PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins, and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. 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 ZO 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 528515972   10 HTVTLSKDSKVGFGFAVSGGLDKPNPANGDAAVVVSDVIPTGPAMGRLQTRDQIVMVNGVSMENVTSLYTIQNLRKCGKT 89
Cdd:cd06727     1 HTVTLHRAPGFGFGIAVSGGRDNPHFQSGDTSIVISDVLKGGPAEGKLQENDRVVSVNGVSMENVEHSFAVQILRKCGKT 80

                  ....*..
gi 528515972   90 ANITVKR 96
Cdd:cd06727    81 ANITVKR 87

PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form domain-swapping dimers; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. 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 ZO 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 528515972  170 IKTTLIKKKPTDEYGMKLGSQIFIKHMTPTGLAAKEGSLQEGDLVLKINGMTTENLSLLETKHLVEKSRGNLTMLVLRD 248
Cdd:cd06728     1 LKVTLTKSRKNDEYGLRLGSRIFVKEITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKLIEKSKDKLQLVVLRD 79

Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates to nucleosides/nucleotides, nucleoside monophosphates, or sugars. Members of this family play a wide variety of essential roles in nucleotide metabolism, the biosynthesis of coenzymes and aromatic compounds, as well as the metabolism of sugar and sulfate.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972    831 RDDLLQLTIQGKFPAYEKVLLKEANFKRPIVILGplNDIANEKlARELPDEFEIAEMVPRSGNDSSSSVIKLDTVRRIAE 910
Cdd:smart00072    5 KGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNG--VDYHFVS-KEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVAE 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972    911 QDKHPLLDITPTAIERLNYIQYHPMVLFLDPHSRKDV-KSMRQKYMPGSSKSSRRLyAQALKLRKNYStLFSARIDLQpN 989
Cdd:smart00072   82 KGKHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELeRRLRQRGTETSERIQKRL-AAAQKEAQEYH-LFDYVIVND-D 158

                           170
                    ....*....|....*.
gi 528515972    990 TNMWYDVLKDKIRQQQ 1005
Cdd:smart00072  159 LEDAYEELKEILEAEQ 174

PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins, and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. 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 ZO 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 528515972   10 HTVTLSKDSKVGFGFAVSGGLDKPNPANGDAAVVVSDVIPTGPAMGRLQTRDQIVMVNGVSMENVTSLYTIQNLRKCGKT 89
Cdd:cd06727     1 HTVTLHRAPGFGFGIAVSGGRDNPHFQSGDTSIVISDVLKGGPAEGKLQENDRVVSVNGVSMENVEHSFAVQILRKCGKT 80

                  ....*..
gi 528515972   90 ANITVKR 96
Cdd:cd06727    81 ANITVKR 87

PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form domain-swapping dimers; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. 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 ZO 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 528515972  170 IKTTLIKKKPTDEYGMKLGSQIFIKHMTPTGLAAKEGSLQEGDLVLKINGMTTENLSLLETKHLVEKSRGNLTMLVLRD 248
Cdd:cd06728     1 LKVTLTKSRKNDEYGLRLGSRIFVKEITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKLIEKSKDKLQLVVLRD 79

Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to GDP. Structure resembles that of adenylate kinase. So-called membrane-associated guanylate kinase homologues (MAGUKs) do not possess guanylate kinase activities; instead at least some possess protein-binding functions.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972    831 RDDLLQLTIQGKFPAYEKVLLKEANFKRPIVILGplNDIANEKlARELPDEFEIAEMVPRSGNDSSSSVIKLDTVRRIAE 910
Cdd:smart00072    5 KGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNG--VDYHFVS-KEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVAE 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972    911 QDKHPLLDITPTAIERLNYIQYHPMVLFLDPHSRKDV-KSMRQKYMPGSSKSSRRLyAQALKLRKNYStLFSARIDLQpN 989
Cdd:smart00072   82 KGKHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELeRRLRQRGTETSERIQKRL-AAAQKEAQEYH-LFDYVIVND-D 158

                           170
                    ....*....|....*.
gi 528515972    990 TNMWYDVLKDKIRQQQ 1005
Cdd:smart00072  159 LEDAYEELKEILEAEQ 174

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 528515972      8 EQHTVTLSKDSKvGFGFAVSGGLDKPNPangdaaVVVSDVIPTGPAMGR-LQTRDQIVMVNGVSMENVTSLYTIQNLRKC 86
Cdd:smart00228    1 EPRLVELEKGGG-GLGFSLVGGKDEGGG------VVVSSVVPGSPAAKAgLRVGDVILEVNGTSVEGLTHLEAVDLLKKA 73

                            90
                    ....*....|.
gi 528515972     87 GKTANITVKRP 97
Cdd:smart00228   74 GGKVTLTVLRG 84

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
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 528515972    191 IFIKHMTPTGLAAKEGsLQEGDLVLKINGMTTENLSLLETKHLVEKSRGNLTMLVLRDD 249
Cdd:smart00228   28 VVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTVLRGG 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972    11 TVTLSKDSKVGFGFAVSGGLDkpnpaNGDAAVVVSDVIPTGPA-MGRLQTRDQIVMVNGVSMENVTSLYTIQNLRKCGKT 89
Cdd:pfam00595    1 QVTLEKDGRGGLGFSLKGGSD-----QGDPGIFVSEVLPGGAAeAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGK 75

                   ....*.
gi 528515972    90 ANITVK 95
Cdd:pfam00595   76 VTLTIL 81

Guanylate kinase;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972   858 RPIVILGPL---NDIANEKLARELPDEF------------------------------------EIAEMVPRSGNDSSSS 898
Cdd:pfam00625    3 RPVVLSGPSgvgKSHIKKALLSEYPDKFgysvphttrpprkgevdgkdyyfvskeemerdisanEFLEYAQFSGNMYGTS 82

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 528515972   899 ViklDTVRRIAEQDKHPLLDITPTAIERLNYIQYHPMVLFLDPHSRKDVKSMRQKYMPGSSKSsrrLYAQALKLRKNYS 977
Cdd:pfam00625   83 V---ETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLKGRGKEQEEK---INKRMAAAEQEFQ 155

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
                   ....*....|....*....|....*....|....*
gi 528515972   652 GIFVGGVQPNSPAQKQGITEGDQILEVNGMDFNHF 686
Cdd:TIGR02037  258 GALVAQVLPGSPAEKAGLKAGDVITSVNGKPISSF 292

Treacher Collins syndrome protein Treacle;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972   262 SPQNSSDERREDSSSELEEISDLDSDLPVTNRASRRK-DRKSNRNRADPVSKKlESP-----PLRSTLTRPAQSMPP--- 332
Cdd:pfam03546   12 ATQAKAGKPEEDSESSSEEESDSEEETPAAKTPLQAKpSGKTPQVRAASAPAK-ESPrkgapPVPPGKTGPAAAQAQagk 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972   333 RRVPSESESDRSNSppprhdtlDHRNKVLSGYSTLPnPRASPITSSSTSRPRRAVSESDSDRSASppprresprpdnhsr 412
Cdd:pfam03546   91 PEEDSESSSEESDS--------DGETPAAATLTTSP-AQVKPLGKNSQVRPASTVGKGPSGKGAN--------------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972   413 ykvlpdLPPPGLKPSSLSMSQdfprrMASPYRPPPRDASESESDESARPQRRQGTPASQESRNRYRAAPevKAAAVMEPP 492
Cdd:pfam03546  147 ------PAPPGKAGSAAPLVQ-----VGKKEEDSESSSEESDSEGEAPPAATQAKPSGKILQVRPASGP--AKGAAPAPP 213

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 528515972   493 KWAKP-STPVQRAPSESESDGSYNSPPKQPPSPVSKSSRIKGPEMQMPIT--SIRQDPPLRAAPARPPP 558
Cdd:pfam03546  214 QKAGPvATQVKAERSKEDSESSEESSDSEEEAPAAATPAQAKPALKTPQTkaSPRKGTPITPTSAKVPP 282

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 528515972    725 DSFYIRTHYDHVADSSVGLSFTRGEVFRVVDTMHRGklgtWLAVRMGN 772
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDG----WWKGRLGR 44

PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins, and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. 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 ZO 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 528515972   10 HTVTLSKDSKVGFGFAVSGGLDKPNPANGDAAVVVSDVIPTGPAMGRLQTRDQIVMVNGVSMENVTSLYTIQNLRKCGKT 89
Cdd:cd06727     1 HTVTLHRAPGFGFGIAVSGGRDNPHFQSGDTSIVISDVLKGGPAEGKLQENDRVVSVNGVSMENVEHSFAVQILRKCGKT 80

                  ....*..
gi 528515972   90 ANITVKR 96
Cdd:cd06727    81 ANITVKR 87

PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form domain-swapping dimers; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. 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 ZO 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 528515972  170 IKTTLIKKKPTDEYGMKLGSQIFIKHMTPTGLAAKEGSLQEGDLVLKINGMTTENLSLLETKHLVEKSRGNLTMLVLRD 248
Cdd:cd06728     1 LKVTLTKSRKNDEYGLRLGSRIFVKEITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKLIEKSKDKLQLVVLRD 79

Src homology 3 domain of the Tight junction proteins, Zonula occludens (ZO) proteins; ZO proteins are scaffolding proteins that associate with each other and with other proteins of the tight junction, zonula adherens, and gap junctions. They play roles in regulating cytoskeletal dynamics at these cell junctions. They are considered members of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. Vertebrates contain three ZO proteins (ZO-1, ZO-2, and ZO-3) with redundant and non-redundant roles. They contain three PDZ domains, followed by SH3 and GuK domains; in addition, ZO-1 and ZO-2 contains a proline-rich (PR) actin binding domain at the C-terminus while ZO-3 contains this PR domain between the second and third PDZ domains. The C-terminal regions of the three ZO proteins are unique. The SH3 domain of ZO-1 has been shown to bind ZONAB, ZAK, afadin, and Galpha12. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528515972  728 YIRTHYDHVADSSVGLSFTRGEVFRVVDTMHRGKLGTWLAVRMGNDLHELDKGTIPNQTRAE 789
Cdd:cd11859     1 YIRTHFDYEKPAKGELSFKKGEVFHVVDTLYQGTVGSWQAVRVGRNHQELERGVIPNKSRAE 62

Src homology 3 domain of the Tight junction protein, Zonula occludens protein 2; ZO-2 is a scaffolding protein that associates with other ZO proteins and other proteins of the tight junction, zonula adherens, and gap junctions. ZO proteins play roles in regulating cytoskeletal dynamics at these cell junctions. ZO-2 plays an essential role in embryonic development. It is critical for the blood-testis barrier integrity and male fertility. It also regulates the expression of cyclin D1 and cell proliferation. It is considered a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. The C-terminal region of ZO-2 contains an actin-binding region and a domain of unknown function designated beta. The SH3 domain of the related protein ZO-1 has been shown to bind ZONAB, ZAK, afadin, and Galpha12. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 528515972  724 GDSFYIRTHYDHVADSSVGLSFTRGEVFRVVDTMHRGKLGTWLAVRMGNdlhELDKGTIPNQTRAE 789
Cdd:cd12027     1 GDSFFIRTHFEYEKELPQSLAFTRGEIFRVVDTLYDGKLGNWLAVRIGN---ELEKGLIPNKSRAE 63

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 528515972   11 TVTLSKDSKVGFGFAVSGGldkpnpANGDAAVVVSDVIPTGPAM--GRLQTRDQIVMVNGVSMENVTSLYTIQNLRKCGK 88
Cdd:cd00136     1 TVTLEKDPGGGLGFSIRGG------KDGGGGIFVSRVEPGGPAArdGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGG 74

                  ....*..
gi 528515972   89 TANITVK 95
Cdd:cd00136    75 EVTLTVR 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        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972      8 EQHTVTLSKDSKvGFGFAVSGGLDKPNPangdaaVVVSDVIPTGPAMGR-LQTRDQIVMVNGVSMENVTSLYTIQNLRKC 86
Cdd:smart00228    1 EPRLVELEKGGG-GLGFSLVGGKDEGGG------VVVSSVVPGSPAAKAgLRVGDVILEVNGTSVEGLTHLEAVDLLKKA 73

                            90
                    ....*....|.
gi 528515972     87 GKTANITVKRP 97
Cdd:smart00228   74 GGKVTLTVLRG 84

PDZ domain of FERM and PDZ domain-containing protein 1 (FRMPD1), FRMPD3, FRMPD4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of FRMPD1, FRMPD3, FRMPD4, and related domains. FRMPD1 (also known as FERM domain-containing protein 2, FRMD2), inhibits the malignant phenotype of lung cancer by activating the Hippo pathway via interaction with WWC3; the FRMPD1 PDZ domain binds WWC3. FRMPD3 is a target gene of the neuron-specific transcription factor NPAS4 that is involved in synaptic plasticity. FRMPD4 (also known as PDZ domain-containing protein 10, PDZD10, PDZK10, PSD-95-interacting regulator of spine morphogenesis, and Preso) regulates dendritic spine morphogenesis, and mGluR1/5 signaling; the FRMPD4 PDZ domain binds PAK-interacting exchange factor-beta (betaPix). 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 FRMPD1,3,4-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 528515972   11 TVTLSKDSKVGFGFAVSGglDKPnpangdaaVVVSDVIPTGPAMGRLQTRDQIVMVNGVSMENVTSLYTIQNLRKCGKTA 90
Cdd:cd06769     1 TVEIQRDAVLGFGFVAGS--ERP--------VVVRSVTPGGPSEGKLLPGDQILKINNEPVEDLPRERVIDLIRECKDSI 70

                  ....
gi 528515972   91 NITV 94
Cdd:cd06769    71 VLTV 74

PDZ domain 1 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 1 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. 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. 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 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 528515972   12 VTLSKDSKVGFGFAVSGGldkPNPANGDAAVVVSDVIPTGPAM--GRLQTRDQIVMVNGVSMENVTSLYTIQNLRKCGKT 89
Cdd:cd06694     5 VTLKKDPQKGLGFTIVGG---ENSGSLDLGIFVKSIIPGGPADkdGRIKPGDRIIAINGQSLEGKTHHAAVEIIQNAPDK 81

                  ....*....
gi 528515972   90 ANITVKRPR 98
Cdd:cd06694    82 VELIISQPK 90

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 528515972  172 TTLIKKKPTDEYGMKLGSQ------IFIKHMTPTGLAAKEGSLQEGDLVLKINGMTTENLSLLETKHLVEKSRGNLTMLV 245
Cdd:cd00136     1 TVTLEKDPGGGLGFSIRGGkdggggIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLTV 80

                  .
gi 528515972  246 L 246
Cdd:cd00136    81 R 81

PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange factor 6, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Rap guanine nucleotide exchange factor 2 (RapGEF2, also named RA-GEF-1, PDZ-GEF1, CNrasGEF and nRapGEP) and Rap guanine nucleotide exchange factor 6 (RapGEF6, also named RA-GEF-2 and PDZ-GEF2). RapGEF2 and RapGEF6 constitute a subfamily of guanine nucleotide exchange factors (GEFs) for RAP small GTPases that is characterized by the possession of the PDZ and Ras/Rap-associating domains. They activate Rap small GTPases, by catalyzing the release of GDP from the inactive GDP-bound forms, thereby accelerating GTP loading to yield the active GTP-bound forms. The PDZ domain of RapGEF6 (also known as PDZ-GEF2) binds junctional adhesion molecule A (JAM-A). 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 RapGEF2 and RapGEF6 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 528515972  637 KEGSVGLRLVGGND--VGIFVGGVQPNSPAQKQGITEGDQILEVNGMDFNHFTREEAAMYLMN 697
Cdd:cd06755    10 RESPLHFSLLGGSEkgFGIFVSKVEKGSKAAEAGLKRGDQILEVNGQNFENITLKKALEILRN 72

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 528515972    8 EQHTVTLSKDSKvGFGFAVSGGLDKPNPANGdaaVVVSDVIPTGPAM--GRLQTRDQIVMVNGVSMENVTSLYTIQNLRK 85
Cdd:cd06792     1 DVFEVELSKKDG-SLGISVTGGINTSVRHGG---IYVKSLVPGGAAEqdGRIQKGDRLLEVNGVSLEGVTHKQAVECLKN 76

                          90
                  ....*....|.
gi 528515972   86 CGKTANITVKR 96
Cdd:cd06792    77 AGQVVTLVLER 87

PDZ domain 3 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 2 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 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528515972  633 ISFVK-EGSVGLRLVGGNDV----------GIFVGGVQPNSPAQKQGITEGDQILEVNGMDFNHFTREEAAMYL 695
Cdd:cd06702     3 IHLVKaGGPLGLSIVGGSDHsshpfgvdepGIFISKVIPDGAAAKSGLRIGDRILSVNGKDLRHATHQEAVSAL 76

PDZ domain of synaptojanin-2-binding protein (SYNJ2BP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNJ2BP, and related domains. SYNJ2BP (also known as mitochondrial outer membrane protein 25, OMP25) regulates endocytosis of activin type 2 receptor kinases through the Ral/RALBP1-dependent pathway and may be involved in suppression of activin-induced signal transduction. Binding partners of the SYNJ2BP PDZ domain include activin type II receptors (ActR-II), and SYNJ2. SYNJ2BP interacts with the PDZ binding motif of the Notch Delta-like ligand 1 (DLL1) and DLL4, promoting Delta-Notch signaling, and inhibiting sprouting angiogenesis. 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 SYNJ2BP-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 528515972   10 HTVTLSKDsKVGFGFAVSGGLDKPNPANgDAAVVVSDVIPTGPAM--GRLQTRDQIVMVNGVSMENVTSLYTIQNLRKCG 87
Cdd:cd06709     1 EEITLKRG-PSGLGFNIVGGTDQPYIPN-DSGIYVAKIKEDGAAAidGRLQEGDKILEINGQSLENLTHQDAVELFRNAG 78

                  ....*...
gi 528515972   88 KTANITVK 95
Cdd:cd06709    79 EDVKLKVQ 86

PDZ domain 1 of 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 1 of FRMPD2 (also known as PDZ domain-containing protein 4, and related domains. 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. 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 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 528515972   12 VTLSKDSKVGFGFAVSGGldkPNPANGDAAVVVSDVIPTGPA--MGRLQTRDQIVMVNGVSMENVTSLYTIQNLRKCGKT 89
Cdd:cd23071     5 VTLKRDPKRGFGFVIVGG---ENTGKLDLGIFIASIIPGGPAekDGRIKPGGRLISLNNISLEGVTFNTAVKILQNSPDE 81

                          90
                  ....*....|.
gi 528515972   90 ANITVKRPRTI 100
Cdd:cd23071    82 VELIISQPKDT 92

PDZ domain 1 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. 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 whirlin 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528515972  637 KEGsVGLRLVGGND--VGIFVGGVQPNSPAQKQGITEGDQILEVNGMDFNHFTREEAAMYLmniRGGERIDM 706
Cdd:cd06740    12 HEG-LGFSIRGGAEhgVGIYVSLVEPGSLAEKEGLRVGDQILRVNDVSFEKVTHAEAVKIL---RVSKKLVL 79

PDZ domain of PDZ domain-containing protein 11, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZD11, and related domains. PDZD11 (also known as ATPase-interacting PDZ protein, plasma membrane calcium ATPase-interacting single-PDZ protein, PMCA-interacting single-PDZ protein, PISP) is involved in the dynamic assembly of apical junctions (AJs). It is recruited by PLEKHA7 to AJs to promote the efficient junctional recruitment and stabilization of nectins, and the efficient early phases of assembly of AJs in epithelial cells. The PDZD11 PDZ domain binds nectin-1 and nectin-3. PDZD11 also binds to a PDZ binding motif located in the C-terminal tail of the human sodium-dependent multivitamin transporter, to the cytoplasmic tail of the Menkes copper ATPase ATP7A, and to the cytoplasmic tail of all plasma membrane Ca2+-ATPase b-splice variants. 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 PDZD11-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 528515972  640 SVGLRLVGGND--VGIFVGGVQPNSPAQKQGITEGDQILEVNGMDFNHFTREEAAMYLMNIRggeRIDMRTQ 709
Cdd:cd06752    12 QLGFNIRGGKAsgLGIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTAR---EIQMRVR 80

PDZ domain 1 of protein tyrosine 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 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], 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). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 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 528515972    8 EQHTVTLSKDSKVGFGFAVSGGLDkpnPANGDAAVVVSDVIPTGPA--MGRLQTRDQIVMVNGVSMENVTSLYTIQNLRK 85
Cdd:cd23072     1 EITLVNLKKDAKYGLGFQIVGGEK---SGRLDLGIFISSITPGGPAdlDGRLKPGDRLISVNDVSLEGLSHDAAVEILQN 77

                          90
                  ....*....|...
gi 528515972   86 CGKTANITVKRPR 98
Cdd:cd23072    78 APEDVTLVVSQPK 90

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972  262 SPQNSSDERREDSSSELEEISDLDSDLPVTNRASRRKDRK----SNRNRADPVSKKLESPPLRSTLTRPAQSMPPrrVPS 337
Cdd:PHA03307  101 AREGSPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPvgspGPPPAASPPAAGASPAAVASDAASSRQAALP--LSS 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972  338 ESESDRSNSPPPRHDTLDHRNKVLSGYSTLPNPRASPITSSSTSRPRRAvSESDSDRSASPPPRRESPRPDNHSRYKVLP 417
Cdd:PHA03307  179 PEETARAPSSPPAEPPPSTPPAAASPRPPRRSSPISASASSPAPAPGRS-AADDAGASSSDSSSSESSGCGWGPENECPL 257

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972  418 DLPPPGLKPSSlsmsqdfPRRMASPYRPPPR--DASESESDESARPQRRQGTPASQESRNRYRAAPEVkaaavmEPPKWA 495
Cdd:PHA03307  258 PRPAPITLPTR-------IWEASGWNGPSSRpgPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSS------SSSRES 324

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528515972  496 KPSTPVQRAPSESESDGSYNSPPKQPPSPVSKSSRIKGPemqmpitsirqdPPLRAAPARPPPEDSSDSerAQSPLRRSD 575
Cdd:PHA03307  325 SSSSTSSSSESSRGAAVSPGPSPSRSPSPSRPPPPADPS------------SPRKRPRPSRAPSSPAAS--AGRPTRRRA 390

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*.
gi 528515972  576 SHNSDHSFPRANGTLRSNVSIPNHTALTSKAVEEPLYVLPPDAVPT 621
Cdd:PHA03307  391 RAAVAGRARRRDATGRFPAGRPRPSPLDAGAASGAFYARYPLLTPS 436