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Conserved domains on  [gi|568933964|ref|XP_006503892|]
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arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 isoform X3 [Mus musculus]

Protein Classification

ArfGap_ARAP2 and RhoGAP_ARAP domain-containing protein (domain architecture ID 12965976)

protein containing domains ArfGap_ARAP2, PH3_ARAP, RhoGAP_ARAP, and RA_ARAP2

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1112-1291 6.71e-95

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


:

Pssm-ID: 239850  Cd Length: 184  Bit Score: 303.85  E-value: 6.71e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1112 DGNALQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDVTGVLKSFL 1191
Cdd:cd04385     1 DGPALEDQQLTDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1192 SDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF 1271
Cdd:cd04385    81 RDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLF 160
                         170       180
                  ....*....|....*....|....
gi 568933964 1272 QTK----GQTSEEVNVIEDLINNY 1291
Cdd:cd04385   161 QTDehsvGQTSHEVKVIEDLIDNY 184
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
678-798 1.28e-77

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: 251.75  E-value: 1.28e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  678 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIG 757
Cdd:cd08856     1 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVVG 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568933964  758 NKRANDFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd08856    81 NKPANLFWAANLFSEEDLHMDSDVEQRTPFITQKYKEGKFR 121
RA_ARAP2 cd17227
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1323-1420 8.32e-59

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


:

Pssm-ID: 340747  Cd Length: 98  Bit Score: 197.03  E-value: 8.32e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1323 AGDLLIEVFVERKEPDCSIIIRISPVMEAEELTNDILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSS 1402
Cdd:cd17227     1 AGDLLIEVYLEKKEPDCSIIIRVSPTMEAEELTNDVLEIKNIIPDKKDIWATFEVIENGELERPLHYKENVLEQVLQWSS 80
                          90
                  ....*....|....*...
gi 568933964 1403 LAEPGSAYLVVKRFLTID 1420
Cdd:cd17227    81 LSEPGSAYLIVKRFQAAD 98
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
890-1000 4.23e-52

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


:

Pssm-ID: 270076  Cd Length: 110  Bit Score: 178.42  E-value: 4.23e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  890 SSFLCDFLYQTAAAASRVSsEKKLLEDTNKKWCVLEGGFLSYYENDRCTTPNGTINISEVICLAVHKEDFYLNTGPIFVF 969
Cdd:cd13256     1 SVFHSGFLYKSPSAAKPTL-ERRAREEFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEIVCLAVSPPDTHPGDGFPFTF 79
                          90       100       110
                  ....*....|....*....|....*....|.
gi 568933964  970 EIYLPSERVFLFGAETSQIQRKWTETIAKRF 1000
Cdd:cd13256    80 ELYLESERLYLFGLETAEALHEWVKAIAKAF 110
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
1426-1530 2.05e-51

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


The actual alignment was detected with superfamily member cd13259:

Pssm-ID: 418428  Cd Length: 121  Bit Score: 176.85  E-value: 2.05e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1426 REKSIKEGILKLKEEPSKILSGNKFQDRCVVLRDGHLFIYKDPKSSKHDKMFPLRAMKFYLGVKKKMKPPTSWGLTVYSE 1505
Cdd:cd13259    10 KVGSTKHGMLKFREEPSKLLSGNKFQDRYFILNDECLLLYKDVKSSKPEKEWPLKSLKVYLGIKKKLKPPTSWGFTVLLE 89
                          90       100
                  ....*....|....*....|....*
gi 568933964 1506 KHHWHLCCDSLQAQMEWMASIFIAQ 1530
Cdd:cd13259    90 KQQWYLCCDSQMEQREWMATILSAQ 114
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
482-573 1.11e-48

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


:

Pssm-ID: 270073  Cd Length: 94  Bit Score: 167.95  E-value: 1.11e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  482 EKCGWLDKLSPQG-KRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRAQGDNKFEIVTTQRTFVFRVEKEEER 560
Cdd:cd13253     1 IKSGYLDKQGGQGnNKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNKFELVTTNRTFVFRAESDDER 80
                          90
                  ....*....|...
gi 568933964  561 NDWISILLSALKS 573
Cdd:cd13253    81 NLWCSTLQAAISE 93
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
583-673 3.50e-47

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: 163.74  E-value: 3.50e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  583 AVAPEKCGYLELRGYKAKIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRavkQSFEIITPYRSFSFTADSE 662
Cdd:cd13254     3 KPNPDKCGYLELRGYKAKVYAALMGDEVWLYKNEQDFRLGIGITVIEMNGANVKDVDR---RSFDLTTPYRSFSFTAESE 79
                          90
                  ....*....|.
gi 568933964  663 REKQEWIEAVQ 673
Cdd:cd13254    80 HEKQEWIEAVQ 90
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
1013-1108 1.85e-45

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


The actual alignment was detected with superfamily member cd13257:

Pssm-ID: 418428  Cd Length: 91  Bit Score: 158.86  E-value: 1.85e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1013 YDLIGQLFYKDCHALDQWRKGWFAMDKSSLCFCLQTQEAqEERMNLRRLQELTISTMVQNgekvDVLLLVEKGRTLYIHG 1092
Cdd:cd13257     1 FERLGRLFYKDGLALDRAREGWFALDKSSLHACLQMQEV-EERMHLRKLQELSIQGDVQL----DVLVLVERRRTLYIQG 75
                          90
                  ....*....|....*.
gi 568933964 1093 HTKLDFTVWHTAIEKA 1108
Cdd:cd13257    76 ERKLDFTGWHTAIQKA 91
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
6-68 6.93e-32

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


:

Pssm-ID: 188889  Cd Length: 63  Bit Score: 118.94  E-value: 6.93e-32
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568933964    6 EVNADIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMIF 68
Cdd:cd09490     1 EADLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLPIIT 63
 
Name Accession Description Interval E-value
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1112-1291 6.71e-95

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


Pssm-ID: 239850  Cd Length: 184  Bit Score: 303.85  E-value: 6.71e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1112 DGNALQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDVTGVLKSFL 1191
Cdd:cd04385     1 DGPALEDQQLTDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1192 SDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF 1271
Cdd:cd04385    81 RDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLF 160
                         170       180
                  ....*....|....*....|....
gi 568933964 1272 QTK----GQTSEEVNVIEDLINNY 1291
Cdd:cd04385   161 QTDehsvGQTSHEVKVIEDLIDNY 184
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
678-798 1.28e-77

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: 251.75  E-value: 1.28e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  678 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIG 757
Cdd:cd08856     1 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVVG 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568933964  758 NKRANDFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd08856    81 NKPANLFWAANLFSEEDLHMDSDVEQRTPFITQKYKEGKFR 121
RA_ARAP2 cd17227
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1323-1420 8.32e-59

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


Pssm-ID: 340747  Cd Length: 98  Bit Score: 197.03  E-value: 8.32e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1323 AGDLLIEVFVERKEPDCSIIIRISPVMEAEELTNDILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSS 1402
Cdd:cd17227     1 AGDLLIEVYLEKKEPDCSIIIRVSPTMEAEELTNDVLEIKNIIPDKKDIWATFEVIENGELERPLHYKENVLEQVLQWSS 80
                          90
                  ....*....|....*...
gi 568933964 1403 LAEPGSAYLVVKRFLTID 1420
Cdd:cd17227    81 LSEPGSAYLIVKRFQAAD 98
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
890-1000 4.23e-52

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


Pssm-ID: 270076  Cd Length: 110  Bit Score: 178.42  E-value: 4.23e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  890 SSFLCDFLYQTAAAASRVSsEKKLLEDTNKKWCVLEGGFLSYYENDRCTTPNGTINISEVICLAVHKEDFYLNTGPIFVF 969
Cdd:cd13256     1 SVFHSGFLYKSPSAAKPTL-ERRAREEFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEIVCLAVSPPDTHPGDGFPFTF 79
                          90       100       110
                  ....*....|....*....|....*....|.
gi 568933964  970 EIYLPSERVFLFGAETSQIQRKWTETIAKRF 1000
Cdd:cd13256    80 ELYLESERLYLFGLETAEALHEWVKAIAKAF 110
PH5_ARAP cd13259
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
1426-1530 2.05e-51

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


Pssm-ID: 270079  Cd Length: 121  Bit Score: 176.85  E-value: 2.05e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1426 REKSIKEGILKLKEEPSKILSGNKFQDRCVVLRDGHLFIYKDPKSSKHDKMFPLRAMKFYLGVKKKMKPPTSWGLTVYSE 1505
Cdd:cd13259    10 KVGSTKHGMLKFREEPSKLLSGNKFQDRYFILNDECLLLYKDVKSSKPEKEWPLKSLKVYLGIKKKLKPPTSWGFTVLLE 89
                          90       100
                  ....*....|....*....|....*
gi 568933964 1506 KHHWHLCCDSLQAQMEWMASIFIAQ 1530
Cdd:cd13259    90 KQQWYLCCDSQMEQREWMATILSAQ 114
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
482-573 1.11e-48

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


Pssm-ID: 270073  Cd Length: 94  Bit Score: 167.95  E-value: 1.11e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  482 EKCGWLDKLSPQG-KRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRAQGDNKFEIVTTQRTFVFRVEKEEER 560
Cdd:cd13253     1 IKSGYLDKQGGQGnNKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNKFELVTTNRTFVFRAESDDER 80
                          90
                  ....*....|...
gi 568933964  561 NDWISILLSALKS 573
Cdd:cd13253    81 NLWCSTLQAAISE 93
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
583-673 3.50e-47

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: 163.74  E-value: 3.50e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  583 AVAPEKCGYLELRGYKAKIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRavkQSFEIITPYRSFSFTADSE 662
Cdd:cd13254     3 KPNPDKCGYLELRGYKAKVYAALMGDEVWLYKNEQDFRLGIGITVIEMNGANVKDVDR---RSFDLTTPYRSFSFTAESE 79
                          90
                  ....*....|.
gi 568933964  663 REKQEWIEAVQ 673
Cdd:cd13254    80 HEKQEWIEAVQ 90
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
1127-1279 4.67e-46

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


Pssm-ID: 395495  Cd Length: 152  Bit Score: 162.73  E-value: 4.67e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  1127 PIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVkLRAGKHQLEDVTGVLKSFLSDIDDALLTKELYPY 1206
Cdd:pfam00620    1 PLIVEKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDSGEDVD-LDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568933964  1207 WVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSE 1279
Cdd:pfam00620   80 FLEAAKSEDEEERIEALRELLEKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPDSESD 152
PH4_ARAP cd13257
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
1013-1108 1.85e-45

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


Pssm-ID: 270077  Cd Length: 91  Bit Score: 158.86  E-value: 1.85e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1013 YDLIGQLFYKDCHALDQWRKGWFAMDKSSLCFCLQTQEAqEERMNLRRLQELTISTMVQNgekvDVLLLVEKGRTLYIHG 1092
Cdd:cd13257     1 FERLGRLFYKDGLALDRAREGWFALDKSSLHACLQMQEV-EERMHLRKLQELSIQGDVQL----DVLVLVERRRTLYIQG 75
                          90
                  ....*....|....*.
gi 568933964 1093 HTKLDFTVWHTAIEKA 1108
Cdd:cd13257    76 ERKLDFTGWHTAIQKA 91
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
1125-1291 5.12e-45

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


Pssm-ID: 214618  Cd Length: 174  Bit Score: 160.89  E-value: 5.12e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   1125 DVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVkLRAGKHQLEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:smart00324    2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPD-LDLSEYDVHDVAGLLKLFLRELPEPLITYELY 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   1205 PYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSEEV--- 1281
Cdd:smart00324   81 EEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLkdi 160
                           170
                    ....*....|....
gi 568933964   1282 ----NVIEDLINNY 1291
Cdd:smart00324  161 rhqnTVIEFLIENA 174
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
683-799 3.15e-43

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: 396132 [Multi-domain]  Cd Length: 117  Bit Score: 153.17  E-value: 3.15e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   683 YEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRAN 762
Cdd:pfam01412    1 KRVLRELLRLPGNKVCADCGAPNPTWASLNLGIFICIDCSGVHRSLGVHISKVRSLTLD--TWTDEQLEFMKAGGNDRAN 78
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 568933964   763 DFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFRK 799
Cdd:pfam01412   79 EFWEANLPDSYKPPPDSDREKRESFIRAKYVEKKFAK 115
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
692-797 2.08e-32

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: 122.45  E-value: 2.08e-32
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964    692 NESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQK 771
Cdd:smart00105    7 IPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDT--WTEEELRLLQKGGNENANSIWESNLDD 84
                            90       100
                    ....*....|....*....|....*..
gi 568933964    772 DEELQVDSPV-EKRKNFITQKYKEGKF 797
Cdd:smart00105   85 FSLKPPDDDDqQKYESFIAAKYEEKLF 111
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
6-68 6.93e-32

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


Pssm-ID: 188889  Cd Length: 63  Bit Score: 118.94  E-value: 6.93e-32
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568933964    6 EVNADIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMIF 68
Cdd:cd09490     1 EADLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLPIIT 63
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
692-799 8.36e-27

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: 112.95  E-value: 8.36e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  692 NESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNLQK 771
Cdd:COG5347    17 DSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLD--NWTEEELRRMEVGGNSNANRFYEKNLLD 94
                          90       100       110
                  ....*....|....*....|....*....|..
gi 568933964  772 DEELQV----DSPVekRKNFITQKYKEGKFRK 799
Cdd:COG5347    95 QLLLPIkakyDSSV--AKKYIRKKYELKKFID 124
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
483-572 1.84e-12

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 64.88  E-value: 1.84e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964    483 KCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYS---KGIIPLTAIS------TVRAQGDNKFEIVTTQR-TFVF 552
Cdd:smart00233    3 KEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTvreapdPDSSKKPHCFEIKTSDRkTLLL 82
                            90       100
                    ....*....|....*....|
gi 568933964    553 RVEKEEERNDWISILLSALK 572
Cdd:smart00233   83 QAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
482-572 8.92e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117  Cd Length: 105  Bit Score: 62.96  E-value: 8.92e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   482 EKCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYS---KGIIPLTAISTVRA------QGDNKFEIVTTQ----R 548
Cdd:pfam00169    2 VKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSKKSkepKGSISLSGCEVVEVvasdspKRKFCFELRTGErtgkR 81
                           90       100
                   ....*....|....*....|....
gi 568933964   549 TFVFRVEKEEERNDWISILLSALK 572
Cdd:pfam00169   82 TYLLQAESEEERKDWIKAIQSAIR 105
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
677-765 6.09e-11

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661  Cd Length: 395  Bit Score: 66.42  E-value: 6.09e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  677 AETLSD-YEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIV 755
Cdd:PLN03114    3 SENLNDkISVFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDS--WSSEQLKMMIY 80
                          90
                  ....*....|
gi 568933964  756 IGNKRANDFW 765
Cdd:PLN03114   81 GGNNRAQVFF 90
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
1430-1526 1.17e-09

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 57.17  E-value: 1.17e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   1430 IKEGILKLKEEPSKilsgNKFQDRCVVLRDGHLFIYKDPK---SSKHDKMFPLRAMKFYLGVKKKMKpPTSWGLTV-YSE 1505
Cdd:smart00233    2 IKEGWLYKKSGGGK----KSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSS-KKPHCFEIkTSD 76
                            90       100
                    ....*....|....*....|.
gi 568933964   1506 KHHWHLCCDSLQAQMEWMASI 1526
Cdd:smart00233   77 RKTLLLQAESEEEREKWVEAL 97
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
586-677 5.81e-09

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 54.86  E-value: 5.81e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964    586 PEKCGYLELRGYKA-----KIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRA----VKQSFEIITPYR-SF 655
Cdd:smart00233    1 VIKEGWLYKKSGGGkkswkKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPdsskKPHCFEIKTSDRkTL 80
                            90       100
                    ....*....|....*....|..
gi 568933964    656 SFTADSEREKQEWIEAVQQSIA 677
Cdd:smart00233   81 LLQAESEEEREKWVEALRKAIA 102
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
919-996 5.93e-09

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 54.86  E-value: 5.93e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964    919 KKWCVLEGGFLSYYEND---RCTTPNGTINISEVICLAVHKEDfylNTGPIFVFEIYLPSERVFLFGAETSQIQRKWTET 995
Cdd:smart00233   20 KRYFVLFNSTLLYYKSKkdkKSYKPKGSIDLSGCTVREAPDPD---SSKKPHCFEIKTSDRKTLLLQAESEEEREKWVEA 96

                    .
gi 568933964    996 I 996
Cdd:smart00233   97 L 97
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
10-67 9.64e-09

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


Pssm-ID: 395427  Cd Length: 64  Bit Score: 53.04  E-value: 9.64e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 568933964    10 DIRDFLMSINLEQYLLHFREfGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:pfam00536    7 DVGEWLESIGLGQYIDSFRA-GYIDGDTLLLLTEDDLLKLGVTLLGHRKKILYSIQGL 63
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
10-67 8.20e-08

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


Pssm-ID: 197735  Cd Length: 68  Bit Score: 50.76  E-value: 8.20e-08
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 568933964     10 DIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:smart00454    8 SVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKL 65
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
1328-1415 1.47e-06

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


Pssm-ID: 395636  Cd Length: 93  Bit Score: 47.71  E-value: 1.47e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  1328 IEVFVERKEPDC-SIIIRISPVMEAEELTNDILAIKNIIPMKGDiWATFEVIENEELERPLHYTENVLEQVLQWSSlaEP 1406
Cdd:pfam00788    5 LKVYTEDGKPGTtYKSILVSSSTTAEEVIRALLEKFGLEDDPRD-YVLVEVLERGGGERRLPDDECPLQIQLQWPR--DA 81

                   ....*....
gi 568933964  1407 GSAYLVVKR 1415
Cdd:pfam00788   82 SDSRFLLRK 90
PH pfam00169
PH domain; PH stands for pleckstrin homology.
919-996 1.81e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117  Cd Length: 105  Bit Score: 45.25  E-value: 1.81e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   919 KKWCVLEGGFLSYYENDRCT---TPNGTINISEVICLAVHKEDfylNTGPIFVFEIYLPS---ERVFLFGAETSQIQRKW 992
Cdd:pfam00169   20 KRYFVLFDGSLLYYKDDKSKkskEPKGSISLSGCEVVEVVASD---SPKRKFCFELRTGErtgKRTYLLQAESEEERKDW 96

                   ....
gi 568933964   993 TETI 996
Cdd:pfam00169   97 IKAI 100
PH pfam00169
PH domain; PH stands for pleckstrin homology.
1430-1526 3.41e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117  Cd Length: 105  Bit Score: 44.47  E-value: 3.41e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  1430 IKEGILKLKEEPSKilsgNKFQDRCVVLRDGHLFIYKDPKSSKHDK---MFPLRAMKFYLGVKKKMKP-PTSWGLTVY-- 1503
Cdd:pfam00169    2 VKEGWLLKKGGGKK----KSWKKRYFVLFDGSLLYYKDDKSKKSKEpkgSISLSGCEVVEVVASDSPKrKFCFELRTGer 77
                           90       100
                   ....*....|....*....|...
gi 568933964  1504 SEKHHWHLCCDSLQAQMEWMASI 1526
Cdd:pfam00169   78 TGKRTYLLQAESEEERKDWIKAI 100
PH pfam00169
PH domain; PH stands for pleckstrin homology.
586-677 1.70e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117  Cd Length: 105  Bit Score: 42.55  E-value: 1.70e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   586 PEKCGYLELRGYKAKI-----FTVLRGNSVWLCKNEQDFKSGLGITIIPMN----VANVKQVDRAVKQSFEIIT----PY 652
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKswkkrYFVLFDGSLLYYKDDKSKKSKEPKGSISLSgcevVEVVASDSPKRKFCFELRTgertGK 80
                           90       100
                   ....*....|....*....|....*
gi 568933964   653 RSFSFTADSEREKQEWIEAVQQSIA 677
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1112-1291 6.71e-95

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


Pssm-ID: 239850  Cd Length: 184  Bit Score: 303.85  E-value: 6.71e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1112 DGNALQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDVTGVLKSFL 1191
Cdd:cd04385     1 DGPALEDQQLTDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1192 SDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF 1271
Cdd:cd04385    81 RDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLF 160
                         170       180
                  ....*....|....*....|....
gi 568933964 1272 QTK----GQTSEEVNVIEDLINNY 1291
Cdd:cd04385   161 QTDehsvGQTSHEVKVIEDLIDNY 184
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
678-798 1.28e-77

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: 251.75  E-value: 1.28e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  678 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIG 757
Cdd:cd08856     1 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVVG 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568933964  758 NKRANDFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd08856    81 NKPANLFWAANLFSEEDLHMDSDVEQRTPFITQKYKEGKFR 121
ArfGap_ARAP cd08837
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily ...
683-798 1.33e-73

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: 239.97  E-value: 1.33e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  683 YEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIGNKRAN 762
Cdd:cd08837     1 YEVAEKIWSNPANRFCADCGAPDPDWASINLCVVICKQCAGEHRSLGSNISKVRSLKMDTKVWTEELVELFLKLGNDRAN 80
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 568933964  763 DFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd08837    81 RFWAANLPPSEALHPDADSEQRREFITAKYREGKYR 116
RA_ARAP2 cd17227
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1323-1420 8.32e-59

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


Pssm-ID: 340747  Cd Length: 98  Bit Score: 197.03  E-value: 8.32e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1323 AGDLLIEVFVERKEPDCSIIIRISPVMEAEELTNDILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSS 1402
Cdd:cd17227     1 AGDLLIEVYLEKKEPDCSIIIRVSPTMEAEELTNDVLEIKNIIPDKKDIWATFEVIENGELERPLHYKENVLEQVLQWSS 80
                          90
                  ....*....|....*...
gi 568933964 1403 LAEPGSAYLVVKRFLTID 1420
Cdd:cd17227    81 LSEPGSAYLIVKRFQAAD 98
ArfGap_ARAP3 cd17902
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily ...
683-798 3.23e-57

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: 193.20  E-value: 3.23e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  683 YEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIGNKRAN 762
Cdd:cd17902     1 YEVAEKIWSNKANRFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKLDTSVWSNEIVQLFIVLGNDRAN 80
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 568933964  763 DFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd17902    81 RFWAARLPASEALHPDATPEQRREFISRKYREGRFR 116
ArfGap_ARAP1 cd17901
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily ...
684-798 5.29e-53

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: 181.16  E-value: 5.29e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  684 EVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIGNKRAND 763
Cdd:cd17901     2 EVAEKIWSVESNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKMDRKVWTEELIELFLLLGNGKANQ 81
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 568933964  764 FWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd17901    82 FWAANVPPSEALCPSSSSEERRHFITAKYKEGKYR 116
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
890-1000 4.23e-52

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


Pssm-ID: 270076  Cd Length: 110  Bit Score: 178.42  E-value: 4.23e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  890 SSFLCDFLYQTAAAASRVSsEKKLLEDTNKKWCVLEGGFLSYYENDRCTTPNGTINISEVICLAVHKEDFYLNTGPIFVF 969
Cdd:cd13256     1 SVFHSGFLYKSPSAAKPTL-ERRAREEFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEIVCLAVSPPDTHPGDGFPFTF 79
                          90       100       110
                  ....*....|....*....|....*....|.
gi 568933964  970 EIYLPSERVFLFGAETSQIQRKWTETIAKRF 1000
Cdd:cd13256    80 ELYLESERLYLFGLETAEALHEWVKAIAKAF 110
PH5_ARAP cd13259
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
1426-1530 2.05e-51

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


Pssm-ID: 270079  Cd Length: 121  Bit Score: 176.85  E-value: 2.05e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1426 REKSIKEGILKLKEEPSKILSGNKFQDRCVVLRDGHLFIYKDPKSSKHDKMFPLRAMKFYLGVKKKMKPPTSWGLTVYSE 1505
Cdd:cd13259    10 KVGSTKHGMLKFREEPSKLLSGNKFQDRYFILNDECLLLYKDVKSSKPEKEWPLKSLKVYLGIKKKLKPPTSWGFTVLLE 89
                          90       100
                  ....*....|....*....|....*
gi 568933964 1506 KHHWHLCCDSLQAQMEWMASIFIAQ 1530
Cdd:cd13259    90 KQQWYLCCDSQMEQREWMATILSAQ 114
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
482-573 1.11e-48

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


Pssm-ID: 270073  Cd Length: 94  Bit Score: 167.95  E-value: 1.11e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  482 EKCGWLDKLSPQG-KRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRAQGDNKFEIVTTQRTFVFRVEKEEER 560
Cdd:cd13253     1 IKSGYLDKQGGQGnNKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNKFELVTTNRTFVFRAESDDER 80
                          90
                  ....*....|...
gi 568933964  561 NDWISILLSALKS 573
Cdd:cd13253    81 NLWCSTLQAAISE 93
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
583-673 3.50e-47

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: 163.74  E-value: 3.50e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  583 AVAPEKCGYLELRGYKAKIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRavkQSFEIITPYRSFSFTADSE 662
Cdd:cd13254     3 KPNPDKCGYLELRGYKAKVYAALMGDEVWLYKNEQDFRLGIGITVIEMNGANVKDVDR---RSFDLTTPYRSFSFTAESE 79
                          90
                  ....*....|.
gi 568933964  663 REKQEWIEAVQ 673
Cdd:cd13254    80 HEKQEWIEAVQ 90
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
1127-1279 4.67e-46

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


Pssm-ID: 395495  Cd Length: 152  Bit Score: 162.73  E-value: 4.67e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  1127 PIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVkLRAGKHQLEDVTGVLKSFLSDIDDALLTKELYPY 1206
Cdd:pfam00620    1 PLIVEKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDSGEDVD-LDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568933964  1207 WVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSE 1279
Cdd:pfam00620   80 FLEAAKSEDEEERIEALRELLEKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPDSESD 152
PH4_ARAP cd13257
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
1013-1108 1.85e-45

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


Pssm-ID: 270077  Cd Length: 91  Bit Score: 158.86  E-value: 1.85e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1013 YDLIGQLFYKDCHALDQWRKGWFAMDKSSLCFCLQTQEAqEERMNLRRLQELTISTMVQNgekvDVLLLVEKGRTLYIHG 1092
Cdd:cd13257     1 FERLGRLFYKDGLALDRAREGWFALDKSSLHACLQMQEV-EERMHLRKLQELSIQGDVQL----DVLVLVERRRTLYIQG 75
                          90
                  ....*....|....*.
gi 568933964 1093 HTKLDFTVWHTAIEKA 1108
Cdd:cd13257    76 ERKLDFTGWHTAIQKA 91
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
1125-1291 5.12e-45

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


Pssm-ID: 214618  Cd Length: 174  Bit Score: 160.89  E-value: 5.12e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   1125 DVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVkLRAGKHQLEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:smart00324    2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPD-LDLSEYDVHDVAGLLKLFLRELPEPLITYELY 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   1205 PYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSEEV--- 1281
Cdd:smart00324   81 EEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLkdi 160
                           170
                    ....*....|....
gi 568933964   1282 ----NVIEDLINNY 1291
Cdd:smart00324  161 rhqnTVIEFLIENA 174
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
683-799 3.15e-43

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: 396132 [Multi-domain]  Cd Length: 117  Bit Score: 153.17  E-value: 3.15e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   683 YEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRAN 762
Cdd:pfam01412    1 KRVLRELLRLPGNKVCADCGAPNPTWASLNLGIFICIDCSGVHRSLGVHISKVRSLTLD--TWTDEQLEFMKAGGNDRAN 78
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 568933964   763 DFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFRK 799
Cdd:pfam01412   79 EFWEANLPDSYKPPPDSDREKRESFIRAKYVEKKFAK 115
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
687-792 2.80e-39

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: 141.48  E-value: 2.80e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  687 EKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWA 766
Cdd:cd08204     2 EELLKLPGNKVCADCGAPDPRWASINLGVFICIRCSGIHRSLGVHISKVRSLTLDS--WTPEQVELMKAIGNARANAYYE 79
                          90       100
                  ....*....|....*....|....*..
gi 568933964  767 GNLQKDEELQ-VDSPVEKRKNFITQKY 792
Cdd:cd08204    80 ANLPPGFKKPtPDSSDEEREQFIRAKY 106
RA_ARAP3 cd17228
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1323-1416 1.73e-37

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


Pssm-ID: 340748  Cd Length: 99  Bit Score: 136.16  E-value: 1.73e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1323 AGDLLIEVFVERKEPDCSIIIRISPVMEAEELTNDILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSS 1402
Cdd:cd17228     1 AGDLIIEVYLEQKLPDCCVTLKVSPTMTAEELTNQVLDMRNIAAASKDVWLTFEVIENGELERPLHPKEKVLEQALQWCK 80
                          90
                  ....*....|....
gi 568933964 1403 LAEPGSAYLVVKRF 1416
Cdd:cd17228    81 LPEPSSAYLLVKKV 94
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
1127-1290 1.91e-35

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


Pssm-ID: 238090  Cd Length: 169  Bit Score: 133.20  E-value: 1.91e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1127 PIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRagKHQLEDVTGVLKSFLSDIDDALLTKELYPY 1206
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLE--DYDVHDVASLLKLYLRELPEPLIPFELYDE 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1207 WVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF-------QTKGQTSE 1279
Cdd:cd00159    79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLrppdsddELLEDIKK 158
                         170
                  ....*....|.
gi 568933964 1280 EVNVIEDLINN 1290
Cdd:cd00159   159 LNEIVEFLIEN 169
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
692-797 2.08e-32

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: 122.45  E-value: 2.08e-32
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964    692 NESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQK 771
Cdd:smart00105    7 IPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDT--WTEEELRLLQKGGNENANSIWESNLDD 84
                            90       100
                    ....*....|....*....|....*..
gi 568933964    772 DEELQVDSPV-EKRKNFITQKYKEGKF 797
Cdd:smart00105   85 FSLKPPDDDDqQKYESFIAAKYEEKLF 111
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
6-68 6.93e-32

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


Pssm-ID: 188889  Cd Length: 63  Bit Score: 118.94  E-value: 6.93e-32
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568933964    6 EVNADIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMIF 68
Cdd:cd09490     1 EADLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLPIIT 63
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1126-1295 8.41e-32

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


Pssm-ID: 239863  Cd Length: 192  Bit Score: 123.67  E-value: 8.41e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLED---VTGVLKSFLSDIDDALLTKE 1202
Cdd:cd04398    16 VPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLISPEDYESDihsVASLLKLFFRELPEPLLTKA 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1203 LYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSEEVN 1282
Cdd:cd04398    96 LSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLMNAAPDNAADMS 175
                         170
                  ....*....|....*..
gi 568933964 1283 ----VIEDLINNYVEIF 1295
Cdd:cd04398   176 fqsrVIETLLDNAYQIF 192
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
695-792 4.56e-29

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


Pssm-ID: 350065 [Multi-domain]  Cd Length: 108  Bit Score: 112.38  E-value: 4.56e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08836    12 NDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDD--WPVELLKVMSAIGNDLANSVWEGNTQGRTK 89
                          90
                  ....*....|....*...
gi 568933964  775 LQVDSPVEKRKNFITQKY 792
Cdd:cd08836    90 PTPDSSREEKERWIRAKY 107
ArfGap_ACAP cd08835
ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP ...
695-797 1.41e-28

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: 111.58  E-value: 1.41e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08835    13 NAQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDS--WEPELLKVMLELGNDVVNRIYEANVPDDGS 90
                          90       100
                  ....*....|....*....|....*
gi 568933964  775 LQ--VDSPVEKRKNFITQKYKEGKF 797
Cdd:cd08835    91 VKptPDSSRQEREAWIRAKYVEKKF 115
RA_ARAPs cd17113
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1323-1416 1.77e-27

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


Pssm-ID: 340633  Cd Length: 95  Bit Score: 107.33  E-value: 1.77e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1323 AGDLLIEVFVERKEpDCSIIIRISPVMEAEELTNDILAIKNIIPMKGDiWATFEVIENEELERPLHYTENVLEQVLQWSS 1402
Cdd:cd17113     1 SGDFLIPVYIEEKE-GTSVNIKVTPTMTAEEVVEQALNKKNLGGPEGN-WALFEVIEDGGLERPLHESEKVLDVVLRWSQ 78
                          90
                  ....*....|....
gi 568933964 1403 LaEPGSAYLVVKRF 1416
Cdd:cd17113    79 W-PRKSNYLCVKKN 91
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
692-799 8.36e-27

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: 112.95  E-value: 8.36e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  692 NESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNLQK 771
Cdd:COG5347    17 DSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLD--NWTEEELRRMEVGGNSNANRFYEKNLLD 94
                          90       100       110
                  ....*....|....*....|....*....|..
gi 568933964  772 DEELQV----DSPVekRKNFITQKYKEGKFRK 799
Cdd:COG5347    95 QLLLPIkakyDSSV--AKKYIRKKYELKKFID 124
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
694-792 1.90e-26

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: 105.08  E-value: 1.90e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNL---- 769
Cdd:cd08833     7 NARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKD--QWPPSLLEMVQTLGNNGANSIWEHSLldps 84
                          90       100
                  ....*....|....*....|....*
gi 568933964  770 --QKDEELQVDSPVEKRKNFITQKY 792
Cdd:cd08833    85 qsGKRKPIPPDPVHPTKEEFIKAKY 109
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
693-792 7.68e-25

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: 100.42  E-value: 7.68e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  693 ESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKD 772
Cdd:cd08839     8 EDNKYCADCGAKGPRWASWNLGVFICIRCAGIHRNLGVHISKVKSVNLDS--WTPEQVQSMQEMGNARANAYYEANLPDG 85
                          90       100
                  ....*....|....*....|.
gi 568933964  773 -EELQVDSPVEkrkNFITQKY 792
Cdd:cd08839    86 fRRPQTDSALE---NFIRDKY 103
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
693-765 2.50e-24

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: 99.26  E-value: 2.50e-24
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568933964  693 ESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFW 765
Cdd:cd08832    15 PGNNTCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDN--WDDSQVEFMEENGNEKAKAKY 85
ArfGap_AGAP2 cd08853
ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation ...
695-793 5.61e-24

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: 98.16  E-value: 5.61e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08853    13 NSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDD--WPVELRKVMSSIGNELANSIWEGSSQGQTK 90
                          90
                  ....*....|....*....
gi 568933964  775 LQVDSPVEKRKNFITQKYK 793
Cdd:cd08853    91 PSSDSTREEKERWIRAKYE 109
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
695-793 1.27e-23

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: 97.05  E-value: 1.27e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08855    14 NSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDD--WPVELSMVMTAIGNAMANSVWEGALDGYSK 91
                          90
                  ....*....|....*....
gi 568933964  775 LQVDSPVEKRKNFITQKYK 793
Cdd:cd08855    92 PGPDSTREEKERWIRAKYE 110
ArfGap_AGAP1 cd08854
ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation ...
695-793 1.91e-23

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: 96.62  E-value: 1.91e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08854    13 NSLCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLD--DWPRELTLVLTAIGNHMANSIWESCTQGRTK 90
                          90
                  ....*....|....*....
gi 568933964  775 LQVDSPVEKRKNFITQKYK 793
Cdd:cd08854    91 PAPDSSREERESWIRAKYE 109
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1126-1295 2.91e-23

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


Pssm-ID: 239860  Cd Length: 196  Bit Score: 99.01  E-value: 2.91e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQ-LEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:cd04395    18 VPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRdVNVVSSLLKSFFRKLPEPLFTNELY 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1205 PYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQT------- 1277
Cdd:cd04395    98 PDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNmetmvth 177
                         170
                  ....*....|....*....
gi 568933964 1278 -SEEVNVIEDLINNYVEIF 1295
Cdd:cd04395   178 mPDQCKIVETLIQHYDWFF 196
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1123-1273 9.78e-23

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


Pssm-ID: 239842  Cd Length: 186  Bit Score: 97.12  E-value: 9.78e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1123 KNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRagKHQLEDVTGVLKSFLSDIDDALLTKE 1202
Cdd:cd04377    12 DRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLE--DYPIHVITSVLKQWLRELPEPLMTFE 89
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568933964 1203 LYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQT 1273
Cdd:cd04377    90 LYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRC 160
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
695-797 1.25e-22

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: 94.59  E-value: 1.25e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08834    15 NDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLD--NLGTSELLLARNLGNEGFNEIMEANLPPGYK 92
                          90       100
                  ....*....|....*....|...
gi 568933964  775 LQVDSPVEKRKNFITQKYKEGKF 797
Cdd:cd08834    93 PTPNSDMEERKDFIRAKYVEKKF 115
ArfGap_ArfGap1 cd08830
Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
693-793 2.56e-22

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


Pssm-ID: 350059 [Multi-domain]  Cd Length: 115  Bit Score: 93.33  E-value: 2.56e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  693 ESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNlqkd 772
Cdd:cd08830    12 PGNNRCFDCGAPNPQWASVSYGIFICLECSGVHRGLGVHISFVRSITMDS--WSEKQLKKMELGGNAKLREFFESY---- 85
                          90       100
                  ....*....|....*....|.
gi 568933964  773 eELQVDSPvekrknfITQKYK 793
Cdd:cd08830    86 -GISPDLP-------IREKYN 98
ArfGap_ACAP1 cd08852
ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs ...
684-797 6.30e-22

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: 92.71  E-value: 6.30e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  684 EVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRAND 763
Cdd:cd08852     2 HAVAQVQSVDGNAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLGVHFSKVRSLTLDS--WEPELVKLMCELGNVIINQ 79
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 568933964  764 FWAGNLqkdEELQV-----DSPVEKRKNFITQKYKEGKF 797
Cdd:cd08852    80 IYEARI---EAMAIkkpgpSSSRQEKEAWIRAKYVEKKF 115
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
695-797 3.55e-21

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: 90.43  E-value: 3.55e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNLQK--D 772
Cdd:cd08851    13 NASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLD--TWEPELLKLMCELGNDVINRIYEARVEKmgA 90
                          90       100
                  ....*....|....*....|....*
gi 568933964  773 EELQVDSPVEKRKNFITQKYKEGKF 797
Cdd:cd08851    91 KKPQPGGQRQEKEAYIRAKYVERKF 115
ArfGap_ACAP3 cd08850
ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs ...
695-797 2.75e-20

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: 87.69  E-value: 2.75e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGnlqKDEE 774
Cdd:cd08850    13 NDQCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDS--WEPELLKLMCELGNSTVNQIYEA---QCEE 87
                          90       100
                  ....*....|....*....|....*...
gi 568933964  775 LQVDSPV-----EKRKNFITQKYKEGKF 797
Cdd:cd08850    88 LGLKKPTasssrQDKEAWIKAKYVEKKF 115
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
1121-1278 5.40e-20

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


Pssm-ID: 239868 [Multi-domain]  Cd Length: 187  Bit Score: 89.37  E-value: 5.40e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1121 LC---KNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELleSFKKDaRSVKLRAGKHQLED---VTGVLKSFLSDI 1194
Cdd:cd04403     8 LCqreNSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKL--RFAVD-HDEKLDLDDSKWEDihvITGALKLFFREL 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1195 DDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTK 1274
Cdd:cd04403    85 PEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLRPE 164

                  ....
gi 568933964 1275 GQTS 1278
Cdd:cd04403   165 QETG 168
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1127-1295 6.19e-20

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


Pssm-ID: 239837  Cd Length: 194  Bit Score: 89.50  E-value: 6.19e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1127 PIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKH-QLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04372    17 PMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYpDINVITGALKLYFRDLPIPVITYDTYP 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1206 YWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTS------- 1278
Cdd:cd04372    97 KFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPEDSAlttlndm 176
                         170
                  ....*....|....*...
gi 568933964 1279 -EEVNVIEDLINNYVEIF 1295
Cdd:cd04372   177 rYQILIVQLLITNEDVLF 194
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1123-1272 2.72e-19

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


Pssm-ID: 239872  Cd Length: 186  Bit Score: 87.35  E-value: 2.72e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1123 KNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRagKHQLEDVTGVLKSFLSDIDDALLTKE 1202
Cdd:cd04407    12 KTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLE--NYPIHAITGLLKQWLRELPEPLMTFA 89
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1203 LYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQ 1272
Cdd:cd04407    90 QYNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLR 159
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1113-1271 4.74e-19

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


Pssm-ID: 239838  Cd Length: 185  Bit Score: 86.74  E-value: 4.74e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1113 GNALQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDaRSVKLRAGKHQLEDVTGVLKSFLS 1192
Cdd:cd04373     2 GVPLANVVTSEKPIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQD-HNLDLVSKDFTVNAVAGALKSFFS 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568933964 1193 DIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF 1271
Cdd:cd04373    81 ELPDPLIPYSMHLELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLM 159
ArfGap_SMAP2 cd08859
Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of ...
693-796 1.25e-18

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: 82.73  E-value: 1.25e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  693 ESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKD 772
Cdd:cd08859     8 EENKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHISRVKSVNLDQ--WTQEQIQCMQEMGNGKANRLYEAFLPEN 85
                          90       100
                  ....*....|....*....|....*
gi 568933964  773 -EELQVDSPVEkrkNFITQKYKEGK 796
Cdd:cd08859    86 fRRPQTDQAVE---GFIRDKYEKKK 107
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1113-1295 1.36e-18

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


Pssm-ID: 239867  Cd Length: 192  Bit Score: 85.43  E-value: 1.36e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1113 GNALQDqqLCKND-VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLEsfkkdarsvKLRAGKHQLED------VTG 1185
Cdd:cd04402     3 GQPLSN--ICEDDnLPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKE---------KLNSGVEVDLKaepvllLAS 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1186 VLKSFLSDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMV 1265
Cdd:cd04402    72 VLKDFLRNIPGSLLSSDLYEEWMSALDQENEEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVC 151
                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 568933964 1266 FSSCLFQTKGQTSEEVNV-------IEDLINNYVEIF 1295
Cdd:cd04402   152 IAPSLLWPPASSELQNEDlkkvtslVQFLIENCQEIF 188
RA_ARAP1 cd17226
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1323-1415 3.61e-18

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


Pssm-ID: 340746  Cd Length: 93  Bit Score: 81.05  E-value: 3.61e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1323 AGDLLIEVFVERKEPDCSIIIRISPVMEAEELTNDILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSS 1402
Cdd:cd17226     1 SPDFICTVYLEEKKEGSEQHVQVPASMTAEELTFEILDRRNIHTREKDYWSCFEVNEREEAERPLHFSEKVLPIFHSLGS 80
                          90
                  ....*....|...
gi 568933964 1403 laepgSAYLVVKR 1415
Cdd:cd17226    81 -----DSHLVVKK 88
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
1126-1272 3.74e-18

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


Pssm-ID: 239852 [Multi-domain]  Cd Length: 196  Bit Score: 84.21  E-value: 3.74e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04387    16 VPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLYFRELPEPLFTDELYP 95
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568933964 1206 YWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQ 1272
Cdd:cd04387    96 NFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLR 162
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1116-1295 4.71e-18

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


Pssm-ID: 239869  Cd Length: 195  Bit Score: 83.93  E-value: 4.71e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1116 LQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDarsvkLRAGKHQLEDV---TGVLKSFLS 1192
Cdd:cd04404    13 LKEKNPEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMG-----EPVDFDQYEDVhlpAVILKTFLR 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1193 DIDDALLTKELYPYwVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQ 1272
Cdd:cd04404    88 ELPEPLLTFDLYDD-IVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLW 166
                         170       180
                  ....*....|....*....|....*....
gi 568933964 1273 TKGQ--TSEEVNVI----EDLINNYVEIF 1295
Cdd:cd04404   167 AKDAsmSLSAINPIntftKFLLDHQDEIF 195
ArfGap_ArfGap2_3_like cd08831
Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
695-794 6.08e-18

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: 81.05  E-value: 6.08e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFW---AGNLQK 771
Cdd:cd08831    15 NKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLGVHISFVRSTNLDS--WTPEQLRRMKVGGNAKAREFFkqhGGLLSG 92
                          90       100
                  ....*....|....*....|...
gi 568933964  772 DEElqvdspvEKRKNFITQKYKE 794
Cdd:cd08831    93 DIK-------QKYTSRAAQKYKE 108
ArfGap_ArfGap1_like cd08959
ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
695-765 1.04e-17

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: 80.25  E-value: 1.04e-17
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFW 765
Cdd:cd08959    14 NKVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGVHISFVRSTTMDK--WTEEQLRKMKVGGNANAREFF 82
ArfGap_ASAP1 cd08848
ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); ...
695-800 1.95e-17

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: 80.08  E-value: 1.95e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDaSIWSNELIeLFIVIGNKRANDFWAGNL-QKDE 773
Cdd:cd08848    15 NEVCCDCGSPDPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELD-KLGTSELL-LAKNVGNNSFNDIMEGNLpSPSP 92
                          90       100
                  ....*....|....*....|....*...
gi 568933964  774 ELQVDSPVEKRKNFITQKYKEGKF-RKT 800
Cdd:cd08848    93 KPSPSSDMTARKEYITAKYVEHRFsRKT 120
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1126-1297 3.53e-17

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239847  Cd Length: 193  Bit Score: 81.57  E-value: 3.53e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLraGKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNL--SKVDIHVICGCLKDFLRSLKEPLITFALWK 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1206 YWVSALDTQDEKE-RTSKYRAfIRSLPGVNRATLAALIEHLYRVQKCSEiNHMNAHNLAMVFSSCLFQTKGQTSEEVNVI 1284
Cdd:cd04382    95 EFMEAAEILDEDNsRAALYQA-ISELPQPNRDTLAFLILHLQRVAQSPE-CKMDINNLARVFGPTIVGYSVPNPDPMTIL 172
                         170
                  ....*....|...
gi 568933964 1285 EDlINNYVEIFEV 1297
Cdd:cd04382   173 QD-TVRQPRVVER 184
ArfGap_ASAP3 cd17900
ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ...
695-797 4.46e-17

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: 78.74  E-value: 4.46e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsIWSNELIeLFIVIGNKRANDFWAGNL--QKD 772
Cdd:cd17900    15 NSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYSRIQSLTLDL-LSTSELL-LAVSMGNTRFNEVMEATLpaHGG 92
                          90       100
                  ....*....|....*....|....*
gi 568933964  773 EELQVDSPVEKRKNFITQKYKEGKF 797
Cdd:cd17900    93 PKPSAESDMGTRKDYIMAKYVEHRF 117
RhoGAP_myosin_IXA cd04406
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1126-1287 6.89e-17

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


Pssm-ID: 239871  Cd Length: 186  Bit Score: 80.43  E-value: 6.89e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLraGKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04406    15 VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVNL--DDYNIHVIASVFKQWLRDLPNPLMTFELYE 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1206 YWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKgQTSEEVNVIE 1285
Cdd:cd04406    93 EFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILRCP-DTTDPLQSVQ 171

                  ..
gi 568933964 1286 DL 1287
Cdd:cd04406   172 DI 173
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
1125-1290 7.92e-17

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


Pssm-ID: 239873  Cd Length: 200  Bit Score: 80.63  E-value: 7.92e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1125 DVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLraGKHQLEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:cd04408    15 EVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDL--SGHSPHDITSVLKHFLKELPEPVLPFQLY 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1205 PYWVS-----ALDTQDEKERTSKYRAFIRS-------LPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFS----- 1267
Cdd:cd04408    93 DDFIAlakelQRDSEKAAESPSIVENIIRSlkellgrLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIVFGptllr 172
                         170       180       190
                  ....*....|....*....|....*....|..
gi 568933964 1268 ---------SCLFQTKGQTseevNVIEDLINN 1290
Cdd:cd04408   173 plvggdvsmICLLDTGYQA----QLVEFLISN 200
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1113-1295 1.06e-16

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


Pssm-ID: 239851  Cd Length: 203  Bit Score: 80.19  E-value: 1.06e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1113 GNALQDQ-QLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFkkDARSVKLRAgKHQLED---VTGVLK 1188
Cdd:cd04386     6 GTPLEEHlKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAAL--DAGTFSLPL-DEFYSDphaVASALK 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1189 SFLSDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSS 1268
Cdd:cd04386    83 SYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAP 162
                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 568933964 1269 CLFQTK----------GQTSEEVNVIEDLINNYVEIF 1295
Cdd:cd04386   163 NLLWAKnegslaemaaGTSVHVVAIVELIISHADWFF 199
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1125-1274 4.12e-16

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


Pssm-ID: 239849 [Multi-domain]  Cd Length: 195  Bit Score: 78.31  E-value: 4.12e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1125 DVPIIVNSCIAFVTQYGLgCKYIYQKDGDPLHISELLESFKKDAR-SVKLRAGKHQLEDVTGVLKSFLSDIDDALLTKEL 1203
Cdd:cd04384    17 DVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIpDLTKDVYIQDIHSVSSLCKLYFRELPNPLLTYQL 95
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568933964 1204 YPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTK 1274
Cdd:cd04384    96 YEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRSK 166
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
695-799 4.66e-16

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: 76.17  E-value: 4.66e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsIWSNELIeLFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08849    15 NDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDV-LGTSELL-LAKNIGNAGFNEIMEACLPAEDV 92
                          90       100
                  ....*....|....*....|....*..
gi 568933964  775 LQVD--SPVEKRKNFITQKYKEGKFRK 799
Cdd:cd08849    93 VKPNpgSDMNARKDYITAKYIERRYAR 119
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
694-763 6.83e-16

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: 75.19  E-value: 6.83e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLgPKDSKVRSLKMDasIWSNELIELFIVIGNKRAND 763
Cdd:cd08844    16 GNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNL-PDISRVKSIRLD--FWEDELVEFMKENGNLKAKA 82
ArfGap_ADAP1 cd08843
ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
695-761 7.24e-16

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: 75.04  E-value: 7.24e-16
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568933964  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLgPKDSKVRSLKMDAsiWSNELIELFIVIGNKRA 761
Cdd:cd08843    17 NARCADCGAPDPDWASYTLGVFICLSCSGIHRNI-PQVSKVKSVRLDA--WEEAQVEFMASHGNDAA 80
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1126-1300 1.02e-15

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


Pssm-ID: 239841  Cd Length: 206  Bit Score: 77.48  E-value: 1.02e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKdARSVKLRAgKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04376     9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDR-GIDVVLDE-NHSVHDVAALLKEFFRDMPDPLLPRELYT 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1206 YWVSALdTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINH-----------MNAHNLAMVFSSCLFQ-T 1273
Cdd:cd04376    87 AFIGTA-LLEPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADSIdedgqevsgnkMTSLNLATIFGPNLLHkQ 165
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 568933964 1274 KGQTSEE-------------VNVIEDLINNYVEIFEVKED 1300
Cdd:cd04376   166 KSGEREFvqaslrieestaiINVVQTMIDNYEELFMVSPE 205
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1126-1290 1.74e-15

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


Pssm-ID: 239843  Cd Length: 203  Bit Score: 76.69  E-value: 1.74e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLraGKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04378    16 VPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVEL--SELSPHDISSVLKLFLRQLPEPLILFRLYN 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1206 YWVS------ALDTQDEKERTS--------KYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFS---- 1267
Cdd:cd04378    94 DFIAlakeiqRDTEEDKAPNTPievnriirKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIVFGptli 173
                         170       180       190
                  ....*....|....*....|....*....|....
gi 568933964 1268 -----------SCLFQTKGQTseevNVIEDLINN 1290
Cdd:cd04378   174 rprpgdadvslSSLVDYGYQA----RLVEFLITN 203
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1116-1271 4.72e-15

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


Pssm-ID: 239858  Cd Length: 189  Bit Score: 75.19  E-value: 4.72e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1116 LQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDplhiSELLESFKKdarsvKLRAGKHQ-------LEDVTGVLK 1188
Cdd:cd04393    10 LQQAGQPENGVPAVVRHIVEYLEQHGLEQEGLFRVNGN----AETVEWLRQ-----RLDSGEEVdlskeadVCSAASLLR 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1189 SFLSDIDDALLTKELYPYWVSAL-DTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFS 1267
Cdd:cd04393    81 LFLQELPEGLIPASLQIRLMQLYqDYNGEDEFGRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFG 160

                  ....
gi 568933964 1268 SCLF 1271
Cdd:cd04393   161 PDVF 164
ArfGap_GIT2 cd08847
GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
694-769 6.70e-15

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: 72.36  E-value: 6.70e-15
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568933964  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNL 769
Cdd:cd08847     7 SSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTS--WPPTLLQMVQTLYNNGANSIWEHSL 80
RhoGap_RalBP1 cd04381
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1125-1267 1.06e-14

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


Pssm-ID: 239846  Cd Length: 182  Bit Score: 74.01  E-value: 1.06e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1125 DVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKkdarsvklRAGKHQLED-----VTGVLKSFLSDIDDALL 1199
Cdd:cd04381    19 DLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYN--------RRESPNLEEyepptVASLLKQYLRELPEPLL 90
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568933964 1200 TKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFS 1267
Cdd:cd04381    91 TKELMPRFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVLS 158
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1125-1271 1.81e-13

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


Pssm-ID: 239844  Cd Length: 207  Bit Score: 70.96  E-value: 1.81e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1125 DVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDV-TGVLKSFLSDIDDALLTKEL 1203
Cdd:cd04379    17 DVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINViTGVLKDYLRELPEPLITPQL 96
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568933964 1204 YPYWVSAL--DTQDEKERTSKY-RAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF 1271
Cdd:cd04379    97 YEMVLEALavALPNDVQTNTHLtLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAVCFGPVLM 167
ArfGap_GIT1 cd08846
GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
698-792 3.28e-13

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: 67.43  E-value: 3.28e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  698 CADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMdaSIWSNELIELFIVIGNKRANDFWAGNLQKDEELQV 777
Cdd:cd08846    11 CADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRH--SAWPPTLLQMVHTLASNGANSIWEHSLLDPAQVQS 88
                          90       100
                  ....*....|....*....|...
gi 568933964  778 D----SPVEK----RKNFITQKY 792
Cdd:cd08846    89 GrrkaNPQDKvhptKSEFIRAKY 111
RhoGAP_fLRG1 cd04397
RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1126-1300 3.71e-13

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


Pssm-ID: 239862  Cd Length: 213  Bit Score: 70.09  E-value: 3.71e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEdVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04397    27 IPALIDDIISAMRQMDMSVEGVFRKNGNIRRLKELTEEIDKNPTEVPDLSKENPVQ-LAALLKKFLRELPDPLLTFKLYR 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1206 YWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEI-----NHMNAHNLAMVFSSCLFQTKGQTSEE 1280
Cdd:cd04397   106 LWISSQKIEDEEERKRVLHLVYCLLPKYHRDTMEVLFSFLKWVSSFSHIdeetgSKMDIHNLATVITPNILYSKTDNPNT 185
                         170       180
                  ....*....|....*....|....*..
gi 568933964 1281 VN-------VIEDLINNYVEIFEVKED 1300
Cdd:cd04397   186 GDeyflaieAVNYLIENNEEFCEVPDE 212
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
483-567 4.30e-13

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


Pssm-ID: 275388  Cd Length: 92  Bit Score: 66.41  E-value: 4.30e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  483 KCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREM--YSKGIIPLTAISTVRAQGD----NKFEIVTT-QRTFVFRVE 555
Cdd:cd00821     1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSsyKPKGSIPLSGILEVEEVSPkerpHCFELVTPdGRTYYLQAD 80
                          90
                  ....*....|..
gi 568933964  556 KEEERNDWISIL 567
Cdd:cd00821    81 SEEERQEWLKAL 92
ArfGap_AGFG cd08838
ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ...
693-797 9.58e-13

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: 66.06  E-value: 9.58e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  693 ESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGpkdSKVRSLKMdaSIWSNELIELFIVIGNKRANDFWAGNL-QK 771
Cdd:cd08838    11 PENKRCFDCGQRGPTYVNLTFGTFVCTTCSGIHREFN---HRVKSISM--STFTPEEVEFLQAGGNEVARKIWLAKWdPR 85
                          90       100
                  ....*....|....*....|....*.
gi 568933964  772 DEELQVDSPVEKRKNFITQKYKEGKF 797
Cdd:cd08838    86 TDPEPDSGDDQKIREFIRLKYVDKRW 111
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
483-572 1.84e-12

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 64.88  E-value: 1.84e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964    483 KCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYS---KGIIPLTAIS------TVRAQGDNKFEIVTTQR-TFVF 552
Cdd:smart00233    3 KEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTvreapdPDSSKKPHCFEIKTSDRkTLLL 82
                            90       100
                    ....*....|....*....|
gi 568933964    553 RVEKEEERNDWISILLSALK 572
Cdd:smart00233   83 QAESEEEREKWVEALRKAIA 102
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1113-1270 2.20e-12

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


Pssm-ID: 239848  Cd Length: 188  Bit Score: 67.45  E-value: 2.20e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1113 GNALQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDVTGVLKSFLS 1192
Cdd:cd04383     5 GSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLKLYFR 84
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568933964 1193 DIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCL 1270
Cdd:cd04383    85 GLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTL 162
ArfGap_ArfGap2 cd09029
Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
694-765 4.90e-12

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: 64.31  E-value: 4.90e-12
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568933964  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASiWSNELIELFIVIGNKRANDFW 765
Cdd:cd09029    18 TNKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHLSFIRSTELDSN-WNWFQLRCMQVGGNANATAFF 88
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
1125-1296 6.26e-12

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


Pssm-ID: 239865  Cd Length: 190  Bit Score: 66.23  E-value: 6.26e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1125 DVPIIVNSCIafvtQYGLGCKYIYQK-----DGDPLHISELLESFKKDARSVKLRAG-KHQLEDVTGVLKSFLSDIDDAL 1198
Cdd:cd04400    21 DLPSVVYRCI----EYLDKNRAIYEEgifrlSGSASVIKQLKERFNTEYDVDLFSSSlYPDVHTVAGLLKLYLRELPTLI 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1199 LTKELYPYWVSALDTQ-DEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLfqtkgQT 1277
Cdd:cd04400    97 LGGELHNDFKRLVEENhDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRNVCIVFSPTL-----NI 171
                         170
                  ....*....|....*....
gi 568933964 1278 SEEVNVIedLINNYVEIFE 1296
Cdd:cd04400   172 PAGIFVL--FLTDFDCIFG 188
PH pfam00169
PH domain; PH stands for pleckstrin homology.
482-572 8.92e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117  Cd Length: 105  Bit Score: 62.96  E-value: 8.92e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   482 EKCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYS---KGIIPLTAISTVRA------QGDNKFEIVTTQ----R 548
Cdd:pfam00169    2 VKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSKKSkepKGSISLSGCEVVEVvasdspKRKFCFELRTGErtgkR 81
                           90       100
                   ....*....|....*....|....
gi 568933964   549 TFVFRVEKEEERNDWISILLSALK 572
Cdd:pfam00169   82 TYLLQAESEEERKDWIKAIQSAIR 105
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1182-1282 1.05e-11

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


Pssm-ID: 239856  Cd Length: 216  Bit Score: 66.22  E-value: 1.05e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1182 DVTGVLKSFLSDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHN 1261
Cdd:cd04391    78 DAASLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWN 157
                          90       100
                  ....*....|....*....|.
gi 568933964 1262 LAMVFSSCLFQTKGQTSEEVN 1282
Cdd:cd04391   158 VAMIMAPNLFPPRGKHSKDNE 178
ArfGap_ArfGap3 cd09028
Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
694-765 2.45e-11

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


Pssm-ID: 350085 [Multi-domain]  Cd Length: 120  Bit Score: 62.39  E-value: 2.45e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568933964  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASiWSNELIELFIVIGNKRANDFW 765
Cdd:cd09028    18 TNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIRSTELDSN-WSWFQLRCMQVGGNANASAFF 88
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
677-765 6.09e-11

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661  Cd Length: 395  Bit Score: 66.42  E-value: 6.09e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  677 AETLSD-YEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIV 755
Cdd:PLN03114    3 SENLNDkISVFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDS--WSSEQLKMMIY 80
                          90
                  ....*....|
gi 568933964  756 IGNKRANDFW 765
Cdd:PLN03114   81 GGNNRAQVFF 90
RhoGAP_Graf cd04374
RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase ...
1129-1290 1.51e-10

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


Pssm-ID: 239839  Cd Length: 203  Bit Score: 62.41  E-value: 1.51e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1129 IVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESF----KKDARSVKLRAGKHQLEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:cd04374    31 FVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGldpkTSTPGDVDLDNSEWEIKTITSALKTYLRNLPEPLMTYELH 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1205 PYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSEEV--- 1281
Cdd:cd04374   111 NDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEETVAAImdi 190
                         170
                  ....*....|...
gi 568933964 1282 ---N-VIEDLINN 1290
Cdd:cd04374   191 kfqNiVVEILIEN 203
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
483-572 2.03e-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: 58.85  E-value: 2.03e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  483 KCGWLDKLSPQGKRmFQKRWVKFDGLSISYYNNDREMYSK--GIIPL-TAISTVRAQGDNKFEIVTTQRTFVFRVEKEEE 559
Cdd:cd13282     1 KAGYLTKLGGKVKT-WKRRWFVLKNGELFYYKSPNDVIRKpqGQIALdGSCEIARAEGAQTFEIVTEKRTYYLTADSEND 79
                          90
                  ....*....|...
gi 568933964  560 RNDWISILLSALK 572
Cdd:cd13282    80 LDEWIRVIQNVLR 92
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1164-1294 4.31e-10

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239859  Cd Length: 202  Bit Score: 60.95  E-value: 4.31e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1164 FKKDARSVKLRAGKHQLE------------DVTGVLKSFLSDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLP 1231
Cdd:cd04394    41 FRKSGSVVRQKELKAKLEggeaclssalpcDVAGLLKQFFRELPEPLLPYDLHEALLKAQELPTDEERKSATLLLTCLLP 120
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568933964 1232 GVNRATLAALIEHLYRV-QKCSEiNHMNAHNLAMVFSSCLFQTKG-----------QTSEEVNVIEDLINNYVEI 1294
Cdd:cd04394   121 DEHVNTLRYFFSFLYDVaQRCSE-NKMDSSNLAVIFAPNLFQSEEggekmssstekRLRLQAAVVQTLIDNASNI 194
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
483-573 7.21e-10

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


Pssm-ID: 241282  Cd Length: 105  Bit Score: 57.60  E-value: 7.21e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  483 KCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYSKGIIPL-----------TAISTVRAQGDNKFEIVTTQRTFV 551
Cdd:cd01251     4 KEGYLEKTGPKQTDGFRKRWFTLDDRRLMYFKDPLDAFPKGEIFIgskeegysvreGLPPGIKGHWGFGFTLVTPDRTFL 83
                          90       100
                  ....*....|....*....|..
gi 568933964  552 FRVEKEEERNDWISILLSALKS 573
Cdd:cd01251    84 LSAETEEERREWITAIQKVLER 105
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
483-567 1.01e-09

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: 57.42  E-value: 1.01e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  483 KCGWLDKLSPQGKRmFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRA----QGDNKFEIVTTQRTFVFRVEKEE 558
Cdd:cd13255     8 KAGYLEKKGERRKT-WKKRWFVLRPTKLAYYKNDKEYRLLRLIDLTDIHTCTEvqlkKHDNTFGIVTPARTFYVQADSKA 86

                  ....*....
gi 568933964  559 ERNDWISIL 567
Cdd:cd13255    87 EMESWISAI 95
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
1430-1526 1.17e-09

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 57.17  E-value: 1.17e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964   1430 IKEGILKLKEEPSKilsgNKFQDRCVVLRDGHLFIYKDPK---SSKHDKMFPLRAMKFYLGVKKKMKpPTSWGLTV-YSE 1505
Cdd:smart00233    2 IKEGWLYKKSGGGK----KSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSS-KKPHCFEIkTSD 76
                            90       100
                    ....*....|....*....|.
gi 568933964   1506 KHHWHLCCDSLQAQMEWMASI 1526
Cdd:smart00233   77 RKTLLLQAESEEEREKWVEAL 97
RhoGAP_ARHGAP19 cd04392
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1107-1301 1.18e-09

RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP19-like proteins. The function of ArhGAP19 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239857  Cd Length: 208  Bit Score: 59.78  E-value: 1.18e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1107 KAAGTDGNALQDQQLckndvpiivnscIAFVTQyGLGCKYIYQKDGDPLHISELLESFKKDArSVKLRAGKHQLEDVTGV 1186
Cdd:cd04392     2 GAPLTEEGIAQIYQL------------IEYLEK-NLRVEGLFRKPGNSARQQELRDLLNSGT-DLDLESGGFHAHDCATV 67
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1187 LKSFLSDIDDALLTKELYPYW--VSALDTQDEKERTSKYRAFIRS----------LPGVNRATLAALIEHLYRVQKCSEI 1254
Cdd:cd04392    68 LKGFLGELPEPLLTHAHYPAHlqIADLCQFDEKGNKTSAPDKERLlealqlllllLPEENRNLLKLILDLLYQTAKHEDK 147
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 568933964 1255 NHMNAHNLAMVFSSCLFQTKGQTSEEVNVIEDLINNYVEiFEVKEDQ 1301
Cdd:cd04392   148 NKMSADNLALLFTPHLICPRNLTPEDLHENAQKLNSIVT-FMIKHSQ 193
RhoGAP_PARG1 cd04409
RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1126-1283 1.75e-09

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


Pssm-ID: 239874  Cd Length: 211  Bit Score: 59.44  E-value: 1.75e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKL-RAGKHqleDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:cd04409    16 IPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLVELsELSPH---DISNVLKLYLRQLPEPLILFRLY 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1205 PYWV-------SALDTQDEKERTS---------------KYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNL 1262
Cdd:cd04409    93 NEFIglakesqHVNETQEAKKNSDkkwpnmctelnrillKSKDLLRQLPAPNYNTLQFLIVHLHRVSEQAEENKMSASNL 172
                         170       180
                  ....*....|....*....|.
gi 568933964 1263 AMVFSSCLFQTKgQTSEEVNV 1283
Cdd:cd04409   173 GIIFGPTLIRPR-PTDATVSL 192
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
483-567 2.79e-09

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: 56.09  E-value: 2.79e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  483 KCGWLDKLSpQGKRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTV----RAQGDNKFEIVTTQRTFVFRVEKEE 558
Cdd:cd13298     8 KSGYLLKRS-RKTKNWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSELLAVaplkDKKRKNVFGIYTPSKNLHFRATSEK 86

                  ....*....
gi 568933964  559 ERNDWISIL 567
Cdd:cd13298    87 DANEWVEAL 95
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
586-677 5.81e-09

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 54.86  E-value: 5.81e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964    586 PEKCGYLELRGYKA-----KIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRA----VKQSFEIITPYR-SF 655
Cdd:smart00233    1 VIKEGWLYKKSGGGkkswkKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPdsskKPHCFEIKTSDRkTL 80
                            90       100
                    ....*....|....*....|..
gi 568933964    656 SFTADSEREKQEWIEAVQQSIA 677
Cdd:smart00233   81 LLQAESEEEREKWVEALRKAIA 102
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
919-996 5.93e-09

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 54.86  E-value: 5.93e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964    919 KKWCVLEGGFLSYYEND---RCTTPNGTINISEVICLAVHKEDfylNTGPIFVFEIYLPSERVFLFGAETSQIQRKWTET 995
Cdd:smart00233   20 KRYFVLFNSTLLYYKSKkdkKSYKPKGSIDLSGCTVREAPDPD---SSKKPHCFEIKTSDRKTLLLQAESEEEREKWVEA 96

                    .
gi 568933964    996 I 996
Cdd:smart00233   97 L 97
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
10-67 9.64e-09

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


Pssm-ID: 395427  Cd Length: 64  Bit Score: 53.04  E-value: 9.64e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 568933964    10 DIRDFLMSINLEQYLLHFREfGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:pfam00536    7 DVGEWLESIGLGQYIDSFRA-GYIDGDTLLLLTEDDLLKLGVTLLGHRKKILYSIQGL 63
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
10-67 8.20e-08

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


Pssm-ID: 197735  Cd Length: 68  Bit Score: 50.76  E-value: 8.20e-08
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 568933964     10 DIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:smart00454    8 SVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKL 65
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
919-996 1.01e-07

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


Pssm-ID: 275388  Cd Length: 92  Bit Score: 51.00  E-value: 1.01e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  919 KKWCVLEGGFLSYY--ENDRCTTPNGTINISEVICLAVHKEDFYLNtgpifVFEIYLPSERVFLFGAETSQIQRKWTETI 996
Cdd:cd00821    18 KRWFVLFEGVLLYYksKKDSSYKPKGSIPLSGILEVEEVSPKERPH-----CFELVTPDGRTYYLQADSEEERQEWLKAL 92
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
483-575 1.59e-07

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: 51.16  E-value: 1.59e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  483 KCGWLDKlspQGK--RMFQKRW-VKFDGLSISYYNNDREMYSK--GIIPLTAISTVRAQGD-----NKFEIVTTQRTFVF 552
Cdd:cd13276     1 KAGWLEK---QGEfiKTWRRRWfVLKQGKLFWFKEPDVTPYSKprGVIDLSKCLTVKSAEDatnkeNAFELSTPEETFYF 77
                          90       100
                  ....*....|....*....|...
gi 568933964  553 RVEKEEERNDWISILLSALKSPS 575
Cdd:cd13276    78 IADNEKEKEEWIGAIGRAIVKHS 100
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
469-567 1.95e-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: 51.08  E-value: 1.95e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964  469 SPYACFYGSSAAKE----KCGWLDKLSpQGKRMFQKRWVKFDGLSISYYNNDREMY-SKGIIPL---TAISTVRAQGDN- 539
Cdd:cd13215     5 SKHLCFFAYLPKRSgaviKSGYLSKRS-KRTLRYTRYWFVLKGDTLSWYNSSTDLYfPAGTIDLryaTSIELSKSNGEAt 83
                          90       100
                  ....*....|....*....|....*....
gi 568933964  540 -KFEIVTTQRTFVFRVEKEEERNDWISIL 567
Cdd:cd13215    84 tSFKIVTNSRTYKFKADSETSADEWVKAL 112
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
1126-1274 2.01e-07

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239855 [Multi-domain]  Cd Length: 199  Bit Score: 53.22  E-value: 2.01e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFkkDARSVKLRAGKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04390    22 VPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAF--DAGERPSFDSDTDVHTVASLLKLYLRELPEPVIPWAQYE 99
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568933964 1206 YWVSA--LDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTK 1274
Cdd:cd04390   100 DFLSCaqLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILRPK 170
RhoGAP_fSAC7_BAG7 cd04396
RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1126-1295 2.60e-07

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


Pssm-ID: 239861  Cd Length: 225  Bit Score: 53.18  E-value: 2.60e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933964 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDAR-SVKLRAGKHQLEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:cd04396    32 IPVVVAKC