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 723539294 1132 FGVKIAIVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEMDVNAIAGTLKLY 1211
Cdd:cd04387     1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1212 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPEPNFVTFLFLLDHLKRVAERESINKMSLHNLATVFGPTL 1291
Cdd:cd04387    81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 723539294 1292 LRPSEKDSKIPANptqpiTMTDSWSLEVMSQVQVLLYFLQL 1332
Cdd:cd04387   161 LRPSEKESKIPTN-----TMTDSWSLEVMSQVQVLLYFLQL 196

C2 domain in the Active BCR (Breakpoint cluster region) Related protein; The ABR protein is similar to the breakpoint cluster region protein. It has homology to guanine nucleotide exchange proteins and GTPase-activating proteins (GAPs). ABR is expressed primarily in the brain, but also includes non-neuronal tissues such as the heart. It has been associated with human diseases such as Miller-Dieker syndrome in which mental retardation and malformations of the heart are present. ABR contains a RhoGEF domain and a PH-like domain upstream of its C2 domain and a RhoGAP domain downstream of this domain. A few members also contain a Bcr-Abl oncoprotein oligomerization domain at the very N-terminal end. Splice variants of ABR have been identified. ABR is found in a wide variety of organisms including chimpanzee, dog, mouse, rat, fruit fly, and mosquito. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294  993 LNVIVHSATGFKQSSNLYCTLEVDSFGYFVNKAKTRVYRDTTEPNWNEEFEIELEGSQTLRILCYEKCYNKTKLtkeDGE 1072
Cdd:cd08686     1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 723539294 1073 STDRIMGKGQIQLEPQALQDKDWQRTVISMNGVEVKLSVKF 1113
Cdd:cd08686    78 GTDAIMGKGQIQLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

Bcr-Abl oncoprotein oligomerization domain; The Bcr-Abl oncoprotein oligomerization domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer. The oligomerization domain is essential for the oncogenicity of the Bcr-Abl protein.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 723539294     3 DPVGFVEAWKAQFADSEPPKMELKSVGDIEQELEMCKASIRRLEMEVNKERFRMIYLQTLLAKEKKSYDRQRW 75
Cdd:pfam09036    1 EPAGFERHWRAEFPEGQVPKMELGSVEDIEQELERCKASLRRLQQELNEEKFKVIYLQTLLARERKSYDRQRW 73

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 723539294 1132 FGVKIAIVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEMDVNAIAGTLKLY 1211
Cdd:cd04387     1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1212 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPEPNFVTFLFLLDHLKRVAERESINKMSLHNLATVFGPTL 1291
Cdd:cd04387    81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 723539294 1292 LRPSEKDSKIPANptqpiTMTDSWSLEVMSQVQVLLYFLQL 1332
Cdd:cd04387   161 LRPSEKESKIPTN-----TMTDSWSLEVMSQVQVLLYFLQL 196

C2 domain in the Active BCR (Breakpoint cluster region) Related protein; The ABR protein is similar to the breakpoint cluster region protein. It has homology to guanine nucleotide exchange proteins and GTPase-activating proteins (GAPs). ABR is expressed primarily in the brain, but also includes non-neuronal tissues such as the heart. It has been associated with human diseases such as Miller-Dieker syndrome in which mental retardation and malformations of the heart are present. ABR contains a RhoGEF domain and a PH-like domain upstream of its C2 domain and a RhoGAP domain downstream of this domain. A few members also contain a Bcr-Abl oncoprotein oligomerization domain at the very N-terminal end. Splice variants of ABR have been identified. ABR is found in a wide variety of organisms including chimpanzee, dog, mouse, rat, fruit fly, and mosquito. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294  993 LNVIVHSATGFKQSSNLYCTLEVDSFGYFVNKAKTRVYRDTTEPNWNEEFEIELEGSQTLRILCYEKCYNKTKLtkeDGE 1072
Cdd:cd08686     1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 723539294 1073 STDRIMGKGQIQLEPQALQDKDWQRTVISMNGVEVKLSVKF 1113
Cdd:cd08686    78 GTDAIMGKGQIQLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294  1148 PYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDvNNKDVSVMMSEMDVNAIAGTLKLYFRELPEPLFTDELYPN 1227
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFD-RGPDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 723539294  1228 FAEGIALSDPVAKESCMLNLLLSLPEPNFVTFLFLLDHLKRVAERESINKMSLHNLATVFGPTLLRPS 1295
Cdd:pfam00620   80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294  579 RKWVLSGILASEETYLSHLEALLLP-MKPLKAaattSQPVLTSQQIETIFFKVPELYEIHKEFYDGLFPRVQQW-SHQQR 656
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVfLKPLDK----ELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWdKSGPR 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294  657 VGDLFQKLASQLGVYRAFVDNYEVAMETAEKCCQANAQFAEISENLKARSTKeskdqttkNSLETLLYKPVDRVTRSTLV 736
Cdd:cd00160    77 IGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESECGR--------LKLESLLLKPVQRLTKYPLL 148

                         170       180       190
                  ....*....|....*....|....*....|...
gi 723539294  737 LHDLLKHTPVSHPDHPLLQDALRISQNFLSSIN 769
Cdd:cd00160   149 LKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181

Bcr-Abl oncoprotein oligomerization domain; The Bcr-Abl oncoprotein oligomerization domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer. The oligomerization domain is essential for the oncogenicity of the Bcr-Abl protein.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 723539294     3 DPVGFVEAWKAQFADSEPPKMELKSVGDIEQELEMCKASIRRLEMEVNKERFRMIYLQTLLAKEKKSYDRQRW 75
Cdd:pfam09036    1 EPAGFERHWRAEFPEGQVPKMELGSVEDIEQELERCKASLRRLQQELNEEKFKVIYLQTLLARERKSYDRQRW 73

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294   991 GFLNVIVHSATG-----FKQSSNLYCTLEVDSFgyfVNKAKTRVYRDTTEPNWNEEFEIEL--EGSQTLRILCYEKcynk 1063
Cdd:pfam00168    1 GRLTVTVIEAKNlppkdGNGTSDPYVKVYLLDG---KQKKKTKVVKNTLNPVWNETFTFSVpdPENAVLEIEVYDY---- 73

                           90       100
                   ....*....|....*....|....*....
gi 723539294  1064 tkltkeDGESTDRIMGKGQIQLEPQALQD 1092
Cdd:pfam00168   74 ------DRFGRDDFIGEVRIPLSELDSGE 96

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 723539294 1132 FGVKIAIVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEMDVNAIAGTLKLY 1211
Cdd:cd04387     1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1212 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPEPNFVTFLFLLDHLKRVAERESINKMSLHNLATVFGPTL 1291
Cdd:cd04387    81 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTL 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 723539294 1292 LRPSEKDSKIPANptqpiTMTDSWSLEVMSQVQVLLYFLQL 1332
Cdd:cd04387   161 LRPSEKESKIPTN-----TMTDSWSLEVMSQVQVLLYFLQL 196

Active breakpoint cluster region-related protein pleckstrin homology (PH) domain; The ABR protein contains multiple domains including a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. It is related to a slightly larger protein, BCR, which is structurally similar, but has an additional N-terminal kinase domain. ABR has GAP activity for both Rac and Cdc42. It promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. It is highly enriched in the brain and found to a lesser extent in heart, lung and muscle. 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 723539294  764 FLSSINEEITPRRQSMTVKKGEHRQLLKDSFMVELVEGARKLRHVFLFTDLFLCAKLKKQIGGKSQQYDCKWYIPLTDLS 843
Cdd:cd13366     1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294  844 FQMVDESEAVPNIPLVPDEELDAMKIKISQIKNDIQREKRANKG-SKVIERLKKKLSEQESLLLLMSPNMAFRVHNRNGK 922
Cdd:cd13366    81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                         170       180
                  ....*....|....*....|....*
gi 723539294  923 SYTFLISSDYERAEWRENIREQQKK 947
Cdd:cd13366   161 SYLFLLSSDYERSEWREAIQKLQKK 185

C2 domain in the Active BCR (Breakpoint cluster region) Related protein; The ABR protein is similar to the breakpoint cluster region protein. It has homology to guanine nucleotide exchange proteins and GTPase-activating proteins (GAPs). ABR is expressed primarily in the brain, but also includes non-neuronal tissues such as the heart. It has been associated with human diseases such as Miller-Dieker syndrome in which mental retardation and malformations of the heart are present. ABR contains a RhoGEF domain and a PH-like domain upstream of its C2 domain and a RhoGAP domain downstream of this domain. A few members also contain a Bcr-Abl oncoprotein oligomerization domain at the very N-terminal end. Splice variants of ABR have been identified. ABR is found in a wide variety of organisms including chimpanzee, dog, mouse, rat, fruit fly, and mosquito. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294  993 LNVIVHSATGFKQSSNLYCTLEVDSFGYFVNKAKTRVYRDTTEPNWNEEFEIELEGSQTLRILCYEKCYNKTKLtkeDGE 1072
Cdd:cd08686     1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 723539294 1073 STDRIMGKGQIQLEPQALQDKDWQRTVISMNGVEVKLSVKF 1113
Cdd:cd08686    78 GTDAIMGKGQIQLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294  1148 PYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDvNNKDVSVMMSEMDVNAIAGTLKLYFRELPEPLFTDELYPN 1227
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFD-RGPDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 723539294  1228 FAEGIALSDPVAKESCMLNLLLSLPEPNFVTFLFLLDHLKRVAERESINKMSLHNLATVFGPTLLRPS 1295
Cdd:pfam00620   80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 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 723539294 1132 FGVKIAIVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEMDVNAIAGTLKLY 1211
Cdd:cd04403     1 FGCHLEALCQRENSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDSKWEDIHVITGALKLF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1212 FRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPEPNFVTFLFLLDHLKRVAERESINKMSLHNLATVFGPTL 1291
Cdd:cd04403    81 FRELPEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTL 160

                         170
                  ....*....|...
gi 723539294 1292 LRPSEKDSKIPAN 1304
Cdd:cd04403   161 LRPEQETGNIAVH 173

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 723539294 1132 FGVKIAIVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNK--DVSVMMSEmDVNAIAGTLK 1209
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEkaDISATVYP-DINVITGALK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1210 LYFRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPEPNFVTFLFLLDHLKRVAERESINKMSLHNLATVFGP 1289
Cdd:cd04372    80 LYFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGP 159

                         170
                  ....*....|
gi 723539294 1290 TLLRPSEKDS 1299
Cdd:cd04372   160 TLMRPPEDSA 169

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 723539294 1132 FGVKIAIVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDvNNKDVsVMMSEMDVNAIAGTLKLY 1211
Cdd:cd04378     1 FGVDFSQVPRDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFE-NGKDL-VELSELSPHDISSVLKLF 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1212 FRELPEPLFTDELYPNFaegIALS--------DPVAKESC---------MLNLLLSLPEPNFVTFLFLLDHLKRVAERES 1274
Cdd:cd04378    79 LRQLPEPLILFRLYNDF---IALAkeiqrdteEDKAPNTPievnriirkLKDLLRQLPASNYNTLQHLIAHLYRVAEQFE 155

                         170       180       190
                  ....*....|....*....|....*....|
gi 723539294 1275 INKMSLHNLATVFGPTLLRPSEKDSKIPAN 1304
Cdd:cd04378   156 ENKMSPNNLGIVFGPTLIRPRPGDADVSLS 185

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294  579 RKWVLSGILASEETYLSHLEALLLP-MKPLKAaattSQPVLTSQQIETIFFKVPELYEIHKEFYDGLFPRVQQW-SHQQR 656
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVfLKPLDK----ELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWdKSGPR 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294  657 VGDLFQKLASQLGVYRAFVDNYEVAMETAEKCCQANAQFAEISENLKARSTKeskdqttkNSLETLLYKPVDRVTRSTLV 736
Cdd:cd00160    77 IGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESECGR--------LKLESLLLKPVQRLTKYPLL 148

                         170       180       190
                  ....*....|....*....|....*....|...
gi 723539294  737 LHDLLKHTPVSHPDHPLLQDALRISQNFLSSIN 769
Cdd:cd00160   149 LKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294    582 VLSGILASEETYLSHLEALL-LPMKPLKAaattSQPVLTSQQIETIFFKVPELYEIHKEFYDGLFPRVQQWSH-QQRVGD 659
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVeVFLKPLKK----ELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDsVERIGD 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294    660 LFQKLASQLGVYRAFVDNYEVAMETAEKCcQANAQFAEISENLkarstkESKDQTTKNSLETLLYKPVDRVTRSTLVLHD 739
Cdd:smart00325   77 VFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEI------ESSPQCRRLTLESLLLKPVQRLTKYPLLLKE 149

                           170       180       190
                    ....*....|....*....|....*....|.
gi 723539294    740 LLKHTPVSHPDHPLLQDALRISQNFLSSINE 770
Cdd:smart00325  150 LLKHTPEDHEDREDLKKALKAIKELANQVNE 180

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1147 VPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFdVNNKDVSvMMSEMDVNAIAGTLKLYFRELPEPLFTDELYP 1226
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKF-LRGKTVP-NLSKVDIHVICGCLKDFLRSLKEPLITFALWK 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1227 NFAEGIALSDPVAKESCMLNLLLSLPEPNFVTFLFLLDHLKRVAErESINKMSLHNLATVFGPTLLrpsekdSKIPANPT 1306
Cdd:cd04382    95 EFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIV------GYSVPNPD 167

                         170       180
                  ....*....|....*....|
gi 723539294 1307 QPITMTDswsleVMSQVQVL 1326
Cdd:cd04382   168 PMTILQD-----TVRQPRVV 182

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 723539294 1131 VFGVKIAIVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDVNNKDVSVMMSEMDVNAIAGTLKL 1210
Cdd:cd04386     4 VFGTPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPLDEFYSDPHAVASALKS 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1211 YFRELPEPLFTDELYPNFAEGIALSDPVAKESCMLNLLLSLPEPNFVTFLFLLDHLKRVAERESINKMSLHNLATVFGPT 1290
Cdd:cd04386    84 YLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPN 163

                  ....*....
gi 723539294 1291 LLRPSEKDS 1299
Cdd:cd04386   164 LLWAKNEGS 172

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 723539294 1150 IVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAA-FDVNNK---DVSVMMSEMDVNAIAGTLKLYFRELPEPLFTDELY 1225
Cdd:cd04374    31 FVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLgLDPKTStpgDVDLDNSEWEIKTITSALKTYLRNLPEPLMTYELH 110

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 723539294 1226 PNFAEGIALSDPVAKESCMLNLLLSLPEPNFVTFLFLLDHLKRVAERESINKMSLHNLATVFGPTLLRPSE 1296
Cdd:cd04374   111 NDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQE 181

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 723539294 1132 FGVKIAIVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDvNNKDVsVMMSEMDVNAIAGTLKLY 1211
Cdd:cd04409     1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFE-NGKDL-VELSELSPHDISNVLKLY 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1212 FRELPEPLFTDELYPNF-------------AEGIALSDPVAKESC---------MLNLLLSLPEPNFVTFLFLLDHLKRV 1269
Cdd:cd04409    79 LRQLPEPLILFRLYNEFiglakesqhvnetQEAKKNSDKKWPNMCtelnrillkSKDLLRQLPAPNYNTLQFLIVHLHRV 158

                         170       180       190
                  ....*....|....*....|....*....|..
gi 723539294 1270 AERESINKMSLHNLATVFGPTLLRPSEKDSKI 1301
Cdd:cd04409   159 SEQAEENKMSASNLGIIFGPTLIRPRPTDATV 190

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 723539294 1132 FGVKIAIVTKRERSKVPYIVRQCVEEIERRGMEEVGIYRVSGVATDIQALKAAFDvNNKDVsVMMSEMDVNAIAGTLKLY 1211
Cdd:cd04408     1 FGVDFSQLPRDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFE-NGRDL-VDLSGHSPHDITSVLKHF 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 723539294 1212 FRELPEPLFTDELYPNFaegIALS-----DPVAKESC----------MLNLLLSLPEPNFVTFLFLLDHLKRVAERESIN 1276
Cdd:cd04408    79 LKELPEPVLPFQLYDDF---IALAkelqrDSEKAAESpsiveniirsLKELLGRLPVSNYNTLRHLMAHLYRVAERFEDN 155