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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700611676  35 RIVEMKKGSNGYGFYLRAGSEQKGQIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLLVVD 114
Cdd:cd06768     1 RLCHLVKGPEGYGFNLHAEKGRPGHFIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTLLVVD 80

mitochondrial ATP synthase gamma subunit; The F-ATPase is found in bacterial plasma membranes, mitochondrial inner membranes and in chloroplast thylakoid membranes. It has also been found in the archaea Methanosarcina barkeri. It uses a proton gradient to drive ATP synthesis and hydrolyzes ATP to build the proton gradient. The extrinisic membrane domain of F-ATPases is composed of alpha, beta, gamma, delta, and epsilon (not present in bacteria) subunits with a stoichiometry of 3:3:1:1:1. Alpha and beta subunit form the globular catalytic moiety, a hexameric ring of alternating subunits. Gamma, delta and epsilon subunits form a stalk, connecting F1 to F0, the integral membrane proton translocating domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1700611676 230 EKVVDRIQSSGKNVTLLVCGKKAYDYFQAKKIPIVSSLADPLDTP 274
Cdd:PRK05621   99 LELIKELEAQGKEVKLIVIGRKGVDFFKRRGINVVAEYTGLGDQP 143

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700611676  35 RIVEMKKGSNGYGFYLRAGSEQKGQIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLLVVD 114
Cdd:cd06768     1 RLCHLVKGPEGYGFNLHAEKGRPGHFIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTLLVVD 80

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 1700611676   33 QPRIVEMKKGSNGYGFYLRAGSEQ-KGQIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLL 111
Cdd:smart00228   1 EPRLVELEKGGGGLGFSLVGGKDEgGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLT 80

                   ..
gi 1700611676  112 VV 113
Cdd:smart00228  81 VL 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700611676  35 RIVEMKKGSNGYGFYLRAGSEQKGQ--IIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLLV 112
Cdd:pfam00595   1 QVTLEKDGRGGLGFSLKGGSDQGDPgiFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700611676  56 QKGQIIKDIDSGSPAEEAGLKNNDLVVAVNGESVEtlDHDSVVEMIR--KGGDQTSLLVV--DKETDNMYRLAhfspfly 131
Cdd:TIGR02037 256 QRGALVAQVLPGSPAEKAGLKAGDVITSVNGKPIS--SFADLRRAIGtlKPGKKVTLGILrkGKEKTITVTLG------- 326

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700611676 132 yQSQELPNGSVKEAPAPTPTSLevssPPDTTEEVDHKpklcrlakgengygfhlNAIRGLpgsFIKEVQKGGPADLAGLE 211
Cdd:TIGR02037 327 -ASPEEQASSSNPFLGLTVANL----SPEIRKELRLK-----------------GDVKGV---VVTKVVSGSPAARAGLQ 381

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1700611676 212 DEDVIIEVNG--VNVLDEpYEKVVDRiQSSGKNVTLLV 247
Cdd:TIGR02037 382 PGDVILSVNQqpVSSVAE-LRKVLAR-AKKGGRVALLI 417

Membrane-associated protease RseP, regulator of RpoE activity [Posttranslational modification, protein turnover, chaperones, Transcription];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1700611676 196 IKEVQKGGPADLAGLEDEDVIIEVNGVNVLDepYEKVVDRIQSS-GKNVTLLV 247
Cdd:COG0750   132 VGEVVPGSPAAKAGLQPGDRIVAINGQPVTS--WDDLVDIIRASpGKPLTLTV 182

serine endoprotease DegS;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1700611676  51 RAGSEQ-KGQIIKDIDSGSPAEEAGLKNNDLVVAVNGE----SVETLDHdsvVEMIRKG 104
Cdd:PRK10898  272 GGGIDQlQGIVVNEVSPDGPAAKAGIQVNDLIISVNNKpaisALETMDQ---VAEIRPG 327

ATP synthase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1700611676 230 EKVVDRIQSSGKNVTLLVCGKKAYDYFQAKKIPIVSSLADPLDTPPD 276
Cdd:pfam00231  98 RALIEELLAEGKEVKLIVVGRKGRDYFKKRGYEVILEFTGSLGDKPT 144

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700611676  35 RIVEMKKGSNGYGFYLRAGSEQKGQIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLLVVD 114
Cdd:cd06768     1 RLCHLVKGPEGYGFNLHAEKGRPGHFIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTLLVVD 80

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 1700611676   33 QPRIVEMKKGSNGYGFYLRAGSEQ-KGQIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLL 111
Cdd:smart00228   1 EPRLVELEKGGGGLGFSLVGGKDEgGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLT 80

                   ..
gi 1700611676  112 VV 113
Cdd:smart00228  81 VL 82

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. 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 SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as 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 1700611676  34 PRIVEMKKGSNGYGFYLRaGSEQKGQI--------------IKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVE 99
Cdd:cd06746     6 PRTVVLQKGDKGFGFVLR-GAKAVGPIleftptpafpalqyLESVDPGGVADKAGLKKGDFLLEINGEDVVKASHEQVVN 84

                          90
                  ....*....|....
gi 1700611676 100 MIRKGGDQTSLLVV 113
Cdd:cd06746    85 LIRQSGNTLVLKVV 98

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700611676  34 PRIVEMKKGSNGYGFYLRAGSEQkgqIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIRK-GGDQTSLLV 112
Cdd:cd06712     1 PRTVHLTKEEGGFGFTLRGDSPV---QVASVDPGSCAAEAGLKEGDYIVSVGGVDCKWSKHSEVVKLLKSaGEEGLELQV 77

                  .
gi 1700611676 113 V 113
Cdd:cd06712    78 V 78

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 1700611676  35 RIVEMKKGSNGYGFYLRAGSEQKGQI-------------IKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMI 101
Cdd:cd23070     1 RVVTIVKSETGFGFNVRGQVSEGGQLrsingelyaplqhVSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVDLI 80

                          90
                  ....*....|..
gi 1700611676 102 RKGGDQTSLLVV 113
Cdd:cd23070    81 KSGGDELTLTVI 92

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 1700611676  35 RIVEMKKGSNGYGFYLragSEQKGQIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMI 101
Cdd:cd06710     1 RTVEIARGRAGYGFTI---SGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLI 64

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. 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 SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as 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 1700611676 168 KPKLCRLAKGENGYGFhlnAIRGLPGS----------------FIKEVQKGGPADLAGLEDEDVIIEVNGVNVLDEPYEK 231
Cdd:cd06746     5 DPRTVVLQKGDKGFGF---VLRGAKAVgpileftptpafpalqYLESVDPGGVADKAGLKKGDFLLEINGEDVVKASHEQ 81

                          90
                  ....*....|....*..
gi 1700611676 232 VVDRIQSSGKNVTLLVC 248
Cdd:cd06746    82 VVNLIRQSGNTLVLKVV 98

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 1700611676 170 KLCRLAKGENGYGFH----------LNAIRG---LPGSFIKEVQKGGPADLAGLEDEDVIIEVNGVNVLDEPYEKVVDRI 236
Cdd:cd23070     1 RVVTIVKSETGFGFNvrgqvseggqLRSINGelyAPLQHVSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVDLI 80

                          90
                  ....*....|.
gi 1700611676 237 QSSGKNVTLLV 247
Cdd:cd23070    81 KSGGDELTLTV 91

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 1700611676  36 IVEMKKGSNGYGFYLRAGSEQKgqiIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLLV 112
Cdd:cd06744     1 TVRVYRGNGSFGFTLRGHAPVY---IESVDPGSAAERAGLKPGDRILFLNGLDVRNCSHDKVVSLLQGSGSMPTLVV 74

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1700611676 177 GENGYGFHL--NAIRGLPGSFIKEVQKGGPADLAGLEDEDVIIEVNGVNVLDEPYEKVVDRIQSSGKNVTLLV 247
Cdd:pfam00595   8 GRGGLGFSLkgGSDQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

PDZ domain 3 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila Dlg1, human Dlg1, 2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197; SAP-97), Dlg2 (also known as channel-associated protein of synapse-110; postsynaptic density protein 93, PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95; synapse-associated protein 90, SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling, regulating surface expression of NMDA receptors in dorsal horn neurons of the spinal cord; it interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. The Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development; postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. 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 Dlg-like family PDZ3 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 1700611676  33 QPRIVEMKKGSNGYGFYLRAGSEQKGQIIKDIDSGSPAEEAG-LKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLL 111
Cdd:cd06795     1 EPRKIVLHKGSTGLGFNIVGGEDGEGIFISFILAGGPADLSGeLRRGDQILSVNGVDLRNATHEQAAAALKNAGQTVTII 80

                  ....
gi 1700611676 112 VVDK 115
Cdd:cd06795    81 AQYK 84

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1700611676 174 LAKGENGYGFhlnAIRGLPGSFIKEVQKGGPADLAGLEDEDVIIEVNGVNVLDEPYEKVVDRIQSSGKNVTLLVC 248
Cdd:cd06710     5 IARGRAGYGF---TISGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLIGKCTGVLRLVIA 76

PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5, and belongs to this MAGI1,2,3-like family. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. 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 MAGI family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as 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 1700611676  37 VEMKKGSNGYGFYLRAGSEQK--GQIIKDIDSGSPAEEAG-LKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLLV 112
Cdd:cd06735     4 VELERGPKGFGFSIRGGREYNnmPLYVLRLAEDGPAQRDGrLRVGDQILEINGESTQGMTHAQAIELIRSGGSVVRLLL 82

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. 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 tamalin-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 1700611676  32 HQPRIVEMKKGSNG-YGF----Y-LRAGSEQKGQIIKDID---SGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIR 102
Cdd:cd06713     1 SQRRTIILEKQDNEtFGFeiqtYgLHHKNSNEVEMCTYVCrvhEDSPAYLAGLTAGDVILSVNGVSVEGASHQEIVELIR 80

                          90
                  ....*....|.
gi 1700611676 103 KGGDQTSLLVV 113
Cdd:cd06713    81 SSGNTLRLETL 91

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 2; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST2 (also known as microtubule-associated serine/threonine kinase-205 kD, MAST205) , and related domains. MAST2 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST2 may function to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Binding partners of MAST2 include beta2-syntrophin, TNF receptor-associated factor 6 (TRAF6), cAMP-regulated phosphoprotein (ARPP-16), Na+/H+ exchanger NHE3 (SLC9A3) and PTEN. MAST2 is also associated with microtubules of the spermatid manchette. 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 MAST2 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 1700611676  33 QPRIVEMKKGSNgYGFYLRAGSEQKG--------QIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIRKG 104
Cdd:cd23074     2 RPPIIIHRAGKK-YGFTLRAIRVYMGdsdvytvhHMVWHVEDGGPASEAGLRQGDLITHVNGEPVHGLVHTEVVELILKS 80

                  ....*.
gi 1700611676 105 GDQTSL 110
Cdd:cd23074    81 GNKVSI 86

PDZ domain 2 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the second PDZ domain of the canonical isoform of PDZD7- isoform 1. 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 PDZD7-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700611676  35 RIVEMKKGSNGY--GFYLRAGSEQK-GQIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDSVVEMIRKggdQTSLL 111
Cdd:cd10834     2 RIVHLYTTSDDYclGFNIRGGSEYGlGIYVSKVDPGGLAEQNGIKVGDQILAVNGVSFEDITHSKAVEVLKS---QTHLM 78

                  ....*.
gi 1700611676 112 VVDKET 117
Cdd:cd10834    79 LTIKEV 84

PDZ domain 7 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 6 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of MUPP1 and PDZ domain 6 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. 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 MUPP1-like family PDZ7 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 1700611676  33 QPRIVEMKK-----------GSNGYGFYLRAGSEQKGQIIKDIDSGSPAEEAG-LKNNDLVVAVNGESVETLDHDSVVEM 100
Cdd:cd06671     1 PPRRVELWRepgkslgisivGGRVMGSRLSNGEEIRGIFIKHVLEDSPAGRNGtLKTGDRILEVNGVDLRNATHEEAVEA 80

                          90
                  ....*....|..
gi 1700611676 101 IRKGGDQTSLLV 112
Cdd:cd06671    81 IRNAGNPVVFLV 92

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1700611676 193 GSFIKEVQKGGPADLAGLEDEDVIIEVNGVNVLDEPYEKVVDRIQSSGKNVTLLV 247
Cdd:cd06704    31 GIFISRVTEGGPAAKAGVRVGDKLLEVNGVDLVDADHHEAVEALKNSGNTVTMVV 85

PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of human PTPN13, and related domains. PTPN13, also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1), negatively regulates FAS-mediated apoptosis and NGFR-mediated pro-apoptotic signaling, and may also regulate phosphoinositide 3-kinase (PI3K) signaling. It contains 5 PDZ domains; interaction partners of its second PDZ domain (PDZ2) include the Fas receptor (TNFRSF6) and thyroid receptor-interacting protein 6 (TRIP6). The second PDZ (PDZ2) domain, but not PDZ1 or PDZ3, of FRMPD2 binds to GluN2A and GluN2B, two subunits of N-methyl-d-aspartic acid (NMDA) receptors. Other binding partners of the FRMPDZ2 PDZ2 domain include NOD2, and catenin family members, delta catenin (CTNND2), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) and p0071 (also known as plakophilin 4; PKP4). 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 PTPN13-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700611676  37 VEMKKGSNGYGFYLRAGSEQK----GQIIKDIDSGSPAEEAG-LKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLL 111
Cdd:cd06792     5 VELSKKDGSLGISVTGGINTSvrhgGIYVKSLVPGGAAEQDGrIQKGDRLLEVNGVSLEGVTHKQAVECLKNAGQVVTLV 84

                  .
gi 1700611676 112 V 112
Cdd:cd06792    85 L 85

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. 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 PTPN13-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 1700611676  37 VEMKKGSNG-YGFYLRAGSEQKGQIIKDIDSGSPAEEAG-LKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLLV 112
Cdd:cd23060     2 IELEKPANGgLGFSLVGGEGGSGIFVKSISPGGVADRDGrLQVGDRLLQVNGESVIGLSHSKAVNILRKAKGTVQLTV 79

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. 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 PTPN13-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 1700611676 174 LAKGENG-YGFHLNAIRGLPGSFIKEVQKGGPADLAG-LEDEDVIIEVNGVNVLDEPYEKVVDRIQSSGKNVTLLVC 248
Cdd:cd23060     4 LEKPANGgLGFSLVGGEGGSGIFVKSISPGGVADRDGrLQVGDRLLQVNGESVIGLSHSKAVNILRKAKGTVQLTVS 80

PDZ domain of Ras-associating and dilute domain-containing protein (Radil) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Radil (also known as protein KIAA1849) and related domains. Radil is required for cell adhesion and migration of neural crest precursors during development. Radil is a component of a Rasip1-Radil-ARHGAP29 complex at endothelial cell-cell junctions. Rap1, via its effectors Radil and Rasip1 and their binding partner ArhGAP29, controls the endothelial barrier by decreasing Rho-mediated radial tension on cell-cell junctions. ArhGAP29 binds the Radil PDZ domain. The Radil PDZ domain also binds kinesin family protein 14 (KIF14); KIF14 negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. 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 Radil-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 1700611676  37 VEMKKGSNGYGFYLRAGSE----QKGQIIKDIDSGSPAEEAG-LKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQTSLL 111
Cdd:cd06690     6 VELERGPKGLGLGLIDGLHtplrSPGIYIRTLVPDSPAARDGrLRLGDRILAVNGTSLVGADYQSAMDLIRTSGDKLRFL 85

                  .
gi 1700611676 112 V 112
Cdd:cd06690    86 V 86

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. 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 tamalin-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 1700611676 195 FIKEVQKGGPADLAGLEDEDVIIEVNGVNVLDEPYEKVVDRIQSSGKNVTLLV 247
Cdd:cd06713    38 YVCRVHEDSPAYLAGLTAGDVILSVNGVSVEGASHQEIVELIRSSGNTLRLET 90

PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. 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). FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ3 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 1700611676  37 VEMKKGSNGYGF-YLRAGSEQKGQI------IKDIDSGSPAEEAG-LKNNDLVVAVNGESVETLDHDSVVEMIRKGGDQT 108
Cdd:cd06695     4 VKLTKGSSGLGFsFLGGENNSPEDPfsglvrIKKLFPGQPAAESGlIQEGDVILAVNGEPLKGLSYQEVLSLLRGAPPEV 83

                  ....
gi 1700611676 109 SLLV 112
Cdd:cd06695    84 TLLL 87

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700611676  34 PRIVEMKKGSNGYGFYLR-------------------AGSEQKGQI----------IKDIDSGSPAEEAGLKNNDLVVAV 84
Cdd:cd06756     1 PKTVTLQRTSQGFGFTLRhfivyppesavheslkdeeNGNRGGKQRsrlepmdtifVKQVKEGGPAHQAGLCTGDRIVKV 80

                          90       100
                  ....*....|....*....|....*...
gi 1700611676  85 NGESVETLDHDSVVEMIRKGGDQTSLLV 112
Cdd:cd06756    81 NGESVIGKTYSQVIALIQNSDSTLELSV 108

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1700611676 173 RLAKGENGYGFHLNAIRGLPGSFIKEVQKGGPADLAGLEDEDVIIEVNGVNVLDEPYEKVVDRIQSSGKNVTLLV 247
Cdd:cd06756    34 KDEENGNRGGKQRSRLEPMDTIFVKQVKEGGPAHQAGLCTGDRIVKVNGESVIGKTYSQVIALIQNSDSTLELSV 108