PDZ domain of ARHGAP21 and ARHGAP23, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGAP21, ARHGAP23, and related domains. This subfamily includes the GAPs (GTPase activating proteins): ARHGAP21 (Rho GTPase-activating protein 21; also known as Rho GTPase-activating protein 10, Rho-type GTPase-activating protein 21) and ARHGAP23 (Rho GTPase-activating protein 23; also known as Rho-type GTPase-activating protein 23). GAPs deactivate Rho GTPases by accelerating GTP hydrolysis. ARHGAP21/23 interact with a planar cell polarity (PCP) protein Pk1 to regulate a lateral signaling pathway in migrating cells. The ARHGAP21 PDZ domain binds claudin-2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGAP21-23-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121   48 PKTVMLKRTSQGFGFTLRHFIVYPPESAIQFSYKDEENGNRGGKQRNRLEPMDTIFVKQVKEGGPAFEAGLCTGDRIIKV 127
Cdd:cd06756      1 PKTVTLQRTSQGFGFTLRHFIVYPPESAVHESLKDEENGNRGGKQRSRLEPMDTIFVKQVKEGGPAHQAGLCTGDRIVKV 80

                           90       100
                   ....*....|....*....|....*....
gi 1864500121  128 NGESVIGKTYSQVIALIQNSDTTLELSVM 156
Cdd:cd06756     81 NGESVIGKTYSQVIALIQNSDSTLELSVM 109

PDZ domain of ARHGAP21 and ARHGAP23, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGAP21, ARHGAP23, and related domains. This subfamily includes the GAPs (GTPase activating proteins): ARHGAP21 (Rho GTPase-activating protein 21; also known as Rho GTPase-activating protein 10, Rho-type GTPase-activating protein 21) and ARHGAP23 (Rho GTPase-activating protein 23; also known as Rho-type GTPase-activating protein 23). GAPs deactivate Rho GTPases by accelerating GTP hydrolysis. ARHGAP21/23 interact with a planar cell polarity (PCP) protein Pk1 to regulate a lateral signaling pathway in migrating cells. The ARHGAP21 PDZ domain binds claudin-2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGAP21-23-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121   48 PKTVMLKRTSQGFGFTLRHFIVYPPESAIQFSYKDEENGNRGGKQRNRLEPMDTIFVKQVKEGGPAFEAGLCTGDRIIKV 127
Cdd:cd06756      1 PKTVTLQRTSQGFGFTLRHFIVYPPESAVHESLKDEENGNRGGKQRSRLEPMDTIFVKQVKEGGPAHQAGLCTGDRIVKV 80

                           90       100
                   ....*....|....*....|....*....
gi 1864500121  128 NGESVIGKTYSQVIALIQNSDTTLELSVM 156
Cdd:cd06756     81 NGESVIGKTYSQVIALIQNSDSTLELSVM 109

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 1864500121  1149 RYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMaDIDIQDDKWrDLNVISSLLKSFFRKLPEPLFTND 1228
Cdd:smart00324    1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGP-DPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYE 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121  1229 KYADFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMThMV 1308
Cdd:smart00324   79 LYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SL 157

                           170
                    ....*....|....*..
gi 1864500121  1309 THMPDQYKIVETLIQHH 1325
Cdd:smart00324  158 KDIRHQNTVIEFLIENA 174

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121   924 KEGWLHfrplvtdkgKRVGGSIRPWKQMYVVLRGHSLYLYKDKrEQTTPSEEEQPISVNACLIDI--SYSETKRKNVFRL 1001
Cdd:smart00233    3 KEGWLY---------KKSGGGKKSWKKRYFVLFNSTLLYYKSK-KDKKSYKPKGSIDLSGCTVREapDPDSSKKPHCFEI 72

                            90       100       110
                    ....*....|....*....|....*....|
gi 1864500121  1002 TTSDCECL-FQAEDRDDMLSWIKTIQESSN 1030
Cdd:smart00233   73 KTSDRKTLlLQAESEEEREKWVEALRKAIA 102

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121  923 AKEGWLHFRPLVTDKGKRVGGSIRPWKQMYVVLRGHSLYLYKDKREQTTPSEEEQPISVNACLIDISYSE---------T 993
Cdd:pfam15410    1 YKKGIVMRKCCFESKGKKTPRGKRSWKMVYAVLKDLVLYLYKDEHPPESSQFEDKKSLKNAPVGKIRLHHalatpapdyT 80

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1864500121  994 KRKNVFRLTTSD-CECLFQAEDRDDMLSWIKTI 1025
Cdd:pfam15410   81 KKSHVFRLQTADgAEYLFQTGSPKELQEWVDTL 113

PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1864500121  103 FVKQVKEGGPAFEAGLCTGDRIIKVNGESVigKTYSQVIALIQNS-DTTLELSV 155
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPV--RSLEDVARLLQGSaGESVTLTV 52

PDZ domain of ARHGAP21 and ARHGAP23, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGAP21, ARHGAP23, and related domains. This subfamily includes the GAPs (GTPase activating proteins): ARHGAP21 (Rho GTPase-activating protein 21; also known as Rho GTPase-activating protein 10, Rho-type GTPase-activating protein 21) and ARHGAP23 (Rho GTPase-activating protein 23; also known as Rho-type GTPase-activating protein 23). GAPs deactivate Rho GTPases by accelerating GTP hydrolysis. ARHGAP21/23 interact with a planar cell polarity (PCP) protein Pk1 to regulate a lateral signaling pathway in migrating cells. The ARHGAP21 PDZ domain binds claudin-2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGAP21-23-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121   48 PKTVMLKRTSQGFGFTLRHFIVYPPESAIQFSYKDEENGNRGGKQRNRLEPMDTIFVKQVKEGGPAFEAGLCTGDRIIKV 127
Cdd:cd06756      1 PKTVTLQRTSQGFGFTLRHFIVYPPESAVHESLKDEENGNRGGKQRSRLEPMDTIFVKQVKEGGPAHQAGLCTGDRIVKV 80

                           90       100
                   ....*....|....*....|....*....
gi 1864500121  128 NGESVIGKTYSQVIALIQNSDTTLELSVM 156
Cdd:cd06756     81 NGESVIGKTYSQVIALIQNSDSTLELSVM 109

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 1864500121  1149 RYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMaDIDIQDDKWrDLNVISSLLKSFFRKLPEPLFTND 1228
Cdd:smart00324    1 KPIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGP-DPDLDLSEY-DVHDVAGLLKLFLRELPEPLITYE 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121  1229 KYADFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMThMV 1308
Cdd:smart00324   79 LYEEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SL 157

                           170
                    ....*....|....*..
gi 1864500121  1309 THMPDQYKIVETLIQHH 1325
Cdd:smart00324  158 KDIRHQNTVIEFLIENA 174

ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with a RhoGAP domain. These proteins functions as a GTPase-activating protein (GAP) for RHOA and CDC42. ARHGAP21 controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. It is recruited to the Golgi by to GTPase, ARF1, through its PH domain and its helical motif. It is also required for CTNNA1 recruitment to adherens junctions. ARHGAP21 and it related proteins all contains a PH domain and a RhoGAP domain. Some of the members have additional N-terminal domains including PDZ, SH3, and SPEC. The ARHGAP21 PH domain interacts with the GTPbound forms of both ARF1 and ARF6 ARF-binding domain/ArfBD. The members here include: ARHGAP15, ARHGAP21, and ARHGAP23. 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 1864500121  923 AKEGWLHFRPLVTDKGKRVggSIRPWKQMYVVLRGHSLYLYKDKREQTTP----SEEEQPISVNACLIDISYSETKRKNV 998
Cdd:cd01253      1 AREGWLHYKQIVTDKGKRV--SDRSWKQAWAVLRGHSLYLYKDKREQTPAlsieLGSEQRISIRGCIVDIAYSYTKRKHV 78

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1864500121  999 FRLTTSD-CECLFQAEDRDDMLSWIKTIQESSNLN 1032
Cdd:cd01253     79 FRLTTSDfSEYLFQAEDRDDMLGWIKAIQENSNAE 113

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 1864500121 1135 FGVRLDDCPPAHtNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDLNVISSLLK 1214
Cdd:cd04372      1 YGCDLTTLVKAH-NTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYPDINVITGALK 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121 1215 SFFRKLPEPLFTNDKYADFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGP 1294
Cdd:cd04372     80 LYFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGP 159

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1864500121 1295 TLVRTSEDNMTHMVTHMPDQYKIVETLIQHHDWFF 1329
Cdd:cd04372    160 TLMRPPEDSALTTLNDMRYQILIVQLLITNEDVLF 194

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 1864500121 1135 FGVRLDDcppaH---TNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIqDDKWRDLNVISS 1211
Cdd:cd04386      5 FGTPLEE----HlkrTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPL-DEFYSDPHAVAS 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121 1212 LLKSFFRKLPEPLFTNDKYADFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIV 1291
Cdd:cd04386     80 ALKSYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIV 159

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1864500121 1292 FGPTLVRTSEDNMTHM--VTHMPDQYKIVETLIQHHDWFFTEE 1332
Cdd:cd04386    160 LAPNLLWAKNEGSLAEmaAGTSVHVVAIVELIISHADWFFPGE 202

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. 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 1864500121 1151 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKgmadiDIQDDKWR--DLNV--ISSLLKSFFRKLPEPLFT 1226
Cdd:cd04385     15 IPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRK-----DARSVQLRegEYTVhdVADVLKRFLRDLPDPLLT 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121 1227 NDKYADFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEdnmtH 1306
Cdd:cd04385     90 SELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDE----H 165

                          170
                   ....*....|....*...
gi 1864500121 1307 MVTHMPDQYKIVETLIQH 1324
Cdd:cd04385    166 SVGQTSHEVKVIEDLIDN 183

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 1864500121 1132 TGTFGVRL----DDCPpahTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMaDIDIQDdkWRDLN 1207
Cdd:cd04404      3 TQQFGVSLqflkEKNP---EQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGE-PVDFDQ--YEDVH 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121 1208 VISSLLKSFFRKLPEPLFTNDKYaDFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRN 1287
Cdd:cd04404     77 LPAVILKTFLRELPEPLLTFDLY-DDIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSN 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1864500121 1288 LAIVFGPTLVRTSEDNMThmVTHMPDQYKIVETLIQHHDWFF 1329
Cdd:cd04404    156 LAVVFGPNLLWAKDASMS--LSAINPINTFTKFLLDHQDEIF 195

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 1864500121 1151 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKwRDLNVISSLLKSFFRKLPEPLFTNDKY 1230
Cdd:cd04387     16 VPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSE-MDVNAIAGTLKLYFRELPEPLFTDELY 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121 1231 ADFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSEDNMTHMVTH 1310
Cdd:cd04387     95 PNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKIPTNT 174

                          170
                   ....*....|...
gi 1864500121 1311 MPDQYKiVETLIQ 1323
Cdd:cd04387    175 MTDSWS-LEVMSQ 186

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 1864500121 1135 FGVRLDDCppAHTNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDdkwRDLNVISSLLK 1214
Cdd:cd04377      1 FGVSLSSL--TSEDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLED---YPIHVITSVLK 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121 1215 SFFRKLPEPLFTNDKYADFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGP 1294
Cdd:cd04377     76 QWLRELPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAP 155

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1864500121 1295 TLVRTSEDnmTHMVTHMPDQYKI---VETLI 1322
Cdd:cd04377    156 CILRCPDT--ADPLQSLQDVSKTttcVETLI 184

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 1864500121 1151 IPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDDKWRDlnvISSLLKSFFRKLPEPLFTNDKY 1230
Cdd:cd04409     16 IPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLVELSELSPHD---ISNVLKLYLRQLPEPLILFRLY 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121 1231 ADFI----------------EANRKEDP-----LDR-LKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNL 1288
Cdd:cd04409     93 NEFIglakesqhvnetqeakKNSDKKWPnmcteLNRiLLKSKDLLRQLPAPNYNTLQFLIVHLHRVSEQAEENKMSASNL 172

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1864500121 1289 AIVFGPTLVR----TSEDNMTHMVTHmPDQYKIVETLIQH 1324
Cdd:cd04409    173 GIIFGPTLIRprptDATVSLSSLVDY-PHQARLVELLITY 211

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 1864500121 1147 TNRYIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGmADIDIQDDKWRDLNVISSLLKSFFRKLPEPLFT 1226
Cdd:cd04383     14 SGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERG-EDPLADDQNDHDINSVAGVLKLYFRGLENPLFP 92

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1864500121 1227 NDKYADFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRTSED 1302
Cdd:cd04383     93 KERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEG 168

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121 1151 IPLIVDICCKLVEERGLeYTGIYRVPGNNAAISSMQEELNKGmADIDIQDDKW-RDLNVISSLLKSFFRKLPEPLFTNDK 1229
Cdd:cd04384     18 VPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSE-QIPDLTKDVYiQDIHSVSSLCKLYFRELPNPLLTYQL 95

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121 1230 YADFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGPTLVRT 1299
Cdd:cd04384     96 YEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRS 165

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. 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 1864500121  925 EGWLHfRPLVTD-KGKRvgGSIRPWKQMYVVLRGHSLYLYKDKR--EQTTPSEEEQPISVNACLIDISYSETKRKNVFRL 1001
Cdd:cd10571      2 EGFLE-RKHEWEsGGKK--ASNRSWKNVYTVLRGQELSFYKDQKaaKSGITYAAEPPLNLYNAVCEVASDYTKKKHVFRL 78

                           90       100
                   ....*....|....*....|....*...
gi 1864500121 1002 TTSD-CECLFQAEDRDDMLSWIKTIQES 1028
Cdd:cd10571     79 KLSDgAEFLFQAKDEEEMNQWVKKISFA 106

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 1864500121 1135 FGVRLDDCPPAHTNryIPLIVDICCKLVEERGLEYTGIYRVPGNNAAISSMQEELNKGMADIDIQDdkwRDLNVISSLLK 1214
Cdd:cd04407      1 FGVRVGSLTSNKTS--VPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLEN---YPIHAITGLLK 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1864500121 1215 SFFRKLPEPLFTNDKYADFIEANRKEDPLDRLKTLKRLIRDLPEHHYETLKFLSAHLKTVAENSEKNKMEPRNLAIVFGP 1294
Cdd:cd04407     76 QWLRELPEPLMTFAQYNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAP 155

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1864500121 1295 TLVRTSEDnmTHMVTHMPDQYKI---VETLIQ 1323
Cdd:cd04407    156 CLLRCPDS--SDPLTSMKDVAKTttcVEMLIK 185

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. 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.