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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 646 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 725
Cdd:cd04403   1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 726 FRELPEPLFTFNHFNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTL 804
Cdd:cd04403  81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                       170       180
                ....*....|....*....|....*..
gi 89242143 805 LKPERETGNIAVHTVYQNQIVELILLE 831
Cdd:cd04403 161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 457 EKYGLLNVTKITENGKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSWFGsNQSKPEFTVDLKGAVIEMAsKDKSSKKNVFE 536
Cdd:cd13233   1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGN-PYSKPESSVDLRGASIEWA-KEKSSRKNVFQ 78

                        90       100       110
                ....*....|....*....|....*....|..
gi 89242143 537 LKTRQGTELLIQSDNDAVINDWFKVLSSTINN 568
Cdd:cd13233  79 ISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

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.

                        10        20        30
                ....*....|....*....|....*....|.
gi 89242143 266 NGEWETHKDSSGRCYYYNRTTQERTWKPPRW 296
Cdd:cd00201   1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 646 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 725
Cdd:cd04403   1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 726 FRELPEPLFTFNHFNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTL 804
Cdd:cd04403  81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                       170       180
                ....*....|....*....|....*..
gi 89242143 805 LKPERETGNIAVHTVYQNQIVELILLE 831
Cdd:cd04403 161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143    659 GTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWeDIHVITGALKMFFRELPEPLFTFNH 738
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143    739 FNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTLLKPERETGNIAVH 817
Cdd:smart00324  80 YEEFIEAAKlEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|..
gi 89242143    818 TVYQNQIVELIL 829
Cdd:smart00324 160 IRHQNTVIEFLI 171

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 457 EKYGLLNVTKITENGKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSWFGsNQSKPEFTVDLKGAVIEMAsKDKSSKKNVFE 536
Cdd:cd13233   1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGN-PYSKPESSVDLRGASIEWA-KEKSSRKNVFQ 78

                        90       100       110
                ....*....|....*....|....*....|..
gi 89242143 537 LKTRQGTELLIQSDNDAVINDWFKVLSSTINN 568
Cdd:cd13233  79 ISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143    471 GKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSwfgsnqSKPEFTVDLKGAVIEMA-SKDKSSKKNVFELKTRQGTELLIQS 549
Cdd:smart00233  11 SGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS------YKPKGSIDLSGCTVREApDPDSSKKPHCFEIKTSDRKTLLLQA 84

                           90
                   ....*....|....*...
gi 89242143    550 DNDAVINDWFKVLSSTIN 567
Cdd:smart00233  85 ESEEEREKWVEALRKAIA 102

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.

                        10        20        30
                ....*....|....*....|....*....|.
gi 89242143 266 NGEWETHKDSSGRCYYYNRTTQERTWKPPRW 296
Cdd:cd00201   1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

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

                          10        20
                  ....*....|....*....|....*.
gi 89242143   269 WETHKDSSGRCYYYNRTTQERTWKPP 294
Cdd:pfam00397   5 WEERWDPDGRVYYYNHETGETQWEKP 30

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 89242143     14 YIEVEYDYEYDAKDRkIVIRQGERYLLVKKTNDDWWQVRpDENSKAFYVPAQYVK 68
Cdd:smart00326   4 QVRALYDYTAQDPDE-LSFKKGDIITVLEKSDDGWWKGR-LGRGKEGLFPSNYVE 56

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 646 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 725
Cdd:cd04403   1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 726 FRELPEPLFTFNHFNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTL 804
Cdd:cd04403  81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                       170       180
                ....*....|....*....|....*..
gi 89242143 805 LKPERETGNIAVHTVYQNQIVELILLE 831
Cdd:cd04403 161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143    659 GTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWeDIHVITGALKMFFRELPEPLFTFNH 738
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143    739 FNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTLLKPERETGNIAVH 817
Cdd:smart00324  80 YEEFIEAAKlEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|..
gi 89242143    818 TVYQNQIVELIL 829
Cdd:smart00324 160 IRHQNTVIEFLI 171

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 662 PKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEklDLNDSKWEDIHVITGALKMFFRELPEPLFTFNHFND 741
Cdd:cd00159   1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 742 FVNAIKQE-PRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTLLKPERETGNIAVHTVY 820
Cdd:cd00159  79 FIELAKIEdEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                ....*....
gi 89242143 821 QNQIVELIL 829
Cdd:cd00159 159 LNEIVEFLI 167

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 457 EKYGLLNVTKITENGKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSWFGsNQSKPEFTVDLKGAVIEMAsKDKSSKKNVFE 536
Cdd:cd13233   1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGN-PYSKPESSVDLRGASIEWA-KEKSSRKNVFQ 78

                        90       100       110
                ....*....|....*....|....*....|..
gi 89242143 537 LKTRQGTELLIQSDNDAVINDWFKVLSSTINN 568
Cdd:cd13233  79 ISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 663 KFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLrFAVNHDEK------LDLNDSKWEdIHVITGALKMFFRELPEPLFTF 736
Cdd:cd04374  30 KFVRKCIEAVETRGINEQGLYRVVGVNSKVQKL-LSLGLDPKtstpgdVDLDNSEWE-IKTITSALKTYLRNLPEPLMTY 107

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 737 NHFNDFVNAIKQE-PRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTLLKPERETGNIA 815
Cdd:cd04374 108 ELHNDFINAAKSEnLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEETVAAI 187

                       170
                ....*....|....*.
gi 89242143 816 VHTVYQNQIVElILLE 831
Cdd:cd04374 188 MDIKFQNIVVE-ILIE 202

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 646 FGSNLANLCQrENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHD-EKLDLNDSKwedIHVITGALKM 724
Cdd:cd04377   1 FGVSLSSLTS-EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDpDSVNLEDYP---IHVITSVLKQ 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 725 FFRELPEPLFTFNHFNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPT 803
Cdd:cd04377  77 WLRELPEPLMTFELYENFLRAMElEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPC 156

                       170       180       190
                ....*....|....*....|....*....|....
gi 89242143 804 LLK------PERETGNIAVHTvyqnQIVELILLE 831
Cdd:cd04377 157 ILRcpdtadPLQSLQDVSKTT----TCVETLIKE 186

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 646 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKWEDIhviTGALKM 724
Cdd:cd04378   1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFeNGKDLVELSELSPHDI---SSVLKL 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 725 FFRELPEPLFTFNHFNDFVNAIKQ---------------EPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKN 789
Cdd:cd04378  78 FLRQLPEPLILFRLYNDFIALAKEiqrdteedkapntpiEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEEN 157

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 89242143 790 RMTYQSIAIVFGPTLLKPERETGNIA----VHTVYQNQIVELIL 829
Cdd:cd04378 158 KMSPNNLGIVFGPTLIRPRPGDADVSlsslVDYGYQARLVEFLI 201

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 644 QVFGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDE-KLDLnDSKWEDIHVITGAL 722
Cdd:cd04386   3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTfSLPL-DEFYSDPHAVASAL 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 723 KMFFRELPEPLFTFNHFNDFVNAI-KQEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFG 801
Cdd:cd04386  82 KSYLRELPDPLLTYNLYEDWVQAAnKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLA 161

                       170       180       190
                ....*....|....*....|....*....|....*...
gi 89242143 802 PTLLKPERETGNI---AVHTVYQNQIVELILLELSTVF 836
Cdd:cd04386 162 PNLLWAKNEGSLAemaAGTSVHVVAIVELIISHADWFF 199

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 646 FGSNLANLCQRENgTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEkldlNDSKWED--IHVITGALK 723
Cdd:cd04407   1 FGVRVGSLTSNKT-SVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADP----ENVKLENypIHAITGLLK 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 724 MFFRELPEPLFTFNHFNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGP 802
Cdd:cd04407  76 QWLRELPEPLMTFAQYNDFLRAVElPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAP 155

                ....
gi 89242143 803 TLLK 806
Cdd:cd04407 156 CLLR 159

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 645 VFGSNLANLCQRENGTVPKFVKLCIEHVEEHGLdVDGIYRVSGNLAVIQKLRFAVNHDEKLDL-NDSKWEDIHVITGALK 723
Cdd:cd04384   2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLtKDVYIQDIHSVSSLCK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 724 MFFRELPEPLFTFNHFNDFVNAIKQEP-RQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGP 802
Cdd:cd04384  81 LYFRELPNPLLTYQLYEKFSEAVSAASdEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                ....*
gi 89242143 803 TLLKP 807
Cdd:cd04384 161 NLLRS 165

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 646 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKWEDIhviTGALKM 724
Cdd:cd04409   1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFeNGKDLVELSELSPHDI---SNVLKL 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 725 FFRELPEPLFTFNHFNDFVNAIKQ-----------------------EPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKR 781
Cdd:cd04409  78 YLRQLPEPLILFRLYNEFIGLAKEsqhvnetqeakknsdkkwpnmctELNRILLKSKDLLRQLPAPNYNTLQFLIVHLHR 157

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 89242143 782 VIENGEKNRMTYQSIAIVFGPTLLKPERETGNIAVHTV----YQNQIVELIL 829
Cdd:cd04409 158 VSEQAEENKMSASNLGIIFGPTLIRPRPTDATVSLSSLvdypHQARLVELLI 209

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 646 FGSNLANLCQRENGT--VPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKL-DLNDSKWEDIHVITGAL 722
Cdd:cd04379   1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAvELSEELYPDINVITGVL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 723 KMFFRELPEPLFTFNHFNDFVNAIKQEPRQRVTAVKDLIRQ----LPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAI 798
Cdd:cd04379  81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQTNTHLTLSiidcLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                       170
                ....*....|....
gi 89242143 799 VFGPTLLKPERETG 812
Cdd:cd04379 161 CFGPVLMFCSQEFS 174

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 646 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKWEDIhviTGALKM 724
Cdd:cd04408   1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFeNGRDLVDLSGHSPHDI---TSVLKH 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 89242143 725 FFRELPEPLFTFNHFNDFVNAIKQ-------------EPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRM 791
Cdd:cd04408  78 FLKELPEPVLPFQLYDDFIALAKElqrdsekaaespsIVENIIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKM 157

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 89242143 792 TYQSIAIVFGPTLLKPErETGNIAV----HTVYQNQIVELIL 829
Cdd:cd04408 158 SPNNLGIVFGPTLLRPL-VGGDVSMicllDTGYQAQLVEFLI 198