DEP domain, named after Dishevelled, Egl-10, and Pleckstrin, where this domain was first discovered. The function of this domain is still not clear, but it is believed to be important for the membrane association of the signaling proteins in which it is present. New studies show that the DEP domain of Sst2, a yeast RGS protein is necessary and sufficient for receptor interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768017740   14 EKLYHMMMNKKVNLIKDRRRKLSTVPKCFLGNEFVAWLLEIGEISKTEEGVNLGQALLENGIIHHVSDKHQFKNEQVMYR 93
Cdd:cd04439     1 GEKLYKMMCKQGSLIKDRRRKLSTFPKCFLGNEFVSWLLEIGEISKPEEGVNLGQALLENGIIHHVSDKHQFKNEQVLYR 80

                  .
gi 768017740   94 F 94
Cdd:cd04439    81 F 81

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
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768017740    235 YGF---DIEEKNKAVVVKSVQRGSLAEVAGLQVGRKIYSINEDLVFLRPFSEVESILNQsfcSRRPLRLLV 302
Cdd:smart00228   14 LGFslvGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKK---AGGKVTLTV 81

DEP (Dishevelled, Egl-10, and Pleckstrin) domain 1 found in P-Rex-like proteins. The P-Rex family is the guanine-nucleotide exchange factor (GEF) for the small GTPase Rac that contains an N-terminal RhoGEF domain, two DEP and PDZ domains. Rac-GEF activity is stimulated by phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), a lipid second messenger, and by the G beta-gamma subunits of heterotrimeric G proteins. The DEP domains are not involved in mediating these stimuli, but may be of importance for basal and stimulated levels Rac-GEF activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768017740   14 EKLYHMMMNKKVNLIKDRRRKLSTVPKCFLGNEFVAWLLEIGEISKTEEGVNLGQALLENGIIHHVSDKHQFKNEQVMYR 93
Cdd:cd04439     1 GEKLYKMMCKQGSLIKDRRRKLSTFPKCFLGNEFVSWLLEIGEISKPEEGVNLGQALLENGIIHHVSDKHQFKNEQVLYR 80

                  .
gi 768017740   94 F 94
Cdd:cd04439    81 F 81

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 768017740    28 IKDRRRKLSTVPKCFLGNEFVAWLLEIGEISKTEEGVNLGQALLENGIIHHVSDKH-QFKNEQVMYRF 94
Cdd:pfam00610    4 LKDRRKHLKTYPNCFTGSEAVDWLMDNLEIITREEAVELGQLLLDQGLIHHVGDKHgLFKDSYYFYRF 71

Domain found in Dishevelled, Egl-10, and Pleckstrin; Domain of unknown function present in signalling proteins that contain PH, rasGEF, rhoGEF, rhoGAP, RGS, PDZ domains. DEP domain in Drosophila dishevelled is essential to rescue planar polarity defects and induce JNK signalling (Cell 94, 109-118).

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768017740    129 IKDRDYHLKTYKSVLPGSKLVDWLLAQGDCQTREEAVALGVGLCNNGFMHHVLEKSE--FRDESQYFRF 195
Cdd:smart00049    7 LRDRKYFLKTYPNCFTGSELVDWLMDNLEIIDREEAVHLGQLLLDEGLIHHVNGPNKhtFKDSKALYRF 75

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
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768017740    235 YGF---DIEEKNKAVVVKSVQRGSLAEVAGLQVGRKIYSINEDLVFLRPFSEVESILNQsfcSRRPLRLLV 302
Cdd:smart00228   14 LGFslvGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKK---AGGKVTLTV 81

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 768017740  227 LILPQEEDYGFDI---EEKNKAVVVKSVQRGSLAEVAG-LQVGRKIYSINEDLVFLRPFSEVESILNQsfcSRRPLRLLV 302
Cdd:cd00136     4 LEKDPGGGLGFSIrggKDGGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKS---AGGEVTLTV 80

                  .
gi 768017740  303 A 303
Cdd:cd00136    81 R 81

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 768017740  235 YGFDIEEKNKAVVVKSVQRGSLAEVAGLQVGRKIYSINEDLVFLRPFSEVESILN 289
Cdd:COG0793    62 LGAELGEEDGKVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLR 116

DEP (Dishevelled, Egl-10, and Pleckstrin) domain 1 found in P-Rex-like proteins. The P-Rex family is the guanine-nucleotide exchange factor (GEF) for the small GTPase Rac that contains an N-terminal RhoGEF domain, two DEP and PDZ domains. Rac-GEF activity is stimulated by phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), a lipid second messenger, and by the G beta-gamma subunits of heterotrimeric G proteins. The DEP domains are not involved in mediating these stimuli, but may be of importance for basal and stimulated levels Rac-GEF activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768017740   14 EKLYHMMMNKKVNLIKDRRRKLSTVPKCFLGNEFVAWLLEIGEISKTEEGVNLGQALLENGIIHHVSDKHQFKNEQVMYR 93
Cdd:cd04439     1 GEKLYKMMCKQGSLIKDRRRKLSTFPKCFLGNEFVSWLLEIGEISKPEEGVNLGQALLENGIIHHVSDKHQFKNEQVLYR 80

                  .
gi 768017740   94 F 94
Cdd:cd04439    81 F 81

Domain found in Dishevelled, Egl-10, and Pleckstrin; Domain of unknown function present in signalling proteins that contain PH, rasGEF, rhoGEF, rhoGAP, RGS, PDZ domains. DEP domain in Drosophila dishevelled is essential to rescue planar polarity defects and induce JNK signalling (Cell 94, 109-118).

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768017740     28 IKDRRRKLSTVPKCFLGNEFVAWLLEIGEISKTEEGVNLGQALLENGIIHHVSD--KHQFKNEQVMYRFR 95
Cdd:smart00049    7 LRDRKYFLKTYPNCFTGSELVDWLMDNLEIIDREEAVHLGQLLLDEGLIHHVNGpnKHTFKDSKALYRFT 76

DEP domain, named after Dishevelled, Egl-10, and Pleckstrin, where this domain was first discovered. The function of this domain is still not clear, but it is believed to be important for the membrane association of the signaling proteins in which it is present. New studies show that the DEP domain of Sst2, a yeast RGS protein is necessary and sufficient for receptor interaction.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768017740  117 LYCRLHSLYTPVIKDRDYHLKTYKSVLPGSKLVDWLLAQGDCQTREEAVALGVGLCNNGFMHHVL-EKSEFRDESQYFR 194
Cdd:cd04371     3 VRIMLDSDSGVPIKDRKYHLKTYPNCFTGSELVDWLLDNLEAITREEAVELGQALLKHGLIHHVSdDKHTFRDSYALYR 81

Domain found in Dishevelled, Egl-10, and Pleckstrin; Domain of unknown function present in signalling proteins that contain PH, rasGEF, rhoGEF, rhoGAP, RGS, PDZ domains. DEP domain in Drosophila dishevelled is essential to rescue planar polarity defects and induce JNK signalling (Cell 94, 109-118).

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768017740    129 IKDRDYHLKTYKSVLPGSKLVDWLLAQGDCQTREEAVALGVGLCNNGFMHHVLEKSE--FRDESQYFRF 195
Cdd:smart00049    7 LRDRKYFLKTYPNCFTGSELVDWLMDNLEIIDREEAVHLGQLLLDEGLIHHVNGPNKhtFKDSKALYRF 75

DEP (Dishevelled, Egl-10, and Pleckstrin) domain 1 found in DEP6-like proteins. DEP6 proteins contain two DEP and a PDZ domain. Their function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768017740   13 GEKLYHMMMNKKVnlIKDRRRKLSTVPKCFLGNEFVAWLLEIGEISKTEEGVNLGQALLENGIIHHVSDKH-QFKNEQVM 91
Cdd:cd04442     2 GEQLRLRLHEAKV--IKDRRHHLRTYPNCFVGKELIDWLIEHKEASDRETAIKIMQKLLDHSIIHHVCDEHkEFKDAKLF 79

                  ...
gi 768017740   92 YRF 94
Cdd:cd04442    80 YRF 82

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in Epac-like proteins. Epac (exchange proteins directly activated by cAMP) proteins are GEFs (guanine-nucleotide-exchange factors) for the small GTPases, Rap1 and Rap2. They are directly regulated by cyclic AMP, a second messenger that plays a role in the control of diverse cellular processes, such as cell adhesion and insulin secretion. Epac-like proteins share a common domain architecture, containing RasGEF, DEP and CAP-effector (cAMP binding) domains. The DEP domain is involved in membrane localization.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768017740  128 VIKDRDYHLKTYKSVLPGSKLVDWLLAQGDC-QTREEAVALGVGLCNNGFMHHVLEKSEFRDESQYFRFHADEE 200
Cdd:cd04437    16 LIRDRKYHLRTYRQCCVGTELVDWLLQQSPCvQSRSQAVGMWQVLLEEGVLLHVDQELHFQDKYQFYRFSDDEC 89

DEP (Dishevelled, Egl-10, and Pleckstrin) domain 1 found in DEP6-like proteins. DEP6 proteins contain two DEP and a PDZ domain. Their function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768017740  114 GVRLYCRLHSlyTPVIKDRDYHLKTYKSVLPGSKLVDWLLAQGDCQTREEAVALGVGLCNNGFMHHVL-EKSEFRDESQY 192
Cdd:cd04442     2 GEQLRLRLHE--AKVIKDRRHHLRTYPNCFVGKELIDWLIEHKEASDRETAIKIMQKLLDHSIIHHVCdEHKEFKDAKLF 79

                  ...
gi 768017740  193 FRF 195
Cdd:cd04442    80 YRF 82

DEP (Dishevelled, Egl-10, and Pleckstrin) domain 2 found in P-Rex-like proteins. The P-Rex family is the guanine-nucleotide exchange factor (GEF) for the small GTPase Rac that contains an N-terminal RhoGEF domain, two DEP and PDZ domains. Rac-GEF activity is stimulated by phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), a lipid second messenger, and the G beta-gamma subunits of heterotrimeric G proteins. The DEP domains are not involved in mediating these stimuli, but may be of importance for basal and stimulated levels Rac-GEF activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768017740    9 IAEKGEKLYHMMMNKKVNLIKDRRRKLSTVPKCFLGNEFVAWLLEIGEISKTEEGVNLGQALLENGIIHHVSDKHQFKNE 88
Cdd:cd04440     5 IMSKGVRLYCRLHSLFTPVVKDRDYHLKTYKSVVPASKLVDWLLAQGDCRTREEAVILGVGLCNNGFMHHVLEKSEFKDE 84

                  ....*....
gi 768017740   89 QVMYRFRYD 97
Cdd:cd04440    85 PLLFRFYAD 93

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 768017740  308 EIIKIPDQPDTLCFQIRGAAPPYVYAVGRGSEAMAAGLCAGQCILKVNGSNV 359
Cdd:cd06710     1 RTVEIARGRAGYGFTISGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINV 52

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in fungal RhoGEF (GDP/GTP exchange factor) PIKfyve-like proteins. PIKfyve contains N-terminal Fyve finger and DEP domains, a central chaperonin-like domain and a C-terminal PIPK (phosphatidylinositol phosphate kinase) domain. PIKfyve-like proteins are important phosphatidylinositol (3)-monophosphate (PtdIns(3)P)-5-kinases, producing PtdIns(3,5)P2, which plays a major role in multivesicular body (MVB) sorting and control of retrograde traffic from the vacuole back to the endosome and/or Golgi. PIKfyve itself has been shown to be play a role in regulating early-endosome-to-trans-Golgi network (TGN) retrograde trafficking.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 768017740  130 KDRDYHLKTYKSVLPGSKLVDWLLAQGDCQTREEAVALGVGLCNNGFMHHVLEKSEFRDESQYFR 194
Cdd:cd04448    16 QDHRYRLRTYTNCILGKELVNWLIRQGKAATRVQAIAIGQALLDAGWIECVSDDDLFRDEYALYK 80

PDZ domain 1 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 1 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which 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 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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 768017740  316 PDTLCFQIRGAAPPYVYAVGRGSEAMAAGLCAGQCILKVNGSNVMNDGAPEVLE 369
Cdd:cd06743     8 PEAFGFSIGGSGPCYILSVEEGSSAHAAGLQPGDQILELDGQDVSSLSCEAIIA 61

PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS3, and related domains. RGS3 down-regulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. It downregulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. In Eph/ephrin signaling, RGS3 binds via its PDZ domain to the cytoplasmic C terminus of Eph receptor tyrosine kinase EphB. 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 RGS3-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
                  ....*....|....*....|....*....|....*....|....*....|
gi 768017740  310 IKIPDQPDTLCFQIRGAAPPYVYAVGRGSEAMAAGLCAGQCILKVNGSNV 359
Cdd:cd06711     3 ITIQRGKDGFGFTICDDSPVRVQAVDPGGPAEQAGLQQGDTVLQINGQPV 52

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
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768017740    235 YGF---DIEEKNKAVVVKSVQRGSLAEVAGLQVGRKIYSINEDLVFLRPFSEVESILNQsfcSRRPLRLLV 302
Cdd:smart00228   14 LGFslvGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKK---AGGKVTLTV 81

PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.

                           10        20        30
                   ....*....|....*....|....*....|..
gi 768017740   330 YVYAVGRGSEAMAAGLCAGQCILKVNGSNVMN 361
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPVRS 32

PDZ domain of DEP domain-containing mTOR-interacting protein (DEPTOR), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of DEPTOR, and related domains. DEPTOR (also known as DEP domain-containing protein 6, DEP6) is a regulatory protein of mTOR signaling; it is a negative regulator of both the mTORC1 and mTORC2 signaling pathways. DEPTOR's PDZ domain binds to mTOR's FAT domain to suppress mTOR's kinase activity. The DEPTOR PDZ domain also binds lysine-specific demethylase 4A (KDM4A), leucine-rich repeat containing 4 (LRRC4), p38gamma, and major intrinsically disordered Notch2-binding receptor 1 (MINAR1, also known as Ubtor). DEPTOR also interacts with salt-inducible kinase 3 (SIK3). 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 DEPTOR-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
                  ....*....|....*....|....*....|....*....|.
gi 768017740  321 FQIRGAAPPYVYAVGRGSEAMAAGLCAGQCILKVNGSNVMN 361
Cdd:cd23067    13 FVVRGSKPCHIQAVDPSGPAAAAGMKVCQFIVSVNGLNVLH 53

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
                  ....*....|....*....|....*....|....*....|....*...
gi 768017740  321 FQIRGAAPPYVYAVGRGSEAMAAGLCAGQCILKVNGSNVMNDGAPEVL 368
Cdd:cd23069    15 LTVSGDNPVFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVV 62

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
                  ....*....|....*....|....*....|....*....|
gi 768017740  330 YVYAVGRGSEAMAAGLCAGQCILKVNGSNVMNDGAPEVLE 369
Cdd:cd06768    26 FIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQVVE 65

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 768017740  235 YGFDIEEKNKAVVVKSVQRGSLAEVAGLQVGRKIYSINEDLVFLRPFSEVESILN 289
Cdd:COG0793    62 LGAELGEEDGKVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLR 116

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

                           10        20
                   ....*....|....*....|....*..
gi 768017740   246 VVVKSVQRGSLAEVAGLQVGRKIYSIN 272
Cdd:pfam00595   27 IFVSEVLPGGAAEAGGLKVGDRILSIN 53