RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called Rho GTPase-activating protein 20 and ARHGAP20 ) is thought to function in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. RARhoGAP was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth. Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions. The mechanism needs to be further studied. RARhoGAP contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003  14 RTLLCQGPVKLKcFQKTKKKRHLSLFNDVLVVSRILNKREFKIKCIIPLHLLWVVVDDVAQRRKNeICTCKTLYLHCPNG 93
Cdd:cd13319   1 RTFLLEGPVQLT-RGLQTQERHLFLFSDVLVVAKPKSKNSFKLKHKIRLSELWLASCVDEVCEGS-KSADKSFVLGWPTT 78

                        90
                ....*....|....*....
gi 85702003  94 HFWATFRSQEQKDQWHYFL 112
Cdd:cd13319  79 NFVATFSSQEEKDLWLSFL 97

RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called Rho GTPase-activating protein 20 and ARHGAP20 ) is thought to function in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. RARhoGAP was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth. Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions. The mechanism needs to be further studied. RARhoGAP contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003  14 RTLLCQGPVKLKcFQKTKKKRHLSLFNDVLVVSRILNKREFKIKCIIPLHLLWVVVDDVAQRRKNeICTCKTLYLHCPNG 93
Cdd:cd13319   1 RTFLLEGPVQLT-RGLQTQERHLFLFSDVLVVAKPKSKNSFKLKHKIRLSELWLASCVDEVCEGS-KSADKSFVLGWPTT 78

                        90
                ....*....|....*....
gi 85702003  94 HFWATFRSQEQKDQWHYFL 112
Cdd:cd13319  79 NFVATFSSQEEKDLWLSFL 97

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 85702003    303 PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEELDLK--KFSVHEVAWILKEFLGHIKGCVLTSTLYEQW 380
Cdd:smart00324   4 PIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDlsEYDVHDVAGLLKLFLRELPEPLITYELYEEF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003    381 LDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWLP-SYRKVINDIDQK 459
Cdd:smart00324  84 IEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPdGEVASLKDIRHQ 163

                          170
                   ....*....|.
gi 85702003    460 ISLITFMIENS 470
Cdd:smart00324 164 NTVIEFLIENA 174

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003   129 LKIHTEDIPTCDSTLSVTATNLDTVNDIIEKLLPMIRM-RNSEDYQLWFSHSREEAPRALQGFKYPHIIIMTNFQNTCNG 207
Cdd:pfam00788   5 LKVYTEDGKPGTTYKTILVSSSTTAEEVIEALLEKFGLeDDPRDYVLVEVLERGGGERRLPDDECPLQIQLQWPRDASDS 84

                  .
gi 85702003   208 S 208
Cdd:pfam00788  85 R 85

RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called Rho GTPase-activating protein 20 and ARHGAP20 ) is thought to function in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. RARhoGAP was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth. Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions. The mechanism needs to be further studied. RARhoGAP contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003  14 RTLLCQGPVKLKcFQKTKKKRHLSLFNDVLVVSRILNKREFKIKCIIPLHLLWVVVDDVAQRRKNeICTCKTLYLHCPNG 93
Cdd:cd13319   1 RTFLLEGPVQLT-RGLQTQERHLFLFSDVLVVAKPKSKNSFKLKHKIRLSELWLASCVDEVCEGS-KSADKSFVLGWPTT 78

                        90
                ....*....|....*....
gi 85702003  94 HFWATFRSQEQKDQWHYFL 112
Cdd:cd13319  79 NFVATFSSQEEKDLWLSFL 97

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003   303 PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEE--LDLKKFSVHEVAWILKEFLGHIKGCVLTSTLYEQW 380
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDvdLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 85702003   381 LDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWLPS 448
Cdd:pfam00620  81 IEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

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 85702003 311 SVIRKQGPSTEGIFVIAPEETSCKALKEKLESGE-ELDLKKF--SVHEVAWILKEFLGHIKGCVLTSTLYEQWLDVPNKV 387
Cdd:cd04386  29 MCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTfSLPLDEFysDPHAVASALKSYLRELPDPLLTYNLYEDWVQAANKP 108

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 388 NNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWLP----SYRKVINDIDQKISLI 463
Cdd:cd04386 109 DEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNLLWAKnegsLAEMAAGTSVHVVAIV 188

                       170
                ....*....|.
gi 85702003 464 TFMIENSPEIF 474
Cdd:cd04386 189 ELIISHADWFF 199

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 303 PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEELDLKKF-SVHEVAWILKEFLGHIKGCVLTSTLYEQWL 381
Cdd:cd04404  24 PPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYeDVHLPAVILKTFLRELPEPLLTFDLYDDIV 103

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 382 DVPNkVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWLPSYRKVINDIDQKIS 461
Cdd:cd04404 104 GFLN-VDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAKDASMSLSAINPINT 182

                       170
                ....*....|...
gi 85702003 462 LITFMIENSPEIF 474
Cdd:cd04404 183 FTKFLLDHQDEIF 195

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 85702003 289 FGTELSCIYHEGKWPKLIVDIL-SVIRKQGPSTEGIFVIAPEETSCKALKEKLESG-EELDLKKFSVHEVAWILKEFLGH 366
Cdd:cd04377   1 FGVSLSSLTSEDRSVPLVLEKLlEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDpDSVNLEDYPIHVITSVLKQWLRE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 367 IKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWL 446
Cdd:cd04377  81 LPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRC 160

                .
gi 85702003 447 P 447
Cdd:cd04377 161 P 161

Ras-associating (RA) domain found in Rho GTPase-activating protein 20 (RHG20) and similar proteins; RHG20, also termed ARHGAP20, is one of GTPase activating proteins for Rho family proteins (RhoGAPs). It contains a PH-like domain, an RA domain, a RhoGap domain, and two Annexin-like (ANXL) repeats. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin that is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 125 TNLSLKIHTEDIPTCDSTLSVTATNLDTVNDIIEKLLPMIRMR-NSEDYQLWFSHSREEAPRALQGFKYPHIIIMT---N 200
Cdd:cd17115   1 KSIPLKVLNRDVGSCAYSKTLTVSNTDTAKDVIKMALQQFGITgDPSDYQLWVKSGKEESPYPLIGHEYPFSIKMShlrD 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 85702003 201 FQNTCNGSNSRILTAfPALPGMfvQDLNSDAQGHFFLKPR 240
Cdd:cd17115  81 AARQSDGDNLNILDL-DHLSSM--ENLPPEAQCQFILRPS 117

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 85702003 288 LFGTELSCIYHE-----GKWPKLIVDILSVIRKQgPSTEGIFVIAPEETSCKALKEKLESGEELdLKKFSVHEVAWILKE 362
Cdd:cd04394   1 VFGVPLHSLPHStvpeyGNVPKFLVDACTFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGGEAC-LSSALPCDVAGLLKQ 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 363 FLGHIKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASS 442
Cdd:cd04394  79 FFRELPEPLLPYDLHEALLKAQELPTDEERKSATLLLTCLLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPN 158

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 85702003 443 ILwlpsyrkVINDIDQKIS------------LITFMIENSPEI 473
Cdd:cd04394 159 LF-------QSEEGGEKMSsstekrlrlqaaVVQTLIDNASNI 194

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 321 EGIFVIAPEETSCKALKEKLESGEELDL----KKFSVHEVAWILKEFLGHIKGCVLTSTLYEQWLDVPNK-VNNKDKLRA 395
Cdd:cd04400  42 EGIFRLSGSASVIKQLKERFNTEYDVDLfsssLYPDVHTVAGLLKLYLRELPTLILGGELHNDFKRLVEEnHDRSQRALE 121

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 85702003 396 VKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNI 435
Cdd:cd04400 122 LKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRNV 161

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 85702003 303 PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESG-EELDLKKFSVHEVAWILKEFLGHIKGCVLTSTLYEQWL 381
Cdd:cd04407  16 PIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADpENVKLENYPIHAITGLLKQWLRELPEPLMTFAQYNDFL 95

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 85702003 382 ---DVPNKvnnKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWLP 447
Cdd:cd04407  96 ravELPEK---QEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCP 161

RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal LRG1-like proteins. Yeast Lrg1p is required for efficient cell fusion, and mother-daughter cell separation, possibly through acting as a RhoGAP specifically regulating 1,3-beta-glucan synthesis. 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 85702003 303 PKLIVDILSVIRKQGPSTEGIFviaPEETSCKALKEKLE-----SGEELDLKKFSVHEVAWILKEFLGHIKGCVLTSTLY 377
Cdd:cd04397  28 PALIDDIISAMRQMDMSVEGVF---RKNGNIRRLKELTEeidknPTEVPDLSKENPVQLAALLKKFLRELPDPLLTFKLY 104

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 378 EQWLdVPNKVNNKDKLRAVKSLL-DKLPLENAALLGNLFRILHTIASSSSI-----NKMKPYNISTGIASSILWLPSYRK 451
Cdd:cd04397 105 RLWI-SSQKIEDEEERKRVLHLVyCLLPKYHRDTMEVLFSFLKWVSSFSHIdeetgSKMDIHNLATVITPNILYSKTDNP 183

                       170       180
                ....*....|....*....|...
gi 85702003 452 VINDIDQ-KISLITFMIENSPEI 473
Cdd:cd04397 184 NTGDEYFlAIEAVNYLIENNEEF 206

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 85702003 289 FGTELSCI--YHEGKWPKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEELDLKKFS------VHEVAWIL 360
Cdd:cd04398   1 FGVPLEDLilREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLISPedyesdIHSVASLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 361 KEFLGHIKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNIstgia 440
Cdd:cd04398  81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNL----- 155

                       170       180       190
                ....*....|....*....|....*....|....*...
gi 85702003 441 sSILWLPSYRKV----INDIDQKISLITFMIENSPEIF 474
Cdd:cd04398 156 -AIIWGPTLMNAapdnAADMSFQSRVIETLLDNAYQIF 192

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. 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 85702003 298 HEGKWPKLIVDI-LSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEE----LDLKKFSVHEVAWILKEFLGHIKGCVL 372
Cdd:cd04395  13 SENPYVPLIVEVcCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFdidlQDPRWRDVNVVSSLLKSFFRKLPEPLF 92

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 85702003 373 TSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNIS 436
Cdd:cd04395  93 TNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLA 156

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 85702003 303 PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEE-LDLKKFSVHEVAWILKEFLGHIKGCVLTSTLyeqWL 381
Cdd:cd04382  18 PALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTvPNLSKVDIHVICGCLKDFLRSLKEPLITFAL---WK 94

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 85702003 382 DVPNKVNNKDKLRAVKSLLD---KLPLENAALLGnlFRILH-TIASSSSINKMKPYNISTGIASSI 443
Cdd:cd04382  95 EFMEAAEILDEDNSRAALYQaisELPQPNRDTLA--FLILHlQRVAQSPECKMDINNLARVFGPTI 158

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 289 FGTELSCIY--HEGKWPKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLE-SGEELDLKKFS---VHEVAWILKE 362
Cdd:cd04372   1 YGCDLTTLVkaHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDrDGEKADISATVypdINVITGALKL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003 363 FLGHIKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASS 442
Cdd:cd04372  81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                       170       180       190
                ....*....|....*....|....*....|....
gi 85702003 443 ILWLP--SYRKVINDIDQKISLITFMIENSPEIF 474
Cdd:cd04372 161 LMRPPedSALTTLNDMRYQILIVQLLITNEDVLF 194

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003   129 LKIHTEDIPTCDSTLSVTATNLDTVNDIIEKLLPMIRM-RNSEDYQLWFSHSREEAPRALQGFKYPHIIIMTNFQNTCNG 207
Cdd:pfam00788   5 LKVYTEDGKPGTTYKTILVSSSTTAEEVIEALLEKFGLeDDPRDYVLVEVLERGGGERRLPDDECPLQIQLQWPRDASDS 84

                  .
gi 85702003   208 S 208
Cdd:pfam00788  85 R 85

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 85702003 289 FGTELS--CIYHEGKWPKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEELDL---KKFSVHEVAWILKEF 363
Cdd:cd04403   1 FGCHLEalCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLddsKWEDIHVITGALKLF 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 85702003 364 LGHIKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNI 435
Cdd:cd04403  81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNL 152

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85702003  18 CQGPVKLKC--FQKTKKKRHLSLFNDVLVVSRILNKREFKIKCIIPLHLLWVVVDDVAQRRKN--EICT--CKTLYLHCP 91
Cdd:cd00821   1 KEGYLLKRGggGLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPKERPHcfELVTpdGRTYYLQAD 80

                        90
                ....*....|....*..
gi 85702003  92 nghfwatfrSQEQKDQW 108
Cdd:cd00821  81 ---------SEEERQEW 88