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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  346 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFL 425
Cdd:cd08753     1 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLVVFLRYIFSQADPGPLLFYLCSEVYQQTSPKDSRSLGKDIWNIFL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578801805  426 EKNAPLRVKIPEMLQAEIDSRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 490
Cdd:cd08753    81 EKNAPLRVKIPEMLQAEIDLRLRNNEDPRGVLCEAQEAVMPEIQEQIQDYRSKRTLGLGSLYGEN 145

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 578801805  781 RQEVINELFVTEASHLRTLRVLDLIFYQRMKKENL-MPREELARLFPNLPELIEIHNSWCEAMKKLREEGPIIKeisDLM 859
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSG---PRI 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  860 LARFDGPAreELQQVAAQFCSYQSIALELIKTKQRKESRFQLFMQEAEShpQCRRLQLRDLIISEMQRLTKYPLLLESII 939
Cdd:cd00160    78 GDVFLKLA--PFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLKELL 153

                         170       180
                  ....*....|....*....|....*...
gi 578801805  940 KHTEGGTSEHEKLCRARDQCREILKYVN 967
Cdd:cd00160   154 KHTPDGHEDREDLKKALEAIKEVASQVN 181

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805 1218 DGENRGIRTRNPIHLAFPGPLFMEG--LADSALEDVENLrHLILWSLLPGHTMETQAAQEPEDdLTPTPSVISVTSHPWD 1295
Cdd:PHA03307   16 EGGEFFPRPPATPGDAADDLLSGSQgqLVSDSAELAAVT-VVAGAAACDRFEPPTGPPPGPGT-EAPANESRSTPTWSLS 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805 1296 PGSPGQAPPGGE-GDNTQLAGLEGERPEQEDmglcslehLPPRTRNSGIWESPELDRNLAEDASSTEAAGGYKVVRKAEV 1374
Cdd:PHA03307   94 TLAPASPAREGSpTPPGPSSPDPPPPTPPPA--------SPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGASPAAVASD 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805 1375 AGSKVVPALPES--GQSEPGPPEveggtkatgncfyvsmPSGPPDSSTDHSEAPMSPPQPDS-LPAGQTEPQPqLQGGND 1451
Cdd:PHA03307  166 AASSRQAALPLSspEETARAPSS----------------PPAEPPPSTPPAAASPRPPRRSSpISASASSPAP-APGRSA 228

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805 1452 DPRRPSRSPPSLALRDVGMIFHTIEQLTLKLNRLKDmeLAHRELLKSLGGESSGGTTPVGSFHTEAARWTDGSLSPPAKE 1531
Cdd:PHA03307  229 ADDAGASSSDSSSSESSGCGWGPENECPLPRPAPIT--LPTRIWEASGWNGPSSRPGPASSSSSPRERSPSPSPSSPGSG 306

                         330       340       350
                  ....*....|....*....|....*....|....*..
gi 578801805 1532 PLASDSRNSHELGPCPEDGSDAPLEDSTADAAASPGP 1568
Cdd:PHA03307  307 PAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSP 343

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  346 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFL 425
Cdd:cd08753     1 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLVVFLRYIFSQADPGPLLFYLCSEVYQQTSPKDSRSLGKDIWNIFL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578801805  426 EKNAPLRVKIPEMLQAEIDSRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 490
Cdd:cd08753    81 EKNAPLRVKIPEMLQAEIDLRLRNNEDPRGVLCEAQEAVMPEIQEQIQDYRSKRTLGLGSLYGEN 145

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 578801805   363 SDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFLEKNAPLRVKIPEMLQAE 442
Cdd:pfam09128    1 QCSCFQSLEQLKSRPAHLAVFLHHVVSQFDPSPLLCYLYADLYQQTNSKETRRVFLDIHNFFLEKNAPLRVPVPESVAAE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805   443 ID---SRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGENDLLDLD-----GDPLRERQVAEKQLAALG 514
Cdd:pfam09128   81 LDrrrPELIPEDLHRRYIQTMQERAVPDIQRQLEDFRQKRSMGLTLAEGELSLLDAErdgdrGTLERERRVAEQILSKIE 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 578801805   515 DIL---SKYEEDRSAPMDFALNTYMSHAGIR 542
Cdd:pfam09128  161 EILstsQTFDEERSATIQYVILTYMKHLGVR 191

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 578801805    784 VINELFVTEASHLRTLRVLDLIFYQRMKKEN-LMPREELARLFPNLPELIEIHNSWCEAMKK-LREEGPIIKEISDLMLA 861
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEErIEEWDDSVERIGDVFLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805    862 RfdgparEELQQVAAQFCSYQSIALELIKtKQRKESRFQLFMQEAESHPQCRRLQLRDLIISEMQRLTKYPLLLESIIKH 941
Cdd:smart00325   81 L------EEFFKIYSEYCSNHPDALELLK-KLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKH 153

                           170       180
                    ....*....|....*....|....*..
gi 578801805    942 TEGGTSEHEKLCRARDQCREILKYVNE 968
Cdd:smart00325  154 TPEDHEDREDLKKALKAIKELANQVNE 180

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578801805   61 QRCVIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLL 136
Cdd:cd23069     1 QRCVVIQRDENGYGLTVSGDNPVFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVALTLL 76

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805     60 VQRCVIIQKDQHGFGFTVSGDRI----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALT 134
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVGGKDegggVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKkAGGKVTLT 80

                    ..
gi 578801805    135 LL 136
Cdd:smart00228   81 VL 82

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  762 WQHTVGKDVVAGLTQREIDRQEVINELFVTEASHLRTLRVLDLIFYQRMKKENLMP---REELAR-LFPNLPELIEIHNS 837
Cdd:COG5422   466 WTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPenaRRNFIKhVFANINEIYAVNSK 545

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  838 WCEAMKKLREEGPIIKEISDLML---ARFDgpareelqqvaaQFCSY---QSIALELIKTKQRKESRFQLFMQEAESHPQ 911
Cdd:COG5422   546 LLKALTNRQCLSPIVNGIADIFLdyvPKFE------------PFIKYgasQPYAKYEFEREKSVNPNFARFDHEVERLDE 613

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  912 CRRLQLRDLIISEMQRLTKYPLLLESIIKHTEGGTSEHEKLCRARDQCREILKYVNEAVKQTENRHRLEGYQKRLDATAl 991
Cdd:COG5422   614 SRKLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKP- 692

                         250       260       270
                  ....*....|....*....|....*....|
gi 578801805  992 ERASNPLAAEFksldlttRKMIHEGPLTWR 1021
Cdd:COG5422   693 EYVNLGLNDEY-------RKIIFKGVLKRK 715

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578801805   72 GFGFTVS-GDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI--KSGAYVALTLL 136
Cdd:COG0793    61 GLGAELGeEDGKVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLrgKAGTKVTLTIK 128

sigma E protease regulator RseP;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 578801805   79 GDRI--VLVQsVRPGGAAMKAGVKEGDRIIKVNGTMVT 114
Cdd:PRK10779  218 GPQIepVLAE-VQPNSAASKAGLQAGDRIVKVDGQPLT 254

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  346 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFL 425
Cdd:cd08753     1 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLVVFLRYIFSQADPGPLLFYLCSEVYQQTSPKDSRSLGKDIWNIFL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578801805  426 EKNAPLRVKIPEMLQAEIDSRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 490
Cdd:cd08753    81 EKNAPLRVKIPEMLQAEIDLRLRNNEDPRGVLCEAQEAVMPEIQEQIQDYRSKRTLGLGSLYGEN 145

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 578801805   363 SDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFLEKNAPLRVKIPEMLQAE 442
Cdd:pfam09128    1 QCSCFQSLEQLKSRPAHLAVFLHHVVSQFDPSPLLCYLYADLYQQTNSKETRRVFLDIHNFFLEKNAPLRVPVPESVAAE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805   443 ID---SRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGENDLLDLD-----GDPLRERQVAEKQLAALG 514
Cdd:pfam09128   81 LDrrrPELIPEDLHRRYIQTMQERAVPDIQRQLEDFRQKRSMGLTLAEGELSLLDAErdgdrGTLERERRVAEQILSKIE 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 578801805   515 DIL---SKYEEDRSAPMDFALNTYMSHAGIR 542
Cdd:pfam09128  161 EILstsQTFDEERSATIQYVILTYMKHLGVR 191

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 578801805  781 RQEVINELFVTEASHLRTLRVLDLIFYQRMKKENL-MPREELARLFPNLPELIEIHNSWCEAMKKLREEGPIIKeisDLM 859
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSG---PRI 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  860 LARFDGPAreELQQVAAQFCSYQSIALELIKTKQRKESRFQLFMQEAEShpQCRRLQLRDLIISEMQRLTKYPLLLESII 939
Cdd:cd00160    78 GDVFLKLA--PFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLKELL 153

                         170       180
                  ....*....|....*....|....*...
gi 578801805  940 KHTEGGTSEHEKLCRARDQCREILKYVN 967
Cdd:cd00160   154 KHTPDGHEDREDLKKALEAIKEVASQVN 181

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 578801805   784 VINELFVTEASHLRTLRVLDLIFYQRMKKENLMPREELARLFPNLPELIEIHNSwcEAMKKLREEGPIIKEISDLMLARF 863
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQ--LLLEELLKEWISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805   864 DGpareelQQVAAQFCSYQSIALELIKTKQRKESRFQLFMQEAESHPQCRRLQLRDLIISEMQRLTKYPLLLESIIKHTE 943
Cdd:pfam00621   79 PG------FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTP 152

                          170       180
                   ....*....|....*....|....
gi 578801805   944 GGTSEHEKLCRARDQCREILKYVN 967
Cdd:pfam00621  153 PDHPDYEDLKKALEAIKEVAKQIN 176

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578801805   61 QRCVIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLL 136
Cdd:cd23069     1 QRCVVIQRDENGYGLTVSGDNPVFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVALTLL 76

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 578801805 1002 FKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDSKQTFSPVLKLNAVLIRS 1081
Cdd:cd14679     1 FKNIDITKKKLVHEGPLTWRVTKDKAIEVHVLLLDDLLVLLQKQDERLVLKCHSRTTTPTPDGKQMLSPIIKLNSAMTRE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 578801805 1082 VATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAV 1124
Cdd:cd14679    81 VATDRKAFYVIFTWEQG-AQIYELVAQTVSERKNWCALISETA 122

Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG); The RGS domain is an essential part of the leukemia-associated RhoGEF protein (LARG), 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 effector, the LARG 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 578801805  347 IIGPEEDYdpgyFNNESDII------FQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDI 420
Cdd:cd08754     2 IIGAEDDD----FPTESEQIngqcscFQNIELLKSRPAHLAVFLHHVVSQFDPAALLCYLYADLYKQTNSKETRRVFLEF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  421 WNIFLEKNAPLRVKIPEMLQAEIDSR---LRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGENDLLDLDG 497
Cdd:cd08754    78 NQFFLDRAANLKVPVPDEVSLDLEKRrpeLIPEELHRHYIQTMQERVSPEVQRNLEDFRQKRSMGLTLAEGELTKLDAER 157

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 578801805  498 DPLR-----ERQVAEKQLAALGDIL---SKYEEDRSAPMDFALNTYMSHAGIRLREAR 547
Cdd:cd08754   158 FRDRntiekERACAEQIVAKIEEVLmtsQTPEEDKSSTIQYVILTYMKHLGVKVKEPR 215

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 578801805  373 LKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFLEKNAPLRVKIPEMLQAEIDsRLR---- 448
Cdd:cd08755     1 VKSRPAHLMVFLQHVMLQFDPAPLLCYLHADMLKNLNTKETKKHFGDFYNTFLEKGAVLKVSVPSNVAFELD-RTRpeli 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  449 NSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGE------NDLLDLDGDPLRERQVAEKQLAALGDILSKY-- 520
Cdd:cd08755    80 NEEQQRRYVNEIQFAQSPAILRQLEDFRQKRMMGMTPNERElndlesHRPTDRIPMEAKEKAVAESLLEKLVEMNPTIvp 159

                         170       180
                  ....*....|....*....|....*.
gi 578801805  521 EEDRSAPMDFALNTYMSHAGIRLREA 546
Cdd:cd08755   160 DEEKSNAIFGAIAYYMKHLGVKTKAF 185

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805     60 VQRCVIIQKDQHGFGFTVSGDRI----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALT 134
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVGGKDegggVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKkAGGKVTLT 80

                    ..
gi 578801805    135 LL 136
Cdd:smart00228   81 VL 82

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578801805   64 VIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVAL 133
Cdd:cd06744     2 VRVYRGNGSFGFTLRGHAPVYIESVDPGSAAERAGLKPGDRILFLNGLDVRNCSHDKVVSLLQgSGSMPTL 72

Regulator of G protein signalling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805    369 DLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQA-SPKDSRSLGKDIWNIFLEKNAPLRVKIPEMLQAEIDSRL 447
Cdd:smart00315    1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAeDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                            90       100
                    ....*....|....*....|....*.
gi 578801805    448 RNSEDARGVLCEAQEAAMPEIQEQIH 473
Cdd:smart00315   81 ESEEPPPDLFDEAQREVYELLEKDSF 106

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805   62 RCVIIQKDQHGFGFTVSGD----------------RIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI 125
Cdd:cd23070     1 RVVTIVKSETGFGFNVRGQvseggqlrsingelyaPLQHVSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVDLI 80

                          90
                  ....*....|..
gi 578801805  126 KSGA-YVALTLL 136
Cdd:cd23070    81 KSGGdELTLTVI 92

Regulator of G protein signaling (RGS) domain superfamily; The RGS domain is an essential part of the Regulator of G-protein Signaling (RGS) protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. While inactive, G-alpha-subunits bind GDP, which is released and replaced by GTP upon agonist activation. GTP binding leads to dissociation of the alpha-subunit and the beta-gamma-dimer, allowing them to interact with effectors molecules and propagate signaling cascades associated with cellular growth, survival, migration, and invasion. Deactivation of the G-protein signaling controlled by the RGS domain accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in the reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins are also involved in apoptosis and cell proliferation, as well as modulation of cardiac development. Several RGS proteins can fine-tune immune responses, while others play important roles in neuronal signals modulation. Some RGS proteins are principal elements needed for proper vision.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578801805  374 KSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDS--RSLGKDIWNIFLEKNAPLRVKIPEMLQAEIDSRLRNSE 451
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTSSDEelKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEEPY 80

                          90
                  ....*....|....*....
gi 578801805  452 DARGVLCEAQEAAMPEIQE 470
Cdd:cd07440    81 PDPDCFDEAQEHILNLLEK 99

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 578801805   62 RCVIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI 125
Cdd:cd06710     1 RTVEIARGRAGYGFTISGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLI 64