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 1785350305 573 FGCRLDALCHRENSTVPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIVDREEKLDLSTSDWEDVHVITGALKMF 652
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 653 FRELPEPLIPFSMFEQYVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGPTL 732
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                         170       180
                  ....*....|....*....|....*..
gi 1785350305 733 MRPEKELfSNIAANMVYQNQVVEHFLT 759
Cdd:cd04403   161 LRPEQET-GNIAVHMVYQNQIVELILL 186

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1785350305  33 FKAPGGSTVNLNEGDTLVVLKKSDKDWWQVRKVEESettKPFHAPSSY 80
Cdd:cd11888    10 YTGKDGRKVSIKEGERFLLLKKSNDDWWQVRRPGDS---KPFYVPAQY 54

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 1785350305 573 FGCRLDALCHRENSTVPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIVDREEKLDLSTSDWEDVHVITGALKMF 652
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 653 FRELPEPLIPFSMFEQYVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGPTL 732
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                         170       180
                  ....*....|....*....|....*..
gi 1785350305 733 MRPEKELfSNIAANMVYQNQVVEHFLT 759
Cdd:cd04403   161 LRPEQET-GNIAVHMVYQNQIVELILL 186

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 589 PKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIVDREEKLDLsTSDWEDVHVITGALKMFFRELPEPLIPFSMFEQ 668
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDL-DLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1785350305 669 YVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGPTLMRP 735
Cdd:pfam00620  80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRP 146

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 1785350305  393 GRKLKKNWSASWVVLTGNSLMFYKDPKvlvpsgwKPSNSKPESSVDLRGATI--DSTQEMSSKKNVIHLRMVTGNEYLLQ 470
Cdd:smart00233  11 SGGGKKSWKKRYFVLFNSTLLYYKSKK-------DKKSYKPKGSIDLSGCTVreAPDPDSSKKPHCFEIKTSDRKTLLLQ 83

                           90
                   ....*....|....*...
gi 1785350305  471 SDKDLLIQEWYDALQRVI 488
Cdd:smart00233  84 AESEEEREKWVEALRKAI 101

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1785350305  33 FKAPGGSTVNLNEGDTLVVLKKSDKDWWQVRKVEESettKPFHAPSSY 80
Cdd:cd11888    10 YTGKDGRKVSIKEGERFLLLKKSNDDWWQVRRPGDS---KPFYVPAQY 54

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 1785350305 215 DNWECHFDPlSGRNFYINTETKEKTWKPPR 244
Cdd:cd00201     2 PGWEERWDP-DGRVYYYNHNTKETQWEDPR 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
                   ....*....|....*....|....*....|....*....|....*....
gi 1785350305   33 FKAPGGSTVNLNEGDTLVVLKKSDKDWWQVRKveESETTKPFhaPSSYI 81
Cdd:smart00326  11 YTAQDPDELSFKKGDIITVLEKSDDGWWKGRL--GRGKEGLF--PSNYV 55

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 1785350305 573 FGCRLDALCHRENSTVPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIVDREEKLDLSTSDWEDVHVITGALKMF 652
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 653 FRELPEPLIPFSMFEQYVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGPTL 732
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                         170       180
                  ....*....|....*....|....*..
gi 1785350305 733 MRPEKELfSNIAANMVYQNQVVEHFLT 759
Cdd:cd04403   161 LRPEQET-GNIAVHMVYQNQIVELILL 186

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 589 PKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIVDREEKLDLsTSDWEDVHVITGALKMFFRELPEPLIPFSMFEQ 668
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDL-DLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1785350305 669 YVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGPTLMRP 735
Cdd:pfam00620  80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRP 146

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 1785350305 589 PKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIVDREEKLDLStsDWEDVHVITGALKMFFRELPEPLIPFSMFEQ 668
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDL--EDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 669 YVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGPTLMRPEKELFSNIaANMV 748
Cdd:cd00159    79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELL-EDIK 157

                         170
                  ....*....|..
gi 1785350305 749 YQNQVVEHFLTY 760
Cdd:cd00159   158 KLNEIVEFLIEN 169

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 1785350305 379 EKASQLNKTKIAEGGRKLKKNWSASWVVLTGNSLMFYKDPKVlvPSGWKPSNSKPESSVDLRGATIDSTQEMSSKKNVIH 458
Cdd:cd13233     1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKS--AAKSGNPYSKPESSVDLRGASIEWAKEKSSRKNVFQ 78

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1785350305 459 LRMVTGNEYLLQSDKDLLIQEWYDALQRVIER 490
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 1785350305 590 KFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIV-DREEK----LDLSTSDWEdVHVITGALKMFFRELPEPLIPFS 664
Cdd:cd04374    30 KFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGlDPKTStpgdVDLDNSEWE-IKTITSALKTYLRNLPEPLMTYE 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 665 MFEQYVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGPTLMRPEKElfsNIA 744
Cdd:cd04374   109 LHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEE---TVA 185

                         170
                  ....*....|...
gi 1785350305 745 A--NMVYQNQVVE 755
Cdd:cd04374   186 AimDIKFQNIVVE 198

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 573 FGCRLDALCHRENSTVPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIVDREEKLDLSTSDWEDVHVITGALKMF 652
Cdd:cd04387     1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 653 FRELPEPLIPFSMFEQYVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGPTL 732
Cdd:cd04387    81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1785350305 733 MRP-EKElfSNIAANMVYQNQVVE-----HFLTYYEEL 764
Cdd:cd04387   161 LRPsEKE--SKIPTNTMTDSWSLEvmsqvQVLLYFLQL 196

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 1785350305 572 VFGCRLDALCHRENSTVPKFVCMCIEAVNERGLeADGIYRVNGNLATIQKLRFIVDREEKLDLSTSDW-EDVHVITGALK 650
Cdd:cd04384     2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYiQDIHSVSSLCK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 651 MFFRELPEPLIPFSMFEQYVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGP 730
Cdd:cd04384    81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1785350305 731 TLMRP---EKELFSNIAANM-VYQNQVVEHFL 758
Cdd:cd04384   161 NLLRSkqiESACFSGTAAFMeVRIQSVVVEFI 192

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 1785350305 573 FGCRLDALCHrENSTVPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIVDReeklDLSTSDWED--VHVITGALK 650
Cdd:cd04377     1 FGVSLSSLTS-EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDT----DPDSVNLEDypIHVITSVLK 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 651 MFFRELPEPLIPFSMFEQYVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGP 730
Cdd:cd04377    76 QWLRELPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAP 155

                  ....
gi 1785350305 731 TLMR 734
Cdd:cd04377   156 CILR 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 1785350305 588 VPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRfivdreEKL-------DLSTSDwedVHVITGALKMFFRELPEPL 660
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALK------EKFlrgktvpNLSKVD---IHVICGCLKDFLRSLKEPL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 661 IPFSMFEQYVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEhSETNRMTTQNIGIVFGPTLM-----RP 735
Cdd:cd04382    88 ITFALWKEFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIVgysvpNP 166

                         170       180
                  ....*....|....*....|...
gi 1785350305 736 EKElfsNIAANMVYQNQVVEHFL 758
Cdd:cd04382   167 DPM---TILQDTVRQPRVVERLL 186

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 1785350305 588 VPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKL--RFIVDREEkLDLSTsdwEDVHVITGALKMFFRELPEPLIPFSM 665
Cdd:cd04408    16 VPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLcqAFENGRDL-VDLSG---HSPHDITSVLKHFLKELPEPVLPFQL 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 666 FEQYV-----------EAVQIPDLDER-IETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNIGIVFGPTLM 733
Cdd:cd04408    92 YDDFIalakelqrdseKAAESPSIVENiIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIVFGPTLL 171

                         170       180
                  ....*....|....*....|....
gi 1785350305 734 RP--EKELFSNIAANMVYQNQVVE 755
Cdd:cd04408   172 RPlvGGDVSMICLLDTGYQAQLVE 195

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 1785350305 573 FGCRLDALCHRENSTVPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKL-RFIVDREEKLDLSTSDwedVHVITGALKM 651
Cdd:cd04409     1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLcQAFENGKDLVELSELS---PHDISNVLKL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 652 FFRELPEPLIPFSMFEQYVE-AVQIPDLDERIET---------------------IKDLVSTLPEPNHDTLKHMLSHLKR 709
Cdd:cd04409    78 YLRQLPEPLILFRLYNEFIGlAKESQHVNETQEAkknsdkkwpnmctelnrillkSKDLLRQLPAPNYNTLQFLIVHLHR 157

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1785350305 710 VMEHSETNRMTTQNIGIVFGPTLMRP---EKELFSNIAANMVYQNQVVEHFLTY 760
Cdd:cd04409   158 VSEQAEENKMSASNLGIIFGPTLIRPrptDATVSLSSLVDYPHQARLVELLITY 211

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 1785350305 572 VFGCRLDALCHRE----NSTVPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIVDREEK--LDLSTsdweDVHVI 645
Cdd:cd04390     2 VFGQRLEDTVAYErkfgPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERpsFDSDT----DVHTV 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 646 TGALKMFFRELPEPLIPFSMFEQYVEAVQIPDLDER--IETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQN 723
Cdd:cd04390    78 ASLLKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEkgLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQN 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1785350305 724 IGIVFGPTLMRPEKELFSNIAANMVYQNQVVEHFLTYYEELF 765
Cdd:cd04390   158 LATVFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

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 1785350305 572 VFGCRLDALCHR-----ENSTVPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRfiVDREEKLDLSTSDWEDVHV-- 644
Cdd:cd04391     1 LFGVPLSTLLERdqkkvPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLC--QELEAKFYEGTFLWDQVKQhd 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 645 ITGALKMFFRELPEPLIPFSMFEQYVEAVQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSETNRMTTQNI 724
Cdd:cd04391    79 AASLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNV 158

                  ....*...
gi 1785350305 725 GIVFGPTL 732
Cdd:cd04391   159 AMIMAPNL 166

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 588 VPKFVCMCIEAVNERGLEADGIYRVNGNLATIQKLRFIVDReeKLDLSTSDWEDVHVITGALKMFFRELPEPLIPFSMFE 667
Cdd:cd04376     9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDR--GIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYT 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1785350305 668 QYVEAvQIPDLDERIETIKDLVSTLPEPNHDTLKHMLSHLKRVMEHSET-----------NRMTTQNIGIVFGPTLMRPE 736
Cdd:cd04376    87 AFIGT-ALLEPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLHKQ 165

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1785350305 737 K--ELFSNIAANMVYQN----QVVEHFLTYYEELFSDGPE 770
Cdd:cd04376   166 KsgEREFVQASLRIEEStaiiNVVQTMIDNYEELFMVSPE 205