PDZ domain of neurabin-1 and neurabin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of neurabin-1 (also known as protein phosphatase 1 regulatory subunit 9A) and neurabin-2 (also known as spinophilin, and protein phosphatase 1 regulatory subunit 9B), and related domains. Neurabin-1 and neurabin-2 are neuronal scaffolding proteins that play important roles in the regulation of synaptic transmission through their ability to interact with and target protein phosphatase 1 (PP1) to dendritic spines where PP1 dephosphorylates and inactivates glutamate receptors. Neurabin-2 interacts with multiple other synaptic proteins, including synaptic signaling and scaffolding proteins (e.g., GluN1 and SAPAP3) and cytoskeletal proteins (e.g., neurofilament medium polypeptide, NF-M). Neurabin-1 and neurabin-2 also binds F-actin. Other binding partners of neurabin-1 include adenosine A1 receptor (A1R), SAD-1 kinase and 70 kDa ribosomal protein S6 kinase (p70-S6K). This PDZ domain is immediately C-terminal to the PP1 binding domain. 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 neurabin-like PDZ 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 2113636763  546 EVFPVEIEKGDSGLGISIIGMGVGADQGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNT 625
Cdd:cd06790      1 DLFPVELEKGSEGLGISIIGMGVGADAGLEKLGIFVKTVTEGGAAQRDGRIQVNDQIVEVDGISLVGVTQAFAASVLRNT 80

                           90
                   ....*....|
gi 2113636763  626 KGTVRFLIGR 635
Cdd:cd06790     81 SGTVRFLIGR 90

SAM domain of SAM_Neurabin-like subfamily; SAM (sterile alpha motif) domain of Neurabin-like (Neural actin-binding) subfamily is a putative protein-protein interaction domain. This group currently includes the SAM domains of neurobin-I, SAMD14 and neurobin-I/SAMD14-like proteins. Most are multidomain proteins and in addition to SAM domain they contain other protein-binding domains such as PDZ and actin-binding domains. Members of this subfamily participate in signal transduction. Neurabin-I is involved in the regulation of Ca signaling intensity in alpha-adrenergic receptors; it forms a functional pair of opposing regulators with neurabin-II. Neurabins are expressed almost exclusively in neuronal cells. They are known to interact with protein phosphatase 1 and inhibit its activity; they also can bind actin filaments; however, the exact role of the SAM domain is unclear, since SAM doesn't participate in these interactions.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2113636763 1229 SRPVSDWSAQQVCHWLMGMNMEQHIEEFTAKNIDGQQLMLLDSDRLKALGVLSHTDRAT 1287
Cdd:cd09512      1 SRPVSEWSVQQVCQWLMGLGLEQYIPEFTANNIDGQQLLQLDSSKLKALGITSSSDRSL 59

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  790 LKETQEQYDTLEKKYTKaKKVLKDFQLKEIEFEKNELE--HKELLREKDRQHA--EQMSLLYARITALENKLGAYEQKLQ 865
Cdd:COG4717     48 LERLEKEADELFKPQGR-KPELNLKELKELEEELKEAEekEEEYAELQEELEEleEELEELEAELEELREELEKLEKLLQ 126

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  866 VIPNHKYENEeftphtatapteAPAELESEGSTL--LESSISDFDACVGEIQRLDTSASRAKAQLALKVKRQRPS-RNKL 942
Cdd:COG4717    127 LLPLYQELEA------------LEAELAELPERLeeLEERLEELRELEEELEELEAELAELQEELEELLEQLSLAtEEEL 194

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2113636763  943 KGLI--VGKEQKLFQEEDEAEETLQAETVSPSEKTDDSEDQLGSQDEDQRIEK 993
Cdd:COG4717    195 QDLAeeLEELQQRLAELEEELEEAQEELEELEEELEQLENELEAAALEERLKE 247

PDZ domain of neurabin-1 and neurabin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of neurabin-1 (also known as protein phosphatase 1 regulatory subunit 9A) and neurabin-2 (also known as spinophilin, and protein phosphatase 1 regulatory subunit 9B), and related domains. Neurabin-1 and neurabin-2 are neuronal scaffolding proteins that play important roles in the regulation of synaptic transmission through their ability to interact with and target protein phosphatase 1 (PP1) to dendritic spines where PP1 dephosphorylates and inactivates glutamate receptors. Neurabin-2 interacts with multiple other synaptic proteins, including synaptic signaling and scaffolding proteins (e.g., GluN1 and SAPAP3) and cytoskeletal proteins (e.g., neurofilament medium polypeptide, NF-M). Neurabin-1 and neurabin-2 also binds F-actin. Other binding partners of neurabin-1 include adenosine A1 receptor (A1R), SAD-1 kinase and 70 kDa ribosomal protein S6 kinase (p70-S6K). This PDZ domain is immediately C-terminal to the PP1 binding domain. 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 neurabin-like PDZ 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 2113636763  546 EVFPVEIEKGDSGLGISIIGMGVGADQGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNT 625
Cdd:cd06790      1 DLFPVELEKGSEGLGISIIGMGVGADAGLEKLGIFVKTVTEGGAAQRDGRIQVNDQIVEVDGISLVGVTQAFAASVLRNT 80

                           90
                   ....*....|
gi 2113636763  626 KGTVRFLIGR 635
Cdd:cd06790     81 SGTVRFLIGR 90

SAM domain of SAM_Neurabin-like subfamily; SAM (sterile alpha motif) domain of Neurabin-like (Neural actin-binding) subfamily is a putative protein-protein interaction domain. This group currently includes the SAM domains of neurobin-I, SAMD14 and neurobin-I/SAMD14-like proteins. Most are multidomain proteins and in addition to SAM domain they contain other protein-binding domains such as PDZ and actin-binding domains. Members of this subfamily participate in signal transduction. Neurabin-I is involved in the regulation of Ca signaling intensity in alpha-adrenergic receptors; it forms a functional pair of opposing regulators with neurabin-II. Neurabins are expressed almost exclusively in neuronal cells. They are known to interact with protein phosphatase 1 and inhibit its activity; they also can bind actin filaments; however, the exact role of the SAM domain is unclear, since SAM doesn't participate in these interactions.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2113636763 1229 SRPVSDWSAQQVCHWLMGMNMEQHIEEFTAKNIDGQQLMLLDSDRLKALGVLSHTDRAT 1287
Cdd:cd09512      1 SRPVSEWSVQQVCQWLMGLGLEQYIPEFTANNIDGQQLLQLDSSKLKALGITSSSDRSL 59

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  550 VEIEK-GDSGLGISIIGMGVGADQGleklgIFVKTIAEGGAAQRDGrIEVNDQIVEVDGTSLVGVTQLFAATVLKNTKGT 628
Cdd:pfam00595    2 VTLEKdGRGGLGFSLKGGSDQGDPG-----IFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGK 75

                   ....*
gi 2113636763  629 VRFLI 633
Cdd:pfam00595   76 VTLTI 80

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2113636763 1233 SDWSAQQVCHWLMGMNMEQHIEEFTAKNIDGQQLMLLDSDRLKALGV 1279
Cdd:pfam00536    1 DGWSVEDVGEWLESIGLGQYIDSFRAGYIDGDALLQLTEDDLLKLGV 47

V-type ATP synthase subunit I; Validated

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  712 DASQLALKFKELqlkhavtTAEVNQLKDRIKAAENEKmdwetNRLKYKQSVEENKEKIKKLETYWLEAQALCKTVNEHLK 791
Cdd:PRK05771    94 ELEKIEKEIKEL-------EEEISELENEIKELEQEI-----ERLEPWGNFDLDLSLLLGFKYVSVFVGTVPEDKLEELK 161

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  792 ETQEQYDTLEKKYTKAKK-----VLKDF------QLKEIEFEKNELEHKELLREKDRQHAEQMSLLYARITALENKLGAY 860
Cdd:PRK05771   162 LESDVENVEYISTDKGYVyvvvvVLKELsdeveeELKKLGFERLELEEEGTPSELIREIKEELEEIEKERESLLEELKEL 241

                   ....
gi 2113636763  861 EQKL 864
Cdd:PRK05771   242 AKKY 245

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  714 SQLALKFKELqlKHAVTTAEVNQLKDRIKAAENEKmdwetnrlkykqsvEENKEKIKKLETywleaqaLCKTVNEHLKET 793
Cdd:TIGR02168  209 AEKAERYKEL--KAELRELELALLVLRLEELREEL--------------EELQEELKEAEE-------ELEELTAELQEL 265

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  794 QEQYDTLEKKYTKAKKVLKDFQ--LKEIEFEKNELEH-KELLREKDRQHAEQMSLLYARITALENKLGAYEQKLQVIpnh 870
Cdd:TIGR02168  266 EEKLEELRLEVSELEEEIEELQkeLYALANEISRLEQqKQILRERLANLERQLEELEAQLEELESKLDELAEELAEL--- 342

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  871 KYENEEFTPHTAtaptEAPAELESEGSTL--LESSISDFDACVGEIQRLDTSASRAKAQLALKVKRQRPSRNKLKGLIVG 948
Cdd:TIGR02168  343 EEKLEELKEELE----SLEAELEELEAELeeLESRLEELEEQLETLRSKVAQLELQIASLNNEIERLEARLERLEDRRER 418

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2113636763  949 KEQKLFQEEDEAEETLQAETVSPSEKTDDSEDQLGSQDEDQRIEKSQTAESL 1000
Cdd:TIGR02168  419 LQQEIEELLKKLEEAELKELQAELEELEEELEELQEELERLEEALEELREEL 470

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  790 LKETQEQYDTLEKKYTKaKKVLKDFQLKEIEFEKNELE--HKELLREKDRQHA--EQMSLLYARITALENKLGAYEQKLQ 865
Cdd:COG4717     48 LERLEKEADELFKPQGR-KPELNLKELKELEEELKEAEekEEEYAELQEELEEleEELEELEAELEELREELEKLEKLLQ 126

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  866 VIPNHKYENEeftphtatapteAPAELESEGSTL--LESSISDFDACVGEIQRLDTSASRAKAQLALKVKRQRPS-RNKL 942
Cdd:COG4717    127 LLPLYQELEA------------LEAELAELPERLeeLEERLEELRELEEELEELEAELAELQEELEELLEQLSLAtEEEL 194

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2113636763  943 KGLI--VGKEQKLFQEEDEAEETLQAETVSPSEKTDDSEDQLGSQDEDQRIEK 993
Cdd:COG4717    195 QDLAeeLEELQQRLAELEEELEEAQEELEELEEELEQLENELEAAALEERLKE 247

PDZ domain of neurabin-1 and neurabin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of neurabin-1 (also known as protein phosphatase 1 regulatory subunit 9A) and neurabin-2 (also known as spinophilin, and protein phosphatase 1 regulatory subunit 9B), and related domains. Neurabin-1 and neurabin-2 are neuronal scaffolding proteins that play important roles in the regulation of synaptic transmission through their ability to interact with and target protein phosphatase 1 (PP1) to dendritic spines where PP1 dephosphorylates and inactivates glutamate receptors. Neurabin-2 interacts with multiple other synaptic proteins, including synaptic signaling and scaffolding proteins (e.g., GluN1 and SAPAP3) and cytoskeletal proteins (e.g., neurofilament medium polypeptide, NF-M). Neurabin-1 and neurabin-2 also binds F-actin. Other binding partners of neurabin-1 include adenosine A1 receptor (A1R), SAD-1 kinase and 70 kDa ribosomal protein S6 kinase (p70-S6K). This PDZ domain is immediately C-terminal to the PP1 binding domain. 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 neurabin-like PDZ 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 2113636763  546 EVFPVEIEKGDSGLGISIIGMGVGADQGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNT 625
Cdd:cd06790      1 DLFPVELEKGSEGLGISIIGMGVGADAGLEKLGIFVKTVTEGGAAQRDGRIQVNDQIVEVDGISLVGVTQAFAASVLRNT 80

                           90
                   ....*....|
gi 2113636763  626 KGTVRFLIGR 635
Cdd:cd06790     81 SGTVRFLIGR 90

PDZ domain 3 of multi-PDZ-domain protein 1 (MUPP1) and 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 3 of MUPP1 and 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 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 2113636763  546 EVFPVEIEKGDSGLGISIIGMgVGADQGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNT 625
Cdd:cd06791      1 ETFEVELVKDEQGLGITIAGY-VGEKASGELSGIFVKSIIPGSAADQDGRIQVNDQIIAVDGVNLQGFTNQEAVEVLRNT 79

                           90
                   ....*....|
gi 2113636763  626 KGTVRFLIGR 635
Cdd:cd06791     80 GQVVHLTLAR 89

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 2113636763  546 EVFPVEIEKGDSGLGISIIGmgvGADQGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNT 625
Cdd:cd06792      1 DVFEVELSKKDGSLGISVTG---GINTSVRHGGIYVKSLVPGGAAEQDGRIQKGDRLLEVNGVSLEGVTHKQAVECLKNA 77

                           90
                   ....*....|
gi 2113636763  626 KGTVRFLIGR 635
Cdd:cd06792     78 GQVVTLVLER 87

PDZ domain 13 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 13 of MUPP1. 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. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ13 domain is therefore absent from PATJ. 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). 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 PDZ13 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 2113636763  550 VEIEKGDSGLGISIIGmGVGADQGleKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNTKGTV 629
Cdd:cd06676      2 ITLERGSDGLGFSIVG-GFGSPHG--DLPIYVKTVFEKGAAAEDGRLKRGDQILAVNGESLEGVTHEEAVNILKKTKGTV 78

PDZ domain 10 of multi-PDZ-domain protein 1 (MUPP1), domain 8 of PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 10 of MUPP1, PDZ domain 8 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 PDZ10 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 2113636763  550 VEIEKGDSGLGISIIGmgvGADQGLEklGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNTKGTV 629
Cdd:cd06673      6 IEINKGKKGLGLSIVG---GSDTLLG--AIIIHEVYEDGAAAKDGRLWAGDQILEVNGEDLRKATHDEAINVLRQTPQKV 80

                   ....*.
gi 2113636763  630 RFLIGR 635
Cdd:cd06673     81 RLLVYR 86

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 2113636763   546 EVFPVEIEKGDSGLGISIIGMGVgadqglEKLGIFVKTIAEGGAAQRDGrIEVNDQIVEVDGTSLVGVTQLFAATVLKNT 625
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVGGKD------EGGGVVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKA 73

                            90
                    ....*....|..
gi 2113636763   626 KGTVRFLIGREK 637
Cdd:smart00228   74 GGKVTLTVLRGG 85

PDZ domain 11 of MUPP1 of multi-PDZ-domain protein 1 (MUPP1), domain 9 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 11 of MUPP1, PDZ domain 9 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 PDZ11 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 2113636763  546 EVFPVEIEK-GDSGLGISIIGMGVGAdqgleklGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKN 624
Cdd:cd06674      2 DIFTVELQKkPGRGLGLSIVGKRNDT-------GVFVSDIVKGGAADADGRLMQGDQILSVNGEDVRNASQEAAAALLKC 74

                           90
                   ....*....|...
gi 2113636763  625 TKGTVRFLIGREK 637
Cdd:cd06674     75 AQGKVRLEVGRLK 87

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 2113636763  546 EVFPVEIEK-GDSGLGISIIGmgvGADQGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKN 624
Cdd:cd06694      1 EIVIVTLKKdPQKGLGFTIVG---GENSGSLDLGIFVKSIIPGGPADKDGRIKPGDRIIAINGQSLEGKTHHAAVEIIQN 77

                           90
                   ....*....|....*
gi 2113636763  625 TKGTVRFLIGREKPG 639
Cdd:cd06694     78 APDKVELIISQPKSV 92

PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2)and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four 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 LNX family PDZ4 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 2113636763  548 FPVEIEKGDSG-LGISIIGmgvGADQGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNTK 626
Cdd:cd06680      1 KDITLRRSSSGsLGFSIVG---GYEESHGNQPFFVKSIVPGTPAYNDGRLKCGDIILAVNGVSTVGMSHAALVPLLKEQR 77

                   ....*..
gi 2113636763  627 GTVRFLI 633
Cdd:cd06680     78 GRVTLTV 84

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 2113636763  546 EVFPVEIEKGDSGLGISIIGmgvGADQGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNT 625
Cdd:cd06690      2 DVFVVELERGPKGLGLGLID---GLHTPLRSPGIYIRTLVPDSPAARDGRLRLGDRILAVNGTSLVGADYQSAMDLIRTS 78

                           90
                   ....*....|
gi 2113636763  626 KGTVRFLIGR 635
Cdd:cd06690     79 GDKLRFLVAK 88

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  548 FPVEIEKGDSGLGISIIGmgvgaDQGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNTKG 627
Cdd:cd06735      2 YSVELERGPKGFGFSIRG-----GREYNNMPLYVLRLAEDGPAQRDGRLRVGDQILEINGESTQGMTHAQAIELIRSGGS 76

                   ....*...
gi 2113636763  628 TVRFLIGR 635
Cdd:cd06735     77 VVRLLLRR 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  550 VEIEK-GDSGLGISIIGMGVGADQGleklgIFVKTIAEGGAAQRDGrIEVNDQIVEVDGTSLVGVTQLFAATVLKNTKGT 628
Cdd:pfam00595    2 VTLEKdGRGGLGFSLKGGSDQGDPG-----IFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGK 75

                   ....*
gi 2113636763  629 VRFLI 633
Cdd:pfam00595   76 VTLTI 80

PDZ1 domain of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains. Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). 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 STXBP4-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 2113636763  558 GLGISIIGmGVGADQGlEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNTKGT--VRFLIGR 635
Cdd:cd06692      9 GLGIKIIG-GYRENTG-EEFGIFIKRILPGGLAATDGRLKEGDLILEVNGESLQGVTNERAVSILRSASASnhMSLLIAR 86

PDZ domain 1 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 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or 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. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. 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 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 2113636763  552 IEKGDSGLGISIIGmgvGADQGLE--KLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNTKGTV 629
Cdd:cd06723      6 LERGNSGLGFSIAG---GTDNPHIgdDPSIYITKIIPGGAAAADGRLRVNDIILRVNDVDVRNVTHSVAVEALKEAGSIV 82

                   ....*.
gi 2113636763  630 RFLIGR 635
Cdd:cd06723     83 RLYVKR 88

PDZ domain 2 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of MUPP1 and 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 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 2113636763  557 SGLGISIIGmGVGAdqgleklGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNTKGTVRFLIGR 635
Cdd:cd06667     10 SGLGFGIVG-GKST-------GVVVKTILPGGVADRDGRLRSGDHILQIGDTNLRGMGSEQVAQVLRQCGSHVRLVVAR 80

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  550 VEIEKGDSGLGISIIGmGVGA------DQGleklgIFVKTIAEGGAAQRDGrIEVNDQIVEVDGTSLVGVTQLFAATVLK 623
Cdd:cd06704      3 ITIERQTGGLGISIAG-GKGStpykgdDEG-----IFISRVTEGGPAAKAG-VRVGDKLLEVNGVDLVDADHHEAVEALK 75

                           90
                   ....*....|..
gi 2113636763  624 NTKGTVRFLIGR 635
Cdd:cd06704     76 NSGNTVTMVVLR 87

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  546 EVFPVEIEKGDSGLGISIIGmgvgadqGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNT 625
Cdd:cd06795      1 EPRKIVLHKGSTGLGFNIVG-------GEDGEGIFISFILAGGPADLSGELRRGDQILSVNGVDLRNATHEQAAAALKNA 73

                   ....
gi 2113636763  626 KGTV 629
Cdd:cd06795     74 GQTV 77

PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of PDZD2, also known as KIAA0300, PIN-1, PAPIN, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family include the PDZ domain of the secreted mature form of human interleukin-16 (IL-16); this is the fourth PDZ domain (PDZ4) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers 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 PDZD2-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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  547 VFPVEIEKGDSGLGISIIGmGVGADQGleKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKN-T 625
Cdd:cd06763      1 AVTVELEKGSAGLGFSLEG-GKGSPLG--DRPLTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLTRFEAWNIIKSlP 77

                   ....*...
gi 2113636763  626 KGTVRFLI 633
Cdd:cd06763     78 EGPVTLLI 85

PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. 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 Par3 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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2113636763  548 FPVEIEKGDSGLGISIIGMGVGADQGLEklgIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNTK- 626
Cdd:cd23058      6 LHIQLKKGPEGLGFSITSRDNPTGGSGP---IYIKNILPKGAAIQDGRLKAGDRLLEVNGVDVTGKTQEEVVSLLRSTKl 82

                           90
                   ....*....|
gi 2113636763  627 -GTVRFLIGR 635
Cdd:cd23058     83 gGTVSLVVSR 92

PDZ1 domain of human syntaxin-binding protein 4 (STXBP4), PDZ2 domain of Gallus gallus uncharacterized STXBP4 isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of human syntaxin-binding protein 4 (STXBP4), PDZ2 domain of Gallus gallus uncharacterized STXBP4 isoform X1, and related domains. Human STXBP4 (also known as Synip) includes a single PDZ domain, a coiled-coil domain, and a WW domain (named for its two conserved tryptophans); Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). Human STXBP4 plays a role in the translocation of transport vesicles from the cytoplasm to the plasma membrane: insulin induces the dissociation of the STXBP4 and STX4 complex liberating STX4 to interact with Vamp2, and to form the SNARE complex thereby promoting vesicle fusion. It may also play a role in the regulation of insulin release by pancreatic beta cells after stimulation by glucose. Human STXBP4 is also known to physically associate with a prominent isoform of TP63 (deltaNp63alpha 9) whose overexpression promotes squamous cell carcinoma development, and in doing so prevents degradation of this isoform by the Cdc20-APC/C complex, Itch, and RACK1. 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 STXBP4-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.

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gi 2113636763  557 SGLGISIIGmgvGADQGlEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNTK 626
Cdd:cd06698     11 TGLGLSIVG---GINRP-EGPMVFIQEVIPGGDCYKDGRLRPGDQLVSINKESLIGVTLEEAKSILTRAK 76

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.

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gi 2113636763  550 VEIEK-GDSGLGISIIG---MGVGADQGLEKLGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSLVGVTQLFAATVLKNT 625
Cdd:cd06671      5 VELWRePGKSLGISIVGgrvMGSRLSNGEEIRGIFIKHVLEDSPAGRNGTLKTGDRILEVNGVDLRNATHEEAVEAIRNA 84

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gi 2113636763  626 KGTVRFLI 633
Cdd:cd06671     85 GNPVVFLV 92

PDZ domain of segment polarity protein dishevelled homolog DVL1, DVL2, DVL3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of DVL1-3, and related domains. The dishevelleds (DVL1, 2 and 3 in humans) act downstream of Frizzled (FZD) receptors in both the canonical and non-canonical WNT signaling pathway; they bind the cytoplasmic C-terminus of frizzled family members and transduce the Wnt signal to down-stream effectors. They bind to several proteins known to modulate Wnt signaling. Binding partners of the DVL1 PDZ domain include nucleoredoxin (NXN), Van Gogh-like (VANGL1), Wnt receptor RYK, Dapper 1 (DACT1), Frizzled7 (FZD7), transmembrane protein 88 (TMEM88), Daple (dishevelled-associating protein with a high frequency of leucines), also known as Ccdc88c), and cysteine-rich protein Idax. The DVL2 PDZ domain has been shown to bind the nuclear export signal sequence of the DVL2 protein. 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 DVL-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.

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gi 2113636763  559 LGISIIGMGVGADQGleklGIFVKTIAEGGAAQRDGRIEVNDQIVEVDGTSL 610
Cdd:cd06717     12 LGISIVGQSNERGDG----GIYVGSIMKGGAVAADGRIEPGDMILQVNDISF 59