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 1039794112  331 HIIGAEDDDFGTEHEQINGQCSCFQSIELLKSRPAHLAVFLHHVVSQFDPATLLCYLYSDLYKQTNSKETRRVFLEFHQF 410
Cdd:cd08754      1 GIIGAEDDDFPTESEQINGQCSCFQNIELLKSRPAHLAVFLHHVVSQFDPAALLCYLYADLYKQTNSKETRRVFLEFNQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112  411 FLDRSAHLKVPVPEEISVDLEKRRPELIPEDLHRLYIQTMQERVHPEVQRHLEDFRQKRSMGLTLAESELTKLDAERDKD 490
Cdd:cd08754     81 FLDRAANLKVPVPDEVSLDLEKRRPELIPEELHRHYIQTMQERVSPEVQRNLEDFRQKRSMGLTLAEGELTKLDAERFRD 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039794112  491 RGTLEKERACAEQIVTKIEEVLMTAQAVEEERSSTMQYVILMYMKYLGVKVKEPRNLEHKRG 552
Cdd:cd08754    161 RNTIEKERACAEQIVAKIEEVLMTSQTPEEDKSSTIQYVILTYMKHLGVKVKEPRNLEQKRG 222

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 1039794112   773 VINELFYTERAHVRTLKVLDQVFYQR-VSREGILSPSELRKIFSNLEDILQLHVGLNEQMKAVRKRNetsviDHIGEDLL 851
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPlKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEW-----DDSVERIG 75

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112   852 IWFSGpgEEKLKHAAATFCSNQPFALEMIKsRQKKDSRFHTFVQDAESNPLCRRLQLKDIIPTQMQRLTKYPLLLDNIAK 931
Cdd:smart00325   76 DVFLK--LEEFFKIYSEYCSNHPDALELLK-KLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLK 152

                           170       180
                    ....*....|....*....|....*...
gi 1039794112   932 YTEW-PPEREKVKKAADHCRQILNYVNQ 958
Cdd:smart00325  153 HTPEdHEDREDLKKALKAIKELANQVNE 180

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 1039794112  331 HIIGAEDDDFGTEHEQINGQCSCFQSIELLKSRPAHLAVFLHHVVSQFDPATLLCYLYSDLYKQTNSKETRRVFLEFHQF 410
Cdd:cd08754      1 GIIGAEDDDFPTESEQINGQCSCFQNIELLKSRPAHLAVFLHHVVSQFDPAALLCYLYADLYKQTNSKETRRVFLEFNQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112  411 FLDRSAHLKVPVPEEISVDLEKRRPELIPEDLHRLYIQTMQERVHPEVQRHLEDFRQKRSMGLTLAESELTKLDAERDKD 490
Cdd:cd08754     81 FLDRAANLKVPVPDEVSLDLEKRRPELIPEELHRHYIQTMQERVSPEVQRNLEDFRQKRSMGLTLAEGELTKLDAERFRD 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039794112  491 RGTLEKERACAEQIVTKIEEVLMTAQAVEEERSSTMQYVILMYMKYLGVKVKEPRNLEHKRG 552
Cdd:cd08754    161 RNTIEKERACAEQIVAKIEEVLMTSQTPEEDKSSTIQYVILTYMKHLGVKVKEPRNLEQKRG 222

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 1039794112  977 DTSNLKLSEYPNVDELRNLDLTKRKMIHEGPLVWKVNRDKSIDLYTLLLEDILVLLQKQDDRLVLRCHSKILASTADSKH 1056
Cdd:cd13390      1 DLSSLKQSEYPMIDELRNLDLTKRKMIHEGPLTWKVNRDKTIDLYTLLLEDILVLLQKQDDRLVLRCHSKILASTADSKH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1039794112 1057 TFSPVIKLSTVLVRQVATDNKALFVISMSDNGAQIYELVAQTVSEKTVWQDLICRMAA 1114
Cdd:cd13390     81 TFSPVIKLNTVLVRQVATDNKAFFVISMSENGAQIYELVAQTVSEKTVWQDLITRMAA 138

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 1039794112   51 QRCVIIQKDDNGFGLTVSGDNPVFVQSVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLIRSGSYVALTVQ 126
Cdd:cd23069      1 QRCVVIQRDENGYGLTVSGDNPVFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVALTLL 76

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 1039794112  773 VINELFYTERAHVRTLKVLDQVFYQRVSREGILSPSELRKIFSNLEDILQLHVG--LNEQMKavrkrnETSVIDHIGEDL 850
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQllLEELLK------EWISIQRIGDIF 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112  851 LIWFSGpgeeklKHAAATFCSNQPFALEMIKSRQKKDSRFHTFVQDAESNPLCRRLQLKDIIPTQMQRLTKYPLLLDNIA 930
Cdd:pfam00621   75 LKFAPG------FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELL 148

                          170       180
                   ....*....|....*....|....*...
gi 1039794112  931 KYT-EWPPEREKVKKAADHCRQILNYVN 957
Cdd:pfam00621  149 KHTpPDHPDYEDLKKALEAIKEVAKQIN 176

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 1039794112    50 VQRCVIIQKDDNGFGLTVSG----DNPVFVQSVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLIR-SGSYVALT 124
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVGgkdeGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKkAGGKVTLT 80

                    ....*.
gi 1039794112   125 VQgRPP 130
Cdd:smart00228   81 VL-RGG 85

PDZ domain; PDZ domains are found in diverse signaling proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112   54 VIIQKD-DNGFGLTVSG-----DNPVFVQSVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLIR-SGSYVALTVQ 126
Cdd:pfam00595    2 VTLEKDgRGGLGFSLKGgsdqgDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKgSGGKVTLTIL 81

sigma E protease regulator RseP;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039794112   72 PVFVQsVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLevVKLIRSGSYVALTVQGRPPGSP 133
Cdd:PRK10779   223 PVLAE-VQPNSAASKAGLQAGDRIVKVDGQPLTQWQTF--VTLVRDNPGKPLALEIERQGSP 281

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 1039794112  331 HIIGAEDDDFGTEHEQINGQCSCFQSIELLKSRPAHLAVFLHHVVSQFDPATLLCYLYSDLYKQTNSKETRRVFLEFHQF 410
Cdd:cd08754      1 GIIGAEDDDFPTESEQINGQCSCFQNIELLKSRPAHLAVFLHHVVSQFDPAALLCYLYADLYKQTNSKETRRVFLEFNQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112  411 FLDRSAHLKVPVPEEISVDLEKRRPELIPEDLHRLYIQTMQERVHPEVQRHLEDFRQKRSMGLTLAESELTKLDAERDKD 490
Cdd:cd08754     81 FLDRAANLKVPVPDEVSLDLEKRRPELIPEELHRHYIQTMQERVSPEVQRNLEDFRQKRSMGLTLAEGELTKLDAERFRD 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039794112  491 RGTLEKERACAEQIVTKIEEVLMTAQAVEEERSSTMQYVILMYMKYLGVKVKEPRNLEHKRG 552
Cdd:cd08754    161 RNTIEKERACAEQIVAKIEEVLMTSQTPEEDKSSTIQYVILTYMKHLGVKVKEPRNLEQKRG 222

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 1039794112  977 DTSNLKLSEYPNVDELRNLDLTKRKMIHEGPLVWKVNRDKSIDLYTLLLEDILVLLQKQDDRLVLRCHSKILASTADSKH 1056
Cdd:cd13390      1 DLSSLKQSEYPMIDELRNLDLTKRKMIHEGPLTWKVNRDKTIDLYTLLLEDILVLLQKQDDRLVLRCHSKILASTADSKH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1039794112 1057 TFSPVIKLSTVLVRQVATDNKALFVISMSDNGAQIYELVAQTVSEKTVWQDLICRMAA 1114
Cdd:cd13390     81 TFSPVIKLNTVLVRQVATDNKAFFVISMSENGAQIYELVAQTVSEKTVWQDLITRMAA 138

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 1039794112  360 LKSRPAHLAVFLHHVVSQFDPATLLCYLYSDLYKQTNSKETRRVFLEFHQFFLDRSAHLKVPVPEEISVDLEKRRPELIP 439
Cdd:cd08755      1 VKSRPAHLMVFLQHVMLQFDPAPLLCYLHADMLKNLNTKETKKHFGDFYNTFLEKGAVLKVSVPSNVAFELDRTRPELIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112  440 EDLHRLYIQTMQERVHPEVQRHLEDFRQKRSMGLTLAESELTKLDAERDKDRGTLE-KERACAEQIVTKIEEVLMTAqAV 518
Cdd:cd08755     81 EEQQRRYVNEIQFAQSPAILRQLEDFRQKRMMGMTPNERELNDLESHRPTDRIPMEaKEKAVAESLLEKLVEMNPTI-VP 159

                          170       180
                   ....*....|....*....|....
gi 1039794112  519 EEERSSTMQYVILMYMKYLGVKVK 542
Cdd:cd08755    160 DEEKSNAIFGAIAYYMKHLGVKTK 183

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 1039794112   773 VINELFYTERAHVRTLKVLDQVFYQR-VSREGILSPSELRKIFSNLEDILQLHVGLNEQMKAVRKRNetsviDHIGEDLL 851
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPlKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEW-----DDSVERIG 75

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112   852 IWFSGpgEEKLKHAAATFCSNQPFALEMIKsRQKKDSRFHTFVQDAESNPLCRRLQLKDIIPTQMQRLTKYPLLLDNIAK 931
Cdd:smart00325   76 DVFLK--LEEFFKIYSEYCSNHPDALELLK-KLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLK 152

                           170       180
                    ....*....|....*....|....*...
gi 1039794112   932 YTEW-PPEREKVKKAADHCRQILNYVNQ 958
Cdd:smart00325  153 HTPEdHEDREDLKKALKAIKELANQVNE 180

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 1039794112  993 RNLDLTKRKMIHEGPLVWKVNRDKSIDLYTLLLEDILVLLQKQDDRLVLRCHSKILASTADSKHTFSPVIKLSTVLVRQV 1072
Cdd:cd14679      2 KNIDITKKKLVHEGPLTWRVTKDKAIEVHVLLLDDLLVLLQKQDERLVLKCHSRTTTPTPDGKQMLSPIIKLNSAMTREV 81

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1039794112 1073 ATDNKALFVISMSDNGAQIYELVAQTVSEKTVWQDLI 1109
Cdd:cd14679     82 ATDRKAFYVIFTWEQGAQIYELVAQTVSERKNWCALI 118

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 1039794112  773 VINELFYTERAHVRTLKVLDQVFYQRVSREGILSPSELRKIFSNLEDILQLHVG--LNEQMKavrkrnETSVIDHIGEDL 850
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQllLEELLK------EWISIQRIGDIF 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112  851 LIWFSGpgeeklKHAAATFCSNQPFALEMIKSRQKKDSRFHTFVQDAESNPLCRRLQLKDIIPTQMQRLTKYPLLLDNIA 930
Cdd:pfam00621   75 LKFAPG------FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELL 148

                          170       180
                   ....*....|....*....|....*...
gi 1039794112  931 KYT-EWPPEREKVKKAADHCRQILNYVN 957
Cdd:pfam00621  149 KHTpPDHPDYEDLKKALEAIKEVAKQIN 176

PH domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112  986 YPNVDELRNLDLTKRKMIHEGPLVWKVNRDKSIDLYTLLLEDILVLLQKQDDRLVLRCHSKILASTaDSKhTFSPVIKLS 1065
Cdd:pfam17838    1 HPLGEEFKKLDLTTRKLIHEGPLTWRNSKGKLVEVHALLLEDILVLLQEKDQKLVLACLSTGSENV-DQK-TQSPIISLK 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1039794112 1066 TVLVRQVATDNKALFVISMSDNGAQIYELVAQTVSEKTVWQDLI 1109
Cdd:pfam17838   79 KLIVREVATDKKAFFLISTSPSDPQMYELHASTKSERNTWTKLI 122

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        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112  361 KSRPAHLAVFLHHVVSQFDPATLLCYLYSDLYKQTNSKETRRVFLEFHQFFLDRSAHLKVP-----VPEEISVDLEKRRP 435
Cdd:cd08756      1 KTHPAHLAVFLNYLLSNSDPSSLFFYLITDLYKSGNIKDMRKWAYEIFSTFLVPNAPLLWPnidesLIQEIDKILQNEQD 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1039794112  436 ELipEDLHRLYIQTmQERVHPEVQRHLEDFRQKRSMGL 473
Cdd:cd08756     81 DE--EILRRVFLKA-REKARDEINDQLADFRQKRTLGL 115

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. 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 NHERF-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 1039794112   52 RCVIIQKDDNGFGLTVSGDNPV---FVQSVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLIR-SGSYVALTV 125
Cdd:cd06768      1 RLCHLVKGPEGYGFNLHAEKGRpghFIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQVVEKIKaSGNQVTLLV 78

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains 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 1039794112   54 VIIQKDDN-GFGLTVSG----DNPVFVQSVKEDGAAMRAG-VQTGDRIIKVNGTLVTHSNHLEVVKLIR-SGSYVALTVQ 126
Cdd:cd00136      2 VTLEKDPGgGLGFSIRGgkdgGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKsAGGEVTLTVR 81

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. 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 rhophilin-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 1039794112   52 RCVIIQKDDNGFGLTVSGDNPVFVQSVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLIRS 117
Cdd:cd06712      2 RTVHLTKEEGGFGFTLRGDSPVQVASVDPGSCAAEAGLKEGDYIVSVGGVDCKWSKHSEVVKLLKS 67

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 1039794112   52 RCVIIQKDDNGFGLTVSGD---------------NPV-FVQSVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLI 115
Cdd:cd23070      1 RVVTIVKSETGFGFNVRGQvseggqlrsingelyAPLqHVSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVDLI 80

                           90
                   ....*....|.
gi 1039794112  116 RSGS-YVALTV 125
Cdd:cd23070     81 KSGGdELTLTV 91

PDZ domain; PDZ domains are found in diverse signaling proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039794112   54 VIIQKD-DNGFGLTVSG-----DNPVFVQSVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLIR-SGSYVALTVQ 126
Cdd:pfam00595    2 VTLEKDgRGGLGFSLKGgsdqgDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKgSGGKVTLTIL 81

circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CPP (also known as tail-specific protease, PRC protein, Protease Re, and Photosystem II D1 protein processing peptidase), and related domains. CPP belongs to the peptidase S41A family. It cleaves a C-terminal 11 residue peptide from the precursor form of penicillin-binding protein 3, and may have a role in protecting bacterium from thermal and osmotic stresses. In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This CPP-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039794112   62 GFGLTVS--GDNPVFVQSVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLIR--SGSYVALTVqgRPPGSPQ 134
Cdd:cd06782      3 GIGIEIGkdDDGYLVVVSPIPGGPAEKAGIKPGDVIVAVDGESVRGMSLDEVVKLLRgpKGTKVKLTI--RRGGEGE 77

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1039794112   62 GFGLTVS-GDNPVFVQSVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLIR--SGSYVALTVQGRPPGSPQ 134
Cdd:COG0793     61 GLGAELGeEDGKVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLRgkAGTKVTLTIKRPGEGEPI 136

PDZ domain 1 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. 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 Scribble-like family PDZ1 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 1039794112   56 IQKDDNGFGLTVSG----------DNPVFVQSVKEDGAAMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLIR-SGSYVALT 124
Cdd:cd06704      5 IERQTGGLGISIAGgkgstpykgdDEGIFISRVTEGGPAAKAGVRVGDKLLEVNGVDLVDADHHEAVEALKnSGNTVTMV 84

                   ..
gi 1039794112  125 VQ 126
Cdd:cd06704     85 VL 86

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. 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 syntrophin-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 1039794112   52 RCVIIQKDD-NGFGLTVSG--DN--PVFVQSVKEDGAAMRAG-VQTGDRIIKVNGTLVTHSNHLEVVKLIR-SGSYVALT 124
Cdd:cd06801      1 RTVRVVKQDvGGLGISIKGgaEHkmPILISKIFKGQAADQTGqLFVGDAILSVNGENLEDATHDEAVQALKnAGDEVTLT 80

                   ..
gi 1039794112  125 VQ 126
Cdd:cd06801     81 VK 82

PDZ domain of ARHGAP21 and ARHGAP23, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGAP21, ARHGAP23, and related domains. This subfamily includes the GAPs (GTPase activating proteins): ARHGAP21 (Rho GTPase-activating protein 21; also known as Rho GTPase-activating protein 10, Rho-type GTPase-activating protein 21) and ARHGAP23 (Rho GTPase-activating protein 23; also known as Rho-type GTPase-activating protein 23). GAPs deactivate Rho GTPases by accelerating GTP hydrolysis. ARHGAP21/23 interact with a planar cell polarity (PCP) protein Pk1 to regulate a lateral signaling pathway in migrating cells. The ARHGAP21 PDZ domain binds claudin-2. 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 ARHGAP21-23-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.