PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called RhoGEF11) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. PRG contains an N-terminal PDZ domain, a regulators of G-protein signaling-like (RGSL) domain, a linker region, and a C-terminal Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. As is the case in p115-RhoGEF, it is thought that the PRG activated by relieving autoinhibition caused by the linker region. 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 530365683  558 RLDATALERASNPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDS 637
Cdd:cd13391     1 RLDATALERASNPLAAEFKNLDLTTRRMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLVLKCHSKTAVGSSDS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530365683  638 KQTFSPVLKLNAVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAVRNA 700
Cdd:cd13391    81 KQTFSPVLKLNSVLIRSVATDKRALFIICTSKLG-PQIYELVALTSSEKNTWMELLEEAVRNA 142

Regulator of G protein signalling-like domain; Members of this family adopt a structure consisting of twelve helices that fold into a compact domain that contains the overall structural scaffold observed in other RGS proteins and three additional helical elements that pack closely to it. Helices 1-9 comprise the RGS (pfam00615) fold, in which helices 4-7 form a classic antiparallel bundle adjacent to the other helices. Like other RGS structures, helices 7 and 8 span the length of the folded domain and form essentially one continuous helix with a kink in the middle. Helices 10-12 form an apparently stable C-terminal extension of the structural domain, and although other RGS proteins lack this structure, these elements are intimately associated with the rest of the structural framework by hydrophobic interactions. Members of the family bind to active G-alpha proteins, promoting GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683     2 LQAEID---SRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGENDLLDLD-----GDPLRERQVAEKQL 73
Cdd:pfam09128   77 VAAELDrrrPELIPEDLHRRYIQTMQERAVPDIQRQLEDFRQKRSMGLTLAEGELSLLDAErdgdrGTLERERRVAEQIL 156

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 530365683    74 AALGDIL---SKYEEDRSAPMDFALNTYMSHAGIR 105
Cdd:pfam09128  157 SKIEEILstsQTFDEERSATIQYVILTYMKHLGVR 191

PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called RhoGEF11) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. PRG contains an N-terminal PDZ domain, a regulators of G-protein signaling-like (RGSL) domain, a linker region, and a C-terminal Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. As is the case in p115-RhoGEF, it is thought that the PRG activated by relieving autoinhibition caused by the linker region. 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 530365683  558 RLDATALERASNPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDS 637
Cdd:cd13391     1 RLDATALERASNPLAAEFKNLDLTTRRMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLVLKCHSKTAVGSSDS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530365683  638 KQTFSPVLKLNAVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAVRNA 700
Cdd:cd13391    81 KQTFSPVLKLNSVLIRSVATDKRALFIICTSKLG-PQIYELVALTSSEKNTWMELLEEAVRNA 142

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 530365683    357 VINELFVTEASHLRTLRVLDLIFYQRMKKEN-LMPREELARLFPNLPELIEIHNSWCEAMKK-LREEGPIIKEISDLMLA 434
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEErIEEWDDSVERIGDVFLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683    435 RfdgparEELQQVAAQFCSYQSIALELIKtKQRKESRFQLFMQEAESHPQCRRLQLRDLIISEMQRLTKYPLLLESIIKH 514
Cdd:smart00325   81 L------EEFFKIYSEYCSNHPDALELLK-KLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKH 153

                           170       180
                    ....*....|....*....|....*..
gi 530365683    515 TEGGTSEHEKLCRARDQCREILKYVNE 541
Cdd:smart00325  154 TPEDHEDREDLKKALKAIKELANQVNE 180

PH domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683   569 NPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSkTAVGSSDSKqTFSPVLKLN 648
Cdd:pfam17838    1 HPLGEEFKKLDLTTRKLIHEGPLTWRNSKGKLVEVHALLLEDILVLLQEKDQKLVLACLS-TGSENVDQK-TQSPIISLK 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 530365683   649 AVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAVR 698
Cdd:pfam17838   79 KLIVREVATDKKAFFLISTSPSD-PQMYELHASTKSERNTWTKLIQDAIE 127

Regulator of G protein signaling (RGS) domain found in the PDZ-Rho guanine nucleotide exchange factor (RhoGEF) protein; The RGS domain is an essential part of the PDZ-RhoGEF (PDZ:Postsynaptic density 95, Disk large, Zona occludens-1; RhoGEF: Rho guanine nucleotide exchange factor; alias PRG) protein, a member of RhoGEFs subfamily of the RGS protein family. The RhoGEFs are peripheral membrane proteins that regulate essential cellular processes, including cell shape, cell migration, and cell cycle progression, as well as gene transcription by linking signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. RhoGEFs subfamily includes leukemia-associated RhoGEF protein (LARG), p115RhoGEF, PDZ-RhoGEF and its rat specific splice variant GTRAP48. The RGS domain of RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and is often refered to as RH (RGS Homology) domain. In contrast to p115RhoGEF and LARG, PDZ-RhoGEF cannot serve as a GTPase-activating protein (GAP), due to the mutation of sites in the RGS domain region that are crucial for GAP activity. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530365683    1 MLQAEIDSRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 53
Cdd:cd08753    93 MLQAEIDLRLRNNEDPRGVLCEAQEAVMPEIQEQIQDYRSKRTLGLGSLYGEN 145

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683  791 DGENRGIRTRNPIHLAFPGPLFMEG--LADSALEDVENLrHLILWSLLPGHTMETQAAQEPEDdLTPTPSVISVTSHPWD 868
Cdd:PHA03307   16 EGGEFFPRPPATPGDAADDLLSGSQgqLVSDSAELAAVT-VVAGAAACDRFEPPTGPPPGPGT-EAPANESRSTPTWSLS 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683  869 PGSPGQAPPGGE-GDNTQLAGLEGERPEQEDmglcslehLPPRTRNSGIWESPELDRNLAEDASSTEAAGGYKVVRKAEV 947
Cdd:PHA03307   94 TLAPASPAREGSpTPPGPSSPDPPPPTPPPA--------SPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGASPAAVASD 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683  948 AGSKVVPALPES--GQSEPGPPEveggtkatgncfyvsmPSGPPDSSTDHSEAPMSPPQPDS-LPAGQTEPQPqLQGGND 1024
Cdd:PHA03307  166 AASSRQAALPLSspEETARAPSS----------------PPAEPPPSTPPAAASPRPPRRSSpISASASSPAP-APGRSA 228

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683 1025 DPRRPSRSPPSLALRDVGMIFHTIEQLTLKLNRLKDmeLAHRELLKSLGGESSGGTTPVGSFHTEAARWTDGSLSPPAKE 1104
Cdd:PHA03307  229 ADDAGASSSDSSSSESSGCGWGPENECPLPRPAPIT--LPTRIWEASGWNGPSSRPGPASSSSSPRERSPSPSPSSPGSG 306

                         330       340       350
                  ....*....|....*....|....*....|....*..
gi 530365683 1105 PLASDSRNSHELGPCPEDGSDAPLEDSTADAAASPGP 1141
Cdd:PHA03307  307 PAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSP 343

PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called RhoGEF11) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. PRG contains an N-terminal PDZ domain, a regulators of G-protein signaling-like (RGSL) domain, a linker region, and a C-terminal Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. As is the case in p115-RhoGEF, it is thought that the PRG activated by relieving autoinhibition caused by the linker region. 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 530365683  558 RLDATALERASNPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDS 637
Cdd:cd13391     1 RLDATALERASNPLAAEFKNLDLTTRRMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLVLKCHSKTAVGSSDS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530365683  638 KQTFSPVLKLNAVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAVRNA 700
Cdd:cd13391    81 KQTFSPVLKLNSVLIRSVATDKRALFIICTSKLG-PQIYELVALTSSEKNTWMELLEEAVRNA 142

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 530365683    357 VINELFVTEASHLRTLRVLDLIFYQRMKKEN-LMPREELARLFPNLPELIEIHNSWCEAMKK-LREEGPIIKEISDLMLA 434
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEErIEEWDDSVERIGDVFLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683    435 RfdgparEELQQVAAQFCSYQSIALELIKtKQRKESRFQLFMQEAESHPQCRRLQLRDLIISEMQRLTKYPLLLESIIKH 514
Cdd:smart00325   81 L------EEFFKIYSEYCSNHPDALELLK-KLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKH 153

                           170       180
                    ....*....|....*....|....*..
gi 530365683    515 TEGGTSEHEKLCRARDQCREILKYVNE 541
Cdd:smart00325  154 TPEDHEDREDLKKALKAIKELANQVNE 180

Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; LARG (also called RhoGEF12) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. LARG contains a N-terminal extension, followed by Dbl homology (DH)-PH domains which bind and catalyze the exchange of GDP for GTP on RhoA in addition to a RGS domain. The active site of RhoA adopts two distinct GDP-excluding conformations among the four unique complexes in the asymmetric unit. The LARG PH domain also contains a potential protein-docking site. LARG forms a homotetramer via its DH domains. 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 530365683  560 DATALERASNPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDSKQ 639
Cdd:cd13390     1 DLSSLKQSEYPMIDELRNLDLTKRKMIHEGPLTWKVNRDKTIDLYTLLLEDILVLLQKQDDRLVLRCHSKILASTADSKH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530365683  640 TFSPVLKLNAVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELL 693
Cdd:cd13390    81 TFSPVIKLNTVLVRQVATDNKAFFVISMSENG-AQIYELVAQTVSEKTVWQDLI 133

Rho guanine nucleotide exchange factor Pleckstrin homology domain; p115RhoGEF (also called LSC, GEF1 or LBCL2) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. In addition to the Dbl homology (DH)-PH domain, p115RhoGEF contains an N-terminal RGS (Regulator of G-protein signalling) domain. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. 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 530365683  575 FKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDSKQTFSPVLKLNAVLIRS 654
Cdd:cd14679     1 FKNIDITKKKLVHEGPLTWRVTKDKAIEVHVLLLDDLLVLLQKQDERLVLKCHSRTTTPTPDGKQMLSPIIKLNSAMTRE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 530365683  655 VATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAV 697
Cdd:cd14679    81 VATDRKAFYVIFTWEQG-AQIYELVAQTVSERKNWCALISETA 122

Regulator of G protein signalling-like domain; Members of this family adopt a structure consisting of twelve helices that fold into a compact domain that contains the overall structural scaffold observed in other RGS proteins and three additional helical elements that pack closely to it. Helices 1-9 comprise the RGS (pfam00615) fold, in which helices 4-7 form a classic antiparallel bundle adjacent to the other helices. Like other RGS structures, helices 7 and 8 span the length of the folded domain and form essentially one continuous helix with a kink in the middle. Helices 10-12 form an apparently stable C-terminal extension of the structural domain, and although other RGS proteins lack this structure, these elements are intimately associated with the rest of the structural framework by hydrophobic interactions. Members of the family bind to active G-alpha proteins, promoting GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683     2 LQAEID---SRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGENDLLDLD-----GDPLRERQVAEKQL 73
Cdd:pfam09128   77 VAAELDrrrPELIPEDLHRRYIQTMQERAVPDIQRQLEDFRQKRSMGLTLAEGELSLLDAErdgdrGTLERERRVAEQIL 156

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 530365683    74 AALGDIL---SKYEEDRSAPMDFALNTYMSHAGIR 105
Cdd:pfam09128  157 SKIEEILstsQTFDEERSATIQYVILTYMKHLGVR 191

Regulator of G protein signaling (RGS) domain found in the Rho guanine nucleotide exchange factor (RhoGEF) protein; The RGS domain found in the Rho guanine nucleotide exchange factor (RhoGEF) protein subfamily of the RGS domain containing protein family, which is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RhoGEFs link signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. The RGS domain of the RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and therefore is often refered to as the RH (RGS Homology) domain. The RGS-GEFs subfamily includes the leukemia-associated RhoGEF (LARG), p115RhoGEF, and PDZ-RhoGEF. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530365683    1 MLQAEIDSRLRNS---EDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 53
Cdd:cd08736    65 SLAAEIDKRLPNLideEDLRRVFQEAQERAMPEIQEQLEDFRQKRTMGLGSLEGEL 120

Rho guanine nucleotide exchange factor 2 Pleckstrin homology (PH) domain; ARHGEF2, also called GEF-H1, acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. It is thought to play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. ARHGEF2 contains a C1 domain followed by Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. 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 530365683  583 RKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKtavgssdskqtfSPVLKLNAVLIRSVATDKRAF 662
Cdd:cd13393     2 RKLIHDGCLLWKTASGRFKDVQVLLMTDVLVFLQEKDQKYIFPTLDK------------PAVISLQNLIVRDIANQEKGM 69

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 530365683  663 FIICTSklgPPQIYELVALTSSDKNTWMELLEEAVR 698
Cdd:cd13393    70 FLISAA---PPEMYEVHAASRDDRNTWMRLIQQTVK 102

Rho guanine nucleotide exchange factor 18 Pleckstrin homology (PH) domain; ARHGEF18, also called p114RhoGEF, is a key regulator of RhoA-Rock2 signaling that is crucial for maintenance of polarity in the vertebrate retinal epithelium, and consequently is essential for cellular differentiation, morphology and eventually organ function. ARHGEF18 contains Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. 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 530365683  583 RKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLkchsktavGSSDSKqtfSPVLKLNAVLIRSVATDKRAF 662
Cdd:cd15794     2 RQLLLEGMLYWKAASGRLKDILALLLTDVLLLLQEKDQKYVF--------ASVDSK---PPVISLQKLIVREVANEEKAM 70

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 530365683  663 FIICTSKLGpPQIYELVALTSSDKNTWMELLEEAV 697
Cdd:cd15794    71 FLISASLNG-PEMYEIHTNSKEDRNTWMAHIRRAV 104

Regulator of G protein signaling (RGS) domain found in the Rho guanine nucleotide exchange factor (RhoGEF) protein; The RGS domain found in the Rho guanine nucleotide exchange factor (RhoGEF) protein subfamily of the RGS domain containing protein family, which is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). The RhoGEFs are peripheral membrane proteins that regulate essential cellular processes, including cell shape, cell migration and cell cycle progression as well as gene transcription by linking signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. The RhoGEF subfamily includes the leukemia-associated RhoGEF protein (LARG), p115RhoGEF, PDZ-RhoGEF, and its rat specific splice variant GTRAP48. The RGS domain of RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and is often refered to as RH (RGS Homology) domain. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530365683    5 EIDSRLRNS----EDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 53
Cdd:cd08756    70 EIDKILQNEqddeEILRRVFLKAREKARDEINDQLADFRQKRTLGLGSIFGPN 122

Regulator of G protein signaling (RGS) domain found in the Rho guanine nucleotide exchange factor (GEF), p115 RhoGEF; The RGS (Regulator of G-protein Signaling) domain is an essential part of the p115RhoGEF protein, a member of the RhoGEF (Rho guanine nucleotide exchange factor) subfamily of the RGS protein family. The RhoGEFs are peripheral membrane proteins that regulate essential cellular processes, including cell shape, cell migration, cell cycle progression of cells, and gene transcription by linking signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. The RhoGEF subfamily includes p115RhoGEF, LARG, PDZ-RhoGEF and its rat specific splice variant GTRAP48. The RGS domain of RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and is often refered to as RH (RGS Homology) domain. In addition to being a G-alpha13/12 effector, the p115RhoGEF protein also functions as a GTPase-activating protein (GAP) for G-alpha13. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683    5 EIDsRLR----NSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGE------NDLLDLDGDPLRERQVAEKQLA 74
Cdd:cd08755    70 ELD-RTRpeliNEEQQRRYVNEIQFAQSPAILRQLEDFRQKRMMGMTPNERElndlesHRPTDRIPMEAKEKAVAESLLE 148

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 530365683   75 ALGDILSKY--EEDRSAPMDFALNTYMSHAGIRLREA 109
Cdd:cd08755   149 KLVEMNPTIvpDEEKSNAIFGAIAYYMKHLGVKTKAF 185

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683  791 DGENRGIRTRNPIHLAFPGPLFMEG--LADSALEDVENLrHLILWSLLPGHTMETQAAQEPEDdLTPTPSVISVTSHPWD 868
Cdd:PHA03307   16 EGGEFFPRPPATPGDAADDLLSGSQgqLVSDSAELAAVT-VVAGAAACDRFEPPTGPPPGPGT-EAPANESRSTPTWSLS 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683  869 PGSPGQAPPGGE-GDNTQLAGLEGERPEQEDmglcslehLPPRTRNSGIWESPELDRNLAEDASSTEAAGGYKVVRKAEV 947
Cdd:PHA03307   94 TLAPASPAREGSpTPPGPSSPDPPPPTPPPA--------SPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGASPAAVASD 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683  948 AGSKVVPALPES--GQSEPGPPEveggtkatgncfyvsmPSGPPDSSTDHSEAPMSPPQPDS-LPAGQTEPQPqLQGGND 1024
Cdd:PHA03307  166 AASSRQAALPLSspEETARAPSS----------------PPAEPPPSTPPAAASPRPPRRSSpISASASSPAP-APGRSA 228

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365683 1025 DPRRPSRSPPSLALRDVGMIFHTIEQLTLKLNRLKDmeLAHRELLKSLGGESSGGTTPVGSFHTEAARWTDGSLSPPAKE 1104
Cdd:PHA03307  229 ADDAGASSSDSSSSESSGCGWGPENECPLPRPAPIT--LPTRIWEASGWNGPSSRPGPASSSSSPRERSPSPSPSSPGSG 306

                         330       340       350
                  ....*....|....*....|....*....|....*..
gi 530365683 1105 PLASDSRNSHELGPCPEDGSDAPLEDSTADAAASPGP 1141
Cdd:PHA03307  307 PAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSP 343