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 637309559 600 FGCNLSSLCQRENTTVPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 679
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 680 FRELPEPLFTFSHFNDFVNAIK-QEPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIVFGPTL 758
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                        170       180
                 ....*....|....*....|....*..
gi 637309559 759 LKPEKETCNIAVHTVYQNQIVELILLE 785
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 637309559 409 EKYGLLNVTKITENGKKLRKNWMPWWAVLQGPSLLFTKTQGGGTSWkfGGNQSKPEFTVDLRGAFIDWAtREKSSKKNVI 488
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKS--GNPYSKPESSVDLRGASIEWA-KEKSSRKNVF 77

                         90       100       110
                 ....*....|....*....|....*....|...
gi 637309559 489 EVKTRQGTELLIQSDNDISVTEWFKVLSYAISK 521
Cdd:cd13233   78 QISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 110

Splicing factor [RNA processing and modification];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 264 EWETHKDSTGRCYYYNKGTQERTWKPPRltrdpSISKGDTLNQVDHEWIKHVDEQGRSYYYNTDGSRSEWALPKYNASPQ 343
Cdd:COG5104   16 EWEELKAPDGRIYYYNKRTGKSSWEKPK-----ELLKGSEEDLDVDPWKECRTADGKVYYYNSITRESRWKIPPERKKVE 90

                         90
                 ....*....|
gi 637309559 344 QPREIIKSRS 353
Cdd:COG5104   91 PIAEQKHDER 100

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 637309559 600 FGCNLSSLCQRENTTVPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 679
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 680 FRELPEPLFTFSHFNDFVNAIK-QEPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIVFGPTL 758
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                        170       180
                 ....*....|....*....|....*..
gi 637309559 759 LKPEKETCNIAVHTVYQNQIVELILLE 785
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 637309559   615 VPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWeDIHVITGALKMFFRELPEPLFTFSHFN 694
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559   695 DFVNAIK-QEPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIVFGPTLLKPEKETCNIAVHTV 773
Cdd:smart00324  82 EFIEAAKlEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKDIR 161

                          170
                   ....*....|
gi 637309559   774 YQNQIVELIL 783
Cdd:smart00324 162 HQNTVIEFLI 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 637309559 409 EKYGLLNVTKITENGKKLRKNWMPWWAVLQGPSLLFTKTQGGGTSWkfGGNQSKPEFTVDLRGAFIDWAtREKSSKKNVI 488
Cdd:cd13233    1 EKQGLLNKTKIAENGKKLRKNWSTSWVVLTSSHLLFYKDAKSAAKS--GNPYSKPESSVDLRGASIEWA-KEKSSRKNVF 77

                         90       100       110
                 ....*....|....*....|....*....|...
gi 637309559 489 EVKTRQGTELLIQSDNDISVTEWFKVLSYAISK 521
Cdd:cd13233   78 QISTVTGTEFLLQSDNDTEIREWFDAIKAVIQR 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 637309559   423 GKKLRKNWMPWWAVLQGPSLLFTKTQGGGTSwkfggnqSKPEFTVDLRGAFIDWATREKSSK-KNVIEVKTRQGTELLIQ 501
Cdd:smart00233  11 SGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS-------YKPKGSIDLSGCTVREAPDPDSSKkPHCFEIKTSDRKTLLLQ 83

                           90
                   ....*....|....*....
gi 637309559   502 SDNDISVTEWFKVLSYAIS 520
Cdd:smart00233  84 AESEEEREKWVEALRKAIA 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 637309559 262 NGEWETHKDSTGRCYYYNKGTQERTWKPPRL 292
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 637309559  265 WETHKDSTGRCYYYNKGTQERTWKPP 290
Cdd:pfam00397   5 WEERWDPDGRVYYYNHETGETQWEKP 30

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 637309559    21 YDYEAKDKR-IVIKQGERYILVKKTNDDWWQVKKeENSKPFYVPAQYVK 68
Cdd:smart00326   9 YDYTAQDPDeLSFKKGDIITVLEKSDDGWWKGRL-GRGKEGLFPSNYVE 56

RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 600 FGCNLSSLCQRENTTVPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWEDIHVITGALKMF 679
Cdd:cd04403    1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 680 FRELPEPLFTFSHFNDFVNAIK-QEPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIVFGPTL 758
Cdd:cd04403   81 FRELPEPLFPYSLFNDFVAAIKlSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                        170       180
                 ....*....|....*....|....*..
gi 637309559 759 LKPEKETCNIAVHTVYQNQIVELILLE 785
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 637309559   615 VPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAVNHDEKLDLNDSKWeDIHVITGALKMFFRELPEPLFTFSHFN 694
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559   695 DFVNAIK-QEPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIVFGPTLLKPEKETCNIAVHTV 773
Cdd:smart00324  82 EFIEAAKlEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKDIR 161

                          170
                   ....*....|
gi 637309559   774 YQNQIVELIL 783
Cdd:smart00324 162 HQNTVIEFLI 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 637309559 616 PKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAVNHDEklDLNDSKWEDIHVITGALKMFFRELPEPLFTFSHFND 695
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGE--DIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 696 FVNAIKQE-PRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIVFGPTLLKPEKETCNIAVHTVY 774
Cdd:cd00159   79 FIELAKIEdEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                 ....*....
gi 637309559 775 QNQIVELIL 783
Cdd:cd00159  159 LNEIVEFLI 167

RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 600 FGCNLSSLCQRENTTVPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLR--FAVNHDEKLDLNDSKWE-DIHVITGAL 676
Cdd:cd04398    1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKelFDKDPLNVLLISPEDYEsDIHSVASLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 677 KMFFRELPEPLFTFSHFNDFVNAIKQE-PRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIVFG 755
Cdd:cd04398   81 KLFFRELPEPLLTKALSREFIEAAKIEdESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWG 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 637309559 756 PTLLKpeKETCNIAvHTVYQNQIVELILLELNSIF 790
Cdd:cd04398  161 PTLMN--AAPDNAA-DMSFQSRVIETLLDNAYQIF 192

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 637309559 600 FGCNLSSLCQRENTTVPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAVNHD-EKLDLNDSKWEDIHVITGALKM 678
Cdd:cd04372    1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVYPDINVITGALKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 679 FFRELPEPLFTFSHFNDFVNAIK-QEPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIVFGPT 757
Cdd:cd04372   81 YFRDLPIPVITYDTYPKFIDAAKiSNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                        170       180       190
                 ....*....|....*....|....*....|....
gi 637309559 758 LLKPEKETCNIAVHTV-YQNQIVELILLELNSIF 790
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 637309559 600 FGCNLSSLCQrENTTVPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAVNHD-EKLDLNDSKwedIHVITGALKM 678
Cdd:cd04377    1 FGVSLSSLTS-EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDpDSVNLEDYP---IHVITSVLKQ 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 679 FFRELPEPLFTFSHFNDFVNAIK-QEPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIVFGPT 757
Cdd:cd04377   77 WLRELPEPLMTFELYENFLRAMElEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPC 156

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 637309559 758 LLKpeketCNIAVHTVY-------QNQIVELILLE 785
Cdd:cd04377  157 ILR-----CPDTADPLQslqdvskTTTCVETLIKE 186

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559  13 LYIEVEYDYDYEAKDKRIVIKQGERYILVKKTNDDWWQVKKEENSKPFYVPAQYVKEVTR 72
Cdd:cd12070    1 TYIEVEYDYDYEAKDRKIVIKQGERYILVKKTNDDWWQVKKDENSKPFYVPAQYVKEVTR 60

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 637309559 600 FGCNLSSLCQRENTTVPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKwedIHVITGALKM 678
Cdd:cd04378    1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFeNGKDLVELSELS---PHDISSVLKL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 679 FFRELPEPLFTFSHFNDFVNAIKQ---------------EPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERN 743
Cdd:cd04378   78 FLRQLPEPLILFRLYNDFIALAKEiqrdteedkapntpiEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEEN 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 637309559 744 RMTYQSIAIVFGPTLLKPEKETCNIA----VHTVYQNQIVELIL 783
Cdd:cd04378  158 KMSPNNLGIVFGPTLIRPRPGDADVSlsslVDYGYQARLVEFLI 201

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 637309559 600 FGCNLSSLCQrENTTVPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAVNHDEkldlNDSKWED--IHVITGALK 677
Cdd:cd04407    1 FGVRVGSLTS-NKTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADP----ENVKLENypIHAITGLLK 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 678 MFFRELPEPLFTFSHFNDFVNAI----KQEPRQRVHAVKElikQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIV 753
Cdd:cd04407   76 QWLRELPEPLMTFAQYNDFLRAVelpeKQEQLQAIYRVLE---QLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIV 152

                 ....*..
gi 637309559 754 FGPTLLK 760
Cdd:cd04407  153 FAPCLLR 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 637309559 615 VPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRfavnhdEKL-------DLNDSkweDIHVITGALKMFFRELPEPL 687
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALK------EKFlrgktvpNLSKV---DIHVICGCLKDFLRSLKEPL 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 688 FTFSHFNDFVNAIKQEPRQRVH-AVKELIKQLPKPNQDTMQVLFRHLKKIVENgERNRMTYQSIAIVFGPTL-----LKP 761
Cdd:cd04382   88 ITFALWKEFMEAAEILDEDNSRaALYQAISELPQPNRDTLAFLILHLQRVAQS-PECKMDINNLARVFGPTIvgysvPNP 166

                        170       180
                 ....*....|....*....|....*....
gi 637309559 762 EKETcnIAVHTVYQNQIVELiLLELNSIF 790
Cdd:cd04382  167 DPMT--ILQDTVRQPRVVER-LLEIPSDY 192

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 637309559 600 FGCNLSSLCQRENTT--VPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAVNHDEKL-DLNDSKWEDIHVITGAL 676
Cdd:cd04379    1 FGVPLSRLVEREGESrdVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAvELSEELYPDINVITGVL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 677 KMFFRELPEPLFTFSHFNDFVNAIK----QEPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAI 752
Cdd:cd04379   81 KDYLRELPEPLITPQLYEMVLEALAvalpNDVQTNTHLTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                        170
                 ....*....|..
gi 637309559 753 VFGPTLLKPEKE 764
Cdd:cd04379  161 CFGPVLMFCSQE 172

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 615 VPKFVKLCIDHVEEHG-LDVDGLYRVSGNLAVIQKL--RFAVNHDEKLdLNDSKWEDIHVITGALKMFFRELPEPLFTFS 691
Cdd:cd04400   22 LPSVVYRCIEYLDKNRaIYEEGIFRLSGSASVIKQLkeRFNTEYDVDL-FSSSLYPDVHTVAGLLKLYLRELPTLILGGE 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 692 HFNDF--VNAIKQEPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKKIVENGERNRMTYQSIAIVFGPTLlkpeketcNIA 769
Cdd:cd04400  101 LHNDFkrLVEENHDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRNVCIVFSPTL--------NIP 172

                        170       180
                 ....*....|....*....|..
gi 637309559 770 VhtvyqnQIVELILLELNSIFG 791
Cdd:cd04400  173 A------GIFVLFLTDFDCIFG 188

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 637309559 600 FGCNLSSLCQRENTTVPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLRFAV-NHDEKLDLNDSKWEDIhviTGALKM 678
Cdd:cd04409    1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFeNGKDLVELSELSPHDI---SNVLKL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 637309559 679 FFRELPEPLFTFSHFNDFVNAIKQ-----------------------EPRQRVHAVKELIKQLPKPNQDTMQVLFRHLKK 735
Cdd:cd04409   78 YLRQLPEPLILFRLYNEFIGLAKEsqhvnetqeakknsdkkwpnmctELNRILLKSKDLLRQLPAPNYNTLQFLIVHLHR 157

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 637309559 736 IVENGERNRMTYQSIAIVFGPTLLKPEKETCNIAVHTV----YQNQIVELIL 783
Cdd:cd04409  158 VSEQAEENKMSASNLGIIFGPTLIRPRPTDATVSLSSLvdypHQARLVELLI 209

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 637309559 615 VPKFVKLCIDHVEEHGLDVDGLYRVSGNLAVIQKLR--FAVNHDEKLDLNDSkwedIHVITGALKMFFRELPEPLFTFSH 692
Cdd:cd04376    9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLReeFDRGIDVVLDENHS----VHDVAALLKEFFRDMPDPLLPREL 84