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 74205461   1 IKNAFERGEDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMR 80
Cdd:cd04383  52 IKNAFERGEDPLADDQNDHDINSVAGVLKLYFRGLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMR 131

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 74205461  81 YLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQVSCQAHVNELIKTIIIQ 137
Cdd:cd04383 132 YLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEGQDQVSCQAHVNELIKTIIIH 188

envelope glycoprotein C; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74205461  426 QSSAKHTPDVVLDTLEPLKTSPVVAPTSEPSSPLhtqllkDPEPAFQRSASTAGDIACAFRPVKSVK---MAAPVKPPAT 502
Cdd:PHA03269  49 AASRAPDPAVAPTSAASRKPDLAQAPTPAASEKF------DPAPAPHQAASRAPDPAVAPQLAAAPKpdaAEAFTSAAQA 122

                         90       100
                 ....*....|....*....|....*....
gi 74205461  503 RPKPTVFPKTNAT---SPGVNSSASPQAT 528
Cdd:PHA03269 123 HEAPADAGTSAASkkpDPAAHTQHSPPPF 151

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 74205461   1 IKNAFERGEDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMR 80
Cdd:cd04383  52 IKNAFERGEDPLADDQNDHDINSVAGVLKLYFRGLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMR 131

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 74205461  81 YLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQVSCQAHVNELIKTIIIQ 137
Cdd:cd04383 132 YLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEGQDQVSCQAHVNELIKTIIIH 188

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 74205461      1 IKNAFERGEDPLAGDqNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMR 80
Cdd:smart00324  37 LRDAFDSGPDPDLDL-SEYDVHDVAGLLKLFLRELPEPLITYELYEEFIEAAKLEDETERLRALRELLSLLPPANRATLR 115

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 74205461     81 YLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQ-VSCQAHVNELIKTIIIQH 138
Cdd:smart00324 116 YLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVAsLKDIRHQNTVIEFLIENA 174

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        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 74205461    192 EPIEAIAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGR-HNGIDGLIPHQYI 245
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRlGRGKEGLFPSNYV 55

envelope glycoprotein C; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74205461  426 QSSAKHTPDVVLDTLEPLKTSPVVAPTSEPSSPLhtqllkDPEPAFQRSASTAGDIACAFRPVKSVK---MAAPVKPPAT 502
Cdd:PHA03269  49 AASRAPDPAVAPTSAASRKPDLAQAPTPAASEKF------DPAPAPHQAASRAPDPAVAPQLAAAPKpdaAEAFTSAAQA 122

                         90       100
                 ....*....|....*....|....*....
gi 74205461  503 RPKPTVFPKTNAT---SPGVNSSASPQAT 528
Cdd:PHA03269 123 HEAPADAGTSAASkkpDPAAHTQHSPPPF 151

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 74205461   1 IKNAFERGEDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMR 80
Cdd:cd04383  52 IKNAFERGEDPLADDQNDHDINSVAGVLKLYFRGLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMR 131

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 74205461  81 YLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQVSCQAHVNELIKTIIIQ 137
Cdd:cd04383 132 YLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEGQDQVSCQAHVNELIKTIIIH 188

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 74205461      1 IKNAFERGEDPLAGDqNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMR 80
Cdd:smart00324  37 LRDAFDSGPDPDLDL-SEYDVHDVAGLLKLFLRELPEPLITYELYEEFIEAAKLEDETERLRALRELLSLLPPANRATLR 115

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 74205461     81 YLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQ-VSCQAHVNELIKTIIIQH 138
Cdd:smart00324 116 YLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVAsLKDIRHQNTVIEFLIENA 174

Src homology 3 domain of Slit-Robo GTPase Activating Proteins 1, 2, and 3; srGAP1, also called Rho GTPase-Activating Protein 13 (ARHGAP13), is a Cdc42- and RhoA-specific GAP and is expressed later in the development of central nervous system tissues. srGAP2 is expressed in zones of neuronal differentiation. It plays a role in the regeneration of neurons and axons. srGAP3, also called MEGAP (MEntal disorder associated GTPase-Activating Protein), is a Rho GAP with activity towards Rac1 and Cdc42. It impacts cell migration by regulating actin and microtubule cytoskeletal dynamics. The association between srGAP3 haploinsufficiency and mental retardation is under debate. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 74205461 195 EAIAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGIDGLIPHQYIVV 247
Cdd:cd11955   1 EAIAKFDYVGRSARELSFKKGASLLLYHRASDDWWEGRHNGIDGLVPHQYIVV 53

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 74205461 193 PIEAIAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGIDGLIPHQYIVV 247
Cdd:cd11956   1 EVEAVACFDYTGRTAQELSFKRGDVLLLHSKASSDWWRGEHNGMRGLIPHKYISV 55

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. 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 74205461  24 IAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMRYLFAFLNHLSQFSEENMMDPYNL 103
Cdd:cd04402  69 LASVLKDFLRNIPGSLLSSDLYEEWMSALDQENEEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNL 148

                        90       100       110
                ....*....|....*....|....*....|..
gi 74205461 104 AICFGPSLMSVPeghDQVSCQAHVNELIKTII 135
Cdd:cd04402 149 AVCIAPSLLWPP---ASSELQNEDLKKVTSLV 177

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74205461   1 IKNAFERGEDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMR 80
Cdd:cd04386  54 LKAALDAGTFSLPLDEFYSDPHAVASALKSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLR 133

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74205461  81 YLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPE----GHDQVSCQAHVNELIKTIIIQHENIFP 143
Cdd:cd04386 134 YLIKFLSKLAQKSDENKMSPSNIAIVLAPNLLWAKNegslAEMAAGTSVHVVAIVELIISHADWFFP 200

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A 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 74205461   1 IKNAFERGEDPLAgdqNDHDMDsIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMR 80
Cdd:cd04394  53 LKAKLEGGEACLS---SALPCD-VAGLLKQFFRELPEPLLPYDLHEALLKAQELPTDEERKSATLLLTCLLPDEHVNTLR 128

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 74205461  81 YLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQVS 122
Cdd:cd04394 129 YFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQSEEGGEKMS 170

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 74205461   1 IKNAFERgeDPLAGD-----QNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPT 75
Cdd:cd04398  50 LKELFDK--DPLNVLlispeDYESDIHSVASLLKLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDAN 127

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 74205461  76 LIIMRYLFAFLNHLSQFSEENMMDPYNLAICFGPSLM-SVPEGHDQVSCQAHVnelIKTIIIQHENIF 142
Cdd:cd04398 128 YATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLMnAAPDNAADMSFQSRV---IETLLDNAYQIF 192

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 74205461   1 IKNAFERGEDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMR 80
Cdd:cd04387  50 LKAAFDTNNKDVSVMLSEMDVNAIAGTLKLYFRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFL 129

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 74205461  81 YLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPE 116
Cdd:cd04387 130 FLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSE 165

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 74205461   1 IKNAFERGEDP-LAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIM 79
Cdd:cd04384  51 LRHEFDSEQIPdLTKDVYIQDIHSVSSLCKLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTL 130

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 74205461  80 RYLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPE----------GHDQVSCQAHVNELI 131
Cdd:cd04384 131 EFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRSKQiesacfsgtaAFMEVRIQSVVVEFI 192

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 74205461   1 IKNAFERGEDPLAgdQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIR--KVLLVLPKPTLII 78
Cdd:cd04390  56 LQDAFDAGERPSF--DSDTDVHTVASLLKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGElmKQVSILPKVNYNL 133

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74205461  79 MRYLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSvPEGHDQVSC---QAHVNELIKTIIIQHENIF 142
Cdd:cd04390 134 LSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILR-PKVEDPATImegTPQIQQLMTVMISKHEPLF 199

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 74205461   1 IKNAFERGED-PLAGDQNDHDmdsIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMdNLQERAVHIRKVLLVLPKPTLIIM 79
Cdd:cd04376  43 LREEFDRGIDvVLDENHSVHD---VAALLKEFFRDMPDPLLPRELYTAFIGTALL-EPDEQLEALQLLIYLLPPCNCDTL 118

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74205461  80 RYLFAFLNHLSQFSEE-----------NMMDPYNLAICFGPSLMSVPEGHDQVSCQAH--------VNELIKTIIIQHEN 140
Cdd:cd04376 119 HRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLHKQKSGEREFVQASlrieestaIINVVQTMIDNYEE 198

                ....*...
gi 74205461 141 IFPNPREL 148
Cdd:cd04376 199 LFMVSPEL 206

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 74205461   1 IKNAFERgeDPLAGDQN-DH--DMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTM---DNLQERAVHIRKVLLVLP-- 72
Cdd:cd04379  52 LRDAFER--NSAAVELSeELypDINVITGVLKDYLRELPEPLITPQLYEMVLEALAValpNDVQTNTHLTLSIIDCLPls 129

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 74205461  73 -KPTLIIMrylfafLNHLS---QFSEENMMDPYNLAICFGPSLMS 113
Cdd:cd04379 130 aKATLLLL------LDHLSlvlSNSERNKMTPQNLAVCFGPVLMF 168

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        50
                ....*....|....*....|....*....|....*....|....*....|
gi 74205461 196 AIAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGID-GLIPHQY 244
Cdd:cd00174   2 ARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNGGReGLFPANY 51

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 74205461 195 EAIAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGIDGLIPHQYIVV 247
Cdd:cd11782   1 EARAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQV 53

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 74205461 197 IAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRH--NGIDGLIPHQY 244
Cdd:cd11845   3 VALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARHlsTGKEGYIPSNY 52

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 74205461   9 EDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMRYLFAFLNH 88
Cdd:cd04377  55 TDPDSVNLEDYPIHVITSVLKQWLRELPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVR 134

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 74205461  89 LSQFSEENMMDPYNLAICFGPSLMSVPeghDQVSCQAHVNELIKT 133
Cdd:cd04377 135 VALQEEVNRMSANALAIVFAPCILRCP---DTADPLQSLQDVSKT 176

RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a START (StAR-related lipid transfer action) domain. DLC1 has tumor suppressor activity in cell culture. 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 74205461  15 DQNDHDmdsIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMRYLFAFLNHLSQFSE 94
Cdd:cd04375  69 GQQAYD---VADMLKQYFRDLPEPLLTNKLSETFIAIFQYVPKEQRLEAVQCAILLLPDENREVLQTLLYFLSDVAANSQ 145

                        90
                ....*....|....*..
gi 74205461  95 ENMMDPYNLAICFGPSL 111
Cdd:cd04375 146 ENQMTATNLAVCLAPSL 162

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 74205461   197 IAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGR-HNGIDGLIPH 242
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRnKGGKEGLIPS 47

Second Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 74205461 195 EAIAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGID--GLIPHQYIVV 247
Cdd:cd11922   2 EAIAKFNFNGDTQVEMSFRKGERITLLRQVDENWYEGRIPGTSrqGIFPITYVDV 56

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 74205461 195 EAIAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGIDGLIPHQYI 245
Cdd:cd11996   2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 52

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 74205461 195 EAIAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGIDGLIPHQYIVV 247
Cdd:cd11919   2 PARAKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYIEL 54

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 74205461  10 DPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMRYLFAFLNHL 89
Cdd:cd04407  56 DPENVKLENYPIHAITGLLKQWLRELPEPLMTFAQYNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKV 135

                        90       100       110
                ....*....|....*....|....*....|
gi 74205461  90 SQFSEENMMDPYNLAICFGPSLMSVPEGHD 119
Cdd:cd04407 136 ALEEDVNRMSPNALAIVFAPCLLRCPDSSD 165

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 74205461 194 IEAIAKFDYVGRTARELSFKKGASLLLYQRASD-DWWEGRHNGIDGLIPHQYI 245
Cdd:cd11946   1 MEAIAKYDFKATADDELSFKRGDILKVLNEECDqNWYKAELNGKDGFIPKNYI 53

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 74205461 192 EPIEAIakFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGIDGLIPHQYI 245
Cdd:cd11920   1 LPARAV--YDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGIFPISYV 52

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 74205461 198 AKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGIDGLIPHQYI 245
Cdd:cd11877   4 AKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYV 51

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 74205461  17 NDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTM---DNLQERavhIRKVLLVLPKPTLIIMRYLFAFLNHLSQfS 93
Cdd:cd04382  65 SKVDIHVICGCLKDFLRSLKEPLITFALWKEFMEAAEIldeDNSRAA---LYQAISELPQPNRDTLAFLILHLQRVAQ-S 140

                        90       100
                ....*....|....*....|
gi 74205461  94 EENMMDPYNLAICFGPSLMS 113
Cdd:cd04382 141 PECKMDINNLARVFGPTIVG 160

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 74205461 194 IEAIAKFDYVGRTARELSFKKGASLLLYQRASD-DWWEGRH-NGIDGLIPHQYI 245
Cdd:cd11769   2 TECIAKYNFNGASEEDLPFKKGDILTIVAVTKDpNWYKAKNkDGREGMIPANYV 55

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 74205461 196 AIAKFDYVGRTARELSFKKGASLLLYQRASDD-WWEGRHNGIDGLIPHQYI 245
Cdd:cd11830   2 AKARYDFCARDMRELSLKEGDVVKIYNKKGQQgWWRGEINGRIGWFPSTYV 52