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 260593694  935 FGVDIQKVVEKENVGLMVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLCENQYPDINVITGVL 1014
Cdd:cd04379     1 FGVPLSRLVEREGESRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1015 KDYLRELPSPLITKQLYEAVLDAMAKSPlkmsssgcENEPSDSR-LTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVNK 1093
Cdd:cd04379    81 KDYLRELPEPLITPQLYEMVLEALAVAL--------PNDVQTNThLTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNK 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 260593694 1094 MTCQNLAVCFGPVLLNQRQEASTHnNRVFTDSEELASALDFKKHIEVLHYLLQLWP 1149
Cdd:cd04379   153 MTPQNLAVCFGPVLMFCSQEFSRY-GISPTSKMAAVSTVDFKQHIEVLHYLLQIWP 207

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694  800 SGLMSVHFYGAEGLKP-----------PRIDSKDVFCAIQVDSVNKARTAllTCRTTFldmDHTFN----IEIENAQHLK 864
Cdd:cd04014     3 TGTLKIKICEAVDLKPtdwstrhavpkKGSQLLDPYVSIDVDDTHIGKTS--TKPKTN---SPVWNeeftTEVHNGRNLE 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 260593694  865 LVVFSWEPTPRRNRVCcHGTVVLPALFRVTKTHQ-LAVKLEPRGLIYVKVTL 915
Cdd:cd04014    78 LTVFHDAAIGPDDFVA-NCTISFEDLIQRGSGSFdLWVDLEPQGKLHVKIEL 128

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 260593694  935 FGVDIQKVVEKENVGLMVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLCENQYPDINVITGVL 1014
Cdd:cd04379     1 FGVPLSRLVEREGESRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1015 KDYLRELPSPLITKQLYEAVLDAMAKSPlkmsssgcENEPSDSR-LTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVNK 1093
Cdd:cd04379    81 KDYLRELPEPLITPQLYEMVLEALAVAL--------PNDVQTNThLTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNK 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 260593694 1094 MTCQNLAVCFGPVLLNQRQEASTHnNRVFTDSEELASALDFKKHIEVLHYLLQLWP 1149
Cdd:cd04379   153 MTPQNLAVCFGPVLMFCSQEFSRY-GISPTSKMAAVSTVDFKQHIEVLHYLLQIWP 207

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694   953 PLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLCENQypDINVITGVLKDYLRELPSPLITKQLYE 1032
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDLEEE--DVHVVASLLKLFLRELPEPLLTFELYE 78

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 260593694  1033 AVLDAMAKsplkmsssgcENEPSDSRLTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVNKMTCQNLAVCFGPVLL 1108
Cdd:pfam00620   79 EFIEAAKL----------PDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLL 144

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694  800 SGLMSVHFYGAEGLKP-----------PRIDSKDVFCAIQVDSVNKARTAllTCRTTFldmDHTFN----IEIENAQHLK 864
Cdd:cd04014     3 TGTLKIKICEAVDLKPtdwstrhavpkKGSQLLDPYVSIDVDDTHIGKTS--TKPKTN---SPVWNeeftTEVHNGRNLE 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 260593694  865 LVVFSWEPTPRRNRVCcHGTVVLPALFRVTKTHQ-LAVKLEPRGLIYVKVTL 915
Cdd:cd04014    78 LTVFHDAAIGPDDFVA-NCTISFEDLIQRGSGSFdLWVDLEPQGKLHVKIEL 128

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 260593694  935 FGVDIQKVVEKENVGLMVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLCENQYPDINVITGVL 1014
Cdd:cd04379     1 FGVPLSRLVEREGESRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1015 KDYLRELPSPLITKQLYEAVLDAMAKSPlkmsssgcENEPSDSR-LTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVNK 1093
Cdd:cd04379    81 KDYLRELPEPLITPQLYEMVLEALAVAL--------PNDVQTNThLTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNK 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 260593694 1094 MTCQNLAVCFGPVLLNQRQEASTHnNRVFTDSEELASALDFKKHIEVLHYLLQLWP 1149
Cdd:cd04379   153 MTPQNLAVCFGPVLMFCSQEFSRY-GISPTSKMAAVSTVDFKQHIEVLHYLLQIWP 207

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694   953 PLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLCENQypDINVITGVLKDYLRELPSPLITKQLYE 1032
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDLEEE--DVHVVASLLKLFLRELPEPLLTFELYE 78

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 260593694  1033 AVLDAMAKsplkmsssgcENEPSDSRLTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVNKMTCQNLAVCFGPVLL 1108
Cdd:pfam00620   79 EFIEAAKL----------PDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLL 144

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 260593694  935 FGVDIQKVVEKENVglMVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLCENQYpDINVITGVL 1014
Cdd:cd04387     1 FGVKISTVTKRERS--KVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEM-DVNAIAGTL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1015 KDYLRELPSPLITKQLYEAVLDAMAKS-PLKMSSSgcenepsdsrlTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVNK 1093
Cdd:cd04387    78 KLYFRELPEPLFTDELYPNFAEGIALSdPVAKESC-----------MLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNK 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 260593694 1094 MTCQNLAVCFGPVLLNQRQEASTHNNRVFTDSEElasaLDFKKHIEVLHYLLQL 1147
Cdd:cd04387   147 MSLHNLATVFGPTLLRPSEKESKIPTNTMTDSWS----LEVMSQVQVLLYFLQL 196

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 260593694  935 FGVDIQKVVEKEnvGLMVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLC--ENQYPDINVITG 1012
Cdd:cd04398     1 FGVPLEDLILRE--GDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLIspEDYESDIHSVAS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1013 VLKDYLRELPSPLITKQLYEAVLDAmAKSplkmsssgcENEPSDSRLTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVN 1092
Cdd:cd04398    79 LLKLFFRELPEPLLTKALSREFIEA-AKI---------EDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVN 148

                         170
                  ....*....|....*...
gi 260593694 1093 KMTCQNLAVCFGPVLLNQ 1110
Cdd:cd04398   149 RMSVNNLAIIWGPTLMNA 166

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 260593694  935 FGVDIQKVVEKENVGlmVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLCENQYPDInviTGVL 1014
Cdd:cd04378     1 FGVDFSQVPRDFPDE--VPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHDI---SSVL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1015 KDYLRELPSPLITKQLYEAVLdAMAKSPLKMSSSGCE-NEPSDSRLTV----DLLDCLPDVEKATLKMLLDHLKLVASYH 1089
Cdd:cd04378    76 KLFLRQLPEPLILFRLYNDFI-ALAKEIQRDTEEDKApNTPIEVNRIIrklkDLLRQLPASNYNTLQHLIAHLYRVAEQF 154

                         170       180
                  ....*....|....*....|....*..
gi 260593694 1090 EVNKMTCQNLAVCFGPVLLNQRQEAST 1116
Cdd:cd04378   155 EENKMSPNNLGIVFGPTLIRPRPGDAD 181

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 260593694  935 FGVDIQKVVEKENVglmVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLceNQYPdINVITGVL 1014
Cdd:cd04377     1 FGVSLSSLTSEDRS---VPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNL--EDYP-IHVITSVL 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1015 KDYLRELPSPLITKQLYEAVLDAMaksplkmsssGCENEPSDSRLTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVNKM 1094
Cdd:cd04377    75 KQWLRELPEPLMTFELYENFLRAM----------ELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRM 144

                         170
                  ....*....|....
gi 260593694 1095 TCQNLAVCFGPVLL 1108
Cdd:cd04377   145 SANALAIVFAPCIL 158

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 260593694  935 FGVDIQKVVEKENVGlmVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLCENQYPDInviTGVL 1014
Cdd:cd04409     1 FGADFAQVAKKSPDG--IPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLVELSELSPHDI---SNVL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1015 KDYLRELPSPLITKQLYEAVLDaMAKSPLKMSSSGCENEPSD----------SRLTV---DLLDCLPDVEKATLKMLLDH 1081
Cdd:cd04409    76 KLYLRQLPEPLILFRLYNEFIG-LAKESQHVNETQEAKKNSDkkwpnmctelNRILLkskDLLRQLPAPNYNTLQFLIVH 154

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 260593694 1082 LKLVASYHEVNKMTCQNLAVCFGPVLLNQRQEAST 1116
Cdd:cd04409   155 LHRVSEQAEENKMSASNLGIIFGPTLIRPRPTDAT 189

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 260593694  947 NVGLMVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKdSKTVGLCENQypDINVITGVLKDYLRELPSPLI 1026
Cdd:cd04382    12 STSPMIPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLR-GKTVPNLSKV--DIHVICGCLKDFLRSLKEPLI 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1027 TKQLYEAVLDAMaksplkmsssgcENE-PSDSRLTV-DLLDCLPDVEKATLKMLLDHLKLVASyHEVNKMTCQNLAVCFG 1104
Cdd:cd04382    89 TFALWKEFMEAA------------EILdEDNSRAALyQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFG 155

                  ...
gi 260593694 1105 PVL 1107
Cdd:cd04382   156 PTI 158

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 260593694  956 IQKCIVEIEKRGCQVVGLYRLCG-SAAVKKELREAFEKDSKT---VGLCENQYpDINVITGVLKDYLRELPSPLITKQLY 1031
Cdd:cd04374    32 VRKCIEAVETRGINEQGLYRVVGvNSKVQKLLSLGLDPKTSTpgdVDLDNSEW-EIKTITSALKTYLRNLPEPLMTYELH 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1032 EAVLDAmAKSplkmsssgcenEPSDSRLTV--DLLDCLPDVEKATLKMLLDHLKLVASYHEVNKMTCQNLAVCFGPVLLN 1109
Cdd:cd04374   111 NDFINA-AKS-----------ENLESRVNAihSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLR 178

                  ....
gi 260593694 1110 QRQE 1113
Cdd:cd04374   179 PQEE 182

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 260593694  935 FGVDIQKVVEKENVGLMVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKdsktvGLCEN--QYPDINVITG 1012
Cdd:cd04404     6 FGVSLQFLKEKNPEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNM-----GEPVDfdQYEDVHLPAV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1013 VLKDYLRELPSPLITKQLYEAVLdamaksplkmsssGCENEPSDSRLTV--DLLDCLPDVEKATLKMLLDHLKLVASYHE 1090
Cdd:cd04404    81 ILKTFLRELPEPLLTFDLYDDIV-------------GFLNVDKEERVERvkQLLQTLPEENYQVLKYLIKFLVQVSAHSD 147

                         170
                  ....*....|....*...
gi 260593694 1091 VNKMTCQNLAVCFGPVLL 1108
Cdd:cd04404   148 QNKMTNSNLAVVFGPNLL 165

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. 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 260593694  935 FGVDIQKVVEKENvglMVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTvGLCENQYPdINVITGVL 1014
Cdd:cd04373     1 FGVPLANVVTSEK---PIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNL-DLVSKDFT-VNAVAGAL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1015 KDYLRELPSPLITKQLYEAVLDAMAKSPLKMSSSGCEnepsdsrltvDLLDCLPDVEKATLKMLLDHLKLVASYHEVNKM 1094
Cdd:cd04373    76 KSFFSELPDPLIPYSMHLELVEAAKINDREQRLHALK----------ELLKKFPPENFDVFKYVITHLNKVSQNSKVNLM 145

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 260593694 1095 TCQNLAVCFGPVLLNQrqeasthnnrVFTDSEELASALDFKKHIEVLHYL 1144
Cdd:cd04373   146 TSENLSICFWPTLMRP----------DFTSMEALSATRIYQTIIETFIQQ 185

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. 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 260593694  935 FGVDIQKVVEKENVglmVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLceNQYpDINVITGVL 1014
Cdd:cd04406     1 FGVELSRLTSEDRS---VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVNL--DDY-NIHVIASVF 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1015 KDYLRELPSPLITKQLYEAVLDAMaksplkmsssGCENEPSDSRLTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVNKM 1094
Cdd:cd04406    75 KQWLRDLPNPLMTFELYEEFLRAM----------GLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRM 144

                         170
                  ....*....|....
gi 260593694 1095 TCQNLAVCFGPVLL 1108
Cdd:cd04406   145 SANALAIVFAPCIL 158

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 260593694  952 VPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKdSKTVGLCENQYPdiNVITGVLKDYLRELPSPLITKQLY 1031
Cdd:cd04376     9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDR-GIDVVLDENHSV--HDVAALLKEFFRDMPDPLLPRELY 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1032 EAVLDAMAKSPlkmsssgcENEPSDSRLTVDLldcLPDVEKATLKMLLDHLKLVASY---------HEV--NKMTCQNLA 1100
Cdd:cd04376    86 TAFIGTALLEP--------DEQLEALQLLIYL---LPPCNCDTLHRLLKFLHTVAEHaadsidedgQEVsgNKMTSLNLA 154

                  ....*...
gi 260593694 1101 VCFGPVLL 1108
Cdd:cd04376   155 TIFGPNLL 162

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 260593694  951 MVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEK------DSKTvglcenqypDINVITGVLKDYLRELPSP 1024
Cdd:cd04390    21 LVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAgerpsfDSDT---------DVHTVASLLKLYLRELPEP 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1025 LITKQLYEAVLDAmAKSPLKMSSSGCENepsdsrlTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVNKMTCQNLAVCFG 1104
Cdd:cd04390    92 VIPWAQYEDFLSC-AQLLSKDEEKGLGE-------LMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFG 163

                  ....*....
gi 260593694 1105 PVLLNQRQE 1113
Cdd:cd04390   164 PNILRPKVE 172

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 260593694  945 KENVGLMVPLLIQKCIVEIEKRGCQVVGLYRLCGSAAVKKELREAFEKDSKTVGLCENQYpDINVITGVLKDYLRELPSP 1024
Cdd:cd04383    11 IQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDH-DINSVAGVLKLYFRGLENP 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260593694 1025 LITKQLYEAVldamaksplkMSSSGCENEPSDSRLTVDLLDCLPDVEKATLKMLLDHLKLVASYHEVNKMTCQNLAVCFG 1104
Cdd:cd04383    90 LFPKERFEDL----------MSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFG 159

                  ....
gi 260593694 1105 PVLL 1108
Cdd:cd04383   160 PTLM 163