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 1958663764  806 AFGIRLEDCQPATENQRVPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPSDINLQDERWQDLNVISSLL 885
Cdd:cd04395      1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  886 KAFFRKLPEPLFTDDKYNDFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFG 965
Cdd:cd04395     81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1958663764  966 PTLVRTSEDNMTDMVTHMPDRYKIVETLIQHSDWFF 1001
Cdd:cd04395    161 PTLVRTSDDNMETMVTHMPDQCKIVETLIQHYDWFF 196

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains 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
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958663764    1 MDTIFVKNVKEGGPAHRAGLRTGDRLVKVNGESVIGKTYSQVIGLIQNSDDTLELSIM 58
Cdd:cd06756     52 MDTIFVKQVKEGGPAHQAGLCTGDRIVKVNGESVIGKTYSQVIALIQNSDSTLELSVM 109

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 1958663764  806 AFGIRLEDCQPATENQRVPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPSDINLQDERWQDLNVISSLL 885
Cdd:cd04395      1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  886 KAFFRKLPEPLFTDDKYNDFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFG 965
Cdd:cd04395     81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1958663764  966 PTLVRTSEDNMTDMVTHMPDRYKIVETLIQHSDWFF 1001
Cdd:cd04395    161 PTLVRTSDDNMETMVTHMPDQCKIVETLIQHYDWFF 196

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  824 PLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPSDINlqDERWQDLNVISSLLKAFFRKLPEPLFTDDKYN 903
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDL--DLEEEDVHVVASLLKLFLRELPEPLLTFELYE 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958663764  904 DFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFGPTLVRTS 972
Cdd:pfam00620   79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147

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
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958663764    1 MDTIFVKNVKEGGPAHRAGLRTGDRLVKVNGESVIGKTYSQVIGLIQNSDDTLELSIM 58
Cdd:cd06756     52 MDTIFVKQVKEGGPAHQAGLCTGDRIVKVNGESVIGKTYSQVIALIQNSDSTLELSVM 109

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 1958663764   593 IRREGWLYYKqiltkkgkkAGGGLRQWKRVYAVLRARSLSLSKERrepgpaaagaaAAGAGEDEAAPVCIGSCLVDI--S 670
Cdd:smart00233    1 VIKEGWLYKK---------SGGGKKSWKKRYFVLFNSTLLYYKSK-----------KDKKSYKPKGSIDLSGCTVREapD 60

                            90       100       110
                    ....*....|....*....|....*....|....*....
gi 1958663764   671 YSETKRRHVFRLTTADFCEYLFQAEDRDDMLGWIRAIRE 709
Cdd:smart00233   61 PDSSKKPHCFEIKTSDRKTLLLQAESEEEREKWVEALRK 99

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1958663764    5 FVKNVKEGGPAHRAGLRTGDRLVKVNGESVigKTYSQVIGLIQNSDDT 52
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPV--RSLEDVARLLQGSAGE 46

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764   89 PEPPPLCYPRKTYAPPTRAPAWATMVPEPISALPtdPRSPAAWSDPGSRVTSATRAhldnssLGMSQPRPSPGAFPHLPS 168
Cdd:PHA03247  2708 PEPAPHALVSATPLPPGPAAARQASPALPAAPAP--PAVPAGPATPGGPARPARPP------TTAGPPAPAPPAAPAAGP 2779

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  169 ESRTPRAFLESGSRVLPSrlecqqALSHWLSNQIPrRAGERRCPAMPPRARSASqdrledvtthhPWPCSTSqdalsqlg 248
Cdd:PHA03247  2780 PRRLTRPAVASLSESRES------LPSPWDPADPP-AAVLAPAAALPPAASPAG-----------PLPPPTS-------- 2833

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  249 qegwhrarsddylsrATRSAEALGPGAlVSPRLERCGWASqrssartSACPSRDLPGPQAPPAsglqglddigyigyrsy 328
Cdd:PHA03247  2834 ---------------AQPTAPPPPPGP-PPPSLPLGGSVA-------PGGDVRRRPPSRSPAA----------------- 2873

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  329 SPSFQRRTgllhalsfrdsPFGGLPTFSLAQSPASFPPEASEPPRVARPDPSTRALEPPAEDHRDEVVLRQKPPTGRKVQ 408
Cdd:PHA03247  2874 KPAAPARP-----------PVRRLARPAVSRSTESFALPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPP 2942

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958663764  409 LTPARQVNLGFGDESLEPEAR--GERPGRKVAPLATTEDSLASIPFIDEPTSPSidlqaKHVPASAVVSSAMNSA 481
Cdd:PHA03247  2943 LAPTTDPAGAGEPSGAVPQPWlgALVPGRVAVPRFRVPQPAPSREAPASSTPPL-----TGHSLSRVSSWASSLA 3012

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]

                           10        20        30
                   ....*....|....*....|....*....|
gi 1958663764    5 FVKNVKEGGPAHRAGLRTGDRLVKVNGESV 34
Cdd:TIGR02037  260 LVAQVLPGSPAEKAGLKAGDVITSVNGKPI 289

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 1958663764  806 AFGIRLEDCQPATENQRVPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPSDINLQDERWQDLNVISSLL 885
Cdd:cd04395      1 TFGVPLDDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  886 KAFFRKLPEPLFTDDKYNDFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFG 965
Cdd:cd04395     81 KSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFG 160

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1958663764  966 PTLVRTSEDNMTDMVTHMPDRYKIVETLIQHSDWFF 1001
Cdd:cd04395    161 PTLVRTSDDNMETMVTHMPDQCKIVETLIQHYDWFF 196

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  824 PLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPSDINlqDERWQDLNVISSLLKAFFRKLPEPLFTDDKYN 903
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDL--DLEEEDVHVVASLLKLFLRELPEPLLTFELYE 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958663764  904 DFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFGPTLVRTS 972
Cdd:pfam00620   79 EFIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147

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 1958663764  807 FGIRLED-CQpaTENQRVPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRgPSDINLQDERWQDLNVISSLL 885
Cdd:cd04403      1 FGCHLEAlCQ--RENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDH-DEKLDLDDSKWEDIHVITGAL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  886 KAFFRKLPEPLFTDDKYNDFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFG 965
Cdd:cd04403     78 KLFFRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFG 157

                          170       180       190
                   ....*....|....*....|....*....|
gi 1958663764  966 PTLVRtSEDNMTDMVTHMPDRYKIVETLIQ 995
Cdd:cd04403    158 PTLLR-PEQETGNIAVHMVYQNQIVELILL 186

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 1958663764  594 RREGWLYYKQILTKKGKKAGggLRQWKRVYAVLRARSLSLSKERREPGPAAAGAAAAGAgedeaaPVCIGSCLVDISYSE 673
Cdd:cd01253      1 AREGWLHYKQIVTDKGKRVS--DRSWKQAWAVLRGHSLYLYKDKREQTPALSIELGSEQ------RISIRGCIVDIAYSY 72

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1958663764  674 TKRRHVFRLTTADFCEYLFQAEDRDDMLGWIRAIRENSRAE 714
Cdd:cd01253     73 TKRKHVFRLTTSDFSEYLFQAEDRDDMLGWIKAIQENSNAE 113

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 1958663764  814 CQPATENQR-----VPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPSDINLqdeRWQDLNV--ISSLLK 886
Cdd:cd04385      1 DGPALEDQQltdndIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQL---REGEYTVhdVADVLK 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  887 AFFRKLPEPLFTDDKYNDFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFGP 966
Cdd:cd04385     78 RFLRDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGP 157

                          170       180       190
                   ....*....|....*....|....*....|
gi 1958663764  967 TLVRTSEDNMTDMVTHMpdryKIVETLIQH 996
Cdd:cd04385    158 TLFQTDEHSVGQTSHEV----KVIEDLIDN 183

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  807 FGIRLEDCqpATENQRVPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPSDINLQDerwQDLNVISSLLK 886
Cdd:cd04377      1 FGVSLSSL--TSEDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLED---YPIHVITSVLK 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  887 AFFRKLPEPLFTDDKYNDFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFGP 966
Cdd:cd04377     76 QWLRELPEPLMTFELYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAP 155

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1958663764  967 TLVRTSEDnmTDMVTHMPDRYKI---VETLI 994
Cdd:cd04377    156 CILRCPDT--ADPLQSLQDVSKTttcVETLI 184

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. 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 1958663764  826 IVAACCRIVEARGLESTGIYRVPGnnaVVSSLQEQLNRG-------PSDINLQDERWqDLNVISSLLKAFFRKLPEPLFT 898
Cdd:cd04374     31 FVRKCIEAVETRGINEQGLYRVVG---VNSKVQKLLSLGldpktstPGDVDLDNSEW-EIKTITSALKTYLRNLPEPLMT 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  899 DDKYNDFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFGPTLVRTSEDNMTD 978
Cdd:cd04374    107 YELHNDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEETVAA 186

                          170       180
                   ....*....|....*....|
gi 1958663764  979 MvthMPDRYK--IVETLIQH 996
Cdd:cd04374    187 I---MDIKFQniVVEILIEN 203

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 1958663764  807 FGIRLEDCQP-ATENQRVPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGpSDINLQDErwQDLNVISSLL 885
Cdd:cd04404      6 FGVSLQFLKEkNPEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMG-EPVDFDQY--EDVHLPAVIL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  886 KAFFRKLPEPLFTDDKYNDFIEANRIEDSrERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFG 965
Cdd:cd04404     83 KTFLRELPEPLLTFDLYDDIVGFLNVDKE-ERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFG 161

                          170
                   ....*....|..
gi 1958663764  966 PTLVRTSEDNMT 977
Cdd:cd04404    162 PNLLWAKDASMS 173

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 1958663764  819 ENQRVPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPSDINLQdERWQDLNVISSLLKAFFRKLPEPLFT 898
Cdd:cd04387     12 ERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVM-LSEMDVNAIAGTLKLYFRELPEPLFT 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  899 DDKYNDFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFGPTLVRTSEDNMTD 978
Cdd:cd04387     91 DELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKI 170

                          170
                   ....*....|....*..
gi 1958663764  979 MVTHMPDRYKiVETLIQ 995
Cdd:cd04387    171 PTNTMTDSWS-LEVMSQ 186

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 1958663764  820 NQRVPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGpSDINLQDERWQDLNVISSLLKAFFRKLPEPLFTD 899
Cdd:cd04383     15 GQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERG-EDPLADDQNDHDINSVAGVLKLYFRGLENPLFPK 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  900 DKYNDFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFGPTLVRTSEDNmtDM 979
Cdd:cd04383     94 ERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEGQ--DQ 171

                          170
                   ....*....|....*..
gi 1958663764  980 VTHMPDRYKIVETLIQH 996
Cdd:cd04383    172 VSCQAHVNELIKTIIIH 188

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 1958663764  805 RAFGIRLEDCQPATeNQRVPLIVAACCRIVEARGLeSTGIYRVPGNNAVVSSLQEQLNRGPSDINLQDERWQDLNVISSL 884
Cdd:cd04384      1 RVFGCDLTEHLLNS-GQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  885 LKAFFRKLPEPLFTDDKYNDFIEANRIEDSRERMKTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNLALVF 964
Cdd:cd04384     79 CKLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVW 158

                   ....*..
gi 1958663764  965 GPTLVRT 971
Cdd:cd04384    159 APNLLRS 165

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 1958663764  823 VPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPSDINLQDERWQDlnvISSLLKAFFRKLPEPLFTDDKY 902
Cdd:cd04409     16 IPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLVELSELSPHD---ISNVLKLYLRQLPEPLILFRLY 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663764  903 NDFI----EANRIEDSRERMKT------------------LRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRNL 960
Cdd:cd04409     93 NEFIglakESQHVNETQEAKKNsdkkwpnmctelnrillkSKDLLRQLPAPNYNTLQFLIVHLHRVSEQAEENKMSASNL 172

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1958663764  961 ALVFGPTLVR----TSEDNMTDMVTHmPDRYKIVETLIQH 996
Cdd:cd04409    173 GIIFGPTLIRprptDATVSLSSLVDY-PHQARLVELLITY 211

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 1958663764  807 FGIRLEDC----QPATENQRVPLIVAACCRIVEA-RGLESTGIYRVPGNNAVVSSLQEQLNRGpSDINL-QDERWQDLNV 880
Cdd:cd04400      2 FGSPLEEAvelsSHKYNGRDLPSVVYRCIEYLDKnRAIYEEGIFRLSGSASVIKQLKERFNTE-YDVDLfSSSLYPDVHT 80