


Pssm-ID: 188941  Cd Length: 63  Bit Score: 41.53  E-value: 1.07e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1050394579   11 IVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQ 65
Cdd:cd09542      7 VSEWLESIRMKRYILHFRSAGLDTMECVLELTAEDLTQMGITLPGHQKRILCSIQ 61
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
488-569 1.16e-04

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 42.53  E-value: 1.16e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  488 KNGYLELKGYKNKI-----FTVINGSKLWFSKNKQDASTG----ITITDLTLTMASVKNIDRKSFELSTPF-RNFSLTAE 557
Cdd:cd00821      1 KEGYLLKRGGGGLKswkkrWFVLFEGVLLYYKSKKDSSYKpkgsIPLSGILEVEEVSPKERPHCFELVTPDgRTYYLQAD 80
                           90
                   ....*....|..
gi 1050394579  558 SEREKQEWTEAI 569
Cdd:cd00821     81 SEEERQEWLKAL 92
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
379-466 1.18e-04

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270090  Cd Length: 114  Bit Score: 43.11  E-value: 1.18e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  379 PSSMPTKTGWLEKLSPHRSCmFQKRWVKVDGMHLSYYSNNRDMFSKGKISLSAIITLNK-------MGENKFEVVTIQRT 451
Cdd:cd13271      4 AGRNVIKSGYCVKQGAVRKN-WKRRFFILDDNTISYYKSETDKEPLRTIPLREVLKVHEclvksllMRDNLFEIITTSRT 82
                           90
                   ....*....|....*
gi 1050394579  452 FVFRAEKEEDRDDWI 466
Cdd:cd13271     83 FYIQADSPEEMHSWI 97
SAM_EPH-B1 cd09551
SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
15-70 1.31e-04

SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B1 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH- B1 receptors. In human vascular endothelial cells it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated. EPH-B1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization; they are involved in converting the crossed retinal projection to ipsilateral retinal projection. They may be potential targets in angiogenesis-related disorders.


Pssm-ID: 188950  Cd Length: 68  Bit Score: 41.56  E-value: 1.31e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1050394579   15 LADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIKEQ 70
Cdd:cd09551     13 LSAIKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRIGVTLAGHQKKILNSIQSMRVQ 68
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
802-894 1.59e-04

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270080  Cd Length: 103  Bit Score: 42.33  E-value: 1.59e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  802 INRKSKEVPEMKRWWCTIENN--FLKYYENETAPVADGVIDLSEVLCLVVHPS-----DCssngmaaftFEI---YFLSE 871
Cdd:cd13260      9 LLKKGGKNKKWKNLYFVLEGKeqHLYFFDNEKRTKPKGLIDLSYCSLYPVHDSlfgrpNC---------FQIvvrALNES 79
                           90       100
                   ....*....|....*....|...
gi 1050394579  872 RMFLFGAENVESRREWTRAIAKN 894
Cdd:cd13260     80 TITYLCADTAELAQEWMRALRAF 102
SAM_EPH-A8 cd09550
SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
15-71 1.73e-04

SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A8 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A8 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A8 receptors are involved in ligand dependent (ephirin A2, A3, A5) regulation of cell adhesion and migration, and in ligand independent regulation of neurite outgrowth in neuronal cells. They perform signaling in kinase dependent and kinase independent manner. EPH-A8 receptors are known to interact with a number of different proteins including PI 3-kinase and AIDA1-like subfamily SAM repeat domain containing proteins. However other domains (not SAM) of EPH-A8 receptors are involved in these interactions.


Pssm-ID: 188949  Cd Length: 65  Bit Score: 41.00  E-value: 1.73e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1050394579   15 LADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIKEQM 71
Cdd:cd09550      9 LDSIKMGRYKDHFAAGGYSSLGMVMRMNIEDIRRLGITLMGHQKKILTSIQVMRAQL 65
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
1326-1423 2.26e-04

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270080  Cd Length: 103  Bit Score: 41.95  E-value: 2.26e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1326 YMMSGYMKfkedpSKLLSGNKFQERYFVLH--ERKLLLYKDIKSIKHEKELPVKSCKVYagvkkkMKPPTRWG----FTI 1399
Cdd:cd13260      3 IDKKGYLL-----KKGGKNKKWKNLYFVLEgkEQHLYFFDNEKRTKPKGLIDLSYCSLY------PVHDSLFGrpncFQI 71
                           90       100
                   ....*....|....*....|....*...
gi 1050394579 1400 ----YSEKSQWHLCCDTQESQKEWLGSL 1423
Cdd:cd13260     72 vvraLNESTITYLCADTAELAQEWMRAL 99
RhoGAP_DLC1 cd04375
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1074-1169 2.64e-04

RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a START (StAR-related lipid transfer action) domain. DLC1 has tumor suppressor activity in cell culture. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239840  Cd Length: 220  Bit Score: 43.95  E-value: 2.64e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1074 QLEDVTDVLKYFFYEIDDALLTKELYPYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLD 1153
Cdd:cd04375     71 QAYDVADMLKQYFRDLPEPLLTNKLSETFIAIFQYVPKEQRLEAVQCAILLLPDENREVLQTLLYFLSDVAANSQENQMT 150
                           90
                   ....*....|....*.
gi 1050394579 1154 TLTLAKAFSSCLFQTN 1169
Cdd:cd04375    151 ATNLAVCLAPSLFHLN 166
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
541-571 2.82e-04

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 41.51  E-value: 2.82e-04
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1050394579  541 KSFELSTPFRNFSLTAESEREKQEWTEAIQQ 571
Cdd:cd13282     59 QTFEIVTEKRTYYLTADSENDLDEWIRVIQN 89
PH pfam00169
PH domain; PH stands for pleckstrin homology.
912-1003 2.86e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 41.78  E-value: 2.86e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  912 GYLYYKNSYSLNQWKKAWFALDKACLHYWNTEDCGKAD----TIQLKKLQ-ELTANSSMLNGEKGNILLLVE--NGRTFY 984
Cdd:pfam00169    5 GWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSKKSKepkgSISLSGCEvVEVVASDSPKRKFCFELRTGErtGKRTYL 84
                           90
                   ....*....|....*....
gi 1050394579  985 IHGHTMLDFTVWHLAIEKA 1003
Cdd:pfam00169   85 LQAESEEERKDWIKAIQSA 103
SAM_caskin1,2_repeat2 cd09498
SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 ...
9-69 3.03e-04

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188897  Cd Length: 71  Bit Score: 40.74  E-value: 3.03e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050394579    9 SDIVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIKE 69
Cdd:cd09498      8 NDLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLTWEDLQDIGITKLGHQKKLMLAIKKLKD 68
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
383-466 3.10e-04

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270083  Cd Length: 114  Bit Score: 41.99  E-value: 3.10e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  383 PTKTGWLEKLsphRSCM--FQKRWVKVDGMHLSYYSNNRDMFSKGKISLSA----IITLNKMGENK--FEVV-------- 446
Cdd:cd13263      3 PIKSGWLKKQ---GSIVknWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGnkvkEVPFNPEEPGKflFEIIpggggdrm 79
                           90       100
                   ....*....|....*....|.
gi 1050394579  447 -TIQRTFVFRAEKEEDRDDWI 466
Cdd:cd13263     80 tSNHDSYLLMANSQAEMEEWV 100
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
488-571 3.41e-04

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 41.63  E-value: 3.41e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  488 KNGYLELKGYKNKIFT----VINGSKLWFSKNKQDAST--GITITDL-TLTMASVKNIDrKSFELSTPFRNFSLTAESER 560
Cdd:cd13255      8 KAGYLEKKGERRKTWKkrwfVLRPTKLAYYKNDKEYRLlrLIDLTDIhTCTEVQLKKHD-NTFGIVTPARTFYVQADSKA 86
                           90
                   ....*....|.
gi 1050394579  561 EKQEWTEAIQQ 571
Cdd:cd13255     87 EMESWISAINL 97
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
381-471 3.49e-04

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 41.16  E-value: 3.49e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  381 SMPTKTGWLEKLSPHRScMFQKRWVKVDGMHLSYYsnnrdmfsKGKISLSAIITLN------------KMGENKFEVVTI 448
Cdd:cd10573      1 SLGSKEGYLTKLGGIVK-NWKTRWFVLRRNELKYF--------KTRGDTKPIRVLDlrecssvqrdysQGKVNCFCLVFP 71
                           90       100
                   ....*....|....*....|...
gi 1050394579  449 QRTFVFRAEKEEDRDDWIGTLQS 471
Cdd:cd10573     72 ERTFYMYANTEEEADEWVKLLKW 94
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
383-477 3.62e-04

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270086  Cd Length: 106  Bit Score: 41.35  E-value: 3.62e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  383 PTKTGWLEKLSPHRSCM---FQKRWVKVDGMHLSYYSNNRDMFSKGKI-----SLSAIITLNKMG--ENKFEVVT-IQRT 451
Cdd:cd13266      1 VIKAGYLEKRRKDHSFFgseWQKRWCAISKNVFYYYGSDKDKQQKGEFaingyDVRMNPTLRKDGkkDCCFELVCpDKRT 80
                           90       100
                   ....*....|....*....|....*.
gi 1050394579  452 FVFRAEKEEDRDDWIGTLQSDSKSEP 477
Cdd:cd13266     81 YQFTAASPEDAEDWVDQISFILQDLS 106
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
912-1007 3.88e-04

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 41.46  E-value: 3.88e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  912 GYLYyKNSYSLNQWKKAWFALDKACLHYWNTEDCGKadtiqLKK---LQELTANSSMLNGEKGNILLLVENGRTFYIHGH 988
Cdd:cd13298     10 GYLL-KRSRKTKNWKKRWVVLRPCQLSYYKDEKEYK-----LRRvinLSELLAVAPLKDKKRKNVFGIYTPSKNLHFRAT 83
                           90
                   ....*....|....*....
gi 1050394579  989 TMLDFTVWHLAIEKAAGTD 1007
Cdd:cd13298     84 SEKDANEWVEALREEFRLD 102
RhoGAP_Graf cd04374
RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase ...
1024-1185 4.14e-04

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239839  Cd Length: 203  Bit Score: 43.15  E-value: 4.14e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1024 IVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDARSIKLKVGKHQLE----DVTDVLKYFFYEIDDALLTKELY 1099
Cdd:cd04374     31 FVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGLDPKTSTPGDVDLDNSEweikTITSALKTYLRNLPEPLMTYELH 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1100 PYWISALDIRNDQERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDTLTLAKAFSSCLFQTngeNEQEVA-- 1177
Cdd:cd04374    111 NDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRP---QEETVAai 187
                          170
                   ....*....|....*.
gi 1050394579 1178 --------VLEDLISN 1185
Cdd:cd04374    188 mdikfqniVVEILIEN 203
SAM_EPH-A6 cd09547
SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
15-68 4.17e-04

SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers.


Pssm-ID: 188946  Cd Length: 64  Bit Score: 39.87  E-value: 4.17e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1050394579   15 LADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISLTGHRKRIIAKLQSIK 68
Cdd:cd09547     10 LDSIKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIGHQRRIVSSIQTLR 63
PRK08581 PRK08581
amidase domain-containing protein;
121-333 4.59e-04

amidase domain-containing protein;


Pssm-ID: 236304 [Multi-domain]  Cd Length: 619  Bit Score: 44.78  E-value: 4.59e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  121 SSVSKEVDHNATSQYQQTEDPNDQNKKSLEIKDHSVKHFSLDTETQLDSQNSSFFafqgpmvendIYDK-SQDDGHKSLL 199
Cdd:PRK08581    40 SHDSKKSNDDETSKDTSSKDTDKADNNNTSNQDNNDKKFSTIDSSTSDSNNIIDF----------IYKNlPQTNINQLLT 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  200 KSPPTKSFILRNRPVPKLPFSVSNTFPKCCCQERHLDNKAAQESSASKPQNQESEEQNINLISpyeetffSNSEFTKETS 279
Cdd:PRK08581   110 KNKYDDNYSLTTLIQNLFNLNSDISDYEQPRNSEKSTNDSNKNSDSSIKNDTDTQSSKQDKAD-------NQKAPSSNNT 182
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1050394579  280 GDKLNFSPNSEHNEKSLERNASTSCGSVPANNGSSPSLGDHISEESIYSTMEEY 333
Cdd:PRK08581   183 KPSTSNKQPNSPKPTQPNQSNSQPASDDTANQKSSSKDNQSMSDSALDSILDQY 236
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
401-470 4.76e-04

Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 is proposed to function in regulation of Akt phosphorylation. ORP9 has 2 forms, a long (ORP9L) and a short (ORP9S). ORP9L contains an N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP1S is truncated and contains a FFAT motif and an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241444  Cd Length: 102  Bit Score: 40.89  E-value: 4.76e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1050394579  401 QKRWVKVD---GMhLSYYSNNRDMFS---KGKISLS-AIITLNKMGENKFEVVTIQRTFVFRAEKEEDRDDWIGTLQ 470
Cdd:cd13290     16 QYRWFVLDdnaGL-LSYYTSKEKMMRgsrRGCVRLKgAVVGIDDEDDSTFTITVDQKTFHFQARDAEERERWIRALE 91
PLN03119 PLN03119
putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional
592-694 4.96e-04

putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional


Pssm-ID: 178666  Cd Length: 648  Bit Score: 44.84  E-value: 4.96e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  592 NRRCADCRAPSPDWASISLGVVICKNCAGQHRSLGSNISKVhslilDTTIWSNELVELFIVVGNEKVNNIWEANL----- 666
Cdd:PLN03119    23 NRRCINCNSLGPQYVCTTFWTFVCMACSGIHREFTHRVKSV-----SMSKFTSKEVEVLQNGGNQRAREIYLKNWdhqrq 97
                           90       100
                   ....*....|....*....|....*....
gi 1050394579  667 -LPENmlhmdSDVSQRRLFITQKYKEGRF 694
Cdd:PLN03119    98 rLPEN-----SNAERVREFIKNVYVQKKY 121
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
824-891 5.07e-04

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269941  Cd Length: 106  Bit Score: 41.16  E-value: 5.07e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1050394579  824 LKYYENETAPVADGVIDLSEVLClvVHPSDCSSNGM-----AAFtFEIYFlSERMFLFGAENVESRREWTRAI 891
Cdd:cd01235     33 LRYYESREDTKCKGFIDLAEVES--VTPATPIIGAPkradeGAF-FDLKT-NKRVYNFCAFDAESAQQWIEKI 101
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
387-471 5.42e-04

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269941  Cd Length: 106  Bit Score: 40.78  E-value: 5.42e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  387 GWLEKLSpHRSCMFQKRWVKVD-GMH-LSYYSNNRDMFSKGKISLSAI---------ITLNKMGENK--FEVVTIQRTFV 453
Cdd:cd01235      7 GYLYKRG-ALLKGWKQRWFVLDsTKHqLRYYESREDTKCKGFIDLAEVesvtpatpiIGAPKRADEGafFDLKTNKRVYN 85
                           90
                   ....*....|....*...
gi 1050394579  454 FRAEKEEDRDDWIGTLQS 471
Cdd:cd01235     86 FCAFDAESAQQWIEKIQS 103
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
803-894 6.29e-04

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270094  Cd Length: 104  Bit Score: 40.78  E-value: 6.29e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  803 NRKSKEVPEMKRWWCTIENNFLKYYE---NETAPVADGVIDLSEvlCLVVHPSDCSSNgmaaFTFEIYFLSERMFLFGAE 879
Cdd:cd13275      6 MKQGSRQGEWSKHWFVLRGAALKYYRdpsAEEAGELDGVIDLSS--CTEVTELPVSRN----YGFQVKTWDGKVYVLSAM 79
                           90
                   ....*....|....*
gi 1050394579  880 NVESRREWTRAIAKN 894
Cdd:cd13275     80 TSGIRTNWIQALRKA 94
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
1223-1309 6.99e-04

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 40.39  E-value: 6.99e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1223 IEVYVERKDPDM-CVIIRVPPTMETAELTNCAMGIKNITLTEEiPWATFEVIENGELERLMHDAEKVLETVLYWSslSDP 1301
Cdd:pfam00788    5 LKVYTEDGKPGTtYKTILVSSSTTAEEVIEALLEKFGLEDDPR-DYVLVEVLERGGGERRLPDDECPLQIQLQWP--RDA 81

                   ....*...
gi 1050394579 1302 GAAHLLVK 1309
Cdd:pfam00788   82 SDSRFLLR 89
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
907-947 7.58e-04

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270081  Cd Length: 136  Bit Score: 41.26  E-value: 7.58e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1050394579  907 DFTLLGYLYYKNSYSlNQWKKAWFALDKACLHYWNTEDCGK 947
Cdd:cd13261      4 DGTKRGYLSKKTSDS-GKWHERWFALYQNLLFYFENESSSR 43
RA cd17043
Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA ...
1222-1309 7.88e-04

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.


Pssm-ID: 340563  Cd Length: 87  Bit Score: 39.99  E-value: 7.88e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1222 LIEVYVE-RKDPDMCVIIRVPPTMETAELTNCAMGIKNITLTEEiPWATFEVIENGELERLMHDAEKVLETVLYWSslSD 1300
Cdd:cd17043      1 VLKVYDDdLAPGSAYKSILVSSTTTAREVVQLLLEKYGLEEDPE-DYSLYEVSEKQETERVLHDDECPLLIQLEWG--PQ 77

                   ....*....
gi 1050394579 1301 PGAAHLLVK 1309
Cdd:cd17043     78 GTEFRFVLK 86
PH_CpORP2-like cd13293
Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) ...
1345-1427 8.42e-04

Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) domain; There are 2 types of ORPs found in Cryptosporidium: CpORP1 and CpORP2. Cryptosporium differs from other apicomplexans like Plasmodium, Toxoplasma, and Eimeria which possess only a single long-type ORP consisting of an N-terminal PH domain followed by a C-terminal ligand binding (LB) domain. CpORP2 is like this, but CpORP1 differs and has a truncated N-terminus resulting in only having a LB domain present. The exact functions of these proteins are largely unknown though CpORP1 is thought to be involved in lipid transport across the parasitophorous vacuole membrane. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241447  Cd Length: 88  Bit Score: 40.00  E-value: 8.42e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1345 NKFQERYFVLHErKLLLYKDIKSIKHEKELPVKSCKVyAGVKKKmkpPTRwgFTIYSEKSQWHLCCDTQESQKEWLGSLF 1424
Cdd:cd13293     13 NSWKPRYFILYP-GILCYSKQKGGPKKGTIHLKICDI-RLVPDD---PLR--IIINTGTNQLHLRASSVEEKLKWYNALK 85

                   ...
gi 1050394579 1425 SAQ 1427
Cdd:cd13293     86 YAQ 88
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
384-473 1.04e-03

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 40.47  E-value: 1.04e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  384 TKTGWLEKL--SPHRSCMFQKRWVKVDGMHLSYYSNNRDMFSKGKISLS-----AIITLNKMGENKFEVVTIQ---RTFV 453
Cdd:cd13308     10 IHSGTLTKKggSQKTLQNWQLRYVIIHQGCVYYYKNDQSAKPKGVFSLNgynrrAAEERTSKLKFVFKIIHLSpdhRTWY 89
                           90       100
                   ....*....|....*....|
gi 1050394579  454 FRAEKEEDRDDWIGTLQSDS 473
Cdd:cd13308     90 FAAKSEDEMSEWMEYIRREI 109
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
788-891 1.26e-03

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain; AGAP (also called centaurin gamma; PIKE/Phosphatidylinositol-3-kinase enhancer) reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. There are 3 isoforms of AGAP (PIKE-A, PIKE-L, and PIKE-S) the longest of which PIKE-L consists of N-terminal proline rich domains (PRDs), followed by a GTPase domain, a split PH domain (PHN and PHC), an ArfGAP domain and two ankyrin repeats. PIKE-S terminates after the PHN domain and PIKE-A is missing the PRD region. Centaurin binds phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241281  Cd Length: 114  Bit Score: 40.00  E-value: 1.26e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  788 GFLHKASSSTskmtINRKSKevpemKRWWCTIENNFLKYY-------ENetapVADGVIDLSEVLCLVVHPSDCSSNGMA 860
Cdd:cd01250      8 GYLYKRSSKS----LNKEWK-----KKYVTLCDDGRLTYHpslhdymEN----VHGKEIDLLRTTVKVPGKRPPRASSKS 74
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1050394579  861 AFTFEIYFLSERMFLFGAENVESRREWTRAI 891
Cdd:cd01250     75 AFEFIIVSLDGKQWHFEAASSEERDEWVQAI 105
SAM_caskin1,2_repeat1 cd09497
SAM domain of caskin protein repeat 1; SAM (sterile alpha motif) domain repeat 1 of caskin1,2 ...
11-65 1.32e-03

SAM domain of caskin protein repeat 1; SAM (sterile alpha motif) domain repeat 1 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and apparently may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188896  Cd Length: 66  Bit Score: 38.78  E-value: 1.32e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   11 IVQLLADINLDTYLSIFLKSGY--YTVSDCenvNHETLQKMGISLTGHRKRI---IAKLQ 65
Cdd:cd09497      7 IFDWLREFGLEEYTPNFIKAGYdlPTISRM---TPEDLTAIGITKPGHRKKLkseIAQLQ 63
SAM_tumor-p63,p73 cd09503
SAM domain of tumor-p63,p73 proteins; SAM (sterile alpha motif) domain of p63, p73 ...
11-70 1.39e-03

SAM domain of tumor-p63,p73 proteins; SAM (sterile alpha motif) domain of p63, p73 transcriptional factors is a putative protein-protein interaction domain and lipid-binding domain. p63 and p73 are homologs to the tumor suppressor p53. They have a C-terminal SAM domain in their longest spliced alpha forms, while p53 doesn't have it. p63 or p73 knockout mice show significant developmental abnormalities but no increased cancer susceptibility, suggesting that p63 and p73 play a role in regulation of normal development. It was shown that SAM domain of p73 is able to bind some membrane lipids. The structural rearrangements in SAM are necessary to accomplish the binding. No evidence for homooligomerization through SAM domains was found for p63/p73 subfamily. It was suggested that the partner proteins should be either more distantly related SAM-containing domain proteins or proteins without the SAM domain.


Pssm-ID: 188902  Cd Length: 65  Bit Score: 38.45  E-value: 1.39e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579   11 IVQLLADINLDTYLSIFLKSGYYTVSDCENVNHETLQKMGISlTGHRKRIIAKLQSIKEQ 70
Cdd:cd09503      7 VASWLTKLGCSNYIDNFHQQGLLSIFQLDEFTLEDLAAMKIP-EQHRNKIWKGLLEYRQA 65
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
788-892 1.47e-03

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270081  Cd Length: 136  Bit Score: 40.49  E-value: 1.47e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  788 GFLHKASSSTSKmtinrkskevpemkrW---WCTIENNFLKYYENETAPVADGVIDLSEVLCLVVHPSDCSSNGMAAFTF 864
Cdd:cd13261      9 GYLSKKTSDSGK---------------WherWFALYQNLLFYFENESSSRPSGLYLLEGCYCERLPTPKGALKGKDHLEK 73
                           90       100       110
                   ....*....|....*....|....*....|....
gi 1050394579  865 EIYFL------SERMFLFGAENVESRREWTRAIA 892
Cdd:cd13261     74 QHYFTisfrheNQRQYELRAETESDCDEWVEAIK 107
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
787-891 1.50e-03

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 39.76  E-value: 1.50e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  787 CGFLHKASSSTSkmTINRKSkevpeMKRWWCTIENNFLKYYENET-APVADGVIDLSEVLCLV-VHPSDcssNGMAAFTf 864
Cdd:cd13296      2 SGWLTKKGGGSS--TLSRRN-----WKSRWFVLRDTVLKYYENDQeGEKLLGTIDIRSAKEIVdNDPKE---NRLSITT- 70
                           90       100
                   ....*....|....*....|....*..
gi 1050394579  865 eiyflSERMFLFGAENVESRREWTRAI 891
Cdd:cd13296     71 -----EERTYHLVAESPEDASQWVNVL 92
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
813-893 1.59e-03

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 39.49  E-value: 1.59e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  813 KRWWCTIENNFLKYYENETAPVADGVIDLSevlclvvHPSDCSS---------NGMAAFTFEIyFLSERMFLFGAENVES 883
Cdd:cd01251     20 RKRWFTLDDRRLMYFKDPLDAFPKGEIFIG-------SKEEGYSvreglppgiKGHWGFGFTL-VTPDRTFLLSAETEEE 91
                           90
                   ....*....|
gi 1050394579  884 RREWTRAIAK 893
Cdd:cd01251     92 RREWITAIQK 101
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
384-476 1.90e-03

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270071  Cd Length: 108  Bit Score: 39.27  E-value: 1.90e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  384 TKTGWLEKLSP---HRscMFQKRWVKVDGMHLSYYSNNRdmfSKGKISLSAI---ITLNKMGENKFEVVTIQRTFVFRAE 457
Cdd:cd13251     11 EKSGYLLKKSEgkiRK--VWQKRRCSIKDGFLTISHADE---NKPPAKLNLLtcqVKLVPEDKKCFDLISHNRTYHFQAE 85
                           90
                   ....*....|....*....
gi 1050394579  458 KEEDRDDWIGTLqSDSKSE 476
Cdd:cd13251     86 DENDANAWMSVL-KNSKEQ 103
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
385-469 1.98e-03

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-hom have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270181  Cd Length: 106  Bit Score: 39.17  E-value: 1.98e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPHRSCM---FQKRWVKVDGMHLSYYSNNRDMFSKGKISLSAII-----TLNKMGENK--FEVVTI-QRTFV 453
Cdd:cd13381      3 KAGYLEKRRKDHSFFgfeWQKRWCALSNSVFYYYGSDKDKQQKGEFAIDGYDvkmnnTLRKDAKKDccFEICAPdKRVYQ 82
                           90
                   ....*....|....*.
gi 1050394579  454 FRAEKEEDRDDWIGTL 469
Cdd:cd13381     83 FTAASPKEAEEWVQQI 98
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
1327-1431 2.28e-03

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 39.19  E-value: 2.28e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1327 MMSGYMKfkedpsKLLSGNKfqeRYFVLHE------RKLLLYKDIKSIKHEKE----LPVKSCkvyAGVKKKMKPPTRWG 1396
Cdd:cd01257      4 RKSGYLK------KLKTMRK---RYFVLRAeshggpARLEYYENEKKFRRNAEpkrvIPLSSC---FNINKRADAKHKHL 71
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1050394579 1397 FTIYSEKSQWHLCCDTQESQKEWLGSLFSAQHPGA 1431
Cdd:cd01257     72 IALYTKDECFGLVAESEEEQDEWYQALLELQRPAR 106
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
912-986 2.41e-03

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 38.68  E-value: 2.41e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1050394579  912 GYLYYKNSYSLNQWKKAWFALDKACLHYWNTEDCGKA---DTIQLKKLQELTANSSmlNGEKGNILLLVENGRTFYIH 986
Cdd:cd00821      3 GYLLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYkpkGSIPLSGILEVEEVSP--KERPHCFELVTPDGRTYYLQ 78
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
385-465 2.42e-03

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 3; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the third PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270076  Cd Length: 110  Bit Score: 39.36  E-value: 2.42e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPHRSCM--FQKRWVKVDGMHLSYYSNNRDMFSKGKISLSAIITL-----NKMGENK----FEVVTI-QRTF 452
Cdd:cd13256     10 KSPSAAKPTLERRAReeFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEIVCLavsppDTHPGDGfpftFELYLEsERLY 89
                           90
                   ....*....|...
gi 1050394579  453 VFRAEKEEDRDDW 465
Cdd:cd13256     90 LFGLETAEALHEW 102
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
385-470 2.50e-03

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270180  Cd Length: 106  Bit Score: 39.07  E-value: 2.50e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPHRSCM---FQKRWVKVDGMHLSYYSNNRDMFSKG-------KISLSAIITLNKMGENKFEVVTI-QRTFV 453
Cdd:cd13380      3 KQGYLEKRSKDHSFFgseWQKRWCVLTNRAFYYYASEKSKQPKGgflikgySAQMAPHLRKDSRRDSCFELTTPgRRTYQ 82
                           90
                   ....*....|....*..
gi 1050394579  454 FRAEKEEDRDDWIGTLQ 470
Cdd:cd13380     83 FTAASPSEARDWVDQIQ 99
RhoGAP_fSAC7_BAG7 cd04396
RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1013-1190 2.90e-03

RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239861  Cd Length: 225  Bit Score: 40.86  E-value: 2.90e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1013 DQQLSKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRDAR-SIKLKVGKHQLEDVTDVLKYFFYEIDD 1091
Cdd:cd04396     24 GEQYVYGYIPVVVAKCGVYLKENATEVEGIFRVAGSSKRIRELQLIFSTPPDyGKSFDWDGYTVHDAASVLRRYLNNLPE 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1092 ALLTKELYPYWISALDIRNDQ-----------------ERVRKYKNIIGTLPDLNKATLAALMEHLFRIQKCFDINHLDT 1154
Cdd:cd04396    104 PLVPLDLYEEFRNPLRKRPRIlqymkgrineplntdidQAIKEYRDLITRLPNLNRQLLLYLLDLLAVFARNSDKNLMTA 183
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1050394579 1155 LTLAKAFS-SCLFQTN-----GENEQEVAVLEDLIsNYVNIF 1190
Cdd:cd04396    184 SNLAAIFQpGILSHPDhemdpKEYKLSRLVVEFLI-EHQDKF 224
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
488-571 3.13e-03

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 38.76  E-value: 3.13e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  488 KNGYLELKGYK----NKIFTVINGSKLWFSKNKQDAST--GITITDLTlTMASVKNIDRKS-FELSTPFRNFSLTAESER 560
Cdd:cd13298      8 KSGYLLKRSRKtknwKKRWVVLRPCQLSYYKDEKEYKLrrVINLSELL-AVAPLKDKKRKNvFGIYTPSKNLHFRATSEK 86
                           90
                   ....*....|.
gi 1050394579  561 EKQEWTEAIQQ 571
Cdd:cd13298     87 DANEWVEALRE 97
PH_ORP_plant cd13294
Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs ...
403-484 3.20e-03

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs contain a N-terminal PH domain and a C-terminal OSBP-related domain. Not much is known about its specific function in plants to date. Members here include: Arabidopsis, spruce, and petunia. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241448  Cd Length: 100  Bit Score: 38.63  E-value: 3.20e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  403 RW-VKVDGMhLSYYSnnrdMFSKGKISLSAIITL-------NKMGENKFEVVTIQRTFVFRAEKEEDRDDWIGTLQSDSK 474
Cdd:cd13294     18 RWfVLQDGV-LSYYK----VHGPDKVKPSGEVHLkvssireSRSDDKKFYIFTGTKTLHLRAESREDRAAWLEALQAAKD 92
                           90
                   ....*....|
gi 1050394579  475 SepyeFPGLS 484
Cdd:cd13294     93 M----FPRMS 98
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
385-470 3.64e-03

Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; Human OSBP is proposed to function is sterol-dependent regulation of ERK dephosphorylation and sphingomyelin synthesis as well as modulation of insulin signaling and hepatic lipogenesis. It contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBPs and Osh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. ORP4 is proposed to function in Vimentin-dependent sterol transport and/or signaling. Human ORP4 has 2 forms, a long (ORP4L) and a short (ORP4S). ORP4L contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP4S is truncated and contains only an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270101  Cd Length: 99  Bit Score: 38.51  E-value: 3.64e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  385 KTGWLEKLSPHRSCmFQKRWVKVDGMHLSYYSNNRDM--FSKGKISLS-AIITlnKMGENKFEVVT-IQRTFVFRAEKEE 460
Cdd:cd13284      1 MKGWLLKWTNYIKG-YQRRWFVLSNGLLSYYRNQAEMahTCRGTINLAgAEIH--TEDSCNFVISNgGTQTFHLKASSEV 77
                           90
                   ....*....|
gi 1050394579  461 DRDDWIGTLQ 470
Cdd:cd13284     78 ERQRWVTALE 87
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
386-469 3.76e-03

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270133  Cd Length: 112  Bit Score: 38.55  E-value: 3.76e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  386 TGWLEKLSPH---RSCMFQKRW--VKVDGMH-----LSYYSNNRDMFSKGKISLS------AIITLN-KMGENK--FEVV 446
Cdd:cd13324      4 EGWLTKSPPEkkiWRAAWRRRWfvLRSGRLSggqdvLEYYTDDHCKKLKGIIDLDqceqvdAGLTFEkKKFKNQfiFDIR 83
                           90       100
                   ....*....|....*....|...
gi 1050394579  447 TIQRTFVFRAEKEEDRDDWIGTL 469
Cdd:cd13324     84 TPKRTYYLVAETEEEMNKWVRCI 106
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
787-893 4.14e-03

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270086  Cd Length: 106  Bit Score: 38.27  E-value: 4.14e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  787 CGFLHKassstskmtinrKSKE----VPEMKRWWCTIENNFLKYYENETAPVADGVIDLSEVlcLVVHPSDCSSNGMAAF 862
Cdd:cd13266      4 AGYLEK------------RRKDhsffGSEWQKRWCAISKNVFYYYGSDKDKQQKGEFAINGY--DVRMNPTLRKDGKKDC 69
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1050394579  863 TFEIYFLSERMFLFGAENVESRREWTRAIAK 893
Cdd:cd13266     70 CFELVCPDKRTYQFTAASPEDAEDWVDQISF 100
RhoGAP_PARG1 cd04409
RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1017-1165 4.59e-03

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239874  Cd Length: 211  Bit Score: 40.18  E-value: 4.59e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1017 SKNNIPIIVNSCIAFVTQYGLGSKSLYLKNGNPSPVRELLEEFKRdarsiklkvGKHQLE-------DVTDVLKYFFYEI 1089
Cdd:cd04409     12 SPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFEN---------GKDLVElselsphDISNVLKLYLRQL 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579 1090 DDALLTKELYPYWIS-ALDIRNDQER---------------------VRKYKNIIGTLPDLNKATLAALMEHLFRIQKCF 1147
Cdd:cd04409     83 PEPLILFRLYNEFIGlAKESQHVNETqeakknsdkkwpnmctelnriLLKSKDLLRQLPAPNYNTLQFLIVHLHRVSEQA 162
                          170
                   ....*....|....*...
gi 1050394579 1148 DINHLDTLTLAKAFSSCL 1165
Cdd:cd04409    163 EENKMSASNLGIIFGPTL 180
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
909-984 5.06e-03

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269941  Cd Length: 106  Bit Score: 38.08  E-value: 5.06e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  909 TLLGYLYYKNSYsLNQWKKAWFALD--KACLHYW-NTED---CGKADTIQLKKLQELTANSSML-NGEKGNILLLVENGR 981
Cdd:cd01235      4 THEGYLYKRGAL-LKGWKQRWFVLDstKHQLRYYeSREDtkcKGFIDLAEVESVTPATPIIGAPkRADEGAFFDLKTNKR 82

                   ...
gi 1050394579  982 TFY 984
Cdd:cd01235     83 VYN 85
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
788-892 6.32e-03

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 37.64  E-value: 6.32e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  788 GFLHKASSSTSKMtinrkskevpeMKRWWCTIENNFLKYYENETAPVADGVIDLSEVLCLVVHPSDCSSNgmaAFTFEIY 867
Cdd:cd13248     11 GWLHKQGGSGLKN-----------WRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEISR---KFAFKAE 76
                           90       100
                   ....*....|....*....|....*
gi 1050394579  868 FLSERMFLFGAENVESRREWTRAIA 892
Cdd:cd13248     77 HANMRTYYFAADTAEEMEQWMNAMS 101
PH pfam00169
PH domain; PH stands for pleckstrin homology.
486-574 6.60e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 37.93  E-value: 6.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  486 TEKNGYLELKGYKNKI-----FTVINGSKLWFSKNKQDASTG-----ITITDLTLT--MASVKNIDRKSFELST----PF 549
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKswkkrYFVLFDGSLLYYKDDKSKKSKepkgsISLSGCEVVevVASDSPKRKFCFELRTgertGK 80
                           90       100
                   ....*....|....*....|....*
gi 1050394579  550 RNFSLTAESEREKQEWTEAIQQSIA 574
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
488-570 7.95e-03

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270180  Cd Length: 106  Bit Score: 37.53  E-value: 7.95e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  488 KNGYLELKGYKNKIF---------TVINGSKLWFS--KNKQDAStGITITDLTLTMA-SVKNIDRKS--FELSTP-FRNF 552
Cdd:cd13380      3 KQGYLEKRSKDHSFFgsewqkrwcVLTNRAFYYYAseKSKQPKG-GFLIKGYSAQMApHLRKDSRRDscFELTTPgRRTY 81
                           90
                   ....*....|....*...
gi 1050394579  553 SLTAESEREKQEWTEAIQ 570
Cdd:cd13380     82 QFTAASPSEARDWVDQIQ 99
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
925-1003 8.10e-03

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270090  Cd Length: 114  Bit Score: 37.72  E-value: 8.10e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  925 WKKAWFALDKACLHYWNTE-DCGKADTIQLK---KLQELTANSSMLngeKGNILLLVENGRTFYIHGHTMLDFTVWHLAI 1000
Cdd:cd13271     24 WKRRFFILDDNTISYYKSEtDKEPLRTIPLRevlKVHECLVKSLLM---RDNLFEIITTSRTFYIQADSPEEMHSWIKAI 100

                   ...
gi 1050394579 1001 EKA 1003
Cdd:cd13271    101 SGA 103
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
912-996 8.27e-03

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and, with the exception of CNK3, a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from mammals, chickens, amphibians, fish, and crustacea. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269962  Cd Length: 114  Bit Score: 37.77  E-value: 8.27e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050394579  912 GYLYYKN---SYSLNQWKKAWFALDKACLHYWNTEDCGKADTiqLKKLQELTANSSMLNGEKGNILLLVENGRTFYIHGH 988
Cdd:cd01260     17 GWLWKKKeakSFFGQKWKKYWFVLKGSSLYWYSNQQDEKAEG--FINLPDFKIERASECKKKYAFKACHPKIKTFYFAAE 94

                   ....*...
gi 1050394579  989 TMLDFTVW 996
Cdd:cd01260     95 NLDDMNKW 102
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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