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 569004648 604 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 683
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 684 FRELPEPLFTFNHFNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTL 762
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                        170       180
                 ....*....|....*....|....*..
gi 569004648 763 LKPERETGNIAVHTVYQNQIVELILLE 789
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 569004648 415 EKYGLLNVTKITENGKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSWFGsNQSKPEFTVDLKGAVIEMAsKDKSSKKNVFE 494
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGN-PYSKPESSVDLRGASIEWA-KEKSSRKNVFQ 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 569004648 495 LKTRQGTELLIQSDNDAVINDWFKVLSSTINN 526
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 569004648 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 569004648 604 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 683
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 684 FRELPEPLFTFNHFNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTL 762
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                        170       180
                 ....*....|....*....|....*..
gi 569004648 763 LKPERETGNIAVHTVYQNQIVELILLE 789
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 569004648   617 GTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWeDIHVITGALKMFFRELPEPLFTFNH 696
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648   697 FNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTLLKPERETGNIAVH 775
Cdd:smart00324  80 YEEFIEAAKlEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|..
gi 569004648   776 TVYQNQIVELIL 787
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 569004648 415 EKYGLLNVTKITENGKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSWFGsNQSKPEFTVDLKGAVIEMAsKDKSSKKNVFE 494
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGN-PYSKPESSVDLRGASIEWA-KEKSSRKNVFQ 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 569004648 495 LKTRQGTELLIQSDNDAVINDWFKVLSSTINN 526
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 569004648   429 GKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSwfgsnqSKPEFTVDLKGAVIEMA-SKDKSSKKNVFELKTRQGTELLIQS 507
Cdd:smart00233  11 SGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS------YKPKGSIDLSGCTVREApDPDSSKKPHCFEIKTSDRKTLLLQA 84

                           90
                   ....*....|....*...
gi 569004648   508 DNDAVINDWFKVLSSTIN 525
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 569004648 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 569004648  269 WETHKDSSGRCYYYNRTTQERTWKPP 294
Cdd:pfam00397   5 WEERWDPDGRVYYYNHETGETQWEKP 30

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

                           10        20
                   ....*....|....*....|....*...
gi 569004648   269 WETHKDSSGRCYYYNRTTQERTWKPPRW 296
Cdd:smart00456   6 WEERKDPDGRPYYYNHETKETQWEKPRE 33

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 569004648 604 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 683
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 684 FRELPEPLFTFNHFNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTL 762
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                        170       180
                 ....*....|....*....|....*..
gi 569004648 763 LKPERETGNIAVHTVYQNQIVELILLE 789
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 569004648   617 GTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWeDIHVITGALKMFFRELPEPLFTFNH 696
Cdd:smart00324   1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648   697 FNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTLLKPERETGNIAVH 775
Cdd:smart00324  80 YEEFIEAAKlEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD 159

                          170
                   ....*....|..
gi 569004648   776 TVYQNQIVELIL 787
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 569004648 620 PKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEklDLNDSKWEDIHVITGALKMFFRELPEPLFTFNHFND 699
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 700 FVNAIKQE-PRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTLLKPERETGNIAVHTVY 778
Cdd:cd00159   79 FIELAKIEdEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                 ....*....
gi 569004648 779 QNQIVELIL 787
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 569004648 415 EKYGLLNVTKITENGKKVRKNWLSSWAVLQGSSLLFTKTQGSSTSWFGsNQSKPEFTVDLKGAVIEMAsKDKSSKKNVFE 494
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKSGN-PYSKPESSVDLRGASIEWA-KEKSSRKNVFQ 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 569004648 495 LKTRQGTELLIQSDNDAVINDWFKVLSSTINN 526
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 569004648 621 KFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLrFAVNHDEK------LDLNDSKWEdIHVITGALKMFFRELPEPLFTF 694
Cdd:cd04374   30 KFVRKCIEAVETRGINEQGLYRVVGVNSKVQKL-LSLGLDPKtstpgdVDLDNSEWE-IKTITSALKTYLRNLPEPLMTY 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 695 NHFNDFVNAIKQE-PRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPTLLKPERETGNIA 773
Cdd:cd04374  108 ELHNDFINAAKSEnLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEETVAAI 187

                        170
                 ....*....|....*.
gi 569004648 774 VHTVYQNQIVElILLE 789
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 569004648 604 FGSNLANLCQrENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHD-EKLDLNDSKwedIHVITGALKM 682
Cdd:cd04377    1 FGVSLSSLTS-EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDpDSVNLEDYP---IHVITSVLKQ 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 683 FFRELPEPLFTFNHFNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGPT 761
Cdd:cd04377   77 WLRELPEPLMTFELYENFLRAMElEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPC 156

                        170       180       190
                 ....*....|....*....|....*....|....
gi 569004648 762 LLK------PERETGNIAVHTvyqnQIVELILLE 789
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 569004648 604 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKWEDIhviTGALKM 682
Cdd:cd04378    1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFeNGKDLVELSELSPHDI---SSVLKL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 683 FFRELPEPLFTFNHFNDFVNAIKQ---------------EPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKN 747
Cdd:cd04378   78 FLRQLPEPLILFRLYNDFIALAKEiqrdteedkapntpiEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEEN 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 569004648 748 RMTYQSIAIVFGPTLLKPERETGNIA----VHTVYQNQIVELIL 787
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 569004648 602 QVFGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDE-KLDLnDSKWEDIHVITGAL 680
Cdd:cd04386    3 PVFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTfSLPL-DEFYSDPHAVASAL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 681 KMFFRELPEPLFTFNHFNDFVNAI-KQEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFG 759
Cdd:cd04386   82 KSYLRELPDPLLTYNLYEDWVQAAnKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLA 161

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 569004648 760 PTLLKPERETGNI---AVHTVYQNQIVELILLELSTVF 794
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 569004648 604 FGSNLANLCQRENgTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEkldlNDSKWED--IHVITGALK 681
Cdd:cd04407    1 FGVRVGSLTSNKT-SVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADP----ENVKLENypIHAITGLLK 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 682 MFFRELPEPLFTFNHFNDFVNAIK-QEPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAIVFGP 760
Cdd:cd04407   76 QWLRELPEPLMTFAQYNDFLRAVElPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAP 155

                 ....
gi 569004648 761 TLLK 764
Cdd:cd04407  156 CLLR 159

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 619 VPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRfavnhdEKL-------DLNDSkweDIHVITGALKMFFRELPEPL 691
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALK------EKFlrgktvpNLSKV---DIHVICGCLKDFLRSLKEPL 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 692 FTFNHFNDFVNAIKQEPRQRV-TAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEkNRMTYQSIAIVFGPTL-----LKP 765
Cdd:cd04382   88 ITFALWKEFMEAAEILDEDNSrAALYQAISELPQPNRDTLAFLILHLQRVAQSPE-CKMDINNLARVFGPTIvgysvPNP 166

                        170       180
                 ....*....|....*....|....*....
gi 569004648 766 ERETgnIAVHTVYQNQIVELiLLELSTVF 794
Cdd:cd04382  167 DPMT--ILQDTVRQPRVVER-LLEIPSDY 192

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 569004648 604 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKWEDIhviTGALKM 682
Cdd:cd04409    1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFeNGKDLVELSELSPHDI---SNVLKL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 683 FFRELPEPLFTFNHFNDFVNAIKQ-----------------------EPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKR 739
Cdd:cd04409   78 YLRQLPEPLILFRLYNEFIGLAKEsqhvnetqeakknsdkkwpnmctELNRILLKSKDLLRQLPAPNYNTLQFLIVHLHR 157

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569004648 740 VIENGEKNRMTYQSIAIVFGPTLLKPERETGNIAVHTV----YQNQIVELIL 787
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 569004648 604 FGSNLANLCQRENGT--VPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAVNHDEKL-DLNDSKWEDIHVITGAL 680
Cdd:cd04379    1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAvELSEELYPDINVITGVL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 681 KMFFRELPEPLFTFNHFNDFVNAIKQEPRQRVTAVKDLIRQ----LPKPNQDTMQILFRHLKRVIENGEKNRMTYQSIAI 756
Cdd:cd04379   81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQTNTHLTLSiidcLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                        170
                 ....*....|....
gi 569004648 757 VFGPTLLKPERETG 770
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 569004648 604 FGSNLANLCQRENGTVPKFVKLCIEHVEEHGLDVDGIYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKWEDIhviTGALKM 682
Cdd:cd04408    1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFeNGRDLVDLSGHSPHDI---TSVLKH 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569004648 683 FFRELPEPLFTFNHFNDFVNAIKQ-------------EPRQRVTAVKDLIRQLPKPNQDTMQILFRHLKRVIENGEKNRM 749
Cdd:cd04408   78 FLKELPEPVLPFQLYDDFIALAKElqrdsekaaespsIVENIIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKM 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 569004648 750 TYQSIAIVFGPTLLKPErETGNIAV----HTVYQNQIVELIL 787
Cdd:cd04408  158 SPNNLGIVFGPTLLRPL-VGGDVSMicllDTGYQAQLVEFLI 198