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Conserved domains on  [gi|398303812|ref|NP_001257626|]
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rho GTPase-activating protein 12 isoform 4 [Homo sapiens]

Protein Classification

ARHGAP family PH domain-containing protein( domain architecture ID 10879141)

ARHGAP family PH (pleckstrin homology) domain-containing protein similar to PH region of Rho/Rac/Cdc42-like GTPase activating proteins, ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
607-792 1.33e-136

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: 401.77  E-value: 1.33e-136
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 686
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 687 FRELPEPLFTFNHFNDFVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTL 765
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160
                        170       180
                 ....*....|....*....|....*..
gi 398303812 766 LKPEKETGNIAVHTVYQNQIVELILLE 792
Cdd:cd04403  161 LRPEQETGNIAVHMVYQNQIVELILLE 187
SH3-WW_linker pfam16618
Linker region between SH3 and WW domains on ARHGAP12; SH3-WW_linker is a natively unstructured ...
71-266 5.91e-100

Linker region between SH3 and WW domains on ARHGAP12; SH3-WW_linker is a natively unstructured region on Rho-GTPase activating factor 12 proteins that lies between the SH3 and the WW domains. it is found in higher eukaryotes, and the function is not known.


:

Pssm-ID: 435468  Cd Length: 197  Bit Score: 307.59  E-value: 5.91e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812   71 EVtRKALMPPVKQVAgLPNNSTKIMQSLHLQRSTENVNKLPELSSFGKPSSSVQG--------TGLIRDANQNFGPSYNQ 142
Cdd:pfam16618   1 EV-RKALMPPPKPIA-HPNSPPKVLDIGPLQRSTENLNKPPELSSFGRPSPSQTTspsshftpPALRRDANQNLGSPTDH 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812  143 GQTVNLSLDLTHNNGKFNNDSHSPKVSSQNRTRSFGHFPGPEFLDVEKTsfsqeQSCDSAGEGSERIHQDSESGDELSSS 222
Cdd:pfam16618  79 EQSLAELLLLTNNNGKFHHGSHSTLPRSRARSPSLGKFPGPEFLDVDKT-----EQCDSAGEGSEKLRNDSESGDELSSS 153
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 398303812  223 STEQIRATTPPNQGRPDSPVYANLQELKISQSALPPLPGSPAIQ 266
Cdd:pfam16618 154 STEHLQPTSPSGQGRSDSPVYTNLQELKISQSSLPPLPSGSPLH 197
PH_ARHGAP9-like cd13233
Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like ...
418-529 2.69e-51

Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. 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: 270053  Cd Length: 110  Bit Score: 174.39  E-value: 2.69e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 418 EKYGLLNVTKIAENGKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSWFGsNQSKPEFTVDLKGATIEMAsKDKSSKKNVFE 497
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGN-PYSKPESSVDLRGASIEWA-KEKSSRKNVFQ 78
                         90       100       110
                 ....*....|....*....|....*....|..
gi 398303812 498 LKTRQGTELLIQSDNDTVINDWFKVLSSTINN 529
Cdd:cd13233   79 ISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110
SH3_ARHGAP12 cd12070
Src Homology 3 domain of Rho GTPase-activating protein 12; Rho GTPase-activating proteins ...
15-74 9.92e-38

Src Homology 3 domain of Rho GTPase-activating protein 12; Rho GTPase-activating proteins (RhoGAPs or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP12 has been shown to display GAP activity towards Rac1. It plays a role in regulating hepatocyte growth factor (HGF)-driven cell growth and invasiveness. It contains SH3, WW, Pleckstin homology (PH), and RhoGAP domains. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


:

Pssm-ID: 213003  Cd Length: 60  Bit Score: 134.72  E-value: 9.92e-38
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812  15 VYIEVEYDYEYEAKDRKIVIKQGERYILVKKTNDDWWQVKPDENSKAFYVPAQYVKEVTR 74
Cdd:cd12070    1 TYIEVEYDYDYEAKDRKIVIKQGERYILVKKTNDDWWQVKKDENSKPFYVPAQYVKEVTR 60
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
268-298 1.55e-07

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


:

Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 47.91  E-value: 1.55e-07
                         10        20        30
                 ....*....|....*....|....*....|.
gi 398303812 268 NGEWETHKDSSGRCYYYNRGTQERTWKPPRW 298
Cdd:cd00201    1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
PRP40 super family cl34905
Splicing factor [RNA processing and modification];
259-365 1.98e-06

Splicing factor [RNA processing and modification];


The actual alignment was detected with superfamily member COG5104:

Pssm-ID: 227435 [Multi-domain]  Cd Length: 590  Bit Score: 51.23  E-value: 1.98e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 259 LPGSPAIQINGEWETHKDSSGRCYYYNRGTQERTWKPPRwtrdaSISKGDFQNPGDQEWLKHVDDQGRQYYYSADGSRSE 338
Cdd:COG5104    5 LLGMASGEARSEWEELKAPDGRIYYYNKRTGKSSWEKPK-----ELLKGSEEDLDVDPWKECRTADGKVYYYNSITRESR 79
                         90       100       110
                 ....*....|....*....|....*....|....
gi 398303812 339 WELP----KYNASSQQQ---REIIKSRSLDRRLQ 365
Cdd:COG5104   80 WKIPperkKVEPIAEQKhdeRSMIGGNGNDMAIT 113
 
Name Accession Description Interval E-value
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
607-792 1.33e-136

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: 401.77  E-value: 1.33e-136
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 686
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 687 FRELPEPLFTFNHFNDFVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTL 765
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160
                        170       180
                 ....*....|....*....|....*..
gi 398303812 766 LKPEKETGNIAVHTVYQNQIVELILLE 792
Cdd:cd04403  161 LRPEQETGNIAVHMVYQNQIVELILLE 187
SH3-WW_linker pfam16618
Linker region between SH3 and WW domains on ARHGAP12; SH3-WW_linker is a natively unstructured ...
71-266 5.91e-100

Linker region between SH3 and WW domains on ARHGAP12; SH3-WW_linker is a natively unstructured region on Rho-GTPase activating factor 12 proteins that lies between the SH3 and the WW domains. it is found in higher eukaryotes, and the function is not known.


Pssm-ID: 435468  Cd Length: 197  Bit Score: 307.59  E-value: 5.91e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812   71 EVtRKALMPPVKQVAgLPNNSTKIMQSLHLQRSTENVNKLPELSSFGKPSSSVQG--------TGLIRDANQNFGPSYNQ 142
Cdd:pfam16618   1 EV-RKALMPPPKPIA-HPNSPPKVLDIGPLQRSTENLNKPPELSSFGRPSPSQTTspsshftpPALRRDANQNLGSPTDH 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812  143 GQTVNLSLDLTHNNGKFNNDSHSPKVSSQNRTRSFGHFPGPEFLDVEKTsfsqeQSCDSAGEGSERIHQDSESGDELSSS 222
Cdd:pfam16618  79 EQSLAELLLLTNNNGKFHHGSHSTLPRSRARSPSLGKFPGPEFLDVDKT-----EQCDSAGEGSEKLRNDSESGDELSSS 153
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 398303812  223 STEQIRATTPPNQGRPDSPVYANLQELKISQSALPPLPGSPAIQ 266
Cdd:pfam16618 154 STEHLQPTSPSGQGRSDSPVYTNLQELKISQSSLPPLPSGSPLH 197
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
620-790 8.19e-59

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: 197.49  E-value: 8.19e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812   620 GTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWeDIHVITGALKMFFRELPEPLFTFNH 699
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812   700 FNDFVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTLLKPEKETGNIAVH 778
Cdd:smart00324  80 YEEFIEAAKlEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159
                          170
                   ....*....|..
gi 398303812   779 TVYQNQIVELIL 790
Cdd:smart00324 160 IRHQNTVIEFLI 171
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
623-768 2.48e-56

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 189.68  E-value: 2.48e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812  623 PKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDsKWEDIHVITGALKMFFRELPEPLFTFNHFND 702
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDL-EEEDVHVVASLLKLFLRELPEPLLTFELYEE 79
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 398303812  703 FVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTLLKP 768
Cdd:pfam00620  80 FIEAAKlPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRP 146
PH_ARHGAP9-like cd13233
Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like ...
418-529 2.69e-51

Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. 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: 270053  Cd Length: 110  Bit Score: 174.39  E-value: 2.69e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 418 EKYGLLNVTKIAENGKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSWFGsNQSKPEFTVDLKGATIEMAsKDKSSKKNVFE 497
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGN-PYSKPESSVDLRGASIEWA-KEKSSRKNVFQ 78
                         90       100       110
                 ....*....|....*....|....*....|..
gi 398303812 498 LKTRQGTELLIQSDNDTVINDWFKVLSSTINN 529
Cdd:cd13233   79 ISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110
SH3_ARHGAP12 cd12070
Src Homology 3 domain of Rho GTPase-activating protein 12; Rho GTPase-activating proteins ...
15-74 9.92e-38

Src Homology 3 domain of Rho GTPase-activating protein 12; Rho GTPase-activating proteins (RhoGAPs or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP12 has been shown to display GAP activity towards Rac1. It plays a role in regulating hepatocyte growth factor (HGF)-driven cell growth and invasiveness. It contains SH3, WW, Pleckstin homology (PH), and RhoGAP domains. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 213003  Cd Length: 60  Bit Score: 134.72  E-value: 9.92e-38
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812  15 VYIEVEYDYEYEAKDRKIVIKQGERYILVKKTNDDWWQVKPDENSKAFYVPAQYVKEVTR 74
Cdd:cd12070    1 TYIEVEYDYDYEAKDRKIVIKQGERYILVKKTNDDWWQVKKDENSKPFYVPAQYVKEVTR 60
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
432-528 6.55e-11

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 59.87  E-value: 6.55e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812   432 GKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSwfgsnqSKPEFTVDLKGATIEMA-SKDKSSKKNVFELKTRQGTELLIQS 510
Cdd:smart00233  11 SGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS------YKPKGSIDLSGCTVREApDPDSSKKPHCFEIKTSDRKTLLLQA 84
                           90
                   ....*....|....*...
gi 398303812   511 DNDTVINDWFKVLSSTIN 528
Cdd:smart00233  85 ESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
432-527 1.38e-08

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 53.34  E-value: 1.38e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812  432 GKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSwfgsnqSKPEFTVDLKGATI-EMASKDKSSKKNVFELKT---RQGTELL 507
Cdd:pfam00169  11 GGGKKKSWKKRYFVLFDGSLLYYKDDKSGKS------KEPKGSISLSGCEVvEVVASDSPKRKFCFELRTgerTGKRTYL 84
                          90       100
                  ....*....|....*....|
gi 398303812  508 IQSDNDTVINDWFKVLSSTI 527
Cdd:pfam00169  85 LQAESEEERKDWIKAIQSAI 104
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
268-298 1.55e-07

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 47.91  E-value: 1.55e-07
                         10        20        30
                 ....*....|....*....|....*....|.
gi 398303812 268 NGEWETHKDSSGRCYYYNRGTQERTWKPPRW 298
Cdd:cd00201    1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
SH3_9 pfam14604
Variant SH3 domain;
19-70 6.72e-07

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 46.46  E-value: 6.72e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 398303812   19 VEYDYEYEAKDrKIVIKQGERYILVKKTNDDWWQVKpdENSKAFYVPAQYVK 70
Cdd:pfam14604   1 ALYPYEPKDDD-ELSLQRGDVITVIEESEDGWWEGI--NTGRTGLVPANYVE 49
PRP40 COG5104
Splicing factor [RNA processing and modification];
259-365 1.98e-06

Splicing factor [RNA processing and modification];


Pssm-ID: 227435 [Multi-domain]  Cd Length: 590  Bit Score: 51.23  E-value: 1.98e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 259 LPGSPAIQINGEWETHKDSSGRCYYYNRGTQERTWKPPRwtrdaSISKGDFQNPGDQEWLKHVDDQGRQYYYSADGSRSE 338
Cdd:COG5104    5 LLGMASGEARSEWEELKAPDGRIYYYNKRTGKSSWEKPK-----ELLKGSEEDLDVDPWKECRTADGKVYYYNSITRESR 79
                         90       100       110
                 ....*....|....*....|....*....|....
gi 398303812 339 WELP----KYNASSQQQ---REIIKSRSLDRRLQ 365
Cdd:COG5104   80 WKIPperkKVEPIAEQKhdeRSMIGGNGNDMAIT 113
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
271-296 2.31e-06

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 44.42  E-value: 2.31e-06
                          10        20
                  ....*....|....*....|....*.
gi 398303812  271 WETHKDSSGRCYYYNRGTQERTWKPP 296
Cdd:pfam00397   5 WEERWDPDGRVYYYNHETGETQWEKP 30
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
271-298 6.03e-05

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 40.66  E-value: 6.03e-05
                           10        20
                   ....*....|....*....|....*...
gi 398303812   271 WETHKDSSGRCYYYNRGTQERTWKPPRW 298
Cdd:smart00456   6 WEERKDPDGRPYYYNHETKETQWEKPRE 33
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
13-70 8.97e-05

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 40.60  E-value: 8.97e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 398303812    13 GQVYIEVEYDYEYEAKDRkIVIKQGERYILVKKTNDDWWQVKpDENSKAFYVPAQYVK 70
Cdd:smart00326   1 EGPQVRALYDYTAQDPDE-LSFKKGDIITVLEKSDDGWWKGR-LGRGKEGLFPSNYVE 56
 
Name Accession Description Interval E-value
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
607-792 1.33e-136

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: 401.77  E-value: 1.33e-136
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 686
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 687 FRELPEPLFTFNHFNDFVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTL 765
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160
                        170       180
                 ....*....|....*....|....*..
gi 398303812 766 LKPEKETGNIAVHTVYQNQIVELILLE 792
Cdd:cd04403  161 LRPEQETGNIAVHMVYQNQIVELILLE 187
SH3-WW_linker pfam16618
Linker region between SH3 and WW domains on ARHGAP12; SH3-WW_linker is a natively unstructured ...
71-266 5.91e-100

Linker region between SH3 and WW domains on ARHGAP12; SH3-WW_linker is a natively unstructured region on Rho-GTPase activating factor 12 proteins that lies between the SH3 and the WW domains. it is found in higher eukaryotes, and the function is not known.


Pssm-ID: 435468  Cd Length: 197  Bit Score: 307.59  E-value: 5.91e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812   71 EVtRKALMPPVKQVAgLPNNSTKIMQSLHLQRSTENVNKLPELSSFGKPSSSVQG--------TGLIRDANQNFGPSYNQ 142
Cdd:pfam16618   1 EV-RKALMPPPKPIA-HPNSPPKVLDIGPLQRSTENLNKPPELSSFGRPSPSQTTspsshftpPALRRDANQNLGSPTDH 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812  143 GQTVNLSLDLTHNNGKFNNDSHSPKVSSQNRTRSFGHFPGPEFLDVEKTsfsqeQSCDSAGEGSERIHQDSESGDELSSS 222
Cdd:pfam16618  79 EQSLAELLLLTNNNGKFHHGSHSTLPRSRARSPSLGKFPGPEFLDVDKT-----EQCDSAGEGSEKLRNDSESGDELSSS 153
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 398303812  223 STEQIRATTPPNQGRPDSPVYANLQELKISQSALPPLPGSPAIQ 266
Cdd:pfam16618 154 STEHLQPTSPSGQGRSDSPVYTNLQELKISQSSLPPLPSGSPLH 197
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
620-790 8.19e-59

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: 197.49  E-value: 8.19e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812   620 GTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWeDIHVITGALKMFFRELPEPLFTFNH 699
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812   700 FNDFVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTLLKPEKETGNIAVH 778
Cdd:smart00324  80 YEEFIEAAKlEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159
                          170
                   ....*....|..
gi 398303812   779 TVYQNQIVELIL 790
Cdd:smart00324 160 IRHQNTVIEFLI 171
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
623-768 2.48e-56

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 189.68  E-value: 2.48e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812  623 PKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDsKWEDIHVITGALKMFFRELPEPLFTFNHFND 702
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDL-EEEDVHVVASLLKLFLRELPEPLLTFELYEE 79
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 398303812  703 FVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTLLKP 768
Cdd:pfam00620  80 FIEAAKlPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRP 146
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
623-790 1.79e-55

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 [Multi-domain]  Cd Length: 169  Bit Score: 188.28  E-value: 1.79e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 623 PKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEklDLNDSKWEDIHVITGALKMFFRELPEPLFTFNHFND 702
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 703 FVNAIKQE-PRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTLLKPEKETGNIAVHTVY 781
Cdd:cd00159   79 FIELAKIEdEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                 ....*....
gi 398303812 782 QNQIVELIL 790
Cdd:cd00159  159 LNEIVEFLI 167
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
606-797 1.35e-52

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: 181.44  E-value: 1.35e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 606 VFGSNLAnLCQ--RENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNH-DEKLDLNDSKWEDIHVITGA 682
Cdd:cd04395    1 TFGVPLD-DCPpsSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRgGFDIDLQDPRWRDVNVVSSL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 683 LKMFFRELPEPLFTFNHFNDFVNAIKQE-PRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVF 761
Cdd:cd04395   80 LKSFFRKLPEPLFTNELYPDFIEANRIEdPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVF 159
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 398303812 762 GPTLLKPEKETGNIAV-HTVYQNQIVELILLELSSIF 797
Cdd:cd04395  160 GPTLVRTSDDNMETMVtHMPDQCKIVETLIQHYDWFF 196
PH_ARHGAP9-like cd13233
Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like ...
418-529 2.69e-51

Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. 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: 270053  Cd Length: 110  Bit Score: 174.39  E-value: 2.69e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 418 EKYGLLNVTKIAENGKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSWFGsNQSKPEFTVDLKGATIEMAsKDKSSKKNVFE 497
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGN-PYSKPESSVDLRGASIEWA-KEKSSRKNVFQ 78
                         90       100       110
                 ....*....|....*....|....*....|..
gi 398303812 498 LKTRQGTELLIQSDNDTVINDWFKVLSSTINN 529
Cdd:cd13233   79 ISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
607-797 2.11e-48

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: 169.51  E-value: 2.11e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLR--FAVNHDEKLDLNDSKWE-DIHVITGAL 683
Cdd:cd04398    1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKelFDKDPLNVLLISPEDYEsDIHSVASLL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 684 KMFFRELPEPLFTFNHFNDFVNAIKQE-PRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFG 762
Cdd:cd04398   81 KLFFRELPEPLLTKALSREFIEAAKIEdESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWG 160
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 398303812 763 PTLLKpeKETGNIAvHTVYQNQIVELILLELSSIF 797
Cdd:cd04398  161 PTLMN--AAPDNAA-DMSFQSRVIETLLDNAYQIF 192
RhoGAP_Graf cd04374
RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase ...
624-792 2.90e-43

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: 155.63  E-value: 2.90e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 624 KFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLrFAVNHDEK------LDLNDSKWEdIHVITGALKMFFRELPEPLFTF 697
Cdd:cd04374   30 KFVRKCIEAVETRGINEQGLYRVVGVNSKVQKL-LSLGLDPKtstpgdVDLDNSEWE-IKTITSALKTYLRNLPEPLMTY 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 698 NHFNDFVNAIKQE-PRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTLLKPEKETGNIA 776
Cdd:cd04374  108 ELHNDFINAAKSEnLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEETVAAI 187
                        170
                 ....*....|....*.
gi 398303812 777 VHTVYQNQIVElILLE 792
Cdd:cd04374  188 MDIKFQNIVVE-ILIE 202
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
607-797 2.57e-42

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 [Multi-domain]  Cd Length: 194  Bit Score: 152.67  E-value: 2.57e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHD-EKLDLNDSKWEDIHVITGALKM 685
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVYPDINVITGALKL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 686 FFRELPEPLFTFNHFNDFVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPT 764
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKiSNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160
                        170       180       190
                 ....*....|....*....|....*....|....
gi 398303812 765 LLKPEKETGNIAVHTV-YQNQIVELILLELSSIF 797
Cdd:cd04372  161 LMRPPEDSALTTLNDMrYQILIVQLLITNEDVLF 194
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
607-792 4.82e-42

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: 151.44  E-value: 4.82e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQrENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHD-EKLDLNDSKwedIHVITGALKM 685
Cdd:cd04377    1 FGVSLSSLTS-EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDpDSVNLEDYP---IHVITSVLKQ 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 686 FFRELPEPLFTFNHFNDFVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPT 764
Cdd:cd04377   77 WLRELPEPLMTFELYENFLRAMElEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPC 156
                        170       180       190
                 ....*....|....*....|....*....|....
gi 398303812 765 LLK------PEKETGNIAVHTvyqnQIVELILLE 792
Cdd:cd04377  157 ILRcpdtadPLQSLQDVSKTT----TCVETLIKE 186
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
607-788 2.67e-39

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: 144.30  E-value: 2.67e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 686
Cdd:cd04387    1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 687 FRELPEPLFTFNHFNDFVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTL 765
Cdd:cd04387   81 FRELPEPLFTDELYPNFAEGIAlSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160
                        170       180
                 ....*....|....*....|...
gi 398303812 766 LKPEKETGNIAVHTVYQNQIVEL 788
Cdd:cd04387  161 LRPSEKESKIPTNTMTDSWSLEV 183
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
607-790 1.22e-38

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: 142.56  E-value: 1.22e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKwedIHVITGALKM 685
Cdd:cd04378    1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFeNGKDLVELSELS---PHDISSVLKL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 686 FFRELPEPLFTFNHFNDFVNAIKQ---------------EPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKN 750
Cdd:cd04378   78 FLRQLPEPLILFRLYNDFIALAKEiqrdteedkapntpiEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEEN 157
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 398303812 751 RMTYQSIAIVFGPTLLKPEKETGNIA----VHTVYQNQIVELIL 790
Cdd:cd04378  158 KMSPNNLGIVFGPTLIRPRPGDADVSlsslVDYGYQARLVEFLI 201
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
605-797 1.92e-38

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 [Multi-domain]  Cd Length: 195  Bit Score: 141.71  E-value: 1.92e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 605 QVFGSNLANLCQR--ENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDskWEDIHVITGA 682
Cdd:cd04404    4 QQFGVSLQFLKEKnpEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQ--YEDVHLPAVI 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 683 LKMFFRELPEPLFTFNHFNDFVNAIKQEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFG 762
Cdd:cd04404   82 LKTFLRELPEPLLTFDLYDDIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFG 161
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 398303812 763 PTLLKPE------KETGNIavhtvyqNQIVELILLELSSIF 797
Cdd:cd04404  162 PNLLWAKdasmslSAINPI-------NTFTKFLLDHQDEIF 195
SH3_ARHGAP12 cd12070
Src Homology 3 domain of Rho GTPase-activating protein 12; Rho GTPase-activating proteins ...
15-74 9.92e-38

Src Homology 3 domain of Rho GTPase-activating protein 12; Rho GTPase-activating proteins (RhoGAPs or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP12 has been shown to display GAP activity towards Rac1. It plays a role in regulating hepatocyte growth factor (HGF)-driven cell growth and invasiveness. It contains SH3, WW, Pleckstin homology (PH), and RhoGAP domains. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 213003  Cd Length: 60  Bit Score: 134.72  E-value: 9.92e-38
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812  15 VYIEVEYDYEYEAKDRKIVIKQGERYILVKKTNDDWWQVKPDENSKAFYVPAQYVKEVTR 74
Cdd:cd12070    1 TYIEVEYDYDYEAKDRKIVIKQGERYILVKKTNDDWWQVKKDENSKPFYVPAQYVKEVTR 60
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
605-797 3.23e-37

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: 138.36  E-value: 3.23e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 605 QVFGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDE-KLDLnDSKWEDIHVITGAL 683
Cdd:cd04386    3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTfSLPL-DEFYSDPHAVASAL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 684 KMFFRELPEPLFTFNHFNDFVNAI-KQEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFG 762
Cdd:cd04386   82 KSYLRELPDPLLTYNLYEDWVQAAnKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLA 161
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 398303812 763 PTLLKPEKETGNI---AVHTVYQNQIVELILLELSSIF 797
Cdd:cd04386  162 PNLLWAKNEGSLAemaAGTSVHVVAIVELIISHADWFF 199
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
607-767 6.43e-35

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


Pssm-ID: 239872 [Multi-domain]  Cd Length: 186  Bit Score: 131.27  E-value: 6.43e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENgTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEkldlNDSKWED--IHVITGALK 684
Cdd:cd04407    1 FGVRVGSLTSNKT-SVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADP----ENVKLENypIHAITGLLK 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 685 MFFRELPEPLFTFNHFNDFVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGP 763
Cdd:cd04407   76 QWLRELPEPLMTFAQYNDFLRAVElPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAP 155

                 ....
gi 398303812 764 TLLK 767
Cdd:cd04407  156 CLLR 159
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
622-797 1.45e-34

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: 130.49  E-value: 1.45e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 622 VPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRfavnhdEKL-------DLNDSkweDIHVITGALKMFFRELPEPL 694
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALK------EKFlrgktvpNLSKV---DIHVICGCLKDFLRSLKEPL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 695 FTFNHFNDFVNAIKQEPRQRV-AAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEkNRMTYQSIAIVFGPTL-----LKP 768
Cdd:cd04382   88 ITFALWKEFMEAAEILDEDNSrAALYQAISELPQPNRDTLAFLILHLQRVAQSPE-CKMDINNLARVFGPTIvgysvPNP 166
                        170       180
                 ....*....|....*....|....*....
gi 398303812 769 EKETgnIAVHTVYQNQIVELiLLELSSIF 797
Cdd:cd04382  167 DPMT--ILQDTVRQPRVVER-LLEIPSDY 192
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
606-770 2.56e-34

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: 129.93  E-value: 2.56e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 606 VFGSNLANLCQRENGTVPKFVKLCIEHVEEHGLdIDGIYRVSGNLAVIQKLRFAVNHDEKLDL-NDSKWEDIHVITGALK 684
Cdd:cd04384    2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLtKDVYIQDIHSVSSLCK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 685 MFFRELPEPLFTFNHFNDFVNAIKQEP-RQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGP 763
Cdd:cd04384   81 LYFRELPNPLLTYQLYEKFSEAVSAASdEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                 ....*..
gi 398303812 764 TLLKPEK 770
Cdd:cd04384  161 NLLRSKQ 167
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
607-789 2.47e-33

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: 126.80  E-value: 2.47e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQREnGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLnDSKWEDIHVITGALKMF 686
Cdd:cd04373    1 FGVPLANVVTSE-KPIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNLDL-VSKDFTVNAVAGALKSF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 687 FRELPEPLFTFNHFNDFVNAIKQEPR-QRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTL 765
Cdd:cd04373   79 FSELPDPLIPYSMHLELVEAAKINDReQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTL 158
                        170       180
                 ....*....|....*....|....*
gi 398303812 766 LKPEKET-GNIAVHTVYQNQIVELI 789
Cdd:cd04373  159 MRPDFTSmEALSATRIYQTIIETFI 183
RhoGAP_PARG1 cd04409
RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
607-790 1.86e-31

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: 122.22  E-value: 1.86e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKWEDIhviTGALKM 685
Cdd:cd04409    1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFeNGKDLVELSELSPHDI---SNVLKL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 686 FFRELPEPLFTFNHFNDFVNAIKQ-----------------------EPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRR 742
Cdd:cd04409   78 YLRQLPEPLILFRLYNEFIGLAKEsqhvnetqeakknsdkkwpnmctELNRILLKSKDLLRQLPAPNYNTLQFLIVHLHR 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 398303812 743 VIENGEKNRMTYQSIAIVFGPTLLKPEKETGNIAVHTV----YQNQIVELIL 790
Cdd:cd04409  158 VSEQAEENKMSASNLGIIFGPTLIRPRPTDATVSLSSLvdypHQARLVELLI 209
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
606-798 2.29e-31

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


Pssm-ID: 239865 [Multi-domain]  Cd Length: 190  Bit Score: 121.31  E-value: 2.29e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 606 VFGSNLA---NLCQRENG--TVPKFVKLCIEHVEEHG-LDIDGIYRVSGNLAVIQKL--RFAVNHDEKLdLNDSKWEDIH 677
Cdd:cd04400    1 IFGSPLEeavELSSHKYNgrDLPSVVYRCIEYLDKNRaIYEEGIFRLSGSASVIKQLkeRFNTEYDVDL-FSSSLYPDVH 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 678 VITGALKMFFRELPEPLFTFNHFNDF--VNAIKQEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQ 755
Cdd:cd04400   80 TVAGLLKLYLRELPTLILGGELHNDFkrLVEENHDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLR 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 398303812 756 SIAIVFGPTLlkpeketgNIAVhtvyqnQIVELILLELSSIFG 798
Cdd:cd04400  160 NVCIVFSPTL--------NIPA------GIFVLFLTDFDCIFG 188
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
622-791 2.93e-31

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: 120.88  E-value: 2.93e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 622 VPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDE---KLDLNDskwEDIHVITGALKMFFRELPEPLFTFN 698
Cdd:cd04385   15 IPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDArsvQLREGE---YTVHDVADVLKRFLRDLPDPLLTSE 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 699 HFNDFVNA--IKQEpRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTLLKPEKETGNIA 776
Cdd:cd04385   92 LHAEWIEAaeLENK-DERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGQT 170
                        170
                 ....*....|....*
gi 398303812 777 VHTVyqNQIVELILL 791
Cdd:cd04385  171 SHEV--KVIEDLIDN 183
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
607-773 5.83e-31

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: 120.65  E-value: 5.83e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGT--VPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKL-DLNDSKWEDIHVITGAL 683
Cdd:cd04379    1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAvELSEELYPDINVITGVL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 684 KMFFRELPEPLFTFNHFNDFVNAIKQEPRQRVAAVKDLIRQ----LPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAI 759
Cdd:cd04379   81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQTNTHLTLSiidcLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160
                        170
                 ....*....|....
gi 398303812 760 VFGPTLLKPEKETG 773
Cdd:cd04379  161 CFGPVLMFCSQEFS 174
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
607-790 2.61e-29

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: 115.68  E-value: 2.61e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKWEDIhviTGALKM 685
Cdd:cd04408    1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFeNGRDLVDLSGHSPHDI---TSVLKH 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 686 FFRELPEPLFTFNHFNDFVNAIKQ-------------EPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRM 752
Cdd:cd04408   78 FLKELPEPVLPFQLYDDFIALAKElqrdsekaaespsIVENIIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKM 157
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 398303812 753 TYQSIAIVFGPTLLKPeKETGNIAV----HTVYQNQIVELIL 790
Cdd:cd04408  158 SPNNLGIVFGPTLLRP-LVGGDVSMicllDTGYQAQLVEFLI 198
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
622-770 2.88e-27

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: 109.84  E-value: 2.88e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 622 VPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLR--FAVNHDEKLDLNDSkwedIHVITGALKMFFRELPEPLFTFNH 699
Cdd:cd04376    9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLReeFDRGIDVVLDENHS----VHDVAALLKEFFRDMPDPLLPREL 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 700 FNDFVNAIKQEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEK-----------NRMTYQSIAIVFGPTLLKP 768
Cdd:cd04376   85 YTAFIGTALLEPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLHK 164

                 ..
gi 398303812 769 EK 770
Cdd:cd04376  165 QK 166
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
606-768 1.82e-26

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: 107.82  E-value: 1.82e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 606 VFGSNLANLCQR-----ENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVnhDEKLDLNDSKWEDIHV-- 678
Cdd:cd04391    1 LFGVPLSTLLERdqkkvPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQEL--EAKFYEGTFLWDQVKQhd 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 679 ITGALKMFFRELPEPLFTFNHFNDF--VNAIKQePRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQS 756
Cdd:cd04391   79 AASLLKLFIRELPQPLLTVEYLPAFysVQGLPS-KKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWN 157
                        170
                 ....*....|..
gi 398303812 757 IAIVFGPTLLKP 768
Cdd:cd04391  158 VAMIMAPNLFPP 169
SH3_ARHGAP9_like cd11888
Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; This subfamily ...
16-68 7.84e-26

Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; This subfamily is composed of Rho GTPase-activating proteins including mammalian ARHGAP9, and vertebrate ARHGAPs 12 and 27. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP9 functions as a GAP for Rac and Cdc42, but not for RhoA. It negatively regulates cell migration and adhesion. It also acts as a docking protein for the MAP kinases Erk2 and p38alpha, and may facilitate cross-talk between the Rho GTPase and MAPK pathways to control actin remodeling. ARHGAP27, also called CAMGAP1, shows GAP activity towards Rac1 and Cdc42. It binds the adaptor protein CIN85 and may play a role in clathrin-mediated endocytosis. ARHGAP12 has been shown to display GAP activity towards Rac1. It plays a role in regulating HFG-driven cell growth and invasiveness. ARHGAPs in this subfamily contain SH3, WW, Pleckstin homology (PH), and RhoGAP domains. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212821 [Multi-domain]  Cd Length: 54  Bit Score: 100.52  E-value: 7.84e-26
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 398303812  16 YIEVEYDYEYEAKD-RKIVIKQGERYILVKKTNDDWWQVKPDENSKAFYVPAQY 68
Cdd:cd11888    1 YVVVLYPFEYTGKDgRKVSIKEGERFLLLKKSNDDWWQVRRPGDSKPFYVPAQY 54
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
607-789 1.12e-24

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: 102.11  E-value: 1.12e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 686
Cdd:cd04383    3 FNGSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLKLY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 687 FRELPEPLFTFNHFNDFVNAIKQE-PRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTL 765
Cdd:cd04383   83 FRGLENPLFPKERFEDLMSCVKLEnPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTL 162
                        170       180
                 ....*....|....*....|....*
gi 398303812 766 LK-PEketGNIAVHtvYQNQIVELI 789
Cdd:cd04383  163 MPvPE---GQDQVS--CQAHVNELI 182
RhoGAP_myosin_IXA cd04406
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
607-792 1.57e-24

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: 101.62  E-value: 1.57e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENgTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHD-EKLDLNDSkweDIHVITGALKM 685
Cdd:cd04406    1 FGVELSRLTSEDR-SVPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDaNSVNLDDY---NIHVIASVFKQ 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 686 FFRELPEPLFTFNHFNDFVNAIK-QEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPT 764
Cdd:cd04406   77 WLRDLPNPLMTFELYEEFLRAMGlQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPC 156
                        170       180       190
                 ....*....|....*....|....*....|
gi 398303812 765 LLK-PEKETGNIAVHTVYQNQI-VELILLE 792
Cdd:cd04406  157 ILRcPDTTDPLQSVQDISKTTTcVELIVCE 186
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
607-798 1.65e-24

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: 101.61  E-value: 1.65e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCqrENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLndsKWEDIHVITGALKMF 686
Cdd:cd04402    2 FGQPLSNIC--EDDNLPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVEVDL---KAEPVLLLASVLKDF 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 687 FRELPEPLFTFNHFNDFVNAIKQEP-RQRVAAVKDLIRQLPKPNqdtmQILFRHLRRVI----ENGEKNRMTYQSIAIVF 761
Cdd:cd04402   77 LRNIPGSLLSSDLYEEWMSALDQENeEEKIAELQRLLDKLPRPN----VLLLKHLICVLhnisQNSETNKMDAFNLAVCI 152
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 398303812 762 GPTLL-KPEKETGNIAVhtvyQNQIVELI--LLE-LSSIFG 798
Cdd:cd04402  153 APSLLwPPASSELQNED----LKKVTSLVqfLIEnCQEIFG 189
RhoGap_RalBP1 cd04381
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
622-765 7.40e-24

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


Pssm-ID: 239846 [Multi-domain]  Cd Length: 182  Bit Score: 99.43  E-value: 7.40e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 622 VPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSkweDIHVITGALKMFFRELPEPLFTFNHFN 701
Cdd:cd04381   20 LPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESPNLEEY---EPPTVASLLKQYLRELPEPLLTKELMP 96
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 398303812 702 DFVNAI-KQEPRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTL 765
Cdd:cd04381   97 RFEEACgRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVLSPTV 161
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
606-771 1.14e-23

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: 99.44  E-value: 1.14e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 606 VFGSNLANLCQRE----NGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKlDLNDSKwEDIHVITG 681
Cdd:cd04390    2 VFGQRLEDTVAYErkfgPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGER-PSFDSD-TDVHTVAS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 682 ALKMFFRELPEPLFTFNHFNDFVNAIKQEPRQRVAAVKDLIRQ---LPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIA 758
Cdd:cd04390   80 LLKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQvsiLPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLA 159
                        170
                 ....*....|...
gi 398303812 759 IVFGPTLLKPEKE 771
Cdd:cd04390  160 TVFGPNILRPKVE 172
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
605-763 3.59e-23

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


Pssm-ID: 239858 [Multi-domain]  Cd Length: 189  Bit Score: 97.53  E-value: 3.59e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 605 QVFGSNLANLCQR---ENGtVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLndSKWEDIHVITG 681
Cdd:cd04393    1 KVFGVPLQELQQAgqpENG-VPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDL--SKEADVCSAAS 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 682 ALKMFFRELPEPLFTFNHFNDFVNAIKQEPRQRV--AAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAI 759
Cdd:cd04393   78 LLRLFLQELPEGLIPASLQIRLMQLYQDYNGEDEfgRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAA 157

                 ....
gi 398303812 760 VFGP 763
Cdd:cd04393  158 VFGP 161
SH3_ARHGAP27 cd12069
Src Homology 3 domain of Rho GTPase-activating protein 27; Rho GTPase-activating proteins ...
16-71 8.73e-21

Src Homology 3 domain of Rho GTPase-activating protein 27; Rho GTPase-activating proteins (RhoGAPs or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP27, also called CAMGAP1, shows GAP activity towards Rac1 and Cdc42. It binds the adaptor protein CIN85 and may play a role in clathrin-mediated endocytosis. It contains SH3, WW, Pleckstin homology (PH), and RhoGAP domains. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 213002  Cd Length: 57  Bit Score: 86.41  E-value: 8.73e-21
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 398303812  16 YIEVEYDYEYEAKDRKIV-IKQGERYILVKKTNDDWWQVKPDENSKAFYVPAQYVKE 71
Cdd:cd12069    1 LVLVEHAFEYTGKDGRLVsIKPNERYILLRRTNEHWWHVRRDKGTRPFYIPAKYVKE 57
RhoGAP_DLC1 cd04375
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
606-765 1.00e-19

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


Pssm-ID: 239840  Cd Length: 220  Bit Score: 88.63  E-value: 1.00e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 606 VFGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSkwEDIHVITGALKM 685
Cdd:cd04375    4 VFGVPLLVNLQRTGQPLPRSIQQAMRWLRNNALDQVGLFRKSGVKSRIQKLRSMIESSTDNVNYDG--QQAYDVADMLKQ 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 686 FFRELPEPLFTFNHFNDFVNAIKQEPR-QRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPT 764
Cdd:cd04375   82 YFRDLPEPLLTNKLSETFIAIFQYVPKeQRLEAVQCAILLLPDENREVLQTLLYFLSDVAANSQENQMTATNLAVCLAPS 161

                 .
gi 398303812 765 L 765
Cdd:cd04375  162 L 162
RhoGAP_fLRG1 cd04397
RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
607-790 2.50e-18

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: 84.34  E-value: 2.50e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQREN-----GT------VPKFVKLCIEHVEEHGLDIDGIYRVSGNlavIQKLRFAVnhdEKLDLNDSKWED 675
Cdd:cd04397    1 FGVPLEILVEKFGadstlGVgpgklrIPALIDDIISAMRQMDMSVEGVFRKNGN---IRRLKELT---EEIDKNPTEVPD 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 676 IH----VITGAL-KMFFRELPEPLFTFNHFNDFVNAIKQE-PRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRV-----I 744
Cdd:cd04397   75 LSkenpVQLAALlKKFLRELPDPLLTFKLYRLWISSQKIEdEEERKRVLHLVYCLLPKYHRDTMEVLFSFLKWVssfshI 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 398303812 745 ENGEKNRMTYQSIAIVFGPTLLKPEKETGNIAVHTVYQNQIVELIL 790
Cdd:cd04397  155 DEETGSKMDIHNLATVITPNILYSKTDNPNTGDEYFLAIEAVNYLI 200
RhoGAP_ARHGAP19 cd04392
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
635-797 1.18e-17

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: 82.12  E-value: 1.18e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 635 EHGLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEdIHVITGALKMFFRELPEPLFTFNHFNDFV---------- 704
Cdd:cd04392   21 EKNLRVEGLFRKPGNSARQQELRDLLNSGTDLDLESGGFH-AHDCATVLKGFLGELPEPLLTHAHYPAHLqiadlcqfde 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 705 ----NAIKQEPRQrVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTLLKPEKETGNiAVHTV 780
Cdd:cd04392  100 kgnkTSAPDKERL-LEALQLLLLLLPEENRNLLKLILDLLYQTAKHEDKNKMSADNLALLFTPHLICPRNLTPE-DLHEN 177
                        170
                 ....*....|....*....
gi 398303812 781 YQ--NQIVELILLELSSIF 797
Cdd:cd04392  178 AQklNSIVTFMIKHSQKLF 196
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
606-799 4.03e-17

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 [Multi-domain]  Cd Length: 202  Bit Score: 80.59  E-value: 4.03e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 606 VFGSNLANLCQR---ENGTVPKFVKLCIEHVEEHgLDIDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEdihvITGA 682
Cdd:cd04394    1 VFGVPLHSLPHStvpEYGNVPKFLVDACTFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGGEACLSSALPCD----VAGL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 683 LKMFFRELPEPLFTFNHFNDFVNAIKQEP-RQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAIVF 761
Cdd:cd04394   76 LKQFFRELPEPLLPYDLHEALLKAQELPTdEERKSATLLLTCLLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIF 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 398303812 762 GPTLL----KPEKETGNIAVHTVYQNQIVElILLELSSIFGR 799
Cdd:cd04394  156 APNLFqseeGGEKMSSSTEKRLRLQAAVVQ-TLIDNASNIGI 196
RhoGAP_fSAC7_BAG7 cd04396
RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
620-766 2.00e-13

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: 70.52  E-value: 2.00e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 620 GTVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKLR--FAVNHDEKLDLNDSKWeDIHVITGALKMFFRELPEPLFTF 697
Cdd:cd04396   30 GYIPVVVAKCGVYLKENATEVEGIFRVAGSSKRIRELQliFSTPPDYGKSFDWDGY-TVHDAASVLRRYLNNLPEPLVPL 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 698 NHFNDFVNAIKQEPR------------------QRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIENGEKNRMTYQSIAI 759
Cdd:cd04396  109 DLYEEFRNPLRKRPRilqymkgrineplntdidQAIKEYRDLITRLPNLNRQLLLYLLDLLAVFARNSDKNLMTASNLAA 188

                 ....*..
gi 398303812 760 VFGPTLL 766
Cdd:cd04396  189 IFQPGIL 195
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
641-775 2.59e-13

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) 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: 239854  Cd Length: 187  Bit Score: 68.96  E-value: 2.59e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 641 DGIYRVSGNLAVIQKLRFAVnhdEKLDLNDSKWEDIHVITGALKMFFRELPEPLFTFNHFNDFVNAIKqEPRQRVAAVKd 720
Cdd:cd04389   41 EGIFRVPGDIDEVNELKLRV---DQWDYPLSGLEDPHVPASLLKLWLRELEEPLIPDALYQQCISASE-DPDKAVEIVQ- 115
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 398303812 721 lirQLPKPNQDTMQILFRHLRRVI--ENGEKNRMTYQSIAIVFGPTLLKPEKETGNI 775
Cdd:cd04389  116 ---KLPIINRLVLCYLINFLQVFAqpENVAHTKMDVSNLAMVFAPNILRCTSDDPRV 169
SH3_ARHGAP9 cd12143
Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; Rho ...
17-68 5.85e-12

Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; Rho GTPase-activating proteins (RhoGAPs or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP9 functions as a GAP for Rac and Cdc42, but not for RhoA. It negatively regulates cell migration and adhesion. It also acts as a docking protein for the MAP kinases Erk2 and p38alpha, and may facilitate cross-talk between the Rho GTPase and MAPK pathways to control actin remodeling. It contains SH3, WW, Pleckstin homology (PH), and RhoGAP domains. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 213019  Cd Length: 57  Bit Score: 61.09  E-value: 5.85e-12
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 398303812  17 IEVEYDYEYEAKD-RKIVIKQGERYILVKKTNDDWWQVK---PDENSKAFYVPAQY 68
Cdd:cd12143    2 LCALYAYQYTGADgRQVSIAEGERFLLLRKTNSDWWQVRrleAPSTSRPLFVPATY 57
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
432-528 6.55e-11

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 59.87  E-value: 6.55e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812   432 GKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSwfgsnqSKPEFTVDLKGATIEMA-SKDKSSKKNVFELKTRQGTELLIQS 510
Cdd:smart00233  11 SGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS------YKPKGSIDLSGCTVREApDPDSSKKPHCFEIKTSDRKTLLLQA 84
                           90
                   ....*....|....*...
gi 398303812   511 DNDTVINDWFKVLSSTIN 528
Cdd:smart00233  85 ESEEEREKWVEALRKAIA 102
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
623-767 2.11e-10

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


Pssm-ID: 239853  Cd Length: 200  Bit Score: 61.04  E-value: 2.11e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 623 PKFVKLcIEHVEEHGLDIDGIYR--VSGNLAVIQKLrfavNHDEKLDLNDSKWeDIHVITGALKMFFRELPEPLFTFNHF 700
Cdd:cd04388   17 PLLIKL-VEAIEKKGLESSTLYRtqSSSSLTELRQI----LDCDAASVDLEQF-DVAALADALKRYLLDLPNPVIPAPVY 90
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 398303812 701 NDFVNAIK--QEPRQRVAAVKDLIRQLPKPNQD--TMQILFRHLRRVIENGEKNRMTYQSIAIVFGPTLLK 767
Cdd:cd04388   91 SEMISRAQevQSSDEYAQLLRKLIRSPNLPHQYwlTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFR 161
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
430-525 3.21e-10

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. 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: 269975  Cd Length: 106  Bit Score: 58.01  E-value: 3.21e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 430 ENGKK-VRKNWLSSWAVLQGSSLLFTKTQGSSTSWFGSNQSKPeftVDLKGATIEMASkDKSSKKNVFELKTRQGTELLI 508
Cdd:cd10571   13 SGGKKaSNRSWKNVYTVLRGQELSFYKDQKAAKSGITYAAEPP---LNLYNAVCEVAS-DYTKKKHVFRLKLSDGAEFLF 88
                         90
                 ....*....|....*..
gi 398303812 509 QSDNDTVINDWFKVLSS 525
Cdd:cd10571   89 QAKDEEEMNQWVKKISF 105
RhoGAP_fRGD2 cd04399
RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
607-772 6.43e-10

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


Pssm-ID: 239864  Cd Length: 212  Bit Score: 59.65  E-value: 6.43e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 607 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDIDG------IYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIH--V 678
Cdd:cd04399    1 FGVDLETRCRLDKKVVPLIVSAILSYLDQLYPDLINdevrrnVWTDPVSLKETHQLRNLLNKPKKPDKEVIILKKFEpsT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 679 ITGALKMFFRELPEPLFTfNHFNDFVNAIKQE--------PRQRVAAVKDLIRQLPKPNQDTMQILFRHLRRVIE--NGE 748
Cdd:cd04399   81 VASVLKLYLLELPDSLIP-HDIYDLIRSLYSAyppsqedsDTARIQGLQSTLSQLPKSHIATLDAIITHFYRLIEitKMG 159
                        170       180
                 ....*....|....*....|....*
gi 398303812 749 KNRMTYQS-IAIVFGPTLLKPEKET 772
Cdd:cd04399  160 ESEEEYADkLATSLSREILRPIIES 184
PH_ARHGAP21-like cd01253
ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho ...
418-525 1.68e-09

ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with a RhoGAP domain. These proteins functions as a GTPase-activating protein (GAP) for RHOA and CDC42. ARHGAP21 controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. It is recruited to the Golgi by to GTPase, ARF1, through its PH domain and its helical motif. It is also required for CTNNA1 recruitment to adherens junctions. ARHGAP21 and it related proteins all contains a PH domain and a RhoGAP domain. Some of the members have additional N-terminal domains including PDZ, SH3, and SPEC. The ARHGAP21 PH domain interacts with the GTPbound forms of both ARF1 and ARF6 ARF-binding domain/ArfBD. The members here include: ARHGAP15, ARHGAP21, and ARHGAP23. 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: 269955  Cd Length: 113  Bit Score: 55.84  E-value: 1.68e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 418 EKYGLLNVTKIA-ENGKKV-RKNWLSSWAVLQGSSLLFTKTQG-SSTSWFGSNQSkpEFTVDLKGATIEMASkDKSSKKN 494
Cdd:cd01253    1 AREGWLHYKQIVtDKGKRVsDRSWKQAWAVLRGHSLYLYKDKReQTPALSIELGS--EQRISIRGCIVDIAY-SYTKRKH 77
                         90       100       110
                 ....*....|....*....|....*....|.
gi 398303812 495 VFELKTRQGTELLIQSDNDTVINDWFKVLSS 525
Cdd:cd01253   78 VFRLTTSDFSEYLFQAEDRDDMLGWIKAIQE 108
PH pfam00169
PH domain; PH stands for pleckstrin homology.
432-527 1.38e-08

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 53.34  E-value: 1.38e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812  432 GKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSwfgsnqSKPEFTVDLKGATI-EMASKDKSSKKNVFELKT---RQGTELL 507
Cdd:pfam00169  11 GGGKKKSWKKRYFVLFDGSLLYYKDDKSGKS------KEPKGSISLSGCEVvEVVASDSPKRKFCFELRTgerTGKRTYL 84
                          90       100
                  ....*....|....*....|
gi 398303812  508 IQSDNDTVINDWFKVLSSTI 527
Cdd:pfam00169  85 LQAESEEERKDWIKAIQSAI 104
SH3_Sla1p_3 cd11775
Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
19-70 5.32e-08

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212709 [Multi-domain]  Cd Length: 57  Bit Score: 50.01  E-value: 5.32e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 398303812  19 VEYDYEYEAKDrKIVIKQGER-YILVKKTNDDWWQVKPDENSKAFYVPAQYVK 70
Cdd:cd11775    5 VLYDFDAQSDD-ELTVKEGDVvYILDDKKSKDWWMVENVSTGKEGVVPASYIE 56
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
268-298 1.55e-07

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 47.91  E-value: 1.55e-07
                         10        20        30
                 ....*....|....*....|....*....|.
gi 398303812 268 NGEWETHKDSSGRCYYYNRGTQERTWKPPRW 298
Cdd:cd00201    1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
SH3_9 pfam14604
Variant SH3 domain;
19-70 6.72e-07

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 46.46  E-value: 6.72e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 398303812   19 VEYDYEYEAKDrKIVIKQGERYILVKKTNDDWWQVKpdENSKAFYVPAQYVK 70
Cdd:pfam14604   1 ALYPYEPKDDD-ELSLQRGDVITVIEESEDGWWEGI--NTGRTGLVPANYVE 49
PRP40 COG5104
Splicing factor [RNA processing and modification];
259-365 1.98e-06

Splicing factor [RNA processing and modification];


Pssm-ID: 227435 [Multi-domain]  Cd Length: 590  Bit Score: 51.23  E-value: 1.98e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 259 LPGSPAIQINGEWETHKDSSGRCYYYNRGTQERTWKPPRwtrdaSISKGDFQNPGDQEWLKHVDDQGRQYYYSADGSRSE 338
Cdd:COG5104    5 LLGMASGEARSEWEELKAPDGRIYYYNKRTGKSSWEKPK-----ELLKGSEEDLDVDPWKECRTADGKVYYYNSITRESR 79
                         90       100       110
                 ....*....|....*....|....*....|....
gi 398303812 339 WELP----KYNASSQQQ---REIIKSRSLDRRLQ 365
Cdd:COG5104   80 WKIPperkKVEPIAEQKhdeRSMIGGNGNDMAIT 113
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
271-296 2.31e-06

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 44.42  E-value: 2.31e-06
                          10        20
                  ....*....|....*....|....*.
gi 398303812  271 WETHKDSSGRCYYYNRGTQERTWKPP 296
Cdd:pfam00397   5 WEERWDPDGRVYYYNHETGETQWEKP 30
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
599-795 2.38e-06

RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. 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: 239845  Cd Length: 220  Bit Score: 49.26  E-value: 2.38e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 599 KGYIKDQVFGSNLANLCQRENG----------------------TVPKFVKLCIEHVEEHGLDIDGIYRVSGNLAVIQKL 656
Cdd:cd04380    5 TGVYLPSCFGSSLETLIRLPDPgirnlidqlelgdnpdysevplSIPKEIWRLVDYLYTRGLAQEGLFEEPGLPSEPGEL 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 657 RFAVNH--DEKLDLNDSKweDIHVITGALKMFFRELPEPLFTFNHFNDFVNAIKQEPRQRvaavKDLIR-QLPKPNQdtm 733
Cdd:cd04380   85 LAEIRDalDTGSPFNSPG--SAESVAEALLLFLESLPDPIIPYSLYERLLEAVANNEEDK----RQVIRiSLPPVHR--- 155
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 398303812 734 qILFRH----LRRVIENGEKNRMTYQSIAIVFGPTLLKPEKETGNIAVHTVYQNQIvELILLELSS 795
Cdd:cd04380  156 -NVFVYlcsfLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKR-AFIEQFLLN 219
SH3_Yes cd12007
Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src ...
21-69 3.02e-06

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212940 [Multi-domain]  Cd Length: 58  Bit Score: 45.03  E-value: 3.02e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 398303812  21 YDYEYEAKDrKIVIKQGERYILVKKTNDDWWQVKPDENSKAFYVPAQYV 69
Cdd:cd12007    7 YDYEARTTE-DLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYV 54
SH3_Tec_like cd11768
Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed ...
21-71 3.45e-06

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212702 [Multi-domain]  Cd Length: 54  Bit Score: 44.57  E-value: 3.45e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 398303812  21 YDYE-YEAKDrkIVIKQGERYILVKKTNDDWWQVKpDENSKAFYVPAQYVKE 71
Cdd:cd11768    6 YDFQpIEPGD--LPLEKGEEYVVLDDSNEHWWRAR-DKNGNEGYIPSNYVTE 54
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
432-523 1.55e-05

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


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 44.07  E-value: 1.55e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 432 GKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSwfgsnqsKPEFTVDLKGaTIEMASKDKSSKKNVFELKTRQGTELLIQSD 511
Cdd:cd00821    9 GGGGLKSWKKRWFVLFEGVLLYYKSKKDSSY-------KPKGSIPLSG-ILEVEEVSPKERPHCFELVTPDGRTYYLQAD 80
                         90
                 ....*....|..
gi 398303812 512 NDTVINDWFKVL 523
Cdd:cd00821   81 SEEERQEWLKAL 92
SH3_Alpha_Spectrin cd11808
Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red ...
16-70 1.62e-05

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212742 [Multi-domain]  Cd Length: 53  Bit Score: 42.86  E-value: 1.62e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 398303812  16 YIEVEYDYEyEAKDRKIVIKQGERYILVKKTNDDWWQVkpDENSKAFYVPAQYVK 70
Cdd:cd11808    1 CVVALYDYQ-EKSPREVSMKKGDILTLLNSSNKDWWKV--EVNDRQGFVPAAYVK 52
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
435-527 2.17e-05

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270113  Cd Length: 108  Bit Score: 44.29  E-value: 2.17e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 435 VRKNWLSSWAVLQGSSLLFTKtqgsstswfGSNQSKPEFTVDLKGATIEMASKDKSSKKNVFELKTRQGTELLIQSDNDT 514
Cdd:cd13301   15 VVNNWKARWFVLKEDGLEYYK---------KKTDSSPKGMIPLKGCTITSPCLEYGKRPLVFKLTTAKGQEHFFQACSRE 85
                         90
                 ....*....|...
gi 398303812 515 VINDWFKVLSSTI 527
Cdd:cd13301   86 ERDAWAKDITKAI 98
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
419-525 2.71e-05

T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; Tiam1 activates Rac GTPases to induce membrane ruffling and cell motility while Tiam2 (also called STEF (SIF (still life) and Tiam1 like-exchange factor) contributes to neurite growth. Tiam1/2 are Dbl-family of GEFs that possess a Dbl(DH) domain with a PH domain in tandem. DH-PH domain catalyzes the GDP/GTP exchange reaction in the GTPase cycle and facillitating the switch between inactive GDP-bound and active GTP-bound states. Tiam1/2 possess two PH domains, which are often referred to as PHn and PHc domains. The DH-PH tandem domain is made up of the PHc domain while the PHn is part of a novel N-terminal PHCCEx domain which is made up of the PHn domain, a coiled coil region(CC), and an extra region (Ex). PHCCEx mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. The PH domain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. CC and Ex form a positively charged surface for protein binding. There are 2 motifs in Tiam1/2-interacting proteins that bind to the PHCCEx domain: Motif-I in CD44, ephrinBs, and the NMDA receptor and Motif-II in Par3 and JIP2.Neither of these fall in the PHn 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: 269937  Cd Length: 127  Bit Score: 44.37  E-value: 2.71e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 419 KYGLLNVTKIAENGKKV------RKNWLSSWAVLQGSSLLFTKTQGSSTSwfgSNQSKPEFTVDLKGAtIEMASKDKSSK 492
Cdd:cd01230    5 KAGWLSVKNFLVHKKNKkvelatRRKWKKYWVCLKGCTLLFYECDERSGI---DENSEPKHALFVEGS-IVQAVPEHPKK 80
                         90       100       110
                 ....*....|....*....|....*....|...
gi 398303812 493 KNVFELKTRQGTELLIQSDNDTVINDWFKVLSS 525
Cdd:cd01230   81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHS 113
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
419-531 4.12e-05

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


Pssm-ID: 241436  Cd Length: 96  Bit Score: 43.05  E-value: 4.12e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 419 KYGLLnvTKIaenGKKVrKNWLSSWAVLQGSSLLFTKTQGSStswfgsnQSKPEFTVDLKGAtIEMAskdKSSKKNVFEL 498
Cdd:cd13282    1 KAGYL--TKL---GGKV-KTWKRRWFVLKNGELFYYKSPNDV-------IRKPQGQIALDGS-CEIA---RAEGAQTFEI 63
                         90       100       110
                 ....*....|....*....|....*....|...
gi 398303812 499 KTRQGTELLIqSDNDTVINDWFKVLSSTINNQA 531
Cdd:cd13282   64 VTEKRTYYLT-ADSENDLDEWIRVIQNVLRRQA 95
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
271-298 6.03e-05

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 40.66  E-value: 6.03e-05
                           10        20
                   ....*....|....*....|....*...
gi 398303812   271 WETHKDSSGRCYYYNRGTQERTWKPPRW 298
Cdd:smart00456   6 WEERKDPDGRPYYYNHETKETQWEKPRE 33
SH3_ITK cd11908
Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) ...
23-71 7.36e-05

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. ITK is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, ITK plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, ITK is crucial for the development of T-helper(Th)2 effector responses. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212841 [Multi-domain]  Cd Length: 56  Bit Score: 41.15  E-value: 7.36e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 398303812  23 YEYEAKD-RKIVIKQGERYILVKKTNDDWWQVKpDENSKAFYVPAQYVKE 71
Cdd:cd11908    7 YDYQTNDpQELALRYNEEYHLLDSSEIHWWRVQ-DKNGHEGYVPSSYLVE 55
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
13-70 8.97e-05

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 40.60  E-value: 8.97e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 398303812    13 GQVYIEVEYDYEYEAKDRkIVIKQGERYILVKKTNDDWWQVKpDENSKAFYVPAQYVK 70
Cdd:smart00326   1 EGPQVRALYDYTAQDPDE-LSFKKGDIITVLEKSDDGWWKGR-LGRGKEGLFPSNYVE 56
SH3_Sla1p_1 cd11773
First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
19-68 1.15e-04

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212707 [Multi-domain]  Cd Length: 57  Bit Score: 40.49  E-value: 1.15e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 398303812  19 VEYDYEYEAkDRKIVIKQGERYILVKKTNDDWWQVK-----PDENSKAFYVPAQY 68
Cdd:cd11773    4 ALYDYEPQT-EDELTIQEDDILYLLEKSDDDWWKVKlkvnsSDDDEPVGLVPATY 57
SH3_Fyn_Yrk cd12006
Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) ...
21-69 1.16e-04

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212939 [Multi-domain]  Cd Length: 56  Bit Score: 40.42  E-value: 1.16e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 398303812  21 YDYEYEAKDrKIVIKQGERYILVKKTNDDWWQVKPDENSKAFYVPAQYV 69
Cdd:cd12006    7 YDYEARTED-DLSFHKGEKFQILNSSEGDWWEARSLTTGETGYIPSNYV 54
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
432-523 1.79e-04

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: 41.84  E-value: 1.79e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 432 GKKVRKNWLSS--WAVLQGSSLlftktqgsstSWFGSnqSK----PEFTVDLKGAT-IEMaSKDKSSKKNVFELKTRQGT 504
Cdd:cd13215   28 SKRSKRTLRYTryWFVLKGDTL----------SWYNS--STdlyfPAGTIDLRYATsIEL-SKSNGEATTSFKIVTNSRT 94
                         90
                 ....*....|....*....
gi 398303812 505 eLLIQSDNDTVINDWFKVL 523
Cdd:cd13215   95 -YKFKADSETSADEWVKAL 112
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
434-519 3.03e-04

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: 40.76  E-value: 3.03e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 434 KVRKNWLSSWAVLQGSSLLFTKTQGSSTSwfgsnqSKPEFTVDLKGATIEMASKDKSSKKNVFELKTRQGTELLIqSDND 513
Cdd:cd13276   10 EFIKTWRRRWFVLKQGKLFWFKEPDVTPY------SKPRGVIDLSKCLTVKSAEDATNKENAFELSTPEETFYFI-ADNE 82

                 ....*.
gi 398303812 514 TVINDW 519
Cdd:cd13276   83 KEKEEW 88
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
436-534 4.46e-04

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


Pssm-ID: 270108  Cd Length: 103  Bit Score: 40.14  E-value: 4.46e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398303812 436 RKNWLSSWAVLQGSSLLFTKTQgsstswfgSNQSKPEFTVDLKGAtieMASKDKSSKKNVFELKTRQGTeLLIQSDNDTV 515
Cdd:cd13296   17 RRNWKSRWFVLRDTVLKYYEND--------QEGEKLLGTIDIRSA---KEIVDNDPKENRLSITTEERT-YHLVAESPED 84
                         90
                 ....*....|....*....
gi 398303812 516 INDWFKVLSSTINNQAVET 534
Cdd:cd13296   85 ASQWVNVLTRVISATDLEL 103
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
23-68 7.86e-04

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 37.95  E-value: 7.86e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 398303812  23 YEYEAK-DRKIVIKQGERYILVKKTNDDWWQVKPDENSKAFYVPAQY 68
Cdd:cd11845    6 YDYEARtDDDLSFKKGDRLQILDDSDGDWWLARHLSTGKEGYIPSNY 52
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
23-66 1.34e-03

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 37.18  E-value: 1.34e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 398303812   23 YEYEAKD-RKIVIKQGERYILVKKTNDDWWQVKPDENSKAfYVPA 66
Cdd:pfam00018   4 YDYTAQEpDELSFKKGDIIIVLEKSEDGWWKGRNKGGKEG-LIPS 47
SH3_Src cd12008
Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or ...
23-69 1.90e-03

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212941 [Multi-domain]  Cd Length: 56  Bit Score: 37.01  E-value: 1.90e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 398303812  23 YEYEAK-DRKIVIKQGERYILVKKTNDDWWQVKPDENSKAFYVPAQYV 69
Cdd:cd12008    6 YDYESRtETDLSFKKGERLQIVNNTEGDWWLAHSLTTGQTGYIPSNYV 53
SH3_BTK cd11906
Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr ...
20-71 2.07e-03

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212839 [Multi-domain]  Cd Length: 55  Bit Score: 37.11  E-value: 2.07e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 398303812  20 EYDYE-YEAKDrkIVIKQGERYILVKKTNDDWWQVKpDENSKAFYVPAQYVKE 71
Cdd:cd11906    6 LYDYTpMNAQD--LQLRKGEEYVILEESNLPWWRAR-DKNGREGYIPSNYVTE 55
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
16-68 5.26e-03

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 35.52  E-value: 5.26e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 398303812  16 YIEVEYDYEYEAKDrKIVIKQGERYILVKKTNDDWWQVKpDENSKAFYVPAQY 68
Cdd:cd00174    1 YARALYDYEAQDDD-ELSFKKGDIITVLEKDDDGWWEGE-LNGGREGLFPANY 51
SH3_SPIN90 cd11849
Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also ...
23-70 5.38e-03

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212783 [Multi-domain]  Cd Length: 53  Bit Score: 35.75  E-value: 5.38e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 398303812  23 YEYEAKDRK-IVIKQGERYILVKKTNDDWWQVKpDENSKAFYVPAQYVK 70
Cdd:cd11849    6 YDFKSAEPNtLSFSEGETFLLLERSNAHWWLVT-NHSGETGYVPANYVK 53
SH3_Tec cd11905
Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a ...
21-71 5.83e-03

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212838 [Multi-domain]  Cd Length: 56  Bit Score: 35.56  E-value: 5.83e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 398303812  21 YDYE-YEAKDrkIVIKQGERYILVKKTNDDWWQVKpDENSKAFYVPAQYVKE 71
Cdd:cd11905    7 YDFQpTEPHD--LRLETGEEYVILEKNDVHWWKAR-DKYGKEGYIPSNYVTG 55
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
18-71 6.63e-03

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212792 [Multi-domain]  Cd Length: 55  Bit Score: 35.44  E-value: 6.63e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 398303812  18 EVEYDYEYEAKDrKIVIKQGERYILVKKTNDDWWQVKPDENSKAFYVPAQYVKE 71
Cdd:cd11858    3 KALYDFAGSVAN-ELSLKKDDIVYIVQKEDNGWWLAKKLDESKEGWVPAAYLEE 55
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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