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 1207147851 455 FGCSLSSLCQRENSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHEEKIDLGDSKWEDIHVTTGALKMF 534
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 535 FRELPEPLFTYTFFSDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVFGPTL 614
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                         170       180
                  ....*....|....*....|....*..
gi 1207147851 615 LRPEIETANMAVHMVYQNQIVELILME 641
Cdd:cd04403   161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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 1207147851  47 DWETHKDQNGRHYYYNRSTQERTWKPP 73
Cdd:pfam00397   4 GWEERWDPDGRVYYYNHETGETQWEKP 30

Splicing factor [RNA processing and modification];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851  48 WETHKDQNGRHYYYNRSTQERTWK-PPRARDSLPRKEEKHDMTDTEVLSSEENCLSSQSDSQygsPPRGWSEEMDEHGHT 126
Cdd:COG5104    58 WKECRTADGKVYYYNSITRESRWKiPPERKKVEPIAEQKHDERSMIGGNGNDMAITDHETSE---PKYLLGRLMSQYGIT 134

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 1207147851 455 FGCSLSSLCQRENSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHEEKIDLGDSKWEDIHVTTGALKMF 534
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 535 FRELPEPLFTYTFFSDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVFGPTL 614
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                         170       180
                  ....*....|....*....|....*..
gi 1207147851 615 LRPEIETANMAVHMVYQNQIVELILME 641
Cdd:cd04403   161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 471 PRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHEEKIDLgDSKWEDIHVTTGALKMFFRELPEPLFTYTFFSD 550
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDL-DLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207147851 551 FISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVFGPTLLRP 617
Cdd:pfam00620  80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRP 146

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 1207147851  47 DWETHKDQNGRHYYYNRSTQERTWKPP 73
Cdd:pfam00397   4 GWEERWDPDGRVYYYNHETGETQWEKP 30

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 1207147851  45 NGDWETHKDQNGRHYYYNRSTQERTWKPPR 74
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPR 30

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 279 GKKVRKNWTSYWTVLQGSLLIFNKGQGggsgwfgRDQKSSVEYSVDLKGGSVDWASK-DKSSKKHVLELKT---RQGTEL 354
Cdd:pfam00169  11 GGGKKKSWKKRYFVLFDGSLLYYKDDK-------SGKSKEPKGSISLSGCEVVEVVAsDSPKRKFCFELRTgerTGKRTY 83

                          90       100
                  ....*....|....*....|..
gi 1207147851 355 LLQSDSDGLVNDWHKALTEAIH 376
Cdd:pfam00169  84 LLQAESEEERKDWIKAIQSAIR 105

Splicing factor [RNA processing and modification];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851  48 WETHKDQNGRHYYYNRSTQERTWK-PPRARDSLPRKEEKHDMTDTEVLSSEENCLSSQSDSQygsPPRGWSEEMDEHGHT 126
Cdd:COG5104    58 WKECRTADGKVYYYNSITRESRWKiPPERKKVEPIAEQKHDERSMIGGNGNDMAITDHETSE---PKYLLGRLMSQYGIT 134

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 1207147851 455 FGCSLSSLCQRENSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHEEKIDLGDSKWEDIHVTTGALKMF 534
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 535 FRELPEPLFTYTFFSDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVFGPTL 614
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                         170       180
                  ....*....|....*....|....*..
gi 1207147851 615 LRPEIETANMAVHMVYQNQIVELILME 641
Cdd:cd04403   161 LRPEQETGNIAVHMVYQNQIVELILLE 187

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 1207147851 471 PRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHEEKIDlgDSKWEDIHVTTGALKMFFRELPEPLFTYTFFSD 550
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDID--DLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 551 FISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVFGPTLLRPEIETANMAVHMVY 630
Cdd:cd00159    79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                  ....*....
gi 1207147851 631 QNQIVELIL 639
Cdd:cd00159   159 LNEIVEFLI 167

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 454 VFGCSLSSlCQ--RENSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHE-EKIDLGDSKWEDIHVTTGA 530
Cdd:cd04395     1 TFGVPLDD-CPpsSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgFDIDLQDPRWRDVNVVSSL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 531 LKMFFRELPEPLFTYTFFSDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVF 610
Cdd:cd04395    80 LKSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVF 159

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1207147851 611 GPTLLRPEIET-ANMAVHMVYQNQIVELILMEYDTIF 646
Cdd:cd04395   160 GPTLVRTSDDNmETMVTHMPDQCKIVETLIQHYDWFF 196

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 455 FGCSLSSLCQRENSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHE-EKIDLGDSKWEDIHVTTGALKM 533
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVYPDINVITGALKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 534 FFRELPEPLFTYTFFSDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVFGPT 613
Cdd:cd04372    81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1207147851 614 LLRPEIETANMAVH-MVYQNQIVELILMEYDTIF 646
Cdd:cd04372   161 LMRPPEDSALTTLNdMRYQILIVQLLITNEDVLF 194

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 1207147851 455 FGCSLSSLCQrENSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHE-EKIDLGDSKwedIHVTTGALKM 533
Cdd:cd04377     1 FGVSLSSLTS-EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDpDSVNLEDYP---IHVITSVLKQ 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 534 FFRELPEPLFTYTFFSDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVFGPT 613
Cdd:cd04377    77 WLRELPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPC 156

                         170       180       190
                  ....*....|....*....|....*....|
gi 1207147851 614 LLR-PEIETANMAVHMVY-QNQIVELILME 641
Cdd:cd04377   157 ILRcPDTADPLQSLQDVSkTTTCVETLIKE 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 1207147851 455 FGCSLSSLCQRENSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAV-NHEEKIDLGDSKWEDIhvtTGALKM 533
Cdd:cd04378     1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFeNGKDLVELSELSPHDI---SSVLKL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 534 FFRELPEPLFTYTFFSDFIS-------------AIKMP-DYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDEN 599
Cdd:cd04378    78 FLRQLPEPLILFRLYNDFIAlakeiqrdteedkAPNTPiEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEEN 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1207147851 600 RMTTQSVAIVFGPTLLRPEIETANMAVHMV----YQNQIVELIL 639
Cdd:cd04378   158 KMSPNNLGIVFGPTLIRPRPGDADVSLSSLvdygYQARLVEFLI 201

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 1207147851 265 EKCATLNMTKITEHGKKVRKNWTSYWTVLQGSLLIFNKgqgggsgwfgrDQKSSV---------EYSVDLKGGSVDWAsK 335
Cdd:cd13233     1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYK-----------DAKSAAksgnpyskpESSVDLRGASIEWA-K 68

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1207147851 336 DKSSKKHVLELKTRQGTELLLQSDSDGLVNDWHKALTEAI 375
Cdd:cd13233    69 EKSSRKNVFQISTVTGTEFLLQSDNDTEIREWFDAIKAVI 108

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 453 QVFGCSLSSLCQR--ENSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHEEKIDLGDskWEDIHVTTGA 530
Cdd:cd04404     4 QQFGVSLQFLKEKnpEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQ--YEDVHLPAVI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 531 LKMFFRELPEPLFTYTFFSDfISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVF 610
Cdd:cd04404    82 LKTFLRELPEPLLTFDLYDD-IVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1207147851 611 GPTLLRPEIETANMAVhMVYQNQIVELILMEYDTIF 646
Cdd:cd04404   161 GPNLLWAKDASMSLSA-INPINTFTKFLLDHQDEIF 195

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 1207147851 455 FGCSLSSLCQRENStVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVnheeKIDLGDSKWED--IHVTTGALK 532
Cdd:cd04407     1 FGVRVGSLTSNKTS-VPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLL----QADPENVKLENypIHAITGLLK 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 533 MFFRELPEPLFTYTFFSDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVFGP 612
Cdd:cd04407    76 QWLRELPEPLMTFAQYNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAP 155

                         170       180       190
                  ....*....|....*....|....*....|.
gi 1207147851 613 TLLR-PEIETANMAVHMVYQNQI-VELILME 641
Cdd:cd04407   156 CLLRcPDSSDPLTSMKDVAKTTTcVEMLIKE 186

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 1207147851 470 VPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHEEKI-DLGDSkweDIHVTTGALKMFFRELPEPLFTYTFF 548
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVpNLSKV---DIHVICGCLKDFLRSLKEPLITFALW 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 549 SDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQhVDENRMTTQSVAIVFGPTL---LRPEIETANMA 625
Cdd:cd04382    94 KEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIvgySVPNPDPMTIL 172

                         170
                  ....*....|....
gi 1207147851 626 VHMVYQNQIVELIL 639
Cdd:cd04382   173 QDTVRQPRVVERLL 186

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 454 VFGCSLSSLCQR-----ENSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVnhEEKIDLGDSKWEDIHV-- 526
Cdd:cd04391     1 LFGVPLSTLLERdqkkvPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQEL--EAKFYEGTFLWDQVKQhd 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 527 TTGALKMFFRELPEPLFTYTFFSDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSV 606
Cdd:cd04391    79 AASLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNV 158

                         170
                  ....*....|.
gi 1207147851 607 AIVFGPTLLRP 617
Cdd:cd04391   159 AMIMAPNLFPP 169

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 470 VPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHEE---KIDLGDskwEDIHVTTGALKMFFRELPEPLFTYT 546
Cdd:cd04385    15 IPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDArsvQLREGE---YTVHDVADVLKRFLRDLPDPLLTSE 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 547 FFSDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVFGPTLLRPEIETANMAV 626
Cdd:cd04385    92 LHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGQTS 171

                         170
                  ....*....|....*.
gi 1207147851 627 HMVyqnQIVELILMEY 642
Cdd:cd04385   172 HEV---KVIEDLIDNY 184

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 455 FGCSLSSLCQRENSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHEEKIDLGDSKWEDIHVTTGALKMF 534
Cdd:cd04383     3 FNGSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLKLY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 535 FRELPEPLFTYTFFSDFISAIKMPDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVAIVFGPTL 614
Cdd:cd04383    83 FRGLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTL 162

                         170       180
                  ....*....|....*....|....*
gi 1207147851 615 LR-PEIETAnmavhMVYQNQIVELI 638
Cdd:cd04383   163 MPvPEGQDQ-----VSCQAHVNELI 182

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 454 VFGCSLSSLCQRE----NSTVPRFVWLCIEQVEKNGLGVDGLYRVSGNLAIIQKLRFAVNHEEKiDLGDSKwEDIHVTTG 529
Cdd:cd04390     2 VFGQRLEDTVAYErkfgPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGER-PSFDSD-TDVHTVAS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207147851 530 ALKMFFRELPEPLFTYTFFSDFISAIKM--PDYKQKVQTVKDLMKKLPRPNHDTIQVLFKHLKKVIQHVDENRMTTQSVA 607
Cdd:cd04390    80 LLKLYLRELPEPVIPWAQYEDFLSCAQLlsKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLA 159

                         170
                  ....*....|...
gi 1207147851 608 IVFGPTLLRPEIE 620
Cdd:cd04390   160 TVFGPNILRPKVE 172