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 767924761 347 RRNARTRNQDSGQAIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPLVDDQNERDINSVAGVLKLYF 426
Cdd:cd04383    4 NGSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLKLYF 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 427 RGLENPLFPKERFQDLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLM 506
Cdd:cd04383   84 RGLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLM 163

                        170       180
                 ....*....|....*....|....*
gi 767924761 507 HIPDGQDPVSCQAHINEVIKTIIIH 531
Cdd:cd04383  164 PVPEGQDQVSCQAHVNELIKTIIIH 188

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 767924761 590 EAIAKFDYMGRSPRELSFKKGASLLLYHRASEDWWEGRHNGVDGLIPHQYIVV 642
Cdd:cd11955    1 EAIAKFDYVGRSARELSFKKGASLLLYHRASDDWWEGRHNGIDGLVPHQYIVV 53

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 767924761 347 RRNARTRNQDSGQAIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPLVDDQNERDINSVAGVLKLYF 426
Cdd:cd04383    4 NGSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLKLYF 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 427 RGLENPLFPKERFQDLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLM 506
Cdd:cd04383   84 RGLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLM 163

                        170       180
                 ....*....|....*....|....*
gi 767924761 507 HIPDGQDPVSCQAHINEVIKTIIIH 531
Cdd:cd04383  164 PVPEGQDQVSCQAHVNELIKTIIIH 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 767924761   361 IPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPLVDDqNERDINSVAGVLKLYFRGLENPLFPKERFQ 440
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDL-SEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761   441 DLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMHIPDGQDP-VSCQA 519
Cdd:smart00324  82 EFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVAsLKDIR 161

                          170
                   ....*....|...
gi 767924761   520 HINEVIKTIIIHH 532
Cdd:smart00324 162 HQNTVIEFLIENA 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 767924761 590 EAIAKFDYMGRSPRELSFKKGASLLLYHRASEDWWEGRHNGVDGLIPHQYIVV 642
Cdd:cd11955    1 EAIAKFDYVGRSARELSFKKGASLLLYHRASDDWWEGRHNGIDGLVPHQYIVV 53

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 767924761  592 IAKFDYMGRSPRELSFKKGASLLLYHRASEDWWEGR-HNGVDGLIPH 637
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRnKGGKEGLIPS 47

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 767924761 347 RRNARTRNQDSGQAIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPLVDDQNERDINSVAGVLKLYF 426
Cdd:cd04383    4 NGSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLKLYF 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 427 RGLENPLFPKERFQDLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLM 506
Cdd:cd04383   84 RGLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLM 163

                        170       180
                 ....*....|....*....|....*
gi 767924761 507 HIPDGQDPVSCQAHINEVIKTIIIH 531
Cdd:cd04383  164 PVPEGQDQVSCQAHVNELIKTIIIH 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 767924761   361 IPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPLVDDqNERDINSVAGVLKLYFRGLENPLFPKERFQ 440
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDL-SEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761   441 DLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMHIPDGQDP-VSCQA 519
Cdd:smart00324  82 EFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVAsLKDIR 161

                          170
                   ....*....|...
gi 767924761   520 HINEVIKTIIIHH 532
Cdd:smart00324 162 HQNTVIEFLIENA 174

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761  362 PLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPlVDDQNERDINSVAGVLKLYFRGLENPLFPKERFQD 441
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDV-DLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767924761  442 LISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMHIPD 510
Cdd:pfam00620  80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Slit-Robo GTPase Activating Protein 1; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Slit-Robo GTPase Activating Proteins (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. Vertebrates contain three isoforms of srGAPs. srGAP1, also called Rho GTPase-Activating Protein 13 (ARHGAP13), is a Cdc42- and RhoA-specific GAP and is expressed later in the development of CNS (central nervous system) tissues. It is an important downstream signaling molecule of Robo1. srGAP1 contains an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. They can induce membrane deformation in the form of long tubules.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761   1 MKTYHMYHAESISAESKLKEAEKQEEKQFNKSGDLSMNLlRHEDRPQRRSSVKKIEKMKEKRQAKYSENKLKCTKARNDY 80
Cdd:cd07683  140 MKTYHMYHTESISAESKLKEAEKQEEKQIGRSGDPVFHI-RLEDRHQRRSSVKKIEKMKEKRQAKYSENKLKSIKARNEY 218

                         90       100       110
                 ....*....|....*....|....*....|....
gi 767924761  81 LLNLAATNAAISKYYIHDVSDLIDCCDLGFHASL 114
Cdd:cd07683  219 LLTLEATNASVFKYYIHDLSDLIDCCDLGYHASL 252

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 767924761 358 GQAIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERgeDP-----LVDDQNERDINSVAGVLKLYFRGLENP 432
Cdd:cd04398   13 GDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDK--DPlnvllISPEDYESDIHSVASLLKLFFRELPEP 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 433 LFPKERFQDLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMhipdGQ 512
Cdd:cd04398   91 LLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLM----NA 166

                        170       180
                 ....*....|....*....|....*..
gi 767924761 513 DPVSCQaHIN---EVIKTIIIHHEAIF 536
Cdd:cd04398  167 APDNAA-DMSfqsRVIETLLDNAYQIF 192

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 767924761 590 EAIAKFDYMGRSPRELSFKKGASLLLYHRASEDWWEGRHNGVDGLIPHQYIVV 642
Cdd:cd11955    1 EAIAKFDYVGRSARELSFKKGASLLLYHRASDDWWEGRHNGIDGLVPHQYIVV 53

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 767924761 361 IPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFErgEDPLVD-DQNERDINSVAGVLKLYFRGLENPLFPKERF 439
Cdd:cd04373   15 IPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFD--QDHNLDlVSKDFTVNAVAGALKSFFSELPDPLIPYSMH 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767924761 440 QDLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMHiPD 510
Cdd:cd04373   93 LELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMR-PD 162

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 767924761 355 QDSGQAIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPLVDDQNERDINSVAGVLKLYFRGLENPLF 434
Cdd:cd04403   10 QRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLFFRELPEPLF 89

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767924761 435 PKERFQDLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMH 507
Cdd:cd04403   90 PYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLR 162

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 767924761 361 IPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGED-PLVDDQNERDinsVAGVLKLYFRGLENPLFPKERF 439
Cdd:cd04376    9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDvVLDENHSVHD---VAALLKEFFRDMPDPLLPRELY 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 440 QDLISTIKLeNPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDE-----------NMMDPYNLAICFGPTLMHI 508
Cdd:cd04376   86 TAFIGTALL-EPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLHK 164

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 767924761 509 PDGQDPVSCQAH--------INEVIKTIIIHHEAIFPSPREL 542
Cdd:cd04376  165 QKSGEREFVQASlrieestaIINVVQTMIDNYEELFMVSPEL 206

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 767924761 357 SGQAIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPLVDDQNERDINSVAGVLKLYFRGLENPLFPK 436
Cdd:cd04386   16 TGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPLDEFYSDPHAVASALKSYLRELPDPLLTY 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 437 ERFQDLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMHIP----DGQ 512
Cdd:cd04386   96 NLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNLLWAKnegsLAE 175

                        170       180
                 ....*....|....*....|....*
gi 767924761 513 DPVSCQAHINEVIKTIIIHHEAIFP 537
Cdd:cd04386  176 MAAGTSVHVVAIVELIISHADWFFP 200

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 767924761 361 IPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPLVDDQNERDINSVAGVLKLYFRGLENPLFPKERFQ 440
Cdd:cd04387   16 VPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLYFRELPEPLFTDELYP 95

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 441 DLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMHIPD 510
Cdd:cd04387   96 NFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSE 165

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 767924761 356 DSGQAIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDpLVD--DQNERDINSVagvLKLYFRGLENPL 433
Cdd:cd04378   11 DFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKD-LVElsELSPHDISSV---LKLFLRQLPEPL 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 434 FPKERFQDLISTIK-------------LENPAER-VHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAI 499
Cdd:cd04378   87 ILFRLYNDFIALAKeiqrdteedkapnTPIEVNRiIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGI 166

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 767924761 500 CFGPTLMHIPDGQDPVSCQA-----HINEVIKTIIIH 531
Cdd:cd04378  167 VFGPTLIRPRPGDADVSLSSlvdygYQARLVEFLITN 203

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a 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 up several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 355 QDSGQ---AIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDplVDDQNERDINSVAGVLKLYFRGLEN 431
Cdd:cd04393   11 QQAGQpenGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEE--VDLSKEADVCSAASLLRLFLQELPE 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 432 PLFPKERFQDLISTI-KLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMHIPD 510
Cdd:cd04393   89 GLIPASLQIRLMQLYqDYNGEDEFGRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFGPDVFHVYT 168

                        170
                 ....*....|....*....
gi 767924761 511 GQDPVSCQAHINEVIKTII 529
Cdd:cd04393  169 DVEDMKEQEICSRIMAKLL 187

RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 355 QDSGQAIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDpLVD--DQNERDINSVagvLKLYFRGLENP 432
Cdd:cd04408   10 RDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRD-LVDlsGHSPHDITSV---LKHFLKELPEP 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 433 LFPKERFQDLISTIKL------------ENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAIC 500
Cdd:cd04408   86 VLPFQLYDDFIALAKElqrdsekaaespSIVENIIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIV 165

                        170
                 ....*....|....*...
gi 767924761 501 FGPTLMHIPDGQD-PVSC 517
Cdd:cd04408  166 FGPTLLRPLVGGDvSMIC 183

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 767924761 361 IPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFErgEDPLVDDQNERDINSVAGVLKLYFRGLENPLFPKERFQ 440
Cdd:cd04377   15 VPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLD--TDPDSVNLEDYPIHVITSVLKQWLRELPEPLMTFELYE 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 441 DLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMHIPDGQDPvscQAH 520
Cdd:cd04377   93 NFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRCPDTADP---LQS 169

                 ....*..
gi 767924761 521 INEVIKT 527
Cdd:cd04377  170 LQDVSKT 176

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 767924761 360 AIP-LVVESCiRYInLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPLVDDQnerdINSVAGVLKLYFRGLENPLFPKER 438
Cdd:cd04394   19 NVPkFLVDAC-TFL-LDHLSTEGLFRKSGSVVRQKELKAKLEGGEACLSSAL----PCDVAGLLKQFFRELPEPLLPYDL 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767924761 439 FQDLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMHIPDGQDPVS 516
Cdd:cd04394   93 HEALLKAQELPTDEERKSATLLLTCLLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQSEEGGEKMS 170

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 767924761 361 IPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFERGEDplVDDQNERDINSVAGVLKLYFRGLENPLFPKERFQ 440
Cdd:cd04382   17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKT--VPNLSKVDIHVICGCLKDFLRSLKEPLITFALWK 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767924761 441 DLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQySDENMMDPYNLAICFGPTLM-HIPDGQDPVS 516
Cdd:cd04382   95 EFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIVgYSVPNPDPMT 170

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) 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 767924761 374 LYGLQQQGIFRVPGSQVEVNDIKNSFERGEDPLvddQNERDINSVAGVLKLYFRGLENPLFPKERFQDLISTikLENPAE 453
Cdd:cd04389   35 LGGFQTEGIFRVPGDIDEVNELKLRVDQWDYPL---SGLEDPHVPASLLKLWLRELEEPLIPDALYQQCISA--SEDPDK 109

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767924761 454 RVHQIQqilvTLPRVVIVVMRYLFAFLNHLSQYS--DENMMDPYNLAICFGP 503
Cdd:cd04389  110 AVEIVQ----KLPIINRLVLCYLINFLQVFAQPEnvAHTKMDVSNLAMVFAP 157

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 767924761 360 AIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFErgEDPLVDDQNERDINSVAGVLKLYFRGLENPLFPKERF 439
Cdd:cd04407   14 SVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQ--ADPENVKLENYPIHAITGLLKQWLRELPEPLMTFAQY 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 440 QDLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLMHIPDGQDPVScqa 519
Cdd:cd04407   92 NDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCPDSSDPLT--- 168

                 ....*...
gi 767924761 520 HINEVIKT 527
Cdd:cd04407  169 SMKDVAKT 176

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 351 RTRNQDSGQAIPLVVESCIRYINLYGLQQQGIFRVPGSQVEVNDIKNSFER---GEDPLVDDQNERDinsVAGVLKLYFR 427
Cdd:cd04391   12 RDQKKVPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAkfyEGTFLWDQVKQHD---AASLLKLFIR 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924761 428 GLENPLFPKERFQDLISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFGPTLM- 506
Cdd:cd04391   89 ELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAMIMAPNLFp 168