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 1720363760 244 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 323
Cdd:cd13366     1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 324 FPSPEESEASPQVHPFPDHELEDMKTKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 402
Cdd:cd13366    81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                         170       180
                  ....*....|....*....|....*
gi 1720363760 403 SYLFLLSSDYERSEWREAIQKLQKK 427
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 1720363760 473 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 552
Cdd:cd08686     1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1720363760 553 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 593
Cdd:cd08686    78 GTDAIMGKGQIQLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

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 1720363760 244 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 323
Cdd:cd13366     1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 324 FPSPEESEASPQVHPFPDHELEDMKTKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 402
Cdd:cd13366    81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                         170       180
                  ....*....|....*....|....*
gi 1720363760 403 SYLFLLSSDYERSEWREAIQKLQKK 427
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 1720363760 473 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 552
Cdd:cd08686     1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1720363760 553 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 593
Cdd:cd08686    78 GTDAIMGKGQIQLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

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 1720363760  627 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 706
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720363760  707 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 781
Cdd:smart00324  82 EFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVAS 156

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 1720363760   82 GPMKPLKATATtsqpVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVTMGHLFQKLASQLGVYKAFVDNYKV 160
Cdd:smart00325  22 VFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDdSVERIGDVFLKLEEFFKIYSEYCSNHPD 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760  161 ALETAEKCsQSNNQFQKISEELKVKGPkdskdsHTSVTMEALLYKPIDRVTRSTLVLHDLLKHTPVDHPDYPLLQDALRI 240
Cdd:smart00325  98 ALELLKKL-KKNPRFQKFLKEIESSPQ------CRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHEDREDLKKALKA 170

                          170
                   ....*....|
gi 1720363760  241 SQNFLSSINE 250
Cdd:smart00325 171 IKELANQVNE 180

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760  472 FLHVIVHSAKGFK-----QSANLYCTLEVDsfGYFVSKAKTRVFRDTTEPKWDEEFEIEL--EGSQSLRIlcyeKCYDKT 544
Cdd:smart00239   1 TLTVKIISARNLPpkdkgGKSDPYVKVSLD--GDPKEKKKTKVVKNTLNPVWNETFEFEVppPELAELEI----EVYDKD 74

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1720363760  545 KVNKDnneivDKImgkGQIQLDPQTVESKNWH 576
Cdd:smart00239  75 RFGRD-----DFI---GQVTIPLSDLLLGGRH 98

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 1720363760  269 LVKDGFLVEMSES---SRKLRHVFLFTDVLLCAKLKKtsagKHQQYDCKWYIPLADLvfpspeeseaspQVHPFPDHELE 345
Cdd:smart00233   1 VIKEGWLYKKSGGgkkSWKKRYFVLFNSTLLYYKSKK----DKKSYKPKGSIDLSGC------------TVREAPDPDSS 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760  346 DMKtkisalkseiqkekankgqsraierlkkkmfenefllllnsptIPFRIHNRNGKSYLFLLSSDYERSEWREAIQKLQ 425
Cdd:smart00233  65 KKP-------------------------------------------HCFEIKTSDRKTLLLQAESEEEREKWVEALRKAI 101

                   .
gi 1720363760  426 K 426
Cdd:smart00233 102 A 102

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760  471 GFLHVIVHSAKGFKQSANlycTLEVDSFGYFV------SKAKTRVFRDTTEPKWDEEFEIELEG-SQSLRIlcyeKCYDK 543
Cdd:COG5038    436 GVVEVKIKSAEGLKKSDS---TINGTVDPYITvtfsdrVIGKTRVKKNTLNPVWNETFYILLNSfTDPLNL----SLYDF 508

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1720363760  544 TKVNKdnneivDKIMGKgqIQLDPQTVESKNWHTDViemngiKVEFSMKF 593
Cdd:COG5038    509 NSFKS------DKVVGS--TQLDLALLHQNPVKKNE------LYEFLRNT 544

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 1720363760 244 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 323
Cdd:cd13366     1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 324 FPSPEESEASPQVHPFPDHELEDMKTKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 402
Cdd:cd13366    81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                         170       180
                  ....*....|....*....|....*
gi 1720363760 403 SYLFLLSSDYERSEWREAIQKLQKK 427
Cdd:cd13366   161 SYLFLLSSDYERSEWREAIQKLQKK 185

Breakpoint Cluster Region-related pleckstrin homology (PH) domain; The BCR gene is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome, a product of a reciprocal translocation between chromosomes 22 and 9. BCR is a GTPase-activating protein (GAP) for RAC1 (primarily) and CDC42. The Dbl region of BCR has the most RhoGEF activity for Cdc42, and less activity towards Rac and Rho. Since BCR possesses both GAP and GEF activities, it may function to temporally regulate the activity of these GTPases. It also displays serine/threonine kinase activity. The BCR protein contains multiple domains including an N-terminal kinase domain, a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. This hierarchy is composed of vertebrate BCRs. 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 1720363760 244 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 323
Cdd:cd13367     1 FLSSINEEITPRRQSMTVKKGEHRQLLKDSFMVELVEGARKLRHVFLFTDLLLCAKLKKQIGGKSQQYDCKWYIPLADLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 324 FPSPEESEASPQVHPFPDHELEDMKTKISALKSEIQKEK-ANKGqSRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 402
Cdd:cd13367    81 FQTVDESEAVPNIPLIPDEEIDALKVKISQIKSDIQREKrANKG-GKVLERLRKKLSEQESLLLLMSPSMAFRVHNRNGK 159

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1720363760 403 SYLFLLSSDYERSEWREAIQKLQKKDLQAFVLSSV 437
Cdd:cd13367   160 SYTFLISSDYERAEWRENIREQQKKCFKSFSLTSL 194

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 1720363760 473 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 552
Cdd:cd08686     1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1720363760 553 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 593
Cdd:cd08686    78 GTDAIMGKGQIQLDPQSLQTKKWQEKVISMNGITVNLSIKF 118

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 1720363760  627 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 706
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720363760  707 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 781
Cdd:smart00324  82 EFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVAS 156

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins 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. The RhoGAPs are one of the major classes of regulators of Rho G proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 628 PYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDanNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYPA 707
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFD--RGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 708 FMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKahltsaa 787
Cdd:cd00159    79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDE------- 151

                         170       180
                  ....*....|....*....|
gi 1720363760 788 diWSHDVMAQVQVLLYYLQH 807
Cdd:cd00159   152 --LLEDIKKLNEIVEFLIEN 169

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 1720363760 612 FGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDAN-NKDILLMLSDMDINAIAGTLKL 690
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVYPDINVITGALKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 691 YFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPT 770
Cdd:cd04372    81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1720363760 771 LLRPSEVESKAHLtsaadiwsHDVMAQVQVLLYYLQHPPISF 812
Cdd:cd04372   161 LMRPPEDSALTTL--------NDMRYQILIVQLLITNEDVLF 194

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 1720363760 611 VFGVKI-SVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAvfDANNKDILLMLSD---MDINAIAG 686
Cdd:cd04395     1 TFGVPLdDCPPSSENPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQE--ELNRGGFDIDLQDprwRDVNVVSS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 687 TLKLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATV 766
Cdd:cd04395    79 LLKSFFRKLPEPLFTNELYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIV 158

                         170
                  ....*....|
gi 1720363760 767 FGPTLLRPSE 776
Cdd:cd04395   159 FGPTLVRTSD 168

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 1720363760 627 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFdaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 706
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKF--LRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFALWK 94

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720363760 707 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKePINKMSLHNLATVFGPTL 771
Cdd:cd04382    95 EFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQS-PECKMDINNLARVFGPTI 158

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 1720363760 611 VFGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEvGIYRISGVATDIQALKAVFDANN-KDILLMLSDMDINAIAGTLK 689
Cdd:cd04384     2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGIVD-GIYRLSGIASNIQRLRHEFDSEQiPDLTKDVYIQDIHSVSSLCK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 690 LYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGP 769
Cdd:cd04384    81 LYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAP 160

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1720363760 770 TLLRPSEVESKAHLTSAADIwshDVMAQVQVLLYYLQH 807
Cdd:cd04384   161 NLLRSKQIESACFSGTAAFM---EVRIQSVVVEFILNH 195

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 1720363760  84 MKPLKATATTsqpvLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVTMGHLFQKLASQLGVYKAFVDNYKVAL 162
Cdd:cd00160    27 LKPLDKELLP----LSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDkSGPRIGDVFLKLAPFFKIYSEYCSNHPDAL 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 163 ETAEKCSQSNNQFQKISEELKvkgpkdskDSHTSVTMEALLYKPIDRVTRSTLVLHDLLKHTPVDHPDYPLLQDALRISQ 242
Cdd:cd00160   103 ELLKKLKKFNKFFQEFLEKAE--------SECGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDGHEDREDLKKALEAIK 174

                  ....*..
gi 1720363760 243 NFLSSIN 249
Cdd:cd00160   175 EVASQVN 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 1720363760 612 FGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDiLLMLSDMDINAIAGTLKLY 691
Cdd:cd04409     1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFE-NGKD-LVELSELSPHDISNVLKLY 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 692 FRELPEPLLTDRLYPAFM-------------EGIALSDPAAKENC---------MMHLLRSLPDPNLITFLFLLEHLKRV 749
Cdd:cd04409    79 LRQLPEPLILFRLYNEFIglakesqhvnetqEAKKNSDKKWPNMCtelnrillkSKDLLRQLPAPNYNTLQFLIVHLHRV 158

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1720363760 750 AEKEPINKMSLHNLATVFGPTLLRPSEVESKAHLTSAAD 788
Cdd:cd04409   159 SEQAEENKMSASNLGIIFGPTLIRPRPTDATVSLSSLVD 197

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 1720363760 624 RSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDR 703
Cdd:cd04385    12 DNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFLRDLPDPLLTSE 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 704 LYPAFMEGIALSDpaAKENCMM--HLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 781
Cdd:cd04385    92 LHAEWIEAAELEN--KDERIARykELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGQ 169

                  .
gi 1720363760 782 H 782
Cdd:cd04385   170 T 170

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720363760 101 QQIETIFYKIQDIYEIHKEFYdnLCPKVQQWDSQVTMGHLFQKLASQLGVYKAFVDNYKVALETAEKCSQSNNQFQKISE 180
Cdd:pfam00621  36 EEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQRIGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLE 113

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720363760 181 ELKvkgpkdSKDSHTSVTMEALLYKPIDRVTRSTLVLHDLLKHTPVDHPDYPLLQDALRISQNFLSSIN 249
Cdd:pfam00621 114 ELE------ANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176