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 1720404197  14 RTLLCQGPVKLKcFQKTKKKRHLSLFNDVLVVSRILNKREFKIKCIIPLHLLWVVVDDVAQRRKNeICTCKTLYLHCPNG 93
Cdd:cd13319     1 RTFLLEGPVQLT-RGLQTQERHLFLFSDVLVVAKPKSKNSFKLKHKIRLSELWLASCVDEVCEGS-KSADKSFVLGWPTT 78

                          90
                  ....*....|....*....
gi 1720404197  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 1720404197  14 RTLLCQGPVKLKcFQKTKKKRHLSLFNDVLVVSRILNKREFKIKCIIPLHLLWVVVDDVAQRRKNeICTCKTLYLHCPNG 93
Cdd:cd13319     1 RTFLLEGPVQLT-RGLQTQERHLFLFSDVLVVAKPKSKNSFKLKHKIRLSELWLASCVDEVCEGS-KSADKSFVLGWPTT 78

                          90
                  ....*....|....*....
gi 1720404197  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 1720404197  303 PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEELDLK--KFSVHEVAWILKEFLGHIKGCVLTSTLYEQW 380
Cdd:smart00324   4 PIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDlsEYDVHDVAGLLKLFLRELPEPLITYELYEEF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197  381 LDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWLP-SYRKVINDIDQK 459
Cdd:smart00324  84 IEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPdGEVASLKDIRHQ 163

                   .
gi 1720404197  460 M 460
Cdd:smart00324 164 N 164

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 1720404197 129 LKIHTEDIPTCDSTLSVTATNLDTVNDIIEKLLPMIRM-RNSEDYQLWFSHSREEAPRALQGFKYPHIIIMTNFQNTCNG 207
Cdd:pfam00788   5 LKVYTEDGKPGTTYKTILVSSSTTAEEVIEALLEKFGLeDDPRDYVLVEVLERGGGERRLPDDECPLQIQLQWPRDASDS 84

                  .
gi 1720404197 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 1720404197  14 RTLLCQGPVKLKcFQKTKKKRHLSLFNDVLVVSRILNKREFKIKCIIPLHLLWVVVDDVAQRRKNeICTCKTLYLHCPNG 93
Cdd:cd13319     1 RTFLLEGPVQLT-RGLQTQERHLFLFSDVLVVAKPKSKNSFKLKHKIRLSELWLASCVDEVCEGS-KSADKSFVLGWPTT 78

                          90
                  ....*....|....*....
gi 1720404197  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 1720404197 303 PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEE--LDLKKFSVHEVAWILKEFLGHIKGCVLTSTLYEQW 380
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDvdLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720404197 381 LDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWLPS 448
Cdd:pfam00620  81 IEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

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 1720404197 287 KLFGTELSCIYHEGKW----PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEELDLKKFS-VHEVAWILK 361
Cdd:cd04393     1 KVFGVPLQELQQAGQPengvPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLSKEAdVCSAASLLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197 362 EFLGHIKGCVLTSTLYEQWLDVPNKVNNKD-KLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIA 440
Cdd:cd04393    81 LFLQELPEGLIPASLQIRLMQLYQDYNGEDeFGRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFG 160

                  ....*...
gi 1720404197 441 SSILWLPS 448
Cdd:cd04393   161 PDVFHVYT 168

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 1720404197 289 FGTELSCIYHEGKWPKLIVDIL-SVIRKQGPSTEGIFVIAPEETSCKALKEKLESG-EELDLKKFSVHEVAWILKEFLGH 366
Cdd:cd04377     1 FGVSLSSLTSEDRSVPLVLEKLlEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDpDSVNLEDYPIHVITSVLKQWLRE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197 367 IKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWL 446
Cdd:cd04377    81 LPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRC 160

                  .
gi 1720404197 447 P 447
Cdd:cd04377   161 P 161

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 1720404197 303 PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEELDLKKF-SVHEVAWILKEFLGHIKGCVLTSTLYEQWL 381
Cdd:cd04404    24 PPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYeDVHLPAVILKTFLRELPEPLLTFDLYDDIV 103

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720404197 382 DVPNkVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWLPS 448
Cdd:cd04404   104 GFLN-VDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAKD 169

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 1720404197 288 LFGTELSCIYHE-----GKWPKLIVDILSVIRKQgPSTEGIFVIAPEETSCKALKEKLESGEELdLKKFSVHEVAWILKE 362
Cdd:cd04394     1 VFGVPLHSLPHStvpeyGNVPKFLVDACTFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGGEAC-LSSALPCDVAGLLKQ 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197 363 FLGHIKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASS 442
Cdd:cd04394    79 FFRELPEPLLPYDLHEALLKAQELPTDEERKSATLLLTCLLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPN 158

                  ..
gi 1720404197 443 IL 444
Cdd:cd04394   159 LF 160

RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP19-like proteins. The function of ArhGAP19 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 1720404197 306 IVDILSVIR--KQGPSTEGIFVIAPEETSCKALKEKLESGEELDLK--KFSVHEVAWILKEFLGHIKGCVLTSTLYEQWL 381
Cdd:cd04392    10 IAQIYQLIEylEKNLRVEGLFRKPGNSARQQELRDLLNSGTDLDLEsgGFHAHDCATVLKGFLGELPEPLLTHAHYPAHL 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720404197 382 DVPNKVNNKDK------------LRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILW 445
Cdd:cd04392    90 QIADLCQFDEKgnktsapdkerlLEALQLLLLLLPEENRNLLKLILDLLYQTAKHEDKNKMSADNLALLFTPHLIC 165

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 1720404197 288 LFGTELSC-------IYHEGKWPKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLES---GEELDLKKFSVHEVA 357
Cdd:cd04391     1 LFGVPLSTllerdqkKVPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAkfyEGTFLWDQVKQHDAA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197 358 WILKEFLGHIKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNIST 437
Cdd:cd04391    81 SLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAM 160

                         170       180
                  ....*....|....*....|..
gi 1720404197 438 GIASSILWLPSYRKVINDIDQK 459
Cdd:cd04391   161 IMAPNLFPPRGKHSKDNESLQE 182

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 1720404197 299 EGKWPKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEELDL--KKFSVHEVAWILKEFLGHIKGCVLTSTL 376
Cdd:cd04373    12 EKPIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNLDLvsKDFTVNAVAGALKSFFSELPDPLIPYSM 91

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720404197 377 YEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNIstgiasSILWLPS 448
Cdd:cd04373    92 HLELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENL------SICFWPT 157

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 1720404197 298 HEGKWPKLIVDI-LSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEE----LDLKKFSVHEVAWILKEFLGHIKGCVL 372
Cdd:cd04395    13 SENPYVPLIVEVcCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFdidlQDPRWRDVNVVSSLLKSFFRKLPEPLF 92

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720404197 373 TSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNIS 436
Cdd:cd04395    93 TNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLA 156

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197 289 FGTELSCIYHEGKW-PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLES-GEELDLKKFSVHEVAWILKEFLGH 366
Cdd:cd04406     1 FGVELSRLTSEDRSvPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTdANSVNLDDYNIHVIASVFKQWLRD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197 367 IKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNISTGIASSILWL 446
Cdd:cd04406    81 LPNPLMTFELYEEFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILRC 160

                  .
gi 1720404197 447 P 447
Cdd:cd04406   161 P 161

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 1720404197 303 PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEEL-DLKKFSVHEVAWILKEFLGHIKGCVLTSTLYEQWL 381
Cdd:cd04378    17 PFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLvELSELSPHDISSVLKLFLRQLPEPLILFRLYNDFI 96

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720404197 382 DVPN---KVNNKDK-----------LRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNIstGI 439
Cdd:cd04378    97 ALAKeiqRDTEEDKapntpievnriIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNL--GI 166

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 1720404197 289 FGTELSCI--YHEGKWPKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEEL-DLKKFSVHEVAWILKEFLG 365
Cdd:cd04408     1 FGVDFSQLprDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLvDLSGHSPHDITSVLKHFLK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197 366 HIKGCVLTSTLYEQWLDVPNKVNN------------KDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPY 433
Cdd:cd04408    81 ELPEPVLPFQLYDDFIALAKELQRdsekaaespsivENIIRSLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPN 160

                  ..
gi 1720404197 434 NI 435
Cdd:cd04408   161 NL 162

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 1720404197 289 FGTELSCI--YHEGKWPKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEELDLKKFS------VHEVAWIL 360
Cdd:cd04398     1 FGVPLEDLilREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLISPedyesdIHSVASLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197 361 KEFLGHIKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNIstgia 440
Cdd:cd04398    81 KLFFRELPEPLLTKALSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNL----- 155

                  ....*...
gi 1720404197 441 sSILWLPS 448
Cdd:cd04398   156 -AIIWGPT 162

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720404197 129 LKIHTEDIPTCDSTLSVTATNLDTVNDIIEKLLPMIRMRNS-EDYQLWFSHSREEAPRALQGFKYPHIIIM 198
Cdd:cd17043     2 LKVYDDDLAPGSAYKSILVSSTTTAREVVQLLLEKYGLEEDpEDYSLYEVSEKQETERVLHDDECPLLIQL 72

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 1720404197 289 FGTELS--CIYHEGKWPKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEELDL---KKFSVHEVAWILKEF 363
Cdd:cd04403     1 FGCHLEalCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLddsKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720404197 364 LGHIKGCVLTSTLYEQWLDVPNKVNNKDKLRAVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNI 435
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNL 152

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 1720404197 289 FGTELSCIYHE----GKWPKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLES---GEELDLKKF-SVHEVAWIL 360
Cdd:cd04379     1 FGVPLSRLVERegesRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERnsaAVELSEELYpDINVITGVL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197 361 KEFLGHIKGCVLTSTLYEQWLDV-----PNKVNNKDKLraVKSLLDKLPLENAALLGNLFRILHTIASSSSINKMKPYNI 435
Cdd:cd04379    81 KDYLRELPEPLITPQLYEMVLEAlavalPNDVQTNTHL--TLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNL 158

                  ..
gi 1720404197 436 ST 437
Cdd:cd04379   159 AV 160

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. 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 1720404197  22 VKLKCFQKTKKK----RHLSLFNDVLV-VSRILNKR-EFKIKCIIPLHllWVVVDDVAQRRKNEICTckTLYlhCPNGHF 95
Cdd:cd01220     9 IREGCLQKLSKKglqqRMFFLFSDVLLyTSRSPTPSlQFKVHGQLPLR--GLMVEESEPEWGVAHCF--TIY--GGNRAL 82

                          90       100
                  ....*....|....*....|....*.
gi 1720404197  96 WATFRSQEQKDQWHYFLQRSIHEAKK 121
Cdd:cd01220    83 TVAASSEEEKERWLEDLQRAIDAAKK 108

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404197 303 PKLIVDILSVIRKQGPSTEGIFVIAPEETSCKALKEKLESGEEL-DLKKFSVHEVAWILKEFLGHIKGCVLTSTLYEQWL 381
Cdd:cd04409    17 PFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLvELSELSPHDISNVLKLYLRQLPEPLILFRLYNEFI 96