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 1958657289 334 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 413
Cdd:cd13366     1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289 414 FPSPEESEASPQVHPFPDHELEDMKVKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 492
Cdd:cd13366    81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                         170       180
                  ....*....|....*....|....*
gi 1958657289 493 SYLFLLSSDYERSEWREAIQKLQKK 517
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 1958657289 563 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 642
Cdd:cd08686     1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958657289 643 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 683
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 1958657289 334 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 413
Cdd:cd13366     1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289 414 FPSPEESEASPQVHPFPDHELEDMKVKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 492
Cdd:cd13366    81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                         170       180
                  ....*....|....*....|....*
gi 1958657289 493 SYLFLLSSDYERSEWREAIQKLQKK 517
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 1958657289 563 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 642
Cdd:cd08686     1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958657289 643 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 683
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 1958657289  717 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 796
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958657289  797 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 871
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 1958657289  152 VLSGFLASEEIYINQLEALL-LPMKPLKATATtsqpVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVTMGH 229
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVeVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDdSVERIGD 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289  230 LFQKLASQLGVYKAFVDNYKVALETAEKCsQSNNQFQKISEELKVKGPkdskdsHTSVTMEALLYKPIDRVTRSTLVLHD 309
Cdd:smart00325  77 VFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQ------CRRLTLESLLLKPVQRLTKYPLLLKE 149

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1958657289  310 LLKHTPVDHPDYPLLQDALRISQNFLSSINE 340
Cdd:smart00325 150 LLKHTPEDHEDREDLKKALKAIKELANQVNE 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 1958657289  562 FLHVIVHSAKGFK-----QSANLYCTLEVDsfGYFVSKAKTRVFRDTTEPKWDEEFEIEL--EGSQSLRIlcyeKCYDKT 634
Cdd:smart00239   1 TLTVKIISARNLPpkdkgGKSDPYVKVSLD--GDPKEKKKTKVVKNTLNPVWNETFEFEVppPELAELEI----EVYDKD 74

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1958657289  635 KVNKDnneivDKImgkGQIQLDPQTVESKNWH 666
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 1958657289  359 LVKDGFLVEMSES---SRKLRHVFLFTDVLLCAKLKKtsagKHQQYDCKWYIPLADLvfpspeeseaspQVHPFPDHELE 435
Cdd:smart00233   1 VIKEGWLYKKSGGgkkSWKKRYFVLFNSTLLYYKSKK----DKKSYKPKGSIDLSGC------------TVREAPDPDSS 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289  436 DMKvkisalkseiqkekankgqsraierlkkkmfenefllllnsptIPFRIHNRNGKSYLFLLSSDYERSEWREAIQKLQ 515
Cdd:smart00233  65 KKP-------------------------------------------HCFEIKTSDRKTLLLQAESEEEREKWVEALRKAI 101

                   .
gi 1958657289  516 K 516
Cdd:smart00233 102 A 102

PH domain; This entry contains a PH domain found in RhoGEF proteins.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958657289 355 ETRQLVKDGFLVEMSESSR------KLRHVFLFTDVLLCA--KLKKTSAGKH----QQYDCKWYIPLAD 411
Cdd:pfam19057   9 GQRYLIRQDDVVETVYNERgevlksKERRLFLLNDLLVCVtvNSKSGSDFGSlpggEKYKLKWSVPLSD 77

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 1958657289 334 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 413
Cdd:cd13366     1 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSEGSRKLRHVFLFTDLLLCAKLKKTAVGKHQQYDCKWYIPLADLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289 414 FPSPEESEASPQVHPFPDHELEDMKVKISALKSEIQKEKANKGQ-SRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 492
Cdd:cd13366    81 FPSPEESESLPQVHTLPDHEIEEMKMKISAIKSEIQKEKKNKKGqSRAIERLKKKMFENESWLLLNSPTIPFRIHNKNGK 160

                         170       180
                  ....*....|....*....|....*
gi 1958657289 493 SYLFLLSSDYERSEWREAIQKLQKK 517
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 1958657289 334 FLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEMSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCKWYIPLADLV 413
Cdd:cd13367     1 FLSSINEEITPRRQSMTVKKGEHRQLLKDSFMVELVEGARKLRHVFLFTDLLLCAKLKKQIGGKSQQYDCKWYIPLADLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289 414 FPSPEESEASPQVHPFPDHELEDMKVKISALKSEIQKEK-ANKGqSRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGK 492
Cdd:cd13367    81 FQTVDESEAVPNIPLIPDEEIDALKVKISQIKSDIQREKrANKG-GKVLERLRKKLSEQESLLLLMSPSMAFRVHNRNGK 159

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1958657289 493 SYLFLLSSDYERSEWREAIQKLQKKDLQAFVLSSV 527
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 1958657289 563 LHVIVHSAKGFKQSANLYCTLEVDSFGYFVSKAKTRVFRDTTEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVnkdNNE 642
Cdd:cd08686     1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKTRVCRDTTEPNWNEEFEIELEGSQTLRILCYEKCYSKVKL---DGE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958657289 643 IVDKIMGKGQIQLDPQTVESKNWHTDVIEMNGIKVEFSMKF 683
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 1958657289  717 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 796
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFD-SGPDPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958657289  797 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKA 871
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 1958657289 718 PYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDanNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYPA 797
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFD--RGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289 798 FMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSEVESKahltsaa 877
Cdd:cd00159    79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDE------- 151

                         170       180
                  ....*....|....*....|
gi 1958657289 878 diWSHDVMAQVQVLLYYLQH 897
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 1958657289 702 FGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDAN-NKDILLMLSDMDINAIAGTLKL 780
Cdd:cd04372     1 YGCDLTTLVKAHNTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDgEKADISATVYPDINVITGALKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289 781 YFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPT 860
Cdd:cd04372    81 YFRDLPIPVITYDTYPKFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPT 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1958657289 861 LLRPSEVESKAHLtsaadiwsHDVMAQVQVLLYYLQHPPISF 902
Cdd:cd04372   161 LMRPPEDSALTTL--------NDMRYQILIVQLLITNEDVLF 194

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 1958657289 149 RKLVLSGFLASEEIYINQLEALLLP-MKPLKATATTsqpvLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVT 226
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVfLKPLDKELLP----LSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDkSGPR 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289 227 MGHLFQKLASQLGVYKAFVDNYKVALETAEKCSQSNNQFQKISEELKvkgpkdskDSHTSVTMEALLYKPIDRVTRSTLV 306
Cdd:cd00160    77 IGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAE--------SECGRLKLESLLLKPVQRLTKYPLL 148

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1958657289 307 LHDLLKHTPVDHPDYPLLQDALRISQNFLSSIN 339
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 1958657289  152 VLSGFLASEEIYINQLEALL-LPMKPLKATATtsqpVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWD-SQVTMGH 229
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVeVFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDdSVERIGD 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289  230 LFQKLASQLGVYKAFVDNYKVALETAEKCsQSNNQFQKISEELKVKGPkdskdsHTSVTMEALLYKPIDRVTRSTLVLHD 309
Cdd:smart00325  77 VFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQ------CRRLTLESLLLKPVQRLTKYPLLLKE 149

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1958657289  310 LLKHTPVDHPDYPLLQDALRISQNFLSSINE 340
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 1958657289 717 VPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFdaNNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLYP 796
Cdd:cd04382    17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKF--LRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFALWK 94

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958657289 797 AFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKePINKMSLHNLATVFGPTL 861
Cdd:cd04382    95 EFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVAQS-PECKMDINNLARVFGPTI 158

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 1958657289 152 VLSGFLASEEIYINQLEALL-----LPMKPLKATAttsqpvltiQQIETIFYKIQDIYEIHKEFYdnLCPKVQQWDSQVT 226
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVevflpPNSKPLSESE---------EEIKTIFSNIEEIYELHRQLL--LEELLKEWISIQR 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289 227 MGHLFQKLASQLGVYKAFVDNYKVALETAEKCSQSNNQFQKISEELKvkgpkdSKDSHTSVTMEALLYKPIDRVTRSTLV 306
Cdd:pfam00621  70 IGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELE------ANPECRGLDLNSFLIKPVQRIPRYPLL 143

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1958657289 307 LHDLLKHTPVDHPDYPLLQDALRISQNFLSSIN 339
Cdd:pfam00621 144 LKELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176

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 1958657289 720 IVRQCIEEVEKRGIEEVGIYRISGVATDIQAL-KAVFD---ANNKDILLMLSDMDINAIAGTLKLYFRELPEPLLTDRLY 795
Cdd:cd04374    31 FVRKCIEAVETRGINEQGLYRVVGVNSKVQKLlSLGLDpktSTPGDVDLDNSEWEIKTITSALKTYLRNLPEPLMTYELH 110

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958657289 796 PAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLATVFGPTLLRPSE 866
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 1958657289 702 FGVKISVVTKRERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDaNNKDiLLMLSDMDINAIAGTLKLY 781
Cdd:cd04409     1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFE-NGKD-LVELSELSPHDISNVLKLY 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958657289 782 FRELPEPLLTDRLYPAFM-------------EGIALSDPAAKENC---------MMHLLRSLPDPNLITFLFLLEHLKRV 839
Cdd:cd04409    79 LRQLPEPLILFRLYNEFIglakesqhvnetqEAKKNSDKKWPNMCtelnrillkSKDLLRQLPAPNYNTLQFLIVHLHRV 158

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1958657289 840 AEKEPINKMSLHNLATVFGPTLLRPSEVESKAHLTSAAD 878
Cdd:cd04409   159 SEQAEENKMSASNLGIIFGPTLIRPRPTDATVSLSSLVD 197

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 1958657289 702 FGVKISVVTKrERSKVPYIVRQCIEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDIllMLSDMDINAIAGTLKLY 781
Cdd:cd04377     1 FGVSLSSLTS-EDRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSV--NLEDYPIHVITSVLKQW 77