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Conserved domains on  [gi|568996617|ref|XP_006522809|]
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arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 isoform X3 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
BAR_ACAP2 cd07638
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 18-217 4.15e-131

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2), also called centaurin beta-2, is an Arf6-specific GTPase activating protein (GAP) which mediates Arf6 signaling. Arf6 is involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration. ACAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


:

Pssm-ID: 153322  Cd Length: 200  Bit Score: 388.59  E-value: 4.15e-131
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  18 RAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETSLTKFSDSLQEMINFHTIL 97
Cdd:cd07638    1 RAALEDVEGDVAELELKLDKLVKLCIGMIDAGKAFCQANKQFMNGIRDLAQYSSKDAVIETSLTKFSDTLQEMINYHTIL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  98 FDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQHEVEEAANILTATRKCFRHIALDYVLQI 177
Cdd:cd07638   81 FDQAQRSIKAQLQTFVKEDLRKFKDAKKQFDKVSEEKENALVKNAQVQRNKQHEVEEATNILTATRKCFRHIALDYVLQI 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 568996617 178 NVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYM 217
Cdd:cd07638  161 NVLQSKRRSEILKSMLSFMYAHLTFFHQGYDLFSELGPYM 200
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
 403-517 1.34e-83

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: 261.84  E-value: 1.34e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 403 ESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRV 482
Cdd:cd08851    1 ESALQRVQCIPGNASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRI 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 568996617 483 YEAKLEKMGVKKPQPG-QRQEKEAYIRAKYVERKFV 517
Cdd:cd08851   81 YEARVEKMGAKKPQPGgQRQEKEAYIRAKYVERKFV 116
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 273-369 1.95e-58

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: 193.59  E-value: 1.95e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 273 MEGYLFKRASNAFKTWNRRWFSIQNNQLVYQKKF-KDSPTVVVEDLRLCTVKHCEDIERRFCFEVVSPTKSCMLQADSEK 351
Cdd:cd13250    1 KEGYLFKRSSNAFKTWKRRWFSLQNGQLYYQKRDkKDEPTVMVEDLRLCTVKPTEDSDRRFCFEVISPTKSYMLQAESEE 80

                         90
                 ....*....|....*...
gi 568996617 352 LRQAWIKAVQTSIATAYR 369
Cdd:cd13250   81 DRQAWIQAIQSAIASALN 98
COG5347 super family cl34987
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
 391-628 2.80e-37

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


The actual alignment was detected with superfamily member COG5347:

Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 142.22  E-value: 2.80e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 391 SGNESKEKLLKgesALQRvqcIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKL 470
Cdd:COG5347    2 STKSEDRKLLK---LLKS---DSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRR 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 471 MCELGNDVINRVYEAKLEKMGVKKPQPG-QRQEKEAYIRAKYVERKFVD---KYSALLSPSEQEKRIISKSCEDQRLSHA 546
Cdd:COG5347   76 MEVGGNSNANRFYEKNLLDQLLLPIKAKyDSSVAKKYIRKKYELKKFIDdssSPSDFSSFSASSTRTVDSVDDRLDSESQ 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 547 RASVHTPVAAVT--SDEARRESLF-CPDELDSLFSyfDTSSKLRSIKSNDSGIQQCSEDGRESLPSTVSANSLYEPEGER 623
Cdd:COG5347  156 SRSSSASLGNSNrpDDELNVESFQsTGSKPRSLTS--TKSNKDNLLNSELLTLNSLLSSNSEVGSGTKSRSDAQEKSSTK 233


                 ....*
gi 568996617 624 QESSV 628
Cdd:COG5347  234 ATESV 238
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
641-772 1.46e-24

Ankyrin repeat [Signal transduction mechanisms];


:

Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 104.65  E-value: 1.46e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 641 LYRASYEKNLpKMAEAL-AHGADVNWANSDENqaTPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTG 719
Cdd:COG0666  124 LHLAAYNGNL-EIVKLLlEAGADVNAQDNDGN--TPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLE 200

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568996617 720 QVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLLRLARMNEEMRESEGL 772
Cdd:COG0666  201 IVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAGADLNAKDKDGL 253
 
Name Accession Description Interval E-value
BAR_ACAP2 cd07638
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 18-217 4.15e-131

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2), also called centaurin beta-2, is an Arf6-specific GTPase activating protein (GAP) which mediates Arf6 signaling. Arf6 is involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration. ACAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153322  Cd Length: 200  Bit Score: 388.59  E-value: 4.15e-131
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  18 RAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETSLTKFSDSLQEMINFHTIL 97
Cdd:cd07638    1 RAALEDVEGDVAELELKLDKLVKLCIGMIDAGKAFCQANKQFMNGIRDLAQYSSKDAVIETSLTKFSDTLQEMINYHTIL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  98 FDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQHEVEEAANILTATRKCFRHIALDYVLQI 177
Cdd:cd07638   81 FDQAQRSIKAQLQTFVKEDLRKFKDAKKQFDKVSEEKENALVKNAQVQRNKQHEVEEATNILTATRKCFRHIALDYVLQI 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 568996617 178 NVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYM 217
Cdd:cd07638  161 NVLQSKRRSEILKSMLSFMYAHLTFFHQGYDLFSELGPYM 200
BAR_3 pfam16746
BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or ...
 5-238 9.52e-111

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.


Pssm-ID: 465256  Cd Length: 235  Bit Score: 337.23  E-value: 9.52e-111
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617    5 VDFEECLKDSPRFRAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETSLTKFS 84
Cdd:pfam16746   1 LEFEECLKDSPQFRSLLEEHEAELDELEKKLKKLLKLCKRMIEAGKEYSAAQRLFANSLLDFKFEFIGDEETDESLKKFS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617   85 DSLQEMINFHTILFDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNK-QHEVEEAANILTATR 163
Cdd:pfam16746  81 QLLQEMENFHTILLDQAQRTIIKPLENFRKEDLKEVKELKKKFDKASEKLDAALEKNAQLSKKKkPSELEEADNELAATR 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568996617  164 KCFRHIALDYVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYMKDLGAQLDRLVVDAAKEKREM 238
Cdd:pfam16746 161 KCFHHASLDYVLQINELQERKKFEILEPLLSFMHAQFTFFHQGYELFKDLEPFMKDLQAQLQQTREDTREEKEEL 235
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
 403-517 1.34e-83

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: 261.84  E-value: 1.34e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 403 ESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRV 482
Cdd:cd08851    1 ESALQRVQCIPGNASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRI 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 568996617 483 YEAKLEKMGVKKPQPG-QRQEKEAYIRAKYVERKFV 517
Cdd:cd08851   81 YEARVEKMGAKKPQPGgQRQEKEAYIRAKYVERKFV 116
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 273-369 1.95e-58

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: 193.59  E-value: 1.95e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 273 MEGYLFKRASNAFKTWNRRWFSIQNNQLVYQKKF-KDSPTVVVEDLRLCTVKHCEDIERRFCFEVVSPTKSCMLQADSEK 351
Cdd:cd13250    1 KEGYLFKRSSNAFKTWKRRWFSLQNGQLYYQKRDkKDEPTVMVEDLRLCTVKPTEDSDRRFCFEVISPTKSYMLQAESEE 80

                         90
                 ....*....|....*...
gi 568996617 352 LRQAWIKAVQTSIATAYR 369
Cdd:cd13250   81 DRQAWIQAIQSAIASALN 98
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
 406-522 1.91e-55

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: 186.39  E-value: 1.91e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617   406 LQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEA 485
Cdd:smart00105   1 LKLLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 568996617   486 KLEKMGVKKPQPGQRQEKEAYIRAKYVERKFVDKYSA 522
Cdd:smart00105  81 NLDDFSLKPPDDDDQQKYESFIAAKYEEKLFVPPESA 117
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
 403-519 1.70e-54

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: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 183.58  E-value: 1.70e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  403 ESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRV 482
Cdd:pfam01412   1 KRVLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEF 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 568996617  483 YEAKLEKmGVKKPQPGQRQEKEAYIRAKYVERKFVDK 519
Cdd:pfam01412  81 WEANLPP-SYKPPPSSDREKRESFIRAKYVEKKFAKP 116
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
 391-628 2.80e-37

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: 142.22  E-value: 2.80e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 391 SGNESKEKLLKgesALQRvqcIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKL 470
Cdd:COG5347    2 STKSEDRKLLK---LLKS---DSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRR 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 471 MCELGNDVINRVYEAKLEKMGVKKPQPG-QRQEKEAYIRAKYVERKFVD---KYSALLSPSEQEKRIISKSCEDQRLSHA 546
Cdd:COG5347   76 MEVGGNSNANRFYEKNLLDQLLLPIKAKyDSSVAKKYIRKKYELKKFIDdssSPSDFSSFSASSTRTVDSVDDRLDSESQ 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 547 RASVHTPVAAVT--SDEARRESLF-CPDELDSLFSyfDTSSKLRSIKSNDSGIQQCSEDGRESLPSTVSANSLYEPEGER 623
Cdd:COG5347  156 SRSSSASLGNSNrpDDELNVESFQsTGSKPRSLTS--TKSNKDNLLNSELLTLNSLLSSNSEVGSGTKSRSDAQEKSSTK 233


                 ....*
gi 568996617 624 QESSV 628
Cdd:COG5347  234 ATESV 238
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
641-772 1.46e-24

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 104.65  E-value: 1.46e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 641 LYRASYEKNLpKMAEAL-AHGADVNWANSDENqaTPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTG 719
Cdd:COG0666  124 LHLAAYNGNL-EIVKLLlEAGADVNAQDNDGN--TPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLE 200

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568996617 720 QVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLLRLARMNEEMRESEGL 772
Cdd:COG0666  201 IVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAGADLNAKDKDGL 253
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 271-365 6.87e-18

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 [Multi-domain]  Cd Length: 102  Bit Score: 79.51  E-value: 6.87e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617   271 IVMEGYLFKRASNAFKTWNRRWFSIQNNQLVYQKKFKDSPTVVVE---DLRLCTVKHCEDI---ERRFCFEVVSPTKSCM 344
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKgsiDLSGCTVREAPDPdssKKPHCFEIKTSDRKTL 80

                           90       100
                   ....*....|....*....|..
gi 568996617   345 -LQADSEKLRQAWIKAVQTSIA 365
Cdd:smart00233  81 lLQAESEEEREKWVEALRKAIA 102
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
 395-477 2.05e-17

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 85.29  E-value: 2.05e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 395 SKEKLLKGESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCEL 474
Cdd:PLN03114   2 ASENLNDKISVFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYG 81


                 ...
gi 568996617 475 GND 477
Cdd:PLN03114  82 GNN 84
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 271-365 6.89e-15

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 71.05  E-value: 6.89e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  271 IVMEGYLFKRASNAFKTWNRRWFSIQNNQLVYQKK---FKDSPTVVVEDLRLCTVKHCEDIE---RRFCFEVVSPTKSCM 344
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDdksGKSKEPKGSISLSGCEVVEVVASDspkRKFCFELRTGERTGK 80

                          90       100
                  ....*....|....*....|....*
gi 568996617  345 ----LQADSEKLRQAWIKAVQTSIA 365
Cdd:pfam00169  81 rtylLQAESEEERKDWIKAIQSAIR 105
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
 673-757 2.06e-11

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 67.62  E-value: 2.06e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 673 ATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANAD 752
Cdd:PTZ00322  83 TVELCQLAASGDAVGARILLTGGADPNCRDYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFRE 162


                 ....*
gi 568996617 753 IVTLL 757
Cdd:PTZ00322 163 VVQLL 167
Ank_2 pfam12796
Ankyrin repeats (3 copies);
676-757 2.08e-10

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 57.82  E-value: 2.08e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  676 LIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTgQVCLFLKRGANQHATDeEGKDPLSIAVEAANADIVT 755
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHL-EIVKLLLEHADVNLKD-NGRTALHYAARSGHLEIVK 78


                  ..
gi 568996617  756 LL 757
Cdd:pfam12796  79 LL 80
BAR smart00721
BAR domain;
6-219 5.39e-03

BAR domain;


Pssm-ID: 214787 [Multi-domain]  Cd Length: 239  Bit Score: 39.29  E-value: 5.39e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617     6 DFEECLKdspRFRAALEEVEGDVAELELKLDKLVKLcIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETsLTKFSD 85
Cdd:smart00721  28 DFEELER---RFDTTEAEIEKLQKDTKLYLQPNPAV-RAKLASQKKLSKSLGEVYEGGDDGEGLGADSSYGKA-LDKLGE 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617    86 SLQEMINFHTILFDQTQRSIKAQLQNFVKEdlrkFKDAKKQFEK--------------VSEEKENALVKNAQVQRNKQHE 151
Cdd:smart00721 103 ALKKLLQVEESLSQVKRTFILPLLNFLLGE----FKEIKKARKKlerklldydsarhkLKKAKKSKEKKKDEKLAKAEEE 178

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568996617   152 VEEAANILTatrkCFRHIALDYVLQINvlqSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYMKD 219
Cdd:smart00721 179 LRKAKQEFE----ESNAQLVEELPQLV---ASRVDFFVNCLQALIEAQLNFHRESYKLLQQLQQQLDK 239
 
Name Accession Description Interval E-value
BAR_ACAP2 cd07638
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 18-217 4.15e-131

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2), also called centaurin beta-2, is an Arf6-specific GTPase activating protein (GAP) which mediates Arf6 signaling. Arf6 is involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration. ACAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153322  Cd Length: 200  Bit Score: 388.59  E-value: 4.15e-131
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  18 RAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETSLTKFSDSLQEMINFHTIL 97
Cdd:cd07638    1 RAALEDVEGDVAELELKLDKLVKLCIGMIDAGKAFCQANKQFMNGIRDLAQYSSKDAVIETSLTKFSDTLQEMINYHTIL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  98 FDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQHEVEEAANILTATRKCFRHIALDYVLQI 177
Cdd:cd07638   81 FDQAQRSIKAQLQTFVKEDLRKFKDAKKQFDKVSEEKENALVKNAQVQRNKQHEVEEATNILTATRKCFRHIALDYVLQI 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 568996617 178 NVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYM 217
Cdd:cd07638  161 NVLQSKRRSEILKSMLSFMYAHLTFFHQGYDLFSELGPYM 200
BAR_3 pfam16746
BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or ...
 5-238 9.52e-111

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.


Pssm-ID: 465256  Cd Length: 235  Bit Score: 337.23  E-value: 9.52e-111
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617    5 VDFEECLKDSPRFRAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETSLTKFS 84
Cdd:pfam16746   1 LEFEECLKDSPQFRSLLEEHEAELDELEKKLKKLLKLCKRMIEAGKEYSAAQRLFANSLLDFKFEFIGDEETDESLKKFS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617   85 DSLQEMINFHTILFDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNK-QHEVEEAANILTATR 163
Cdd:pfam16746  81 QLLQEMENFHTILLDQAQRTIIKPLENFRKEDLKEVKELKKKFDKASEKLDAALEKNAQLSKKKkPSELEEADNELAATR 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568996617  164 KCFRHIALDYVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYMKDLGAQLDRLVVDAAKEKREM 238
Cdd:pfam16746 161 KCFHHASLDYVLQINELQERKKFEILEPLLSFMHAQFTFFHQGYELFKDLEPFMKDLQAQLQQTREDTREEKEEL 235
BAR_ACAPs cd07603
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 18-217 1.35e-109

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of ACAPs (ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins), which are Arf GTPase activating proteins (GAPs) containing an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. Vertebrates contain at least three members, ACAP1, ACAP2, and ACAP3. ACAP1 and ACAP2 are Arf6-specific GAPs, involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration, by mediating Arf6 signaling. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153287  Cd Length: 200  Bit Score: 333.12  E-value: 1.35e-109
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  18 RAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETSLTKFSDSLQEMINFHTIL 97
Cdd:cd07603    1 RASLEQVEADVSELETRLEKLLKLCNGMVDSGKTYVNANSLFVNSLNDLSDYFRDDSLVQNCLNKFIQALQEMNNFHTIL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  98 FDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQHEVEEAANILTATRKCFRHIALDYVLQI 177
Cdd:cd07603   81 LDQAQRTVSTQLQNFVKEDIKKVKESKKHFEKISDDLDNALVKNAQAPRSKPQEAEEATNILTATRSCFRHTALDYVLQI 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 568996617 178 NVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYM 217
Cdd:cd07603  161 NVLQAKKRHEILSTLLSYMHAQFTFFHQGYDLLEDLEPYM 200
BAR_ACAP3 cd07637
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 18-217 4.26e-93

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 3), also called centaurin beta-5, is presumed to be an Arf GTPase activating protein (GAP) based on its similarity to the Arf6-specific GAPs ACAP1 and ACAP2. The specific function of ACAP3 is still unknown. ACAP3 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153321  Cd Length: 200  Bit Score: 289.98  E-value: 4.26e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  18 RAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETSLTKFSDSLQEMINFHTIL 97
Cdd:cd07637    1 RATIDEVETDVVEIEAKLDKLVKLCSGMIEAGKAYATTNKLFVSGIRDLSQQCKKDEMISECLDKFGDSLQEMVNYHMIL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  98 FDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQHEVEEAANILTATRKCFRHIALDYVLQI 177
Cdd:cd07637   81 FDQAQRSVRQQLHSFVKEDVRKFKETKKQFDKVREDLEIALVKNAQAPRHKPHEVEEATSTLTITRKCFRHLALDYVLQI 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 568996617 178 NVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYM 217
Cdd:cd07637  161 NVLQAKKKFEILDSMLSFMHAQYTFFQQGYSLLHELDPYM 200
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
 403-517 1.34e-83

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: 261.84  E-value: 1.34e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 403 ESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRV 482
Cdd:cd08851    1 ESALQRVQCIPGNASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRI 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 568996617 483 YEAKLEKMGVKKPQPG-QRQEKEAYIRAKYVERKFV 517
Cdd:cd08851   81 YEARVEKMGAKKPQPGgQRQEKEAYIRAKYVERKFV 116
ArfGap_ACAP cd08835
ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP ...
 403-517 1.29e-77

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: 246.02  E-value: 1.29e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 403 ESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRV 482
Cdd:cd08835    1 GSALEQVLSVPGNAQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDSWEPELLKVMLELGNDVVNRI 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 568996617 483 YEAKLEKMGVKKPQPG-QRQEKEAYIRAKYVERKFV 517
Cdd:cd08835   81 YEANVPDDGSVKPTPDsSRQEREAWIRAKYVEKKFV 116
ArfGap_ACAP3 cd08850
ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs ...
 403-517 8.46e-70

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: 225.21  E-value: 8.46e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 403 ESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRV 482
Cdd:cd08850    1 ESILQRVQSIAGNDQCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDSWEPELLKLMCELGNSTVNQI 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 568996617 483 YEAKLEKMGVKKPQPG-QRQEKEAYIRAKYVERKFV 517
Cdd:cd08850   81 YEAQCEELGLKKPTASsSRQDKEAWIKAKYVEKKFL 116
ArfGap_ACAP1 cd08852
ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs ...
 405-519 3.90e-66

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: 215.59  E-value: 3.90e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 405 ALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYE 484
Cdd:cd08852    3 AVAQVQSVDGNAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLGVHFSKVRSLTLDSWEPELVKLMCELGNVIINQIYE 82

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 568996617 485 AKLEKMGVKKPQPG-QRQEKEAYIRAKYVERKFVDK 519
Cdd:cd08852   83 ARIEAMAIKKPGPSsSRQEKEAWIRAKYVEKKFITK 118
BAR_ACAP1 cd07639
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 18-216 6.57e-63

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 1), also called centaurin beta-1, is an Arf6-specific GTPase activating protein (GAP) which mediates Arf6 signaling. Arf6 is involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration. ACAP1 also participates in the cargo sorting and recycling of the transferrin receptor and integrin beta1. It may also play a role in innate immune responses. ACAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153323  Cd Length: 200  Bit Score: 209.77  E-value: 6.57e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  18 RAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETSLTKFSDSLQEMINFHTIL 97
Cdd:cd07639    1 RAAIEEVEAEVSELETRLEKLVKLGSGMLEGGRHYCAASRAFVDGLCDLAHHGPKDPMMAECLEKFSDGLNHILDSHAEL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  98 FDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQHEVEEAANILTATRKCFRHIALDYVLQI 177
Cdd:cd07639   81 LEATQFSFKQQLQLLVKEDLRGFRDARKEFERGAESLEAALQHNAETPRRKAQEVEEAAAALLGARATFRDRALDYALQI 160

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 568996617 178 NVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPY 216
Cdd:cd07639  161 NVIEDKKKFDILEFMLQLMEAQASFFQQGHEALSALHQY 199
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 273-369 1.95e-58

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: 193.59  E-value: 1.95e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 273 MEGYLFKRASNAFKTWNRRWFSIQNNQLVYQKKF-KDSPTVVVEDLRLCTVKHCEDIERRFCFEVVSPTKSCMLQADSEK 351
Cdd:cd13250    1 KEGYLFKRSSNAFKTWKRRWFSLQNGQLYYQKRDkKDEPTVMVEDLRLCTVKPTEDSDRRFCFEVISPTKSYMLQAESEE 80

                         90
                 ....*....|....*...
gi 568996617 352 LRQAWIKAVQTSIATAYR 369
Cdd:cd13250   81 DRQAWIQAIQSAIASALN 98
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
 406-511 1.43e-56

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: 188.86  E-value: 1.43e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 406 LQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEA 485
Cdd:cd08204    1 LEELLKLPGNKVCADCGAPDPRWASINLGVFICIRCSGIHRSLGVHISKVRSLTLDSWTPEQVELMKAIGNARANAYYEA 80

                         90       100
                 ....*....|....*....|....*..
gi 568996617 486 KLEKmGVKKPQPGQ-RQEKEAYIRAKY 511
Cdd:cd08204   81 NLPP-GFKKPTPDSsDEEREQFIRAKY 106
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
 406-522 1.91e-55

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: 186.39  E-value: 1.91e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617   406 LQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEA 485
Cdd:smart00105   1 LKLLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 568996617   486 KLEKMGVKKPQPGQRQEKEAYIRAKYVERKFVDKYSA 522
Cdd:smart00105  81 NLDDFSLKPPDDDDQQKYESFIAAKYEEKLFVPPESA 117
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
 403-519 1.70e-54

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: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 183.58  E-value: 1.70e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  403 ESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRV 482
Cdd:pfam01412   1 KRVLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEF 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 568996617  483 YEAKLEKmGVKKPQPGQRQEKEAYIRAKYVERKFVDK 519
Cdd:pfam01412  81 WEANLPP-SYKPPPSSDREKRESFIRAKYVEKKFAKP 116
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
 405-512 4.74e-49

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: 168.24  E-value: 4.74e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 405 ALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYE 484
Cdd:cd08836    2 ALQAIRNVRGNDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDDWPVELLKVMSAIGNDLANSVWE 81

                         90       100
                 ....*....|....*....|....*....
gi 568996617 485 AKLEkmGVKKPQP-GQRQEKEAYIRAKYV 512
Cdd:cd08836   82 GNTQ--GRTKPTPdSSREEKERWIRAKYE 108
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
 404-517 7.11e-45

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: 157.00  E-value: 7.11e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 404 SALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVY 483
Cdd:cd08834    4 SIIAEVKRLPGNDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDNLGTSELLLARNLGNEGFNEIM 83

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568996617 484 EAKLEkmGVKKPQPG-QRQEKEAYIRAKYVERKFV 517
Cdd:cd08834   84 EANLP--PGYKPTPNsDMEERKDFIRAKYVEKKFV 116
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
 413-511 5.65e-39

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: 139.71  E-value: 5.65e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 413 PGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEAKLEKmGV 492
Cdd:cd08839    8 EDNKYCADCGAKGPRWASWNLGVFICIRCAGIHRNLGVHISKVKSVNLDSWTPEQVQSMQEMGNARANAYYEANLPD-GF 86

                         90
                 ....*....|....*....
gi 568996617 493 KKPQPgqRQEKEAYIRAKY 511
Cdd:cd08839   87 RRPQT--DSALENFIRDKY 103
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
 405-511 4.54e-38

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: 137.39  E-value: 4.54e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 405 ALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYE 484
Cdd:cd08832    7 RLLELLKLPGNNTCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDNWDDSQVEFMEENGNEKAKAKYE 86

                         90       100
                 ....*....|....*....|....*...
gi 568996617 485 AKLEKmGVKKPQPGQRQE-KEAYIRAKY 511
Cdd:cd08832   87 AHVPA-FYRRPTPTDPQVlREQWIRAKY 113
ArfGap_AGAP2 cd08853
ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation ...
 405-511 1.43e-37

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: 135.91  E-value: 1.43e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 405 ALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYE 484
Cdd:cd08853    3 ALQSIRNMRGNSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDDWPVELRKVMSSIGNELANSIWE 82

                         90       100
                 ....*....|....*....|....*...
gi 568996617 485 AklEKMGVKKPQ-PGQRQEKEAYIRAKY 511
Cdd:cd08853   83 G--SSQGQTKPSsDSTREEKERWIRAKY 108
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
 391-628 2.80e-37

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: 142.22  E-value: 2.80e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 391 SGNESKEKLLKgesALQRvqcIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKL 470
Cdd:COG5347    2 STKSEDRKLLK---LLKS---DSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRR 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 471 MCELGNDVINRVYEAKLEKMGVKKPQPG-QRQEKEAYIRAKYVERKFVD---KYSALLSPSEQEKRIISKSCEDQRLSHA 546
Cdd:COG5347   76 MEVGGNSNANRFYEKNLLDQLLLPIKAKyDSSVAKKYIRKKYELKKFIDdssSPSDFSSFSASSTRTVDSVDDRLDSESQ 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 547 RASVHTPVAAVT--SDEARRESLF-CPDELDSLFSyfDTSSKLRSIKSNDSGIQQCSEDGRESLPSTVSANSLYEPEGER 623
Cdd:COG5347  156 SRSSSASLGNSNrpDDELNVESFQsTGSKPRSLTS--TKSNKDNLLNSELLTLNSLLSSNSEVGSGTKSRSDAQEKSSTK 233


                 ....*
gi 568996617 624 QESSV 628
Cdd:COG5347  234 ATESV 238
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
 405-511 4.86e-37

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: 134.41  E-value: 4.86e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 405 ALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYE 484
Cdd:cd08855    4 AIQSIRNVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDDWPVELSMVMTAIGNAMANSVWE 83

                         90       100
                 ....*....|....*....|....*...
gi 568996617 485 AKLEkmGVKKPQP-GQRQEKEAYIRAKY 511
Cdd:cd08855   84 GALD--GYSKPGPdSTREEKERWIRAKY 109
ArfGap_ASAP3 cd17900
ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ...
 409-519 8.45e-37

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: 134.20  E-value: 8.45e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 409 VQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEAKLE 488
Cdd:cd17900    9 VKSRPGNSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYSRIQSLTLDLLSTSELLLAVSMGNTRFNEVMEATLP 88

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568996617 489 KMGVKKPQP----GQRQEkeaYIRAKYVERKFVDK 519
Cdd:cd17900   89 AHGGPKPSAesdmGTRKD---YIMAKYVEHRFVRK 120
ArfGap_AGAP1 cd08854
ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation ...
 405-511 3.49e-35

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: 129.36  E-value: 3.49e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 405 ALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYE 484
Cdd:cd08854    3 AIQAIRNAKGNSLCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNHMANSIWE 82

                         90       100
                 ....*....|....*....|....*...
gi 568996617 485 AKLEkmGVKKPQP-GQRQEKEAYIRAKY 511
Cdd:cd08854   83 SCTQ--GRTKPAPdSSREERESWIRAKY 108
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
 406-519 1.94e-33

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: 124.70  E-value: 1.94e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 406 LQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEA 485
Cdd:cd08849    6 ISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEA 85

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568996617 486 KLEKMGVKKPQPGQ-RQEKEAYIRAKYVERKFVDK 519
Cdd:cd08849   86 CLPAEDVVKPNPGSdMNARKDYITAKYIERRYARK 120
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
 418-511 2.13e-32

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: 121.25  E-value: 2.13e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 418 CCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEAKL---EKMGVKK 494
Cdd:cd08833   11 CADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKDQWPPSLLEMVQTLGNNGANSIWEHSLldpSQSGKRK 90

                         90
                 ....*....|....*....
gi 568996617 495 PQPGQ--RQEKEAYIRAKY 511
Cdd:cd08833   91 PIPPDpvHPTKEEFIKAKY 109
ArfGap_ASAP1 cd08848
ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); ...
 403-519 1.67e-31

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: 119.37  E-value: 1.67e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 403 ESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRV 482
Cdd:cd08848    3 KAIIDDVQRLPGNEVCCDCGSPDPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDI 82

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568996617 483 YEAKLEKMGVKKPQPGQRQEKEAYIRAKYVERKFVDK 519
Cdd:cd08848   83 MEGNLPSPSPKPSPSSDMTARKEYITAKYVEHRFSRK 119
ArfGap_ArfGap1 cd08830
Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
 406-511 4.50e-30

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: 114.90  E-value: 4.50e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 406 LQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVyea 485
Cdd:cd08830    5 LRELQKLPGNNRCFDCGAPNPQWASVSYGIFICLECSGVHRGLGVHISFVRSITMDSWSEKQLKKMELGGNAKLREF--- 81

                         90       100
                 ....*....|....*....|....*.
gi 568996617 486 kLEKMGVKKPQPgqrqekeayIRAKY 511
Cdd:cd08830   82 -FESYGISPDLP---------IREKY 97
ArfGap_ARAP cd08837
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily ...
 406-516 1.38e-29

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: 113.63  E-value: 1.38e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 406 LQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDT--WEPELLKLMCELGNDVINRVY 483
Cdd:cd08837    4 AEKIWSNPANRFCADCGAPDPDWASINLCVVICKQCAGEHRSLGSNISKVRSLKMDTkvWTEELVELFLKLGNDRANRFW 83

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568996617 484 EAKLEKMGVKKPQ--PGQRQEkeaYIRAKYVERKF 516
Cdd:cd08837   84 AANLPPSEALHPDadSEQRRE---FITAKYREGKY 115
ArfGap_ArfGap1_like cd08959
ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
 406-471 8.26e-28

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: 108.37  E-value: 8.26e-28
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568996617 406 LQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLM 471
Cdd:cd08959    5 FKKLRSKPENKVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGVHISFVRSTTMDKWTEEQLRKM 70
ArfGap_SMAP2 cd08859
Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of ...
 415-515 1.05e-27

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: 107.77  E-value: 1.05e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 415 NTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEAKLEKmGVKK 494
Cdd:cd08859   10 NKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHISRVKSVNLDQWTQEQIQCMQEMGNGKANRLYEAFLPE-NFRR 88

                         90       100
                 ....*....|....*....|.
gi 568996617 495 PQpgQRQEKEAYIRAKYVERK 515
Cdd:cd08859   89 PQ--TDQAVEGFIRDKYEKKK 107
ArfGap_ArfGap2_3_like cd08831
Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
 406-477 2.84e-25

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: 101.08  E-value: 2.84e-25
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568996617 406 LQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGND 477
Cdd:cd08831    6 FKKLRSKPENKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLGVHISFVRSTNLDSWTPEQLRRMKVGGNA 77
ArfGap_ADAP1 cd08843
ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
 406-511 1.10e-24

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: 99.31  E-value: 1.10e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 406 LQRvqciPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGvHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEA 485
Cdd:cd08843   12 LQR----PGNARCADCGAPDPDWASYTLGVFICLSCSGIHRNIP-QVSKVKSVRLDAWEEAQVEFMASHGNDAARARFES 86

                         90       100
                 ....*....|....*....|....*..
gi 568996617 486 KLEKMgVKKPQPGQRQ-EKEAYIRAKY 511
Cdd:cd08843   87 KVPSF-YYRPTPSDCQlLREQWIRAKY 112
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
641-772 1.46e-24

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 104.65  E-value: 1.46e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 641 LYRASYEKNLpKMAEAL-AHGADVNWANSDENqaTPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTG 719
Cdd:COG0666  124 LHLAAYNGNL-EIVKLLlEAGADVNAQDNDGN--TPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLE 200

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568996617 720 QVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLLRLARMNEEMRESEGL 772
Cdd:COG0666  201 IVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAGADLNAKDKDGL 253
ArfGap_ARAP1 cd17901
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily ...
 407-516 2.66e-24

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: 98.35  E-value: 2.66e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 407 QRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLD--TWEPELLKLMCELGNDVINRVYE 484
Cdd:cd17901    5 EKIWSVESNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKMDrkVWTEELIELFLLLGNGKANQFWA 84

                         90       100       110
                 ....*....|....*....|....*....|..
gi 568996617 485 AKLEKMGVKKPQpGQRQEKEAYIRAKYVERKF 516
Cdd:cd17901   85 ANVPPSEALCPS-SSSEERRHFITAKYKEGKY 115
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
641-757 3.29e-24

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 103.50  E-value: 3.29e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 641 LYRASYEKNLPKMAEALAHGADVNwaNSDENQATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQ 720
Cdd:COG0666   91 LHAAARNGDLEIVKLLLEAGADVN--ARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEI 168

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568996617 721 VCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLL 757
Cdd:COG0666  169 VKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLL 205
BAR cd07307
The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects ...
 27-216 8.73e-24

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.


Pssm-ID: 153271 [Multi-domain]  Cd Length: 194  Bit Score: 99.44  E-value: 8.73e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  27 DVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQYSSN--DAVVETSLTKFSDSLQEMINFHTILFDQTQRS 104
Cdd:cd07307    1 KLDELEKLLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKELPDlsNTDLGEALEKFGKIQKELEEFRDQLEQKLENK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 105 IKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQR--NKQHEVEEAANILTATRKCFRHIALDYVLQINVLQS 182
Cdd:cd07307   81 VIEPLKEYLKKDLKEIKKRRKKLDKARLDYDAAREKLKKLRKkkKDSSKLAEAEEELQEAKEKYEELREELIEDLNKLEE 160

                        170       180       190
                 ....*....|....*....|....*....|....
gi 568996617 183 KRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPY 216
Cdd:cd07307  161 KRKELFLSLLLSFIEAQSEFFKEVLKILEQLLPY 194
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
 413-511 7.46e-23

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: 94.06  E-value: 7.46e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 413 PGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGvHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEAKLEKMGV 492
Cdd:cd08844   15 PGNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNLP-DISRVKSIRLDFWEDELVEFMKENGNLKAKAKFEAFVPPFYY 93

                         90
                 ....*....|....*....
gi 568996617 493 KKPQPGQRQEKEAYIRAKY 511
Cdd:cd08844   94 RPQANDCDVLKEQWIRAKY 112
ArfGap_GIT2 cd08847
GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
 418-511 1.06e-22

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: 93.55  E-value: 1.06e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 418 CCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEAKLEK-----MGV 492
Cdd:cd08847   11 CADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSLLDpasimSGK 90

                         90       100
                 ....*....|....*....|.
gi 568996617 493 KKPQPGQR--QEKEAYIRAKY 511
Cdd:cd08847   91 RKANPQDKvhPNKAEFIRAKY 111
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
 415-516 2.32e-22

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: 93.05  E-value: 2.32e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 415 NTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDT--WEPELLKLMCELGNDVINRVYEAKLEKmGV 492
Cdd:cd08856   18 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVVGNKPANLFWAANLFS-EE 96

                         90       100
                 ....*....|....*....|....
gi 568996617 493 KKPQPGQRQEKEAYIRAKYVERKF 516
Cdd:cd08856   97 DLHMDSDVEQRTPFITQKYKEGKF 120
ArfGap_ARAP3 cd17902
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily ...
 413-516 4.36e-22

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: 91.89  E-value: 4.36e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 413 PGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDT--WEPELLKLMCELGNDVINRVYEAKLEKM 490
Cdd:cd17902   11 KANRFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKLDTsvWSNEIVQLFIVLGNDRANRFWAARLPAS 90

                         90       100
                 ....*....|....*....|....*...
gi 568996617 491 GVKKPQ--PGQRQEkeaYIRAKYVERKF 516
Cdd:cd17902   91 EALHPDatPEQRRE---FISRKYREGRF 115
ArfGap_ArfGap2 cd09029
Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
 403-476 2.94e-20

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: 87.04  E-value: 2.94e-20
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568996617 403 ESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDT-WEPELLKLMCELGN 476
Cdd:cd09029    7 QTLFKRLRAIPTNKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHLSFIRSTELDSnWNWFQLRCMQVGGN 81
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
628-757 9.35e-20

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 90.40  E-value: 9.35e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 628 VFLDSKHLNPGLQLYRASYEKNLPKMAEALAHGADVNwaNSDENQATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRG 707
Cdd:COG0666   45 LALALADALGALLLLAAALAGDLLVALLLLAAGADIN--AKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGET 122

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 568996617 708 PLHHATVLGHTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLL 757
Cdd:COG0666  123 PLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEIVKLL 172
ArfGap_AGFG cd08838
ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ...
 413-518 1.20e-19

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: 84.94  E-value: 1.20e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 413 PGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGvHfsKVRSLTLDTWEPELLKLMCELGNDVINRVYEAKLEKMGV 492
Cdd:cd08838   11 PENKRCFDCGQRGPTYVNLTFGTFVCTTCSGIHREFN-H--RVKSISMSTFTPEEVEFLQAGGNEVARKIWLAKWDPRTD 87

                         90       100
                 ....*....|....*....|....*.
gi 568996617 493 KKPQPGQRQEKEAYIRAKYVERKFVD 518
Cdd:cd08838   88 PEPDSGDDQKIREFIRLKYVDKRWYD 113
BAR_GRAF2 cd07635
The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion 2; BAR ...
 22-216 2.77e-19

The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. GTPase Regulator Associated with Focal adhesion kinase 2 (GRAF2), also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA which regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle and also interacts with PKNbeta, which is a target of Rho. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein GRAF directly interacts with its Rho GAP domain and inhibits its activity. Autoinhibited GRAF is capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153319  Cd Length: 207  Bit Score: 86.98  E-value: 2.77e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  22 EEVEGDVAELElKLDKLVKLCIA----MIDTGKAFCVANKQFMNGIRDLAQYSSNDAV------VETSLTKFSDSLQEMI 91
Cdd:cd07635    2 ERIRAHEAELE-RTNRFIKELLKdgknLIAATKSLSAAQRKFAHSLRDFKFEFIGDAEtddercIDASLQEFSNFLKNLE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  92 NFHTILFDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQ-RNKQHEVEEAANILTATRKCFRHIA 170
Cdd:cd07635   81 EQREIMALNVTETLIKPLERFRKEQLGAVKEEKKKFDKETEKNYSLLEKHLNLSaKKKEPQLQEADVQVEQNRQHFYELS 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 568996617 171 LDYVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPY 216
Cdd:cd07635  161 LEYVCKLQEIQERKKFECVEPMLSFFQGVFTFYHQGYELAKDFNHY 206
ArfGap_ArfGap3 cd09028
Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
 406-476 2.87e-19

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: 84.35  E-value: 2.87e-19
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568996617 406 LQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDT-WEPELLKLMCELGN 476
Cdd:cd09028   10 FKRLRSVPTNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIRSTELDSnWSWFQLRCMQVGGN 81
BAR_SFC_plant cd07606
The Bin/Amphiphysin/Rvs (BAR) domain of the plant protein SCARFACE (SFC); BAR domains are ...
 19-216 1.84e-18

The Bin/Amphiphysin/Rvs (BAR) domain of the plant protein SCARFACE (SFC); BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. The plant protein SCARFACE (SFC), also called VAscular Network 3 (VAN3), is a plant ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein), an Arf GTPase Activating Protein (GAP) that plays a role in the trafficking of auxin efflux regulators from the plasma membrane to the endosome. It is required for the normal vein patterning in leaves. SCF contains an N-terminal BAR domain, followed by a Pleckstrin Homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153290  Cd Length: 202  Bit Score: 84.46  E-value: 1.84e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  19 AALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLaqYSSND-----AVVETSLTKFSDSLQEMINF 93
Cdd:cd07606    1 KQLQELEGSADELRDRSLKLYKGCRKYRDALGEAYDGDSAFAESLEEF--GGGHDdpisvAVGGPVMTKFTSALREIGSY 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  94 HTILFDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQHEVEEAA-NILTATRKCFRHIALD 172
Cdd:cd07606   79 KEVLRSQVEHMLNDRLAQFADTDLQEVKDARRRFDKASLDYEQARSKFLSLTKDAKPEILAAAeEDLGTTRSAFETARFD 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 568996617 173 YVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPY 216
Cdd:cd07606  159 LMNRLHAADARKRVEFLERLSGSMDAHLAFFKSGYELLRQLEPY 202
BAR_RhoGAP_OPHN1-like cd07602
The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin1-like Rho GTPase Activating Proteins; BAR ...
 38-217 6.22e-18

The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin1-like Rho GTPase Activating Proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of Rho and Rac GTPase activating proteins (GAPs) with similarity to oligophrenin1 (OPHN1). Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, and a Rho GAP domain. Some members contain a C-terminal SH3 domain. Vertebrates harbor at least three Rho GAPs in this subfamily including OPHN1, GTPase Regulator Associated with Focal adhesion kinase (GRAF), GRAF2, and an uncharacterized protein called GAP10-like. OPHN1, GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. In addition, OPHN1 is active towards Rac. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domains of OPHN1 and GRAF directly interact with their Rho GAP domains and inhibit their activity. The autoinhibited proteins are able to bind membranes and tubulate liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domains can occur simultaneously.


Pssm-ID: 153286  Cd Length: 207  Bit Score: 83.13  E-value: 6.22e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  38 LVKLCIAMIDTGKAFCVANKQFMNGIRDL-------AQySSNDAVVETSLTKFSDSLQEMINFHTILFDQTQRSIKAQLQ 110
Cdd:cd07602   21 LIKECKNLISATKNLSKAQRSFAQTLQNFkfecigeTQ-TDDEIEIAESLKEFGRLIETVEDERDRMLENAEEQLIEPLE 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 111 NFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQHEV-EEAANILTATRKCFRHIALDYVLQINVLQSKRRSEIL 189
Cdd:cd07602  100 KFRKEQIGGAKEEKKKFDKETEKFCSSLEKHLNLSTKKKENQlQEADAQLDMERRNFHQASLEYVFKLQEVQERKKFEFV 179

                        170       180
                 ....*....|....*....|....*...
gi 568996617 190 KSMLSFMYAHLAFFHQGYDLFSELGPYM 217
Cdd:cd07602  180 ETLLSFMYGWLTFYHQGHEVAKDFKPYL 207
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 271-365 6.87e-18

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 [Multi-domain]  Cd Length: 102  Bit Score: 79.51  E-value: 6.87e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617   271 IVMEGYLFKRASNAFKTWNRRWFSIQNNQLVYQKKFKDSPTVVVE---DLRLCTVKHCEDI---ERRFCFEVVSPTKSCM 344
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKgsiDLSGCTVREAPDPdssKKPHCFEIKTSDRKTL 80

                           90       100
                   ....*....|....*....|..
gi 568996617   345 -LQADSEKLRQAWIKAVQTSIA 365
Cdd:smart00233  81 lLQAESEEEREKWVEALRKAIA 102
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
641-761 8.97e-18

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 84.62  E-value: 8.97e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 641 LYRASYEKNLpKMAEAL-AHGADVNwaNSDENQATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTG 719
Cdd:COG0666  157 LHLAAANGNL-EIVKLLlEAGADVN--ARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLE 233

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 568996617 720 QVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLLRLAR 761
Cdd:COG0666  234 IVKLLLEAGADLNAKDKDGLTALLLAAAAGAALIVKLLLLAL 275
ArfGap_GIT1 cd08846
GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
 412-511 1.18e-17

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: 79.38  E-value: 1.18e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 412 IPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRVYEAKL---- 487
Cdd:cd08846    5 GPRAEVCADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRHSAWPPTLLQMVHTLASNGANSIWEHSLldpa 84

                         90       100
                 ....*....|....*....|....*..
gi 568996617 488 -EKMGVKK--PQPGQRQEKEAYIRAKY 511
Cdd:cd08846   85 qVQSGRRKanPQDKVHPTKSEFIRAKY 111
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
 395-477 2.05e-17

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 85.29  E-value: 2.05e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 395 SKEKLLKGESALQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCEL 474
Cdd:PLN03114   2 ASENLNDKISVFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYG 81


                 ...
gi 568996617 475 GND 477
Cdd:PLN03114  82 GNN 84
BAR_GAP10-like cd07634
The Bin/Amphiphysin/Rvs (BAR) domain of Rho GTPase activating protein 10-like; BAR domains are ...
 30-216 6.94e-17

The Bin/Amphiphysin/Rvs (BAR) domain of Rho GTPase activating protein 10-like; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This group is composed of uncharacterized proteins called Rho GTPase activating protein (GAP) 10-like. GAP10-like may be a GAP with activity towards RhoA and Cdc42. Similar to GRAF and GRAF2, it contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domains of the related proteins GRAF and OPHN1, directly interact with their Rho GAP domains and inhibit theiractivity. The autoinhibited proteins are capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153318 [Multi-domain]  Cd Length: 207  Bit Score: 80.07  E-value: 6.94e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  30 ELELK-----LDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETSLTkFSDSLQEMINFHTILFDQTQRS 104
Cdd:cd07634    8 EIELErtnkfIKELIKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEIS-IAQSLKEFARLLIAVEEERRRL 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 105 IK-------AQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQH-EVEEAANILTATRKCFRHIALDYVLQ 176
Cdd:cd07634   87 IQnandvliAPLEKFRKEQIGAAKDGKKKFDKESEKYYSILEKHLNLSAKKKEsHLQRADTQIDREHQNFYEASLEYVFK 166

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 568996617 177 INVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPY 216
Cdd:cd07634  167 IQEVQEKKKFEFVEPLLAFLQGLFTFYHEGYELAQEFAPY 206
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 273-360 2.76e-16

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: 74.50  E-value: 2.76e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 273 MEGYLFKRASNAFKTWNRRWFSIQNNQLVYQKKFKDSPTVVVEDLRL---CTVKHCEDIERRFCFEVVSPTKSCM-LQAD 348
Cdd:cd00821    1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLsgiLEVEEVSPKERPHCFELVTPDGRTYyLQAD 80

                         90
                 ....*....|..
gi 568996617 349 SEKLRQAWIKAV 360
Cdd:cd00821   81 SEEERQEWLKAL 92
BAR_GRAF cd07636
The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion kinase; ...
 32-216 5.73e-15

The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion kinase; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. GTPase Regulator Associated with Focal adhesion kinase (GRAF), also called Rho GTPase activating protein 26 (ARHGAP26), is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of GRAF directly interacts with its Rho GAP domain and inhibits its activity. Autoinhibited GRAF is capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153320 [Multi-domain]  Cd Length: 207  Bit Score: 74.32  E-value: 5.73e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  32 ELKLDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQY-------------SSNDAVVETSLTKFSDSLQEMINFHTILF 98
Cdd:cd07636    8 EAELDKTNKFIKELIKDGKSLIAALKNLSSAKRKFADSlnefkfqcigdaeTDDEICIARSLQEFAAVLRNLEDERTRMI 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  99 DQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQ-RNKQHEVEEAANILTATRKCFRHIALDYVLQI 177
Cdd:cd07636   88 ENASEVLITPLEKFRKEQIGAAKEAKKKYDKETEKYCAVLEKHLNLSsKKKESQLHEADSQVDLVRQHFYEVSLEYVFKV 167

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 568996617 178 NVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPY 216
Cdd:cd07636  168 QEVQERKMFEFVEPLLAFLQGLFTFYHHGYELAKDFSDF 206
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 271-365 6.89e-15

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 71.05  E-value: 6.89e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  271 IVMEGYLFKRASNAFKTWNRRWFSIQNNQLVYQKK---FKDSPTVVVEDLRLCTVKHCEDIE---RRFCFEVVSPTKSCM 344
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDdksGKSKEPKGSISLSGCEVVEVVASDspkRKFCFELRTGERTGK 80

                          90       100
                  ....*....|....*....|....*
gi 568996617  345 ----LQADSEKLRQAWIKAVQTSIA 365
Cdd:pfam00169  81 rtylLQAESEEERKDWIKAIQSAIR 105
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 274-373 8.24e-15

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: 70.81  E-value: 8.24e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 274 EGYLFKRaSNAFKTWNRRWFSIQNNQLVYqkkFKDS-------PTVVVeDLRLC-TVKHCED-IERRFCFEVVSPTKSCM 344
Cdd:cd13276    2 AGWLEKQ-GEFIKTWRRRWFVLKQGKLFW---FKEPdvtpyskPRGVI-DLSKClTVKSAEDaTNKENAFELSTPEETFY 76

                         90       100
                 ....*....|....*....|....*....
gi 568996617 345 LQADSEKLRQAWIKAVQTSIATAYREKGD 373
Cdd:cd13276   77 FIADNEKEKEEWIGAIGRAIVKHSRSVTD 105
BAR_APPL cd07601
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
 18-221 4.32e-13

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains, and are localized to cytoplasmic membranes. Vertebrates contain two APPL proteins, APPL1 and APPL2. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153285  Cd Length: 215  Bit Score: 69.17  E-value: 4.32e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  18 RAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMngiRDLAQYSS-------NDAVVETSLTKFSDSLQEM 90
Cdd:cd07601    1 RSLLNVFEEDALQLSSYMNQLLQACKRVYDAQNELKSATQALS---KKLGEYEKqkfelgrDDEILVSTLKQFSKVVDEL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  91 INFHTILFDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQHEVE--EAANILTATRKCFRH 168
Cdd:cd07601   78 STMHSTLSSQLADTVLHPISQFMESDLAEIMTLKELFKAASNDHDGVLSKYSRLSKKRENTKVkiEVNDEVYACRKKQHQ 157

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568996617 169 IALDYVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSE-LGPYMKDLG 221
Cdd:cd07601  158 TAMNYYCALNLLQYKKTTALLEPMIGYLQAQIAFFKMGPEMFTRqTEEFLSDIN 211
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
 263-365 1.39e-12

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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: 269954  Cd Length: 119  Bit Score: 65.03  E-value: 1.39e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 263 YNVDaangivMEGYLFKRASNAfKTWNRRWFSIQNNQLVYQKKFKDSPTVVVEDLRLCTVKHCEDIERRFCFEVVSPT-- 340
Cdd:cd01252    1 FNPD------REGWLLKLGGRV-KSWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSVREVEDKKKPFCFELYSPSng 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 568996617 341 ---KSCMLQAD----------------SEKLRQAWIKAVQTSIA 365
Cdd:cd01252   74 qviKACKTDSDgkvvegnhtvyrisaaSEEERDEWIKSIKASIS 117
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 274-361 4.20e-12

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: 62.73  E-value: 4.20e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 274 EGYLFKRAsNAFKTWNRRWFSIQNNQLVYQKKFKDSPTVVVEDLRLCT-VKHCEDIERRFCFEVVSPTKSCMLQADSEKL 352
Cdd:cd10573    6 EGYLTKLG-GIVKNWKTRWFVLRRNELKYFKTRGDTKPIRVLDLRECSsVQRDYSQGKVNCFCLVFPERTFYMYANTEEE 84


                 ....*....
gi 568996617 353 RQAWIKAVQ 361
Cdd:cd10573   85 ADEWVKLLK 93
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 269-360 9.18e-12

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: 62.26  E-value: 9.18e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 269 NGIVMEGYLFKRaSNAFKTWNRRWFSIQNNQLVYQKKFKDSPTVVVEDLR-LCTVKHCEDIERRFCFEVVSPTKSCMLQA 347
Cdd:cd13298    4 DRVLKSGYLLKR-SRKTKNWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSeLLAVAPLKDKKRKNVFGIYTPSKNLHFRA 82

                         90
                 ....*....|...
gi 568996617 348 DSEKLRQAWIKAV 360
Cdd:cd13298   83 TSEKDANEWVEAL 95
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
 673-757 2.06e-11

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 67.62  E-value: 2.06e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 673 ATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANAD 752
Cdd:PTZ00322  83 TVELCQLAASGDAVGARILLTGGADPNCRDYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFRE 162


                 ....*
gi 568996617 753 IVTLL 757
Cdd:PTZ00322 163 VVQLL 167
BAR_APPL1 cd07631
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
 72-224 3.37e-11

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. APPL1 interacts with diverse receptors (e.g. NGF receptor TrkA, FSHR, adiponectin receptors) and signaling proteins (e.g. Akt, PI3K), and may function as an adaptor linked to many distinct signaling pathways. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153315  Cd Length: 215  Bit Score: 63.57  E-value: 3.37e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  72 NDAVVETSLTKFSDSLQEMINFHTILFDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQRNKQHE 151
Cdd:cd07631   59 DDEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKRRENE 138

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568996617 152 --VEEAANILTATRKCFRHIALDYVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYD-LFSELGPYMKDLGAQL 224
Cdd:cd07631  139 kvKYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSEnLNEQLEEFLTNIGTSV 214
BAR-PH_APPL cd13247
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin ...
 275-360 3.97e-11

Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain; APPL (also called DCC-interacting protein (DIP)-13alpha) interacts with oncoprotein serine/threonine kinase AKT2, tumor suppressor protein DCC (deleted in colorectal cancer), Rab5, GIPC (GAIP-interacting protein, C terminus), human follicle-stimulating hormone receptor (FSHR), and the adiponectin receptors AdipoR1 and AdipoR2. There are two isoforms of human APPL: APPL1 and APPL2, which share about 50% sequence identity. APPL has a BAR and a PH domain near its N terminus, and the two domains are thought to function as a unit (BAR-PH domain). C-terminal to this is a PTB domain. Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. 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: 270067  Cd Length: 125  Bit Score: 61.23  E-value: 3.97e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 275 GYLFKRASNAF--KTWNRRWFSIQNNQLVYQKKfKDSPTVVVEDLRLCTVKHCEDIERRFCFEVVSPT--KSCMLQADSE 350
Cdd:cd13247   31 GYLFIRSKTGLvtNKWDRTYFFTQGGNLMSQPR-DEVAGSLVLDLDNCSVQAADCEDRRNVFQITSPDgkKAIVLQAESK 109

                         90
                 ....*....|
gi 568996617 351 KLRQAWIKAV 360
Cdd:cd13247  110 KDYEEWIATI 119
BAR_APPL2 cd07632
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
 18-212 4.74e-11

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. Both APPL proteins interact with the transcriptional repressor Reptin, acting as activators of beta-catenin/TCF-mediated trancription. APPL2 is essential for cell proliferation. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153316  Cd Length: 215  Bit Score: 63.12  E-value: 4.74e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  18 RAALEEVEGDVAELELKLDKLVKLCIAMIDTGKAFCVANKQFMngiRDLAQYSSN-------DAVVETSLTKFSDSLQEM 90
Cdd:cd07632    1 RSLLSVFEEDAGTLTDYTNQLLQAMQRVYGAQNEMCLATQQLS---KQLLAYEKQnfalgkgDEEVISTLQYFAKVVDEL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  91 INFHTILFDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQV---QRNKQHEVEEAANILTATRKcfR 167
Cdd:cd07632   78 NVLHSELAKQLADTMVLPIIQFREKDLTEVSTLKDLFGIASNEHDLSMAKYSRLpkkRENEKVKAEVAKEVAYSRRK--Q 155

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 568996617 168 HIA-LDYVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSE 212
Cdd:cd07632  156 HLSsLQYYCALNALQYRKRVAMLEPMLGYTHGQINFFKKGAELFSK 201
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
630-757 1.10e-10

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 63.43  E-value: 1.10e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 630 LDSKHLNPGLQLYRASYEKNLPKMAEALAHGADVNWANSDENQATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPL 709
Cdd:COG0666   12 LAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGDLLVALLLLAAGADINAKDDGGNTLL 91

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 568996617 710 HHATVLGHTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLL 757
Cdd:COG0666   92 HAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLL 139
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 274-362 1.65e-10

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: 58.46  E-value: 1.65e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 274 EGYLFKrASNAFKTWNRRWFSIQNNQLVYQKKFKDSPTVVVEDLRLCTVKHCEDIERRFCFEVVSPTKSCMLQADSEKLR 353
Cdd:cd13282    2 AGYLTK-LGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80


                 ....*....
gi 568996617 354 QAWIKAVQT 362
Cdd:cd13282   81 DEWIRVIQN 89
Ank_2 pfam12796
Ankyrin repeats (3 copies);
676-757 2.08e-10

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 57.82  E-value: 2.08e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  676 LIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTgQVCLFLKRGANQHATDeEGKDPLSIAVEAANADIVT 755
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHL-EIVKLLLEHADVNLKD-NGRTALHYAARSGHLEIVK 78


                  ..
gi 568996617  756 LL 757
Cdd:pfam12796  79 LL 80
Ank_2 pfam12796
Ankyrin repeats (3 copies);
641-735 3.95e-10

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 57.05  E-value: 3.95e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  641 LYRASYEKNLPKMAEALAHGADVNWANSDENqaTPLIQAVLGGSLVTCEFLLQNgANVNQRDvQGRGPLHHATVLGHTGQ 720
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKNGR--TALHLAAKNGHLEIVKLLLEH-ADVNLKD-NGRTALHYAARSGHLEI 76

                          90
                  ....*....|....*
gi 568996617  721 VCLFLKRGANQHATD 735
Cdd:pfam12796  77 VKLLLEKGADINVKD 91
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 270-364 4.11e-10

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first 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: 270113  Cd Length: 108  Bit Score: 57.77  E-value: 4.11e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 270 GIVMEGYLFKRASnAFKTWNRRWFSIQNNQLVYQKKFKDSPTVVVEDLRLCTV-KHCEDIERR-FCFEVVSPTKS-CMLQ 346
Cdd:cd13301    2 GIIKEGYLVKKGH-VVNNWKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCTItSPCLEYGKRpLVFKLTTAKGQeHFFQ 80

                         90
                 ....*....|....*...
gi 568996617 347 ADSEKLRQAWIKAVQTSI 364
Cdd:cd13301   81 ACSREERDAWAKDITKAI 98
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 273-361 5.65e-10

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: 57.63  E-value: 5.65e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 273 MEGYLFKRASNAfKTWNRRWFSIQNNQLVYQ-KKFKDSP--TVVVEDlrlCTVKHCEDiERRFCFEVV---SPTKSCMLQ 346
Cdd:cd13288   10 KEGYLWKKGERN-TSYQKRWFVLKGNLLFYFeKKGDREPlgVIVLEG---CTVELAED-AEPYAFAIRfdgPGARSYVLA 84

                         90
                 ....*....|....*
gi 568996617 347 ADSEKLRQAWIKAVQ 361
Cdd:cd13288   85 AENQEDMESWMKALS 99
BAR_OPHN1 cd07633
The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin-1; BAR domains are dimerization, lipid ...
 22-216 1.55e-09

The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin-1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Oligophrenin-1 (OPHN1) is a GTPase activating protein (GAP) with activity towards RhoA, Rac, and Cdc42, that is expressed in developing spinal cord and in adult brain areas with high plasticity. It plays a role in regulating the actin cystoskeleton as well as morphology changes in axons and dendrites, and may also function in modulating neuronal connectivity. Mutations in the OPHN1 gene causes X-linked mental retardation associated with cerebellar hypoplasia, lateral ventricle enlargement and epilepsy. OPHN1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, and a Rho GAP domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153317 [Multi-domain]  Cd Length: 207  Bit Score: 58.48  E-value: 1.55e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  22 EEVEGDVAELElKLDKLVKLCI----AMIDTGKAFCVANKQFMNGIRDLA------QYSSNDAVVETSLTKFSDSLQEMI 91
Cdd:cd07633    2 ERLKCYEQELE-RTNKFIKDVIkdgnALISAIKEYSSAVQKFSQTLQSFQfdfigdTLTDDEINIAESFKEFAELLQEVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  92 NFHTILFDQTQRSIKAQLQNFVKEDLRKFKDAKKQFEKVSEEKENALVKNAQVQ-RNKQHEVEEAANILTATRKCFRHIA 170
Cdd:cd07633   81 EERMMMVQNASDLLIKPLENFRKEQIGFTKERKKKFEKDSEKFYSLLDRHVNLSsKKKESQLQEADLQVDKERQNFYESS 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 568996617 171 LDYVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPY 216
Cdd:cd07633  161 LEYVYQIQEVQESKKFDVVEPVLAFLHSLFTSNNLTVELTQDFLPY 206
PHA03100 PHA03100
ankyrin repeat protein; Provisional
 641-766 2.27e-09

ankyrin repeat protein; Provisional


Pssm-ID: 222984 [Multi-domain]  Cd Length: 422  Bit Score: 60.45  E-value: 2.27e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 641 LYRASYEKNLPKMAEAL-AHGADVNWANSD-ENqatpLIQAVLGGSLVT---CEFLLQNGANVNQ--------------- 700
Cdd:PHA03100 111 LYAISKKSNSYSIVEYLlDNGANVNIKNSDgEN----LLHLYLESNKIDlkiLKLLIDKGVDINAknrvnyllsygvpin 186

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568996617 701 -RDVQGRGPLHHATVLGHTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLLRLARMNEEM 766
Cdd:PHA03100 187 iKDVYGFTPLHYAVYNNNPEFVKYLLDLGANPNLVNKYGDTPLHIAILNNNKEIFKLLLNNGPSIKT 253
BAR-PH_GRAF_family cd01249
GTPase Regulator Associated with Focal adhesion and related proteins Pleckstrin homology (PH) ...
 272-359 3.30e-09

GTPase Regulator Associated with Focal adhesion and related proteins Pleckstrin homology (PH) domain; This hierarchy contains GRAF family members: OPHN1/oligophrenin1, GRAF1 (also called ARHGAP26/Rho GTPase activating protein 26), GRAF2 (also called ARHGAP10/ARHGAP42), AK057372, and LOC129897, all of which are members of the APPL family. OPHN1 is a RhoGAP involved in X-linked mental retardation, epilepsy, rostral ventricular enlargement, and cerebellar hypoplasia. Affected individuals have morphological abnormalities of their brain with enlargement of the cerebral ventricles and cerebellar hypoplasia. OPHN1 negatively regulates RhoA, Cdc42, and Rac1 in neuronal and non-neuronal cells. GRAF1 sculpts the endocytic membranes of the CLIC/GEEC (clathrin-independent carriers/GPI-enriched early endosomal compartments) endocytic pathway. It strongly interacts with dynamin and inhibition of dynamin abolishes CLIC/GEEC endocytosis. GRAF2, GRAF3 and oligophrenin are likely to play similar roles during clathrin-independent endocytic events. GRAF1 mutations are linked to leukaemia. All members are composed of a N-terminal BAR-PH domain, followed by a RhoGAP domain, a proline rich region, and a C-terminal 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: 269953  Cd Length: 105  Bit Score: 55.03  E-value: 3.30e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 272 VMEGYLF---KRASNAfkTW----------NRRWFSIQNNQlvyQKKFKDSPTVVVEdLRLCTVKHCEDIERRFCFEVVS 338
Cdd:cd01249    1 TKEGYLYlqeKKPLGS--TWtkhyctyrkeSKMFTMIPYNQ---QSSGKLGTTEVVT-LKSCVRRKTDSIDRRFCFDIEV 74

                         90       100
                 ....*....|....*....|...
gi 568996617 339 PTKSC--MLQADSEKLRQAWIKA 359
Cdd:cd01249   75 VDRPTvlTLQALSEEDRKLWLEA 97
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 269-365 7.58e-09

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: 54.22  E-value: 7.58e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 269 NGIVMEGYLFKRASnAFKTWNRRWFSIQNNQLVYQKK--FKDSPTVVVEDLRlCTVKHCEDIERRFC-FEVVSPTKSCML 345
Cdd:cd13273    6 LDVIKKGYLWKKGH-LLPTWTERWFVLKPNSLSYYKSedLKEKKGEIALDSN-CCVESLPDREGKKCrFLVKTPDKTYEL 83

                         90       100
                 ....*....|....*....|
gi 568996617 346 QADSEKLRQAWIKAVQTSIA 365
Cdd:cd13273   84 SASDHKTRQEWIAAIQTAIR 103
BAR_ASAPs cd07604
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
 22-220 9.92e-09

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of ASAPs (ArfGAP with SH3 domain, ANK repeat and PH domain containing proteins), which are Arf GTPase activating proteins (GAPs) with similarity to ACAPs (ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins) in that they contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and ankyrin (ANK) repeats. However, ASAPs contain an additional C-terminal SH3 domain. ASAPs function in regulating cell growth, migration, and invasion. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3. ASAP1 and ASAP2 shows GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but is able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153288  Cd Length: 215  Bit Score: 56.27  E-value: 9.92e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  22 EEVEGDVAELElkldKLVKLCIAMIDTGKAFcVANK-QFMNGIRDLA-QYSSNDA-VVETSLTKFSDSLQEMINFHTILF 98
Cdd:cd07604    9 ESLEGDRVGLQ----KLKKAVKAIHNSGLAH-VENElQFAEALEKLGsKALSREEeDLGAAFLKFSVFTKELAALFKNLM 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  99 DQTQRSIKAQLQNFVKEDLRKFK-DAKKQFEKVSEEKENalvKNAQVQRNKQHEVEEAANILTAT------------RKC 165
Cdd:cd07604   84 QNLNNIIMFPLDSLLKGDLKGSKgDLKKPFDKAWKDYET---KASKIEKEKKQLAKEAGMIRTEItgaeiaeemekeRRM 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568996617 166 FRHIALDYVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYMKDL 220
Cdd:cd07604  161 FQLQMCEYLIKVNEIKTKKGVDLLQHLVEYYHAQNSYFQDGLKVIEHFRPYIEKL 215
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 266-360 1.29e-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: 53.57  E-value: 1.29e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 266 DAANGIVMEGYLFKRASNAfKTWNRRWFSIQNNQLVYQKKFKDSPT---VVVEDLRLCT---VKHCEdierrFCFEVVSP 339
Cdd:cd13255    1 MISEAVLKAGYLEKKGERR-KTWKKRWFVLRPTKLAYYKNDKEYRLlrlIDLTDIHTCTevqLKKHD-----NTFGIVTP 74

                         90       100
                 ....*....|....*....|.
gi 568996617 340 TKSCMLQADSEKLRQAWIKAV 360
Cdd:cd13255   75 ARTFYVQADSKAEMESWISAI 95
PH_SIP3 cd13280
Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein ...
 287-363 2.53e-08

Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein kinase and activates transcription when anchored to DNA. It may function in the SNF1 pathway. SIP3 contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain followed by a PH domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. 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: 270098  Cd Length: 105  Bit Score: 52.26  E-value: 2.53e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 287 TWNRRWFSIQNNQLVYqkkFKDSP--TVVVEDLR----LCTVKHCEDIERRFCFEVVSPTK-SCMLQADSEKLRQAWIKA 359
Cdd:cd13280   19 IWVRRWCFVKNGVFGM---LSLSPskTYVEETDKfgvlLCSVRYAPEEDRRFCFEVKIFKDiSIILQAETLKELKSWLTV 95


                 ....
gi 568996617 360 VQTS 363
Cdd:cd13280   96 FENA 99
PHA03095 PHA03095
ankyrin-like protein; Provisional
 639-770 2.87e-08

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 56.96  E-value: 2.87e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 639 LQLYRASYEKNLPKMAEAL-AHGADVNWAnsDENQATPLIQAVLGGSLV-TCEFLLQNGANVNQRDVQGRGPLH-HATVL 715
Cdd:PHA03095  51 LHLYLHYSSEKVKDIVRLLlEAGADVNAP--ERCGFTPLHLYLYNATTLdVIKLLIKAGADVNAKDKVGRTPLHvYLSGF 128

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568996617 716 G-HTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLLRLARMNEEMRESE 770
Cdd:PHA03095 129 NiNPKVIRLLLRKGADVNALDLYGMTPLAVLLKSRNANVELLRLLIDAGADVYAVD 184
PHA03095 PHA03095
ankyrin-like protein; Provisional
 639-755 5.46e-08

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 56.19  E-value: 5.46e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 639 LQLYRASYEKnlpkMAEALAHGADVNWANSDENqaTPLIQAVLGGSlvtC-----EFLLQNGANVNQRDVQGRGPLHHAT 713
Cdd:PHA03095 195 LQSFKPRARI----VRELIRAGCDPAATDMLGN--TPLHSMATGSS---CkrslvLPLLIAGISINARNRYGQTPLHYAA 265

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 568996617 714 VLGHTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVT 755
Cdd:PHA03095 266 VFNNPRACRRLIALGADINAVSSDGNTPLSLMVRNNNGRAVR 307
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 271-359 5.64e-08

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: 51.50  E-value: 5.64e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 271 IVMEGYLFKRASNAFKTWNRRWFSIQNNQLVYQKKFKDS--------PTVVVedlRLCTVKhcEDIERRFCFEVVSP-TK 341
Cdd:cd13248    7 VVMSGWLHKQGGSGLKNWRKRWFVLKDNCLYYYKDPEEEkalgsillPSYTI---SPAPPS--DEISRKFAFKAEHAnMR 81

                         90
                 ....*....|....*...
gi 568996617 342 SCMLQADSEKLRQAWIKA 359
Cdd:cd13248   82 TYYFAADTAEEMEQWMNA 99
ArfGap_AGFG1 cd08857
ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain ...
 406-516 9.72e-08

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: 51.19  E-value: 9.72e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 406 LQRVQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHfSKVRSLTLDTWEPELLKLMCELGNDVINRVYEA 485
Cdd:cd08857    5 LREMTSLPHNRKCFDCDQRGPTYANMTVGSFVCTSCSGILRGLNPP-HRVKSISMTTFTQQEIEFLQKHGNEVCKQIWLG 83

                         90       100       110
                 ....*....|....*....|....*....|.
gi 568996617 486 KLEKMGVKKPQPGQRQEKEAYIRAKYVERKF 516
Cdd:cd08857   84 LFDDRSSAIPDFRDPQKVKEFLQEKYEKKRW 114
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
 275-365 2.20e-07

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: 49.51  E-value: 2.20e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 275 GYLFkRASNAFKTWNRRWFSIQNNQL-VYQKKfKDSPTVVVEDLRLCTVKHCEDIE----RRFCFEVVSPTKSCMLQADS 349
Cdd:cd01233   10 GYLL-FLEDATDGWVRRWVVLRRPYLhIYSSE-KDGDERGVINLSTARVEYSPDQEallgRPNVFAVYTPTNSYLLQARS 87

                         90
                 ....*....|....*.
gi 568996617 350 EKLRQAWIKAVQTSIA 365
Cdd:cd01233   88 EKEMQDWLYAIDPLLA 103
PLN03131 PLN03131
hypothetical protein; Provisional
 394-553 2.85e-07

hypothetical protein; Provisional


Pssm-ID: 178677 [Multi-domain]  Cd Length: 705  Bit Score: 54.01  E-value: 2.85e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 394 ESKEKLLKGESALqrvqciPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLgVHfsKVRSLTLDTWEPELLKLMCE 473
Cdd:PLN03131   8 ERNEKIIRGLMKL------PPNRRCINCNSLGPQFVCTNFWTFICMTCSGIHREF-TH--RVKSVSMSKFTSQDVEALQN 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 474 LGNDVINRVYEAKLEKMGVKKPQPGQRQEKEAYIRAKYVERKFV-----DKysallsPSEQEKRIISKSCEDQRLSHARA 548
Cdd:PLN03131  79 GGNQRAREIYLKDWDQQRQRLPDNSKVDKIREFIKDIYVDKKYAggkthDK------PPRDLQRIRSHEDETRRACSYHS 152


                 ....*
gi 568996617 549 SVHTP 553
Cdd:PLN03131 153 YSQSP 157
BAR_ASAP3 cd07640
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
 19-220 3.63e-07

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP3 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 3) is also known as ACAP4 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 4), DDEFL1 (Development and Differentiation Enhancing Factor-Like 1), or centaurin beta-6. It is an Arf6-specific GTPase activating protein (GAP) and is co-localized with Arf6 in ruffling membranes upon EGF stimulation. ASAP3 is implicated in the pathogenesis of hepatocellular carcinoma and plays a role in regulating cell migration and invasion. ASAP3 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153324  Cd Length: 213  Bit Score: 51.54  E-value: 3.63e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  19 AALEE-VEGDVAELElKLDKLVKlciAMIDTGKAFCVANKQFMNGIRDL--AQYSSNDAVVETSLTKFSDSLQEMINFHT 95
Cdd:cd07640    5 AALEEsLEGDQASLQ-RIKKIVK---AIHNSGLNHVENEEQYTEALENLgnSHLSQNNHELSTGFLNLAVFTREVTALFK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  96 ILFDQTQRSIKAQLQNFVKEDLRKFK-DAKKQFEKVSEEKEN--ALVKNAQVQRNKQHEVEEAANILTAT-----RKCFR 167
Cdd:cd07640   81 NLVQNLNNIVSFPLDSLLKGQLRDGRlESKKQMEKAWKDYEAkiGKLEKERREKQKQHGLIRLDMTDTAEdmqreRRNFQ 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568996617 168 HIALDYVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYMKDL 220
Cdd:cd07640  161 LHMCEYLLKAQESQMKQGPDFLQSLIKFFHAQHNFFQDGWKAAQNLGPFIEKL 213
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
 270-360 4.17e-07

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: 49.30  E-value: 4.17e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 270 GIVMEGYLfKRASNAFKTWNRRWFSIQNNQLVYQKKFKDSP---TVVVEDLRLCTVKHCEDIERRFCFEVVsPTK----- 341
Cdd:cd13263    2 RPIKSGWL-KKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKpqgTIPLPGNKVKEVPFNPEEPGKFLFEII-PGGggdrm 79

                         90       100
                 ....*....|....*....|....
gi 568996617 342 -----SCMLQADSEKLRQAWIKAV 360
Cdd:cd13263   80 tsnhdSYLLMANSQAEMEEWVKVI 103
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 271-361 5.22e-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: 49.16  E-value: 5.22e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 271 IVMEGYLFKRaSNAFKTWNRRWFSIQNNQLVYqkkFKDS-----PTVVVeDLRLCT----VKHCEdiERRFCFEVVSPTK 341
Cdd:cd13215   21 VIKSGYLSKR-SKRTLRYTRYWFVLKGDTLSW---YNSStdlyfPAGTI-DLRYATsielSKSNG--EATTSFKIVTNSR 93

                         90       100
                 ....*....|....*....|
gi 568996617 342 SCMLQADSEKLRQAWIKAVQ 361
Cdd:cd13215   94 TYKFKADSETSADEWVKALK 113
PLN03119 PLN03119
putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional
 394-553 6.83e-07

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


Pssm-ID: 178666  Cd Length: 648  Bit Score: 52.93  E-value: 6.83e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 394 ESKEKLLKGESALqrvqciPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLgVHfsKVRSLTLDTWEPELLKLMCE 473
Cdd:PLN03119   8 ERNEKIIRGLMKL------PPNRRCINCNSLGPQYVCTTFWTFVCMACSGIHREF-TH--RVKSVSMSKFTSKEVEVLQN 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 474 LGNDVINRVYEAKLEKMGVKKPQPGQRQEKEAYIRAKYVERKFVDKYSALLSPSEQEKRIISKSCEDQRLSHARASVHTP 553
Cdd:PLN03119  79 GGNQRAREIYLKNWDHQRQRLPENSNAERVREFIKNVYVQKKYAGANDADKPSKDSQDHVSSEDMTRRANSYHSYSQSPP 158
BAR_ASAP2 cd07642
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
 35-220 1.03e-06

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP2 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2) is also known as DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. ASAP2 mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153326  Cd Length: 215  Bit Score: 50.42  E-value: 1.03e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  35 LDKLVKLCIAMIDTGKAFCVANKQFMNGIRDLAQ--YSSNDAVVETSLTKFSDSLQEMINFHTILFDQTQRSIKAQLQNF 112
Cdd:cd07642   18 LYKMKKSVKAIHTSGLAHVENEEQYTQALEKFGSncVCRDDPDLGSAFLKFSVFTKELTALFKNLVQNMNNIITFPLDSL 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 113 VKEDLRKFK-DAKKQFEKVSEEKENALVK--NAQVQRNKQHEV-------EEAANILTATRKCFRHIALDYVLQINVLQS 182
Cdd:cd07642   98 LKGDLKGVKgDLKKPFDKAWKDYETKVTKieKEKKEHAKMHGMirteisgAEIAEEMEKERRFFQLQMCEYLLKVNEIKI 177

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 568996617 183 KRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYMKDL 220
Cdd:cd07642  178 KKGVDLLQNLIKYFHAQCNFFQDGLKAVETLKPSIEKL 215
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
 274-370 1.63e-06

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: 47.01  E-value: 1.63e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 274 EGYLFKRaSNAFKTWNRRWFSIQNNQLVYQkkfKDSPTVVVEDLRLCTVKHCEDIERRFC--FEVVSPTKSCMLQADSEK 351
Cdd:cd13274    3 EGPLLKQ-TSSFQRWKRRYFKLKGRKLYYA---KDSKSLIFEEIDLSDASVAECSTKNVNnsFTVITPFRKLILCAESRK 78

                         90
                 ....*....|....*....
gi 568996617 352 LRQAWIKAVQTSIATAYRE 370
Cdd:cd13274   79 EMEEWISALKTVQQREFYE 97
PHA02875 PHA02875
ankyrin repeat protein; Provisional
 641-757 1.68e-06

ankyrin repeat protein; Provisional


Pssm-ID: 165206 [Multi-domain]  Cd Length: 413  Bit Score: 51.15  E-value: 1.68e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 641 LYRASYEKNLPKMAEALAHGADVNWANSDenQATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQ 720
Cdd:PHA02875 106 LHLATILKKLDIMKLLIARGADPDIPNTD--KFSPLHLAVMMGDIKGIELLIDHKACLDIEDCCGCTPLIIAMAKGDIAI 183

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 568996617 721 VCLFLKRGANqhaTDEEGKDP----LSIAVEAANADIVTLL 757
Cdd:PHA02875 184 CKMLLDSGAN---IDYFGKNGcvaaLCYAIENNKIDIVRLF 221
BAR_ASAP1 cd07641
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
 70-220 4.54e-06

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1) is also known as DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. ASAP1 is an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6 However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153325  Cd Length: 215  Bit Score: 48.52  E-value: 4.54e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  70 SSNDAVVETSLTKFSDSLQEMINFHTILFDQTQRSIKAQLQNFVKEDLRKFK-DAKKQFEKVSEEKENALVKNAQVQRN- 147
Cdd:cd07641   55 SRDNPDLGTAFVKFSTLTKELSTLLKNLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYETKFTKIEKEKREh 134

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 148 -KQHEV-------EEAANILTATRKCFRHIALDYVLQINVLQSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYMKD 219
Cdd:cd07641  135 aKQHGMirteitgAEIAEEMEKERRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEK 214


                 .
gi 568996617 220 L 220
Cdd:cd07641  215 L 215
ArfGap_AGFG2 cd17903
ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain ...
 409-516 5.52e-06

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: 46.14  E-value: 5.52e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 409 VQCIPGNTSCCDCGLADPRWASINLGITLCIECSGIHRSLGVHfSKVRSLTLDTW-EPELLKLMCElGNDVINRVYEAKL 487
Cdd:cd17903    8 GGCSAANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISMTTFtEPEVLFLQAR-GNEVCRKIWLGLF 85

                         90       100
                 ....*....|....*....|....*....
gi 568996617 488 EKMGVKKPQPGQRQEKEAYIRAKYVERKF 516
Cdd:cd17903   86 DARTSLIPDSRDPQKVKEFLQEKYEKKRW 114
PH_CpORP2-like cd13293
Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) ...
 273-361 7.48e-06

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: 45.01  E-value: 7.48e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 273 MEGYLfKRASNAFKTWNRRWFSIQNNQLVYQKKfKDSPTVVVEDLRLCTVKHCEDIERRFcfEVVSPTKSCMLQADSEKL 352
Cdd:cd13293    1 MEGYL-KKWTNIFNSWKPRYFILYPGILCYSKQ-KGGPKKGTIHLKICDIRLVPDDPLRI--IINTGTNQLHLRASSVEE 76


                 ....*....
gi 568996617 353 RQAWIKAVQ 361
Cdd:cd13293   77 KLKWYNALK 85
Ank_4 pfam13637
Ankyrin repeats (many copies);
674-725 1.80e-05

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 42.65  E-value: 1.80e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568996617  674 TPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQVCLFL 725
Cdd:pfam13637   3 TALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFAASNGNVEVLKLLL 54
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
 271-366 1.98e-05

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: 44.27  E-value: 1.98e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 271 IVMEGYLFKRAsNAFKTWNRRWFSIQNNQLVYQKKFKDSPTVVVEDLR-LCTVKHCEDIE---RRFCFEVVSPTKSCMLQ 346
Cdd:cd13271    8 VIKSGYCVKQG-AVRKNWKRRFFILDDNTISYYKSETDKEPLRTIPLReVLKVHECLVKSllmRDNLFEIITTSRTFYIQ 86

                         90       100
                 ....*....|....*....|
gi 568996617 347 ADSEKLRQAWIKAVQTSIAT 366
Cdd:cd13271   87 ADSPEEMHSWIKAISGAIVA 106
PH_GAP1_mammal-like cd13371
GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras ...
 271-357 2.53e-05

GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras GTPase-activating protein 3, and RAS p21 protein activator (GTPase activating protein) 3/GAPIII/MGC46517/MGC47588)) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(m), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(IP4BP) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1M, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(IP4BP) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate) and PIP2 (phosphatidylinositol 4,5-bisphosphate). It suppresses RAS, 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. GAP1(IP4BP) binds tyrosine-protein kinase, HCK. Members here include humans, chickens, frogs, and fish. 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: 241522  Cd Length: 125  Bit Score: 44.64  E-value: 2.53e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 271 IVMEGYLFKRASN----AFKTWNRRWFSIQNNQLVYQKKFKDSP--TVVVEDLRLCTVKHCEDIERRFCFEVVSPTKSCM 344
Cdd:cd13371   16 LLKEGFMIKRAQGrkrfGMKNFKKRWFRLTNHEFTYHKSKGDHPlcSIPIENILAVERLEEESFKMKNMFQVIQPERALY 95

                         90
                 ....*....|...
gi 568996617 345 LQADSEKLRQAWI 357
Cdd:cd13371   96 IQANNCVEAKDWI 108
PHA03100 PHA03100
ankyrin repeat protein; Provisional
 629-757 2.54e-05

ankyrin repeat protein; Provisional


Pssm-ID: 222984 [Multi-domain]  Cd Length: 422  Bit Score: 47.35  E-value: 2.54e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 629 FLDSKHLNPGLQLYRA-SYEKnlPKMAEAL-AHGADVNWANSDENQATPL---IQAVLGGSLVTCEFLLQNGANVNQRDV 703
Cdd:PHA03100  27 LNDYSYKKPVLPLYLAkEARN--IDVVKILlDNGADINSSTKNNSTPLHYlsnIKYNLTDVKEIVKLLLEYGANVNAPDN 104

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 568996617 704 QGRGPLHHA--TVLGHTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANAD--IVTLL 757
Cdd:PHA03100 105 NGITPLLYAisKKSNSYSIVEYLLDNGANVNIKNSDGENLLHLYLESNKIDlkILKLL 162
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
 266-369 2.55e-05

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. 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: 270099  Cd Length: 139  Bit Score: 44.62  E-value: 2.55e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 266 DAANGIVMEGYLFKRASNAFKT-WNRRWFSIQNNQLVY-----------QKKFKDSPTVVVEdLRLCTVKHCEDIERRFC 333
Cdd:cd13281    7 DITTKVQLHGILWKKPFGHQSAkWSKRFFIIKEGFLLYysesekkdfekTRHFNIHPKGVIP-LGGCSIEAVEDPGKPYA 85

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568996617 334 FEVVSP--TKSCMLQADSEKLRQAWIKAVQTSIATAYR 369
Cdd:cd13281   86 ISISHSdfKGNIILAADSEFEQEKWLDMLRESGKITWK 123
PHA02876 PHA02876
ankyrin repeat protein; Provisional
 685-763 3.11e-05

ankyrin repeat protein; Provisional


Pssm-ID: 165207 [Multi-domain]  Cd Length: 682  Bit Score: 47.75  E-value: 3.11e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568996617 685 LVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLLRLARMN 763
Cdd:PHA02876 158 LLIAEMLLEGGADVNAKDIYCITPIHYAAERGNAKMVNLLLSYGADVNIIALDDLSVLECAVDSKNIDTIKAIIDNRSN 236
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
 273-369 3.52e-05

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: 43.14  E-value: 3.52e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 273 MEGYLFKrASNAFKTWNRRWFSIQNNQLVYQKkfkdSPTVVVEDLR--LCTVKHCEDIERRFCFeVVSP--TKSCMLQAD 348
Cdd:cd13284    1 MKGWLLK-WTNYIKGYQRRWFVLSNGLLSYYR----NQAEMAHTCRgtINLAGAEIHTEDSCNF-VISNggTQTFHLKAS 74

                         90       100
                 ....*....|....*....|.
gi 568996617 349 SEKLRQAWIKAVQTSIATAYR 369
Cdd:cd13284   75 SEVERQRWVTALELAKAKAIR 95
PH_MELT_VEPH1 cd01264
Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone ...
 272-370 4.64e-05

Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. 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: 269965  Cd Length: 105  Bit Score: 43.22  E-value: 4.64e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 272 VMEGYLFKRASN--AFKTWNRRWFSIQNNQLVYQ--KKFKDSPTVVVEDLRLCTVKHCEDIERRFCFEVVSPTKSCMLQA 347
Cdd:cd01264    3 VIEGQLKEKKGRwkFFKRWRTRYFTLSGAQLSYRggKSKPDAPPIELSKIRSVKVVRKKDRSIPKAFEIFTDDKTYVLKA 82

                         90       100
                 ....*....|....*....|...
gi 568996617 348 DSEKLRQAWIKAVQTSIATAYRE 370
Cdd:cd01264   83 KDEKNAEEWLQCLSIAVAQAHAR 105
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
 266-370 5.69e-05

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: 43.12  E-value: 5.69e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 266 DAANGIVMEGYLFKRASNAF-KTWNRRWFSIQNNQLVYQKKFKDSPTVVVeDLRLCTVKHCEDIERrfCFEVVSPTKSCM 344
Cdd:cd13251    5 NKSHGTEKSGYLLKKSEGKIrKVWQKRRCSIKDGFLTISHADENKPPAKL-NLLTCQVKLVPEDKK--CFDLISHNRTYH 81

                         90       100
                 ....*....|....*....|....*.
gi 568996617 345 LQADSEKLRQAWIKAVQTSIATAYRE 370
Cdd:cd13251   82 FQAEDENDANAWMSVLKNSKEQALNK 107
PH_ORP_plant cd13294
Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs ...
 275-362 7.99e-05

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: 42.48  E-value: 7.99e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 275 GYLFKRAsNAFKTWNRRWFSIQNNQLVYQK-----KFKDSPTVvveDLRLCTVKHCEDIERRFcfEVVSPTKSCMLQADS 349
Cdd:cd13294    3 GILYKWV-NYGKGWRSRWFVLQDGVLSYYKvhgpdKVKPSGEV---HLKVSSIRESRSDDKKF--YIFTGTKTLHLRAES 76

                         90
                 ....*....|...
gi 568996617 350 EKLRQAWIKAVQT 362
Cdd:cd13294   77 REDRAAWLEALQA 89
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 270-361 8.79e-05

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: 8.79e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 270 GIVMEGYLFKRaSNAFKTWNRRWFSIQNN--QLVY---QKKFKdsPTVVVeDLRLCTVKHCED--IERRFCFEVVS---P 339
Cdd:cd13260    2 GIDKKGYLLKK-GGKNKKWKNLYFVLEGKeqHLYFfdnEKRTK--PKGLI-DLSYCSLYPVHDslFGRPNCFQIVVralN 77

                         90       100
                 ....*....|....*....|...
gi 568996617 340 TKSCM-LQADSEKLRQAWIKAVQ 361
Cdd:cd13260   78 ESTITyLCADTAELAQEWMRALR 100
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
 273-365 1.39e-04

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.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: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 42.60  E-value: 1.39e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 273 MEGYLFKRASNAFKT----WNRRWFSIQNNQLVY-------QKKFKDSptVVVEDLRLC-TVKHCEDIERRFCFEVVSPT 340
Cdd:cd01238    1 LEGLLVKRSQGKKRFgpvnYKERWFVLTKSSLSYyegdgekRGKEKGS--IDLSKVRCVeEVKDEAFFERKYPFQVVYDD 78

                         90       100
                 ....*....|....*....|....*
gi 568996617 341 KSCMLQADSEKLRQAWIKAVQTSIA 365
Cdd:cd01238   79 YTLYVFAPSEEDRDEWIAALRKVCR 103
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
 275-362 1.50e-04

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: 41.54  E-value: 1.50e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 275 GYLFKRASNAF--KTWNRRWFSI--QNNQLVYQKKFKDSPTVVVEDLRLCTVKHceDIERRFC-FEVVSPTKSCMLQADS 349
Cdd:cd01265    4 GYLNKLETRGLglKGWKRRWFVLdeSKCQLYYYRSPQDATPLGSIDLSGAAFSY--DPEAEPGqFEIHTPGRVHILKAST 81

                         90
                 ....*....|...
gi 568996617 350 EKLRQAWIKAVQT 362
Cdd:cd01265   82 RQAMLYWLQALQS 94
PHA02874 PHA02874
ankyrin repeat protein; Provisional
 641-757 2.51e-04

ankyrin repeat protein; Provisional


Pssm-ID: 165205 [Multi-domain]  Cd Length: 434  Bit Score: 44.18  E-value: 2.51e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 641 LYRASYEKNLPKMAEALAHGADVNWanSDENQATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQ 720
Cdd:PHA02874 128 LHYAIKKGDLESIKMLFEYGADVNI--EDDNGCYPIHIAIKHNFFDIIKLLLEKGAYANVKDNNGESPLHNAAEYGDYAC 205

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568996617 721 VCLFLKRGANQHATDEEGKDPLSIAVeAANADIVTLL 757
Cdd:PHA02874 206 IKLLIDHGNHIMNKCKNGFTPLHNAI-IHNRSAIELL 241
Ank_5 pfam13857
Ankyrin repeats (many copies);
657-712 2.56e-04

Ankyrin repeats (many copies);


Pssm-ID: 433530 [Multi-domain]  Cd Length: 56  Bit Score: 39.64  E-value: 2.56e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568996617  657 LAHG-ADVNWanSDENQATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHA 712
Cdd:pfam13857   2 LEHGpIDLNR--LDGEGYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56
PLN03192 PLN03192
Voltage-dependent potassium channel; Provisional
 661-757 4.19e-04

Voltage-dependent potassium channel; Provisional


Pssm-ID: 215625 [Multi-domain]  Cd Length: 823  Bit Score: 44.09  E-value: 4.19e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 661 ADVNWANSDENQATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQVCLFLKRGANQHATDEEGKD 740
Cdd:PLN03192 514 GDNGGEHDDPNMASNLLTVASTGNAALLEELLKAKLDPDIGDSKGRTPLHIAASKGYEDCVLVLLKHACNVHIRDANGNT 593

                         90
                 ....*....|....*..
gi 568996617 741 PLSIAVEAANADIVTLL 757
Cdd:PLN03192 594 ALWNAISAKHHKIFRIL 610
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 306-361 4.80e-04

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: 39.71  E-value: 4.80e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568996617 306 FKDSPTVVVEDLRLCTVKhceDIERRfCFEVVSPTKSCMLQADSEKLRQAWIKAVQ 361
Cdd:cd13254   39 FRLGIGITVIEMNGANVK---DVDRR-SFDLTTPYRSFSFTAESEHEKQEWIEAVQ 90
PHA02874 PHA02874
ankyrin repeat protein; Provisional
 657-757 5.71e-04

ankyrin repeat protein; Provisional


Pssm-ID: 165205 [Multi-domain]  Cd Length: 434  Bit Score: 43.03  E-value: 5.71e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 657 LAHGADVNWANSDENqaTPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQVCLFLKRGANQHATDE 736
Cdd:PHA02874 111 LDCGIDVNIKDAELK--TFLHYAIKKGDLESIKMLFEYGADVNIEDDNGCYPIHIAIKHNFFDIIKLLLEKGAYANVKDN 188

                         90       100
                 ....*....|....*....|.
gi 568996617 737 EGKDPLSIAVEAANADIVTLL 757
Cdd:PHA02874 189 NGESPLHNAAEYGDYACIKLL 209
PHA02878 PHA02878
ankyrin repeat protein; Provisional
 641-771 5.85e-04

ankyrin repeat protein; Provisional


Pssm-ID: 222939 [Multi-domain]  Cd Length: 477  Bit Score: 43.33  E-value: 5.85e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 641 LYRASYEKNLPKMAEALAHGADVNWANSDENqaTPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHA-------- 712
Cdd:PHA02878 172 LHYATENKDQRLTELLLSYGANVNIPDKTNN--SPLHHAVKHYNKPIVHILLENGASTDARDKCGNTPLHISvgyckdyd 249

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 713 ----------------TVLGHTG---------QVCLFLKRGANQHATDEEGKDPLSIAV------EAANADIVTLLRLAR 761
Cdd:PHA02878 250 ilklllehgvdvnaksYILGLTAlhssikserKLKLLLEYGADINSLNSYKLTPLSSAVkqylciNIGRILISNICLLKR 329

                        170
                 ....*....|
gi 568996617 762 MNEEMRESEG 771
Cdd:PHA02878 330 IKPDIKNSEG 339
BAR_SIP3_fungi cd07609
The Bin/Amphiphysin/Rvs (BAR) domain of fungal Snf1p-interacting protein 3; BAR domains are ...
 35-183 6.20e-04

The Bin/Amphiphysin/Rvs (BAR) domain of fungal Snf1p-interacting protein 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. This group is composed of mostly uncharacterized fungal proteins with similarity to Saccharomyces cerevisiae Snf1p-interacting protein 3 (SIP3). These proteins contain an N-terminal BAR domain followed by a Pleckstrin Homology (PH) domain. SIP3 interacts with SNF1 protein kinase and activates transcription when anchored to DNA. It may function in the SNF1 pathway. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153293  Cd Length: 214  Bit Score: 41.89  E-value: 6.20e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617  35 LDKLVKLCIAMIDTGKAFcvanKQFMNGIRD--LAQYSSNDAVVE-----TSLTKFSDSLQEMIN--FHTILFDQTqrSI 105
Cdd:cd07609   17 LDGYVSSTKKLYSSLDEL----ERVINSFLShlLPPLLVSGGVIDqdytpLALKRFGDGLKDFWGgvLSALKGNDS--LI 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 106 KAQLQNFVKEDLRKFKDAKKQFEkVSEEKENALVKNAQVQRNKQ--HEVEEAANILTATRKCFRHIALDYVLQINVLQSK 183
Cdd:cd07609   91 LDPLRSFVKSDIRPYKELRKNFE-YYQRKYDSMLARYVAQSKTKepSSLREDAFQLFEARKAYLKASLDLVIAIPQLRLT 169
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
 275-367 6.85e-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: 39.62  E-value: 6.85e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 275 GYLFKRASNAfKTWNRRWFSIQNNQLVYqkkFKDS----PTVV--VEDLRLCTVKHCEDIERRFCFEVVS-PTKSCMLQA 347
Cdd:cd13275    3 GWLMKQGSRQ-GEWSKHWFVLRGAALKY---YRDPsaeeAGELdgVIDLSSCTEVTELPVSRNYGFQVKTwDGKVYVLSA 78

                         90       100
                 ....*....|....*....|
gi 568996617 348 DSEKLRQAWIKAVQTSIATA 367
Cdd:cd13275   79 MTSGIRTNWIQALRKAAGLP 98
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
 272-357 1.09e-03

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE 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: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 39.55  E-value: 1.09e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 272 VMEGYLFK--RasnafKTWNRRWFSIQNNQLVY------QKKFKDSPTVVVEDLRLCTVkhCEDIERRFCFEVVSPTKSC 343
Cdd:cd01218   31 VGEGVLTKvcR-----KKPKPRQFFLFNDILVYgsivinKKKYNKQRIIPLEDVKIEDL--EDTGELKNGWQIISPKKSF 103

                         90
                 ....*....|....
gi 568996617 344 MLQADSEKLRQAWI 357
Cdd:cd01218  104 VVYAATATEKSEWM 117
Ank_5 pfam13857
Ankyrin repeats (many copies);
691-745 1.71e-03

Ankyrin repeats (many copies);


Pssm-ID: 433530 [Multi-domain]  Cd Length: 56  Bit Score: 37.33  E-value: 1.71e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568996617  691 LLQNG-ANVNQRDVQGRGPLHHATVLGHTGQVCLFLKRGANQHATDEEGKDPLSIA 745
Cdd:pfam13857   1 LLEHGpIDLNRLDGEGYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56
PHA02875 PHA02875
ankyrin repeat protein; Provisional
 621-757 2.17e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165206 [Multi-domain]  Cd Length: 413  Bit Score: 41.13  E-value: 2.17e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 621 GERQESSVFLDSkHLNPGLQLYR-------ASYEKNLPKMAEALAHGA--DVNWANSDenqaTPLIQAVLGGSLVTCEFL 691
Cdd:PHA02875  13 GELDIARRLLDI-GINPNFEIYDgispiklAMKFRDSEAIKLLMKHGAipDVKYPDIE----SELHDAVEEGDVKAVEEL 87

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568996617 692 LQNGANVNqrDV---QGRGPLHHATVLGHTGQVCLFLKRGANQHATDEEGKDPLSIAVEAANADIVTLL 757
Cdd:PHA02875  88 LDLGKFAD--DVfykDGMTPLHLATILKKLDIMKLLIARGADPDIPNTDKFSPLHLAVMMGDIKGIELL 154
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
 269-364 2.24e-03

Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents 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: 270111  Cd Length: 102  Bit Score: 38.38  E-value: 2.24e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 269 NGIVMEGYLFKRASNAFKTWNRRWFSIQNNQL-VYQKKFKDSPTVVVEDLRLCTVKHCEDIER--RFCFEVVSPTKSCML 345
Cdd:cd13299    4 ERVIEQGYLQVLKKKGVNQWKKYWLVLRNRSLsFYKDQSEYSPVKIIPIDDIIDVVELDPLSKskKWCLQIITPEKRIRF 83

                         90
                 ....*....|....*....
gi 568996617 346 QADSEKLRQAWIKAVQTSI 364
Cdd:cd13299   84 CADDEESLIKWLGALKSLL 102
PH_PKB cd01241
Protein Kinase B-like pleckstrin homology (PH) domain; PKB (also called Akt), a member of the ...
 271-363 2.44e-03

Protein Kinase B-like pleckstrin homology (PH) domain; PKB (also called Akt), a member of the AGC kinase family, is a phosphatidylinositol 3'-kinase (PI3K)-dependent Ser/Thr kinase which alters the activity of the targeted protein. The name AGC is based on the three proteins that it is most similar to cAMP-dependent protein kinase 1 (PKA; also known as PKAC), cGMP-dependent protein kinase (PKG; also known as CGK1) and protein kinase C (PKC). Human Akt has three isoforms derived for distinct genes: Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma. All Akts have an N-terminal PH domain with an activating Thr phosphorylation site, a kinase domain, and a short C-terminal regulatory tail with an activating Ser phosphorylation site. The PH domain recruits Akt to the plasma membrane by binding to phosphoinositides (PtdIns-3,4-P2) and is required for activation. The phosphorylation of Akt at its Thr and Ser phosphorylation sites leads to increased Akt activity toward forkhead transcription factors, the mammalian target of rapamycin (mTOR), and the Bcl-xL/Bcl-2-associated death promoter (BAD), all of which possess a consensus motif R-X-R-XX-ST-B (X = amino acid, B = bulky hydrophobic residue) for Akt phosphorylation. 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: 269947  Cd Length: 107  Bit Score: 38.38  E-value: 2.44e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 271 IVMEGYLFKRASNaFKTWNRRWFSIQNNQLVYqkKFKDSPTVVVED-------LRLCTVKHCED------IERrfCFEVV 337
Cdd:cd01241    3 VVKEGWLLKRGEY-IKNWRPRYFVLKSDGSFI--GYKEKPKPNQDPpplnnfsVAECQLMKTEKpkpntfIIR--CLQWT 77

                         90       100
                 ....*....|....*....|....*.
gi 568996617 338 SPTKScMLQADSEKLRQAWIKAVQTS 363
Cdd:cd01241   78 TVIER-TFHVESEEEREEWMKAIQGV 102
PH2_FGD4_insect-like cd13238
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) ...
 273-359 2.70e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) domain, C-terminus, in insect and related arthropods; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. This cd contains insects, crustaceans, and chelicerates. 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: 270058  Cd Length: 97  Bit Score: 38.01  E-value: 2.70e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 273 MEGYLFKRaSNAFKTWNRRWFSIQNNQLVY-----QKKFKDSPT-----VVVEDLRLCTVKHCEDIERRFCFEVVSPTKS 342
Cdd:cd13238    1 LSGYLKLK-TNGRKTWSRRWFALQPDFVLYsyksqEDKLPLTATpvpgfLVTLLEKGSAVDPLNDPKRPRTFKMFHVKKS 79

                         90
                 ....*....|....*..
gi 568996617 343 CMLQADSEKLRQAWIKA 359
Cdd:cd13238   80 YYFQANDGDEQKKWVLT 96
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
 274-359 2.82e-03

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS 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. PH domains 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: 269950  Cd Length: 107  Bit Score: 38.04  E-value: 2.82e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 274 EGYLFKRASNA-----FKTWNRRWFSIQNNQLVYQKKFKDSPTVVVEDLRLCTVKHCED--IERRFCFEVVSPTKSCMLQ 346
Cdd:cd01244    2 EGYLIKRAQGRkkkfgRKNFKKRYFRLTNEALSYSKSKGKQPLCSIPLEDILAVERVEEesFKMKNMFQIVQPDRTLYLQ 81

                         90
                 ....*....|....
gi 568996617 347 A-DSEKLRQaWIKA 359
Cdd:cd01244   82 AkNVVELNE-WLSA 94
PHA03095 PHA03095
ankyrin-like protein; Provisional
 657-787 2.97e-03

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 40.78  E-value: 2.97e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 657 LAHGADVNWANSdeNQATPLIQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQVCLFLKRGANQHATDE 736
Cdd:PHA03095 244 LIAGISINARNR--YGQTPLHYAAVFNNPRACRRLIALGADINAVSSDGNTPLSLMVRNNNGRAVRAALAKNPSAETVAA 321

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568996617 737 EgkdpLSIAVEAANADIVTLLRLARMNEEMRESEGLYGQPGDETYQDIFRD 787
Cdd:PHA03095 322 T----LNTASVAGGDIPSDATRLCVAKVVLRGAFSLLPEPIRAYHADFIRE 368
PHA02876 PHA02876
ankyrin repeat protein; Provisional
 657-750 3.25e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165207 [Multi-domain]  Cd Length: 682  Bit Score: 41.20  E-value: 3.25e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 657 LAHGADVNWANSDENqaTPLIQA-VLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLGHTGQVCLFLKRGANQHATD 735
Cdd:PHA02876 328 IMLGADVNAADRLYI--TPLHQAsTLDRNKDIVITLLELGANVNARDYCDKTPIHYAAVRNNVVIINTLLDYGADIEALS 405

                         90
                 ....*....|....*
gi 568996617 736 EEGKDPLSIAVEAAN 750
Cdd:PHA02876 406 QKIGTALHFALCGTN 420
Ank pfam00023
Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the ...
 674-702 3.90e-03

Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin- actin cytoskeleton. This repeat-domain is a 'membrane-binding' domain of up to 24 repeated units, and it mediates most of the protein's binding activities. Repeats 13-24 are especially active, with known sites of interaction for the Na/K ATPase, Cl/HCO(3) anion exchanger, voltage-gated sodium channel, clathrin heavy chain and L1 family cell adhesion molecules. The ANK repeats are found to form a contiguous spiral stack such that ion transporters like the anion exchanger associate in a large central cavity formed by the ANK repeat spiral, while clathrin and cell adhesion molecules associate with specific regions outside this cavity.


Pssm-ID: 459634 [Multi-domain]  Cd Length: 34  Bit Score: 35.73  E-value: 3.90e-03
                          10        20        30
                  ....*....|....*....|....*....|
gi 568996617  674 TPLIQAVL-GGSLVTCEFLLQNGANVNQRD 702
Cdd:pfam00023   4 TPLHLAAGrRGNLEIVKLLLSKGADVNARD 33
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
 273-370 4.37e-03

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. 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: 241446  Cd Length: 103  Bit Score: 37.29  E-value: 4.37e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 273 MEGYLfKRASNAFKTWNRRWFSIQNNQLVYQKKfKDSPTVVVED---LRLCTVKHceDIERRFCFEVVSPTKSC---MLQ 346
Cdd:cd13292    4 MKGYL-KKWTNYAKGYKTRWFVLEDGVLSYYRH-QDDEGSACRGsinMKNARLVS--DPSEKLRFEVSSKTSGSpkwYLK 79

                         90       100
                 ....*....|....*....|....
gi 568996617 347 ADSEKLRQAWIKAVQTSIATAYRE 370
Cdd:cd13292   80 ANHPVEAARWIQALQKAIEWAKDE 103
BAR smart00721
BAR domain;
6-219 5.39e-03

BAR domain;


Pssm-ID: 214787 [Multi-domain]  Cd Length: 239  Bit Score: 39.29  E-value: 5.39e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617     6 DFEECLKdspRFRAALEEVEGDVAELELKLDKLVKLcIAMIDTGKAFCVANKQFMNGIRDLAQYSSNDAVVETsLTKFSD 85
Cdd:smart00721  28 DFEELER---RFDTTEAEIEKLQKDTKLYLQPNPAV-RAKLASQKKLSKSLGEVYEGGDDGEGLGADSSYGKA-LDKLGE 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617    86 SLQEMINFHTILFDQTQRSIKAQLQNFVKEdlrkFKDAKKQFEK--------------VSEEKENALVKNAQVQRNKQHE 151
Cdd:smart00721 103 ALKKLLQVEESLSQVKRTFILPLLNFLLGE----FKEIKKARKKlerklldydsarhkLKKAKKSKEKKKDEKLAKAEEE 178

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568996617   152 VEEAANILTatrkCFRHIALDYVLQINvlqSKRRSEILKSMLSFMYAHLAFFHQGYDLFSELGPYMKD 219
Cdd:smart00721 179 LRKAKQEFE----ESNAQLVEELPQLV---ASRVDFFVNCLQALIEAQLNFHRESYKLLQQLQQQLDK 239
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
 270-371 6.35e-03

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: 37.69  E-value: 6.35e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 270 GIVMEGYLFK-------RASNAF-KTWNRRWFSIQnnQLV-------YQKKFKDSPTVVVEDLRLCT--VKHCEdiERRF 332
Cdd:cd13267    5 GITKEGYLYKgpenssdSFISLAmKSFKRRFFHLK--QLVdgsyileFYKDEKKKEAKGTIFLDSCTgvVQNSK--RRKF 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 568996617 333 CFEV-VSPTKSCMLQADSEKLRQAWI----KAVQTSIATAYREK 371
Cdd:cd13267   81 CFELrMQDKKSYVLAAESEAEMDEWIsklnKILQSSKEQSIQKK 124
PHA02876 PHA02876
ankyrin repeat protein; Provisional
 645-757 8.98e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165207 [Multi-domain]  Cd Length: 682  Bit Score: 39.66  E-value: 8.98e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996617 645 SYEKNLPKMAEalaHGADVNWANSdeNQATPL-IQAVLGGSLVTCEFLLQNGANVNQRDVQGRGPLHHATVLG-HTGQVC 722
Cdd:PHA02876 285 SLSRLVPKLLE---RGADVNAKNI--KGETPLyLMAKNGYDTENIRTLIMLGADVNAADRLYITPLHQASTLDrNKDIVI 359

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568996617 723 LFLKRGANQHATDEEGKDPLSIAVEAANADIVTLL 757
Cdd:PHA02876 360 TLLELGANVNARDYCDKTPIHYAAVRNNVVIINTL 394
Ank_4 pfam13637
Ankyrin repeats (many copies);
641-692 9.14e-03

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 34.94  E-value: 9.14e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568996617  641 LYRASYEKNLPKMAEALAHGADVNwaNSDENQATPLIQAVLGGSLVTCEFLL 692
Cdd:pfam13637   5 LHAAAASGHLELLRLLLEKGADIN--AVDGNGETALHFAASNGNVEVLKLLL 54
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
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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