NCBI Conserved Domain Search

PDZ domain 1 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 1 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. 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 PDZ1 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.

Pssm-ID: 467213 [Multi-domain] Cd Length: 85 Bit Score: 184.34 E-value: 1.51e-54

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  466 FLSTTLKKSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPIGQSVN 545
Cdd:cd06731      1 LIRTSLKKSARGFGFTIIGGDEPDEFLQIKSVVPDGPAALDGKLRTGDVLVSVNDTCVLGYTHADVVKLFQSIPIGQSVN 80


                   ....*
gi 1034657569  546 LVLCR 550
Cdd:cd06731     81 LEVCR 85

PDZ domain 3 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 3 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. 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 PDZ3 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.

Pssm-ID: 467215 [Multi-domain] Cd Length: 85 Bit Score: 168.56 E-value: 5.53e-49

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  818 ELDVHLRRMESGFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARNGQVN 897
Cdd:cd06733      1 ELTVFLRRQETGFGFRILGGTEEGSQVSIGAIVPGGAADLDGRLRTGDELLSVDGVNVVGASHHKVVDLMGNAARNGQVN 80


                   ....*
gi 1034657569  898 LTVRR 902
Cdd:cd06733     81 LTVRR 85

PDZ domain 4 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 4 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. 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 PDZ4 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.

Pssm-ID: 467216 [Multi-domain] Cd Length: 84 Bit Score: 166.25 E-value: 2.87e-48

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  962 DVVIHRKENEGFGFVIISSLNRpesgstiTVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:cd06734      3 DVTLTRRENEGFGFVIISSVNK-------KSGSKIGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKDSG 75


                   ....*....
gi 1034657569 1042 LSVTLRIIP 1050
Cdd:cd06734     76 LSVTLTIVP 84

PDZ domain 2 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 2 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. 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 PDZ2 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.

Pssm-ID: 467214 [Multi-domain] Cd Length: 82 Bit Score: 166.19 E-value: 2.87e-48

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  643 AELMTLTIVKGAQGFGFTIADSPTGQRVKQILDIQGCPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCPIGSETSLIIH 722
Cdd:cd06732      1 PELVTVPIVKGPMGFGFTIADSPQGQRVKQILDPQRCRGLQEGDLIVEINGQNVQNLSHAQVVDVLKECPKGSEVTLLVQ 80


                   ..
gi 1034657569  723 RG 724
Cdd:cd06732     81 RG 82

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.

Pssm-ID: 467217 [Multi-domain] Cd Length: 84 Bit Score: 165.06 E-value: 8.14e-48

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1187 YFTVDMEKGAKGFGFSIRGGREY-KMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd06735      1 YYSVELERGPKGFGFSIRGGREYnNMPLYVLRLAEDGPAQRDGRLRVGDQILEINGESTQGMTHAQAIELIRSGGSVVRL 80


                   ....
gi 1034657569 1266 LLKR 1269
Cdd:cd06735     81 LLRR 84

PDZ domain 0 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 0 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. 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 PDZ0 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.

Pssm-ID: 467212 [Multi-domain] Cd Length: 85 Bit Score: 162.75 E-value: 6.00e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569   14 KVHESVIGRNPEGQLGFELKGGAENGQFPYLGEVKPGKVAYESGsKLVSEELLLEVNETPVAGLTIRDVLAVIKHCKDPL 93
Cdd:cd06730      1 KVHECVVSRGPDGELNLEIRGGAENGQFPYLGEVKEDKVVYKSG-KLHPGELLLEVNGTPVSGLTLRDVLAVIKHCKEPV 79


                   ....*.
gi 1034657569   94 RLKCVK 99
Cdd:cd06730     80 RLKTVK 85

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.

Pssm-ID: 214504 [Multi-domain] Cd Length: 174 Bit Score: 124.33 E-value: 2.42e-32

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569   118 KGSVDHELQQIIRDnLYLRTVPCTTRPHKEGEVPGVDYIFITVEDFMELEKSGALLESGTYEDNYYGTPKPPAEP--APL 195
Cdd:smart00072    5 KGTLLAELIQEIPD-AFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQvaEKG 83

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569   196 LLNVTDQILPGATPSaegkrkrNKSVSNMEKASIEPPEEEEEERPVVN--GNGVVVTPESSEHEDKSAGASGEMPSQPYP 273
Cdd:smart00072   84 KHCLLDIDPQGVKQL-------RKAQLYPIVIFIAPPSSEELERRLRQrgTETSERIQKRLAAAQKEAQEYHLFDYVIVN 156

                           170
                    ....*....|....*...
gi 1034657569   274 APVYSQPEELKEQMDDTK 291
Cdd:smart00072  157 DDLEDAYEELKEILEAEQ 174

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.

Pssm-ID: 467153 [Multi-domain] Cd Length: 81 Bit Score: 105.32 E-value: 5.68e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1189 TVDMEKGA-KGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLL 1267
Cdd:cd00136      1 TVTLEKDPgGGLGFSIRGGKDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLTV 80


                   .
gi 1034657569 1268 K 1268
Cdd:cd00136     81 R 81

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467153 [Multi-domain] Cd Length: 81 Bit Score: 93.38 E-value: 9.06e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  962 DVVIHRKENEGFGFVIISslnrpesGSTITVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:cd00136      1 TVTLEKDPGGGLGFSIRG-------GKDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAG 73


                   ....*..
gi 1034657569 1042 LSVTLRI 1048
Cdd:cd00136     74 GEVTLTV 80

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

Pssm-ID: 214570 [Multi-domain] Cd Length: 85 Bit Score: 92.06 E-value: 3.91e-22

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  1188 FTVDMEKGAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLL 1267
Cdd:smart00228    3 RLVELEKGGGGLGFSLVGGKDEGGGVVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTV 81


                    ...
gi 1034657569  1268 KRG 1270
Cdd:smart00228   82 LRG 84

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.

Pssm-ID: 467153 [Multi-domain] Cd Length: 81 Bit Score: 90.29 E-value: 1.24e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  820 DVHLRRME-SGFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAArnGQVNL 898
Cdd:cd00136      1 TVTLEKDPgGGLGFSIRGGKDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAG--GEVTL 78


                   ...
gi 1034657569  899 TVR 901
Cdd:cd00136     79 TVR 81

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467153 [Multi-domain] Cd Length: 81 Bit Score: 86.44 E-value: 2.66e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  470 TLKKSNM-GFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSvpIGQSVNLVL 548
Cdd:cd00136      3 TLEKDPGgGLGFSIRGGKDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKS--AGGEVTLTV 80


                   .
gi 1034657569  549 C 549
Cdd:cd00136     81 R 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.

Pssm-ID: 214570 [Multi-domain] Cd Length: 85 Bit Score: 81.27 E-value: 2.13e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569   817 KELDVHLRRMESGFGFRILGGDEPGQPILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLMHHAarNGQV 896
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVGGKDEGGGVVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKA--GGKV 77


                    ....*..
gi 1034657569   897 NLTVRRK 903
Cdd:smart00228   78 TLTVLRG 84

PDZ domain 1 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. 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 INAD-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.

Pssm-ID: 467276 [Multi-domain] Cd Length: 87 Bit Score: 81.02 E-value: 2.75e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVIISSLNRpESGSTITVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd23063      2 VVIEKTEKKSFGICIVRGEVK-VSPNTKTTGIFIKGIIPDSPAHKCGRLKVGDRILSVNGNDVRNSTEQAAIDLIKEADF 80


                   ....*.
gi 1034657569 1043 SVTLRI 1048
Cdd:cd23063     81 KIVLEI 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.

Pssm-ID: 214570 [Multi-domain] Cd Length: 85 Bit Score: 80.12 E-value: 5.75e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569   470 TLKKSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNLVLC 549
Cdd:smart00228    6 ELEKGGGGLGFSLVGGKDEGGGVVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKA--GGKVTLTVL 82


                    ..
gi 1034657569   550 RG 551
Cdd:smart00228   83 RG 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.

Pssm-ID: 214570 [Multi-domain] Cd Length: 85 Bit Score: 79.35 E-value: 8.83e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569   963 VVIHRKENEGFGFVIISslnrpesGSTITVPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:smart00228    4 LVELEKGGGGLGFSLVG-------GKDEGGGVVVSSVVPGSPAAK-AGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGG 75


                    ....*....
gi 1034657569  1043 SVTLRIIPQ 1051
Cdd:smart00228   76 KVTLTVLRG 84

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.

Pssm-ID: 467254 [Multi-domain] Cd Length: 87 Bit Score: 79.56 E-value: 9.35e-18

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1186 DYFTVDMEKGAKGFGFSIRGGREYKMDL---YVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRR 1262
Cdd:cd06792      1 DVFEVELSKKDGSLGISVTGGINTSVRHggiYVKSLVPGGAAEQDGRIQKGDRLLEVNGVSLEGVTHKQAVECLKNAGQV 80


                   ....*..
gi 1034657569 1263 VRLLLKR 1269
Cdd:cd06792     81 VTLVLER 87

PDZ domain 1 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 1 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. 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 PDZ1 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.

Pssm-ID: 467213 [Multi-domain] Cd Length: 85 Bit Score: 79.18 E-value: 1.16e-17

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  819 LDVHLRRMESGFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARNGQVNL 898
Cdd:cd06731      2 IRTSLKKSARGFGFTIIGGDEPDEFLQIKSVVPDGPAALDGKLRTGDVLVSVNDTCVLGYTHADVVKLFQSIPIGQSVNL 81


                   ....
gi 1034657569  899 TVRR 902
Cdd:cd06731     82 EVCR 85

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467249 [Multi-domain] Cd Length: 80 Bit Score: 78.63 E-value: 1.36e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  967 RKENEGFGFVIISSLNRPesGstitvpHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTL 1046
Cdd:cd06768      6 VKGPEGYGFNLHAEKGRP--G------HFIREVDPGSPAER-AGLKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTL 76

PDZ domain 3 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 3 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. 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 PDZ3 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.

Pssm-ID: 467215 [Multi-domain] Cd Length: 85 Bit Score: 78.04 E-value: 2.57e-17

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  470 TLKKSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPIGQSVNLVLC 549
Cdd:cd06733      5 FLRRQETGFGFRILGGTEEGSQVSIGAIVPGGAADLDGRLRTGDELLSVDGVNVVGASHHKVVDLMGNAARNGQVNLTVR 84


                   .
gi 1034657569  550 R 550
Cdd:cd06733     85 R 85

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.

Pssm-ID: 467193 [Multi-domain] Cd Length: 86 Bit Score: 77.33 E-value: 4.54e-17

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1189 TVDMEKGAKGFGFSIRGG--REYKMD---LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRV 1263
Cdd:cd06709      2 EITLKRGPSGLGFNIVGGtdQPYIPNdsgIYVAKIKEDGAAAIDGRLQEGDKILEINGQSLENLTHQDAVELFRNAGEDV 81


                   ....*
gi 1034657569 1264 RLLLK 1268
Cdd:cd06709     82 KLKVQ 86

guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP kinase. This enzyme transfers a phosphate from ATP to GMP, yielding ADP and GDP. [Purines, pyrimidines, nucleosides, and nucleotides, Nucleotide and nucleoside interconversions]

Pssm-ID: 213788 Cd Length: 179 Bit Score: 79.84 E-value: 7.73e-17

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gi 1034657569  118 KGSVDHELQQIIrDNLYLrTVPCTTRPHKEGEVPGVDYIFITVEDFMELEKSGALLESGTYEDNYYGTPKPPAEPA 193
Cdd:TIGR03263   13 KSTLVKALLEED-PNLKF-SISATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTPKSPVEEA 86

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 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 3 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). 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 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.

Pssm-ID: 467240 [Multi-domain] Cd Length: 87 Bit Score: 76.54 E-value: 9.82e-17

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gi 1034657569 1189 TVDMEKGAKGFGFSIRGGREYK---MDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06759      4 VLMKGAGGKGLGFSIVGGRDSPrgpMGIYVKTIFPGGAAAEDGRLKEGDEILEVNGESLQGLTHQEAIQKFKQ 76

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. 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 Lin-7-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.

Pssm-ID: 467258 [Multi-domain] Cd Length: 86 Bit Score: 76.32 E-value: 1.21e-16

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gi 1034657569 1190 VDMEKGAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLK 1268
Cdd:cd06796      5 VELPKTEEGLGFNVMGGKEQNSPIYISRIIPGGVADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQGSVKLVVR 83

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467249 [Multi-domain] Cd Length: 80 Bit Score: 75.94 E-value: 1.38e-16

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gi 1034657569 1192 MEKGAKGFGFSIRGGREyKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLL 1267
Cdd:cd06768      5 LVKGPEGYGFNLHAEKG-RPGHFIREVDPGSPAERAG-LKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTLLV 78

Guanylate kinase [Nucleotide transport and metabolism];

Pssm-ID: 439964 Cd Length: 190 Bit Score: 78.57 E-value: 3.25e-16

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gi 1034657569  118 KGSVDHELQQIiRDNLYLrTVPCTTRPHKEGEVPGVDYIFITVEDFMELEKSGALLESGTYEDNYYGTPKPPAE 191
Cdd:COG0194     15 KTTLVKALLER-DPDLRF-SVSATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPKAEVE 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.

Pssm-ID: 467206 [Multi-domain] Cd Length: 89 Bit Score: 74.27 E-value: 6.19e-16

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gi 1034657569 1187 YFTVDMEKGAKGFGFSIRGGREYKM-----DLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGR 1261
Cdd:cd06723      1 YEEITLERGNSGLGFSIAGGTDNPHigddpSIYITKIIPGGAAAADGRLRVNDIILRVNDVDVRNVTHSVAVEALKEAGS 80


                   ....*...
gi 1034657569 1262 RVRLLLKR 1269
Cdd:cd06723     81 IVRLYVKR 88

guanylate kinase; Provisional

Pssm-ID: 234719 Cd Length: 205 Bit Score: 77.44 E-value: 9.05e-16

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gi 1034657569  118 KGSVDHELQQIiRDNLYLrTVPCTTRPHKEGEVPGVDYIFITVEDFMELEKSGALLESGTYEDNYYGTPKPPAE 191
Cdd:PRK00300    18 KSTLVKALLER-DPNLQL-SVSATTRAPRPGEVDGVDYFFVSKEEFEEMIENGEFLEWAEVFGNYYGTPRSPVE 89

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.

Pssm-ID: 467161 [Multi-domain] Cd Length: 86 Bit Score: 73.48 E-value: 1.09e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1189 TVDMEKGAKGFGFSIRGGREYKMD-LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLL 1267
Cdd:cd06673      5 TIEINKGKKGLGLSIVGGSDTLLGaIIIHEVYEDGAAAKDGRLWAGDQILEVNGEDLRKATHDEAINVLRQTPQKVRLLV 84


                   ..
gi 1034657569 1268 KR 1269
Cdd:cd06673     85 YR 86

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

Pssm-ID: 395476 [Multi-domain] Cd Length: 81 Bit Score: 72.70 E-value: 1.81e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  962 DVVIHRKENEGFGFVIisSLNRPESGSTITvphkIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:pfam00595    1 QVTLEKDGRGGLGFSL--KGGSDQGDPGIF----VSEVLPGGAAEA-GGLKVGDRILSINGQDVENMTHEEAVLALKGSG 73


                   ....*...
gi 1034657569 1042 LSVTLRII 1049
Cdd:pfam00595   74 GKVTLTIL 81

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.

Pssm-ID: 467177 [Multi-domain] Cd Length: 88 Bit Score: 72.71 E-value: 2.11e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1186 DYFTVDMEKGAKGFGFSIRGGREYKMD---LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRR 1262
Cdd:cd06690      2 DVFVVELERGPKGLGLGLIDGLHTPLRspgIYIRTLVPDSPAARDGRLRLGDRILAVNGTSLVGADYQSAMDLIRTSGDK 81


                   ....*..
gi 1034657569 1263 VRLLLKR 1269
Cdd:cd06690     82 LRFLVAK 88

Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), catalyzes the reversible phosphoryl transfer from adenosine triphosphate (ATP) to guanosine monophosphate (GMP) to yield adenosine diphosphate (ADP) and guanosine diphosphate (GDP). It plays an essential role in the biosynthesis of guanosine triphosphate (GTP). This enzyme is also important for the activation of some antiviral and anticancer agents, such as acyclovir, ganciclovir, carbovir, and thiopurines.

Pssm-ID: 238026 Cd Length: 137 Bit Score: 74.11 E-value: 2.54e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569  118 KGSVDHELQQIIRDNLYLrTVPCTTRPHKEGEVPGVDYIFITVEDFMELEKSGALLESGTYEDNYYGTPKPPAEPA 193
Cdd:cd00071     12 KSTLLKRLLEEFDPNFGF-SVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKAAVEEA 86

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 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 PDLIM-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.

Pssm-ID: 467235 [Multi-domain] Cd Length: 79 Bit Score: 71.79 E-value: 3.54e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569 1199 FGFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLKR 1269
Cdd:cd06753     10 WGFRLQGGKDFNQPLTISRVTPGGKAAQAN-LRPGDVILAINGESTEGMTHLEAQNKIKAATGSLSLTLER 79

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. 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 Lin-7-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.

Pssm-ID: 467258 [Multi-domain] Cd Length: 86 Bit Score: 71.70 E-value: 4.86e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  821 VHLRRMESGFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAArnGQVNLTV 900
Cdd:cd06796      5 VELPKTEEGLGFNVMGGKEQNSPIYISRIIPGGVADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQ--GSVKLVV 82


                   .
gi 1034657569  901 R 901
Cdd:cd06796     83 R 83

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. 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 Zasp52-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.

Pssm-ID: 467281 [Multi-domain] Cd Length: 82 Bit Score: 71.41 E-value: 5.11e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569 1199 FGFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLKR 1269
Cdd:cd23068     13 WGFRLQGGADFGQPLSIQKVNPGSPADKAG-LRRGDVILRINGTDTSNLTHKQAQDLIKRAGNDLQLTVQR 82

PDZ domain 2 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the second PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467270 [Multi-domain] Cd Length: 85 Bit Score: 71.26 E-value: 7.22e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569 1200 GFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd10834     16 GFNIRGGSEYGLGIYVSKVDPGGLAEQNG-IKVGDQILAVNGVSFEDITHSKAVEVLKS 73

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467262 [Multi-domain] Cd Length: 83 Bit Score: 70.68 E-value: 9.15e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVIisslnrpESGSTITVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd06801      3 VRVVKQDVGGLGISI-------KGGAEHKMPILISKIFKGQAADQTGQLFVGDAILSVNGENLEDATHDEAVQALKNAGD 75


                   ....
gi 1034657569 1043 SVTL 1046
Cdd:cd06801     76 EVTL 79

PDZ domain 2 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 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.

Pssm-ID: 467187 [Multi-domain] Cd Length: 92 Bit Score: 70.75 E-value: 1.27e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGRE---YKMD---LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGR 1261
Cdd:cd06703      3 ITTTLIRDGKGLGFSIAGGKGstpFRDGdegIFISRITEGGAADRDGKLQVGDRVLSINGVDVTEARHDQAVALLTSSSP 82


                   ....*...
gi 1034657569 1262 RVRLLLKR 1269
Cdd:cd06703     83 TITLVVER 90

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467273 [Multi-domain] Cd Length: 80 Bit Score: 69.69 E-value: 1.99e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1189 TVDMEKGAKG-FGFSIRGGREyKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLL 1267
Cdd:cd23060      1 QIELEKPANGgLGFSLVGGEG-GSGIFVKSISPGGVADRDGRLQVGDRLLQVNGESVIGLSHSKAVNILRKAKGTVQLTV 79

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.

Pssm-ID: 467244 [Multi-domain] Cd Length: 86 Bit Score: 69.56 E-value: 3.00e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGREY-KMD--LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06763      2 VTVELEKGSAGLGFSLEGGKGSpLGDrpLTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLTRFEAWNIIKS 75

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.

Pssm-ID: 467168 [Multi-domain] Cd Length: 89 Bit Score: 69.68 E-value: 3.07e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1188 FTVDMEKGAKG-FGFSIRGGREY---KMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRV 1263
Cdd:cd06680      1 KDITLRRSSSGsLGFSIVGGYEEshgNQPFFVKSIVPGTPAYNDGRLKCGDIILAVNGVSTVGMSHAALVPLLKEQRGRV 80


                   ..
gi 1034657569 1264 RL 1265
Cdd:cd06680     81 TL 82

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467262 [Multi-domain] Cd Length: 83 Bit Score: 69.14 E-value: 3.09e-14

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569 1198 GFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd06801     12 GLGISIKGGAEHKMPILISKIFKGQAADQTGQLFVGDAILSVNGENLEDATHDEAVQALKNAGDEVTL 79

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.

Pssm-ID: 214570 [Multi-domain] Cd Length: 85 Bit Score: 69.33 E-value: 3.63e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569   644 ELMTLTIVKGAQGFGFTIA---DSPTGQRVKQIldIQGCP----GLCEGDLIVEINQQNVQNLSHTEVVDILKDCpiGSE 716
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVggkDEGGGVVVSSV--VPGSPaakaGLRVGDVILEVNGTSVEGLTHLEAVDLLKKA--GGK 76


                    ....*....
gi 1034657569   717 TSLIIHRGG 725
Cdd:smart00228   77 VTLTVLRGG 85

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.

Pssm-ID: 467164 [Multi-domain] Cd Length: 83 Bit Score: 69.29 E-value: 3.66e-14

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034657569 1189 TVDMEKGAKGFGFSIRGGR---EYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIK 1257
Cdd:cd06676      1 TITLERGSDGLGFSIVGGFgspHGDLPIYVKTVFEKGAAAEDGRLKRGDQILAVNGESLEGVTHEEAVNILK 72

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.

Pssm-ID: 467153 [Multi-domain] Cd Length: 81 Bit Score: 68.34 E-value: 6.15e-14

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034657569   22 RNPEGQLGFELKGGAENGQFPYLGEVKPGKVAYESGsKLVSEELLLEVNETPVAGLTIRDVLAVIKHCKDPLRLKCV 98
Cdd:cd00136      6 KDPGGGLGFSIRGGKDGGGGIFVSRVEPGGPAARDG-RLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLTVR 81

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.

Pssm-ID: 467271 [Multi-domain] Cd Length: 93 Bit Score: 68.82 E-value: 6.75e-14

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  464 GTFLSTTLKKSNMGFGFTI------IGGDEPdefLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQS 537
Cdd:cd23058      3 GKKLHIQLKKGPEGLGFSItsrdnpTGGSGP---IYIKNILPKGAAIQDGRLKAGDRLLEVNGVDVTGKTQEEVVSLLRS 79

                           90
                   ....*....|...
gi 1034657569  538 VPIGQSVNLVLCR 550
Cdd:cd23058     80 TKLGGTVSLVVSR 92

PDZ domain 1 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467188 [Multi-domain] Cd Length: 87 Bit Score: 67.69 E-value: 1.30e-13

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGR---EYKMD---LYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGR 1261
Cdd:cd06704      1 LTITIERQTGGLGISIAGGKgstPYKGDdegIFISRVTEGGPAAKAG-VRVGDKLLEVNGVDLVDADHHEAVEALKNSGN 79


                   ....*...
gi 1034657569 1262 RVRLLLKR 1269
Cdd:cd06704     80 TVTMVVLR 87

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.

Pssm-ID: 467217 [Multi-domain] Cd Length: 84 Bit Score: 66.83 E-value: 2.12e-13

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  466 FLSTTLKKSNMGFGFTIIGGDEPDEF-LQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSV 544
Cdd:cd06735      1 YYSVELERGPKGFGFSIRGGREYNNMpLYVLRLAEDGPAQRDGRLRVGDQILEINGESTQGMTHAQAIELIRSG--GSVV 78


                   ....*.
gi 1034657569  545 NLVLCR 550
Cdd:cd06735     79 RLLLRR 84

PDZ domain 8 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 7 of protein-associated tight junction (PATJ), PDZ domain 2 of Drosophila melanogaster inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 8 of MUPP1, PDZ domain 7 of PATJ, and PDZ domain 2 of Drosophila melanogaster INAD, 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. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C. 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 PDZ8 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.

Pssm-ID: 467160 [Multi-domain] Cd Length: 84 Bit Score: 66.55 E-value: 3.04e-13

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gi 1034657569 1190 VDMEKGAKGFGFSIRGGREY-KMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLK 1268
Cdd:cd06672      4 IELEKGSSGLGLSLAGNKDRsRMSVFVVGIDPDGAAGKDGRIQVGDELLEINGQVLYGRSHLNASAIIKSAPSKVKIVFL 83


                   .
gi 1034657569 1269 R 1269
Cdd:cd06672     84 R 84

PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467169 [Multi-domain] Cd Length: 89 Bit Score: 66.49 E-value: 3.31e-13

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gi 1034657569  960 TSDVVIHrKENEGFGFVI------ISSLNRPesgstITVPHkigrIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADI 1033
Cdd:cd06681      2 TVEVTLE-KEGNSFGFVIrggaheDRNKSRP-----LTVTH----VRPGGPADREGTIKPGDRLLSVDGISLHGATHAEA 71

                           90
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gi 1034657569 1034 VKLIKDAGLSVTLRI 1048
Cdd:cd06681     72 MSILKQCGQEATLLI 86

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.

Pssm-ID: 467180 [Multi-domain] Cd Length: 92 Bit Score: 66.65 E-value: 3.38e-13

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gi 1034657569 1186 DYFTVDMEKGA-KGFGFSIRGGrEYK--MDL--YVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGG 1260
Cdd:cd06694      1 EIVIVTLKKDPqKGLGFTIVGG-ENSgsLDLgiFVKSIIPGGPADKDGRIKPGDRIIAINGQSLEGKTHHAAVEIIQNAP 79


                   ....*..
gi 1034657569 1261 RRVRLLL 1267
Cdd:cd06694     80 DKVELII 86

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.

Pssm-ID: 467252 [Multi-domain] Cd Length: 90 Bit Score: 66.29 E-value: 3.89e-13

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gi 1034657569 1186 DYFTVDMEKGAKGFGFSIRG-------GREyKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06790      1 DLFPVELEKGSEGLGISIIGmgvgadaGLE-KLGIFVKTVTEGGAAQRDGRIQVNDQIVEVDGISLVGVTQAFAASVLRN 79

                           90
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gi 1034657569 1259 GGRRVRLLLKR 1269
Cdd:cd06790     80 TSGTVRFLIGR 90

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.

Pssm-ID: 467159 [Multi-domain] Cd Length: 96 Bit Score: 66.58 E-value: 4.74e-13

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gi 1034657569 1189 TVDMEKGA-KGFGFSIRGGREYKMDL---------YVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06671      4 RVELWREPgKSLGISIVGGRVMGSRLsngeeirgiFIKHVLEDSPAGRNGTLKTGDRILEVNGVDLRNATHEEAVEAIRN 83

                           90
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gi 1034657569 1259 GGRRVRLLLKR 1269
Cdd:cd06671     84 AGNPVVFLVQS 94

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467228 [Multi-domain] Cd Length: 101 Bit Score: 66.46 E-value: 4.89e-13

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gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGREYKMDL------------YVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIEL 1255
Cdd:cd06746      7 RTVVLQKGDKGFGFVLRGAKAVGPILeftptpafpalqYLESVDPGGVADKAG-LKKGDFLLEINGEDVVKASHEQVVNL 85

                           90
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gi 1034657569 1256 IKSGGRRVRL 1265
Cdd:cd06746     86 IRQSGNTLVL 95

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.

Pssm-ID: 467271 [Multi-domain] Cd Length: 93 Bit Score: 66.13 E-value: 4.98e-13

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gi 1034657569  817 KELDVHLRRMESGFGFRILGGDEPGQ---PILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARN 893
Cdd:cd23058      4 KKLHIQLKKGPEGLGFSITSRDNPTGgsgPIYIKNILPKGAAIQDGRLKAGDRLLEVNGVDVTGKTQEEVVSLLRSTKLG 83

                           90
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gi 1034657569  894 GQVNLTVRRK 903
Cdd:cd23058     84 GTVSLVVSRQ 93

PDZ domain 1 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 1 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. 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 PDZ1 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.

Pssm-ID: 467213 [Multi-domain] Cd Length: 85 Bit Score: 65.69 E-value: 6.43e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS--GGRRVRL 1265
Cdd:cd06731      2 IRTSLKKSARGFGFTIIGGDEPDEFLQIKSVVPDGPAALDGKLRTGDVLVSVNDTCVLGYTHADVVKLFQSipIGQSVNL 81


                   ....
gi 1034657569 1266 LLKR 1269
Cdd:cd06731     82 EVCR 85

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

Pssm-ID: 395476 [Multi-domain] Cd Length: 81 Bit Score: 65.38 E-value: 7.12e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1189 TVDMEKGAKG-FGFSIRGGREYKMD-LYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLL 1266
Cdd:pfam00595    1 QVTLEKDGRGgLGFSLKGGSDQGDPgIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLT 79


                   ..
gi 1034657569 1267 LK 1268
Cdd:pfam00595   80 IL 81

PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467181 [Multi-domain] Cd Length: 90 Bit Score: 65.36 E-value: 8.68e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGR------EYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGR 1261
Cdd:cd06695      2 FEVKLTKGSSGLGFSFLGGEnnspedPFSGLVRIKKLFPGQPAAESGLIQEGDVILAVNGEPLKGLSYQEVLSLLRGAPP 81


                   ....*...
gi 1034657569 1262 RVRLLLKR 1269
Cdd:cd06695     82 EVTLLLCR 89

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. 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 harmonin 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.

Pssm-ID: 467219 [Multi-domain] Cd Length: 85 Bit Score: 65.36 E-value: 9.10e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1193 EKGAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSggrRVRLLLK-RGT 1271
Cdd:cd06737      9 RRGPESLGFSVRGGLEHGCGLFVSHVSPGSQADNKG-LRVGDEIVRINGYSISQCTHEEVINLIKT---KKTVSLKvRHV 84


                   .
gi 1034657569 1272 G 1272
Cdd:cd06737     85 G 85

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467283 [Multi-domain] Cd Length: 93 Bit Score: 65.51 E-value: 9.12e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1190 VDMEKGAKGFGFSIRG------------GREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIK 1257
Cdd:cd23070      3 VTIVKSETGFGFNVRGqvseggqlrsinGELYAPLQHVSAVLEGGAADKAG-VRKGDRILEVNGVNVEGATHKQVVDLIK 81

                           90
                   ....*....|
gi 1034657569 1258 SGGRRVRLLL 1267
Cdd:cd23070     82 SGGDELTLTV 91

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.

Pssm-ID: 467253 [Multi-domain] Cd Length: 89 Bit Score: 65.33 E-value: 9.77e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1186 DYFTVDMEKGAKGFGFSIRG--GREYKMDL---YVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGG 1260
Cdd:cd06791      1 ETFEVELVKDEQGLGITIAGyvGEKASGELsgiFVKSIIPGSAADQDGRIQVNDQIIAVDGVNLQGFTNQEAVEVLRNTG 80


                   ....*....
gi 1034657569 1261 RRVRLLLKR 1269
Cdd:cd06791     81 QVVHLTLAR 89

PDZ domain 1 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as (X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2), which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins such as APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 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 APBA1,2,3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467203 [Multi-domain] Cd Length: 86 Bit Score: 64.97 E-value: 9.91e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  962 DVVIHRKENEGFGFVIIsslnrpESG-----STITVPHkigrIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKL 1036
Cdd:cd06720      2 EVVVEKQKGEILGVVIV------ESGwgsllPTVVVAN----MMPGGPAARSGKLNIGDQIMSINGTSLVGLPLSTCQAI 71

                           90
                   ....*....|....*
gi 1034657569 1037 IKD--AGLSVTLRII 1049
Cdd:cd06720     72 IKNlkNQTKVKLTVV 86

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.

Pssm-ID: 467217 [Multi-domain] Cd Length: 84 Bit Score: 64.91 E-value: 1.02e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  962 DVVIHRKENeGFGFVIisslnrpeSGST--ITVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKD 1039
Cdd:cd06735      3 SVELERGPK-GFGFSI--------RGGReyNNMPLYVLRLAEDGPAQRDGRLRVGDQILEINGESTQGMTHAQAIELIRS 73


                   ....*..
gi 1034657569 1040 AGLSVTL 1046
Cdd:cd06735     74 GGSVVRL 80

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.

Pssm-ID: 467254 [Multi-domain] Cd Length: 87 Bit Score: 64.92 E-value: 1.05e-12

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  466 FLSTTLKKSNMGFGFTIIGGdePDEFLQ-----VKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPi 540
Cdd:cd06792      2 VFEVELSKKDGSLGISVTGG--INTSVRhggiyVKSLVPGGAAEQDGRIQKGDRLLEVNGVSLEGVTHKQAVECLKNAG- 78

                           90
                   ....*....|
gi 1034657569  541 gQSVNLVLCR 550
Cdd:cd06792     79 -QVVTLVLER 87

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This tamalin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467197 [Multi-domain] Cd Length: 91 Bit Score: 64.95 E-value: 1.41e-12

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gi 1034657569 1189 TVDMEKGAKG-FGFSI-------RGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGG 1260
Cdd:cd06713      5 TIILEKQDNEtFGFEIqtyglhhKNSNEVEMCTYVCRVHEDSPAYLAG-LTAGDVILSVNGVSVEGASHQEIVELIRSSG 83


                   ....*.
gi 1034657569 1261 RRVRLL 1266
Cdd:cd06713     84 NTLRLE 89

PDZ domain 2 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 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.

Pssm-ID: 467207 [Multi-domain] Cd Length: 85 Bit Score: 64.60 E-value: 1.47e-12

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1190 VDMEKGAKGFGFSIRGGREYKM-----DLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVR 1264
Cdd:cd06724      2 IKLVKGPKGLGFSIAGGVGNQHipgdnGIYVTKIIEGGAAQKDGRLQVGDKLLAVNDVSLEEVTHEEAVAALKNTSDVVY 81


                   ...
gi 1034657569 1265 LLL 1267
Cdd:cd06724     82 LKV 84

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

Pssm-ID: 440556 [Multi-domain] Cd Length: 341 Bit Score: 70.67 E-value: 1.50e-12

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gi 1034657569  945 SNASPPEGFASHSLQTSDVVihrkenEGFGFVIisslnRPESGSTitvphKIGRIIDGSPADRcAKLKVGDRILAVNGQS 1024
Cdd:COG0793     40 SYYLDPEEYEDFQESTSGEF------GGLGAEL-----GEEDGKV-----VVVSVIPGSPAEK-AGIKPGDIILAIDGKS 102

                           90       100       110
                   ....*....|....*....|....*....|
gi 1034657569 1025 IINMPHADIVKLIK-DAGLSVTLRIIPQEE 1053
Cdd:COG0793    103 VAGLTLDDAVKLLRgKAGTKVTLTIKRPGE 132

PDZ domain 3 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 3 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. 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 PDZ3 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.

Pssm-ID: 467215 [Multi-domain] Cd Length: 85 Bit Score: 64.56 E-value: 1.77e-12

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gi 1034657569  962 DVVIHRKENeGFGFVIISSlnrPESGSTITvphkIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:cd06733      3 TVFLRRQET-GFGFRILGG---TEEGSQVS----IGAIVPGGAADLDGRLRTGDELLSVDGVNVVGASHHKVVDLMGNAA 74


                   ....*....
gi 1034657569 1042 LS--VTLRI 1048
Cdd:cd06733     75 RNgqVNLTV 83

PDZ domain 2 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 2 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 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.

Pssm-ID: 467223 [Multi-domain] Cd Length: 84 Bit Score: 64.21 E-value: 1.83e-12

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gi 1034657569 1194 KGAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06741      9 EDGQSLGLMIRGGAEYGLGIYVTGVDPGSVAENAG-LKVGDQILEVNGRSFLDITHDEAVKILKS 72

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.

Pssm-ID: 467153 [Multi-domain] Cd Length: 81 Bit Score: 64.10 E-value: 1.90e-12

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gi 1034657569  647 TLTIVKGA-QGFGFTIA---DSPTGQRVKQILD---IQGCPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCP 712
Cdd:cd00136      1 TVTLEKDPgGGLGFSIRggkDGGGGIFVSRVEPggpAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAG 73

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.

Pssm-ID: 467168 [Multi-domain] Cd Length: 89 Bit Score: 64.29 E-value: 2.09e-12

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gi 1034657569  468 STTLKKSNMG-FGFTIIGGDEPDEFLQ---VKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPigQS 543
Cdd:cd06680      2 DITLRRSSSGsLGFSIVGGYEESHGNQpffVKSIVPGTPAYNDGRLKCGDIILAVNGVSTVGMSHAALVPLLKEQR--GR 79


                   ...
gi 1034657569  544 VNL 546
Cdd:cd06680     80 VTL 82

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.

Pssm-ID: 467180 [Multi-domain] Cd Length: 92 Bit Score: 64.34 E-value: 2.51e-12

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gi 1034657569  470 TLKKS-NMGFGFTIIGGDEP---DEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVP 539
Cdd:cd06694      6 TLKKDpQKGLGFTIVGGENSgslDLGIFVKSIIPGGPADKDGRIKPGDRIIAINGQSLEGKTHHAAVEIIQNAP 79

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467228 [Multi-domain] Cd Length: 101 Bit Score: 64.15 E-value: 3.49e-12

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gi 1034657569  963 VVIHRKENeGFGFVIISSLN-RPESGSTIT--VP--HKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLI 1037
Cdd:cd06746      9 VVLQKGDK-GFGFVLRGAKAvGPILEFTPTpaFPalQYLESVDPGGVADK-AGLKKGDFLLEINGEDVVKASHEQVVNLI 86

                           90
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gi 1034657569 1038 KDAGLSVTLRII 1049
Cdd:cd06746     87 RQSGNTLVLKVV 98

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.

Pssm-ID: 467209 [Multi-domain] Cd Length: 87 Bit Score: 63.45 E-value: 3.91e-12

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gi 1034657569  963 VVIHRKENEGFGFVIISSLNRP--ESGSTITVphkIGRIIDGSPADrcAKLKVGDRILAVNGQSIINMPHADIVKLIKDA 1040
Cdd:cd06727      3 VTLHRAPGFGFGIAVSGGRDNPhfQSGDTSIV---ISDVLKGGPAE--GKLQENDRVVSVNGVSMENVEHSFAVQILRKC 77


                   ....*....
gi 1034657569 1041 GLSVTLRII 1049
Cdd:cd06727     78 GKTANITVK 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.

Pssm-ID: 467206 [Multi-domain] Cd Length: 89 Bit Score: 63.49 E-value: 4.75e-12

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gi 1034657569  466 FLSTTLKKSNMGFGFTIIGG-DEP----DEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpi 540
Cdd:cd06723      1 YEEITLERGNSGLGFSIAGGtDNPhigdDPSIYITKIIPGGAAAADGRLRVNDIILRVNDVDVRNVTHSVAVEALKEA-- 78

                           90
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gi 1034657569  541 GQSVNLVLCR 550
Cdd:cd06723     79 GSIVRLYVKR 88

PDZ domain 4 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 4 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 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.

Pssm-ID: 467182 [Multi-domain] Cd Length: 85 Bit Score: 62.71 E-value: 6.31e-12

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gi 1034657569  467 LSTTLKKS-NMGFGFTIIGGDEpDEFLQVKSVIPDgPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPigQSVN 545
Cdd:cd06696      4 LEVTLTKSeKGSLGFTVTKGKD-DNGCYIHDIVQD-PAKSDGRLRPGDRLIMVNGVDVTNMSHTEAVSLLRAAP--KEVT 79


                   ....*.
gi 1034657569  546 LVLCRG 551
Cdd:cd06696     80 LVLGRA 85

PDZ domain of densin, erbin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of densin, erbin, and related domains. Densin (also known as leucine-rich repeat-containing protein 7, LRRC7, densin-180, protein LAP1) and erbin (also known as densin-180-like protein, Erbb2-interacting protein, protein LAP2) belong to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play roles in the maintenance of cell shape and apical-basal polarity. Densin and erbin are components of the excitatory postsynaptic compartment and are regulators of dendritic morphology and postsynaptic structure. The densin PDZ domain binds CaV1.3 alpha1 subunit, delta-catenin, and MAGUIN-1. Binding partners of the erbin PDZ domain include ErbB receptor tyrosine kinase ErbB2, HTLV-1 Tax1, Cav1.3 Ca2+channels, and constituents of the cadherin:catenin cell adhesion complex, in particular delta-catenin, p0071 and ARVCF. The erbin PDZ domain binds Smad3, a transductor of the TGFbeta pathway, possibly by a novel interface of binding. Erbin and two other LAP proteins (scribble and lano) redundantly regulate epithelial polarity and apical adhesion 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 densin and erbin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467231 [Multi-domain] Cd Length: 87 Bit Score: 62.73 E-value: 7.11e-12

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gi 1034657569 1188 FTVDMEKGAkGFGFSIRGG--------REYKMDLYVLRLAEDGPAirNGRMRVGDQIIEINGESTRDMTHARAIELIKSG 1259
Cdd:cd06749      1 IRVRIEKNP-GLGFSISGGigsqgnpfRPDDDGIFVTKVQPDGPA--SKLLQPGDKILEVNGYDFVNIEHGQAVSLLKSF 77

                           90
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gi 1034657569 1260 GRRVRLLLKR 1269
Cdd:cd06749     78 QNTVDLVVER 87

PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GOPC and related domains. GOPC, also known as PIST (PDZ domain protein interacting specifically with TC10), FIG (fused in glioblastoma), and CAL (CFTR-associated ligand), regulates the trafficking of a wide array of proteins, including small GTPases, receptors, and cell surface molecules such as cadherin 23 and CFTR. It may regulate CFTR chloride currents and acid-sensing ASIC3 currents by modulating cell surface expression of both channels, and may play a role in autophagy. Interaction partners of the GOPC PDZ domains include: FZD5, FZD8, ASIC3, CFTR, MUC3, ARFRP1, Ggamma13, neuroligin, and Stargazin. 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 GOPC-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.

Pssm-ID: 467261 [Multi-domain] Cd Length: 83 Bit Score: 62.39 E-value: 7.87e-12

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gi 1034657569  963 VVIHRKENEGFGfviISSLNRPESGstitVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd06800      3 VLLSKEPHEGLG---ISITGGKEHG----VPILISEIHEGQPADRCGGLYVGDAILSVNGIDLRDAKHKEAVTILSQQRG 75


                   ....*..
gi 1034657569 1043 SVTLRII 1049
Cdd:cd06800     76 EITLEVV 82

PDZ domain 3 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 3 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. 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 PDZ3 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.

Pssm-ID: 467215 [Multi-domain] Cd Length: 85 Bit Score: 62.63 E-value: 7.95e-12

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gi 1034657569 1187 YFTVDMEKGAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGR--RVR 1264
Cdd:cd06733      1 ELTVFLRRQETGFGFRILGGTEEGSQVSIGAIVPGGAADLDGRLRTGDELLSVDGVNVVGASHHKVVDLMGNAARngQVN 80


                   ....*
gi 1034657569 1265 LLLKR 1269
Cdd:cd06733     81 LTVRR 85

PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467181 [Multi-domain] Cd Length: 90 Bit Score: 62.66 E-value: 8.33e-12

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  470 TLKKSNMGFGFTIIGG--DEPDE----FLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPigQS 543
Cdd:cd06695      5 KLTKGSSGLGFSFLGGenNSPEDpfsgLVRIKKLFPGQPAAESGLIQEGDVILAVNGEPLKGLSYQEVLSLLRGAP--PE 82


                   ....*..
gi 1034657569  544 VNLVLCR 550
Cdd:cd06695     83 VTLLLCR 89

PDZ domain 4 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 4 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 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.

Pssm-ID: 467182 [Multi-domain] Cd Length: 85 Bit Score: 62.32 E-value: 8.70e-12

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gi 1034657569 1188 FTVDMEKGAKG-FGFSIRGGreyKMDL--YVLRLAEDgPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVR 1264
Cdd:cd06696      4 LEVTLTKSEKGsLGFTVTKG---KDDNgcYIHDIVQD-PAKSDGRLRPGDRLIMVNGVDVTNMSHTEAVSLLRAAPKEVT 79


                   ....*.
gi 1034657569 1265 LLLKRG 1270
Cdd:cd06696     80 LVLGRA 85

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.

Pssm-ID: 467180 [Multi-domain] Cd Length: 92 Bit Score: 62.41 E-value: 1.01e-11

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034657569  827 ESGFGFRILGGDEPGQ---PILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHA 890
Cdd:cd06694     12 QKGLGFTIVGGENSGSldlGIFVKSIIPGGPADKDGRIKPGDRIIAINGQSLEGKTHHAAVEIIQNA 78

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.

Pssm-ID: 467164 [Multi-domain] Cd Length: 83 Bit Score: 61.97 E-value: 1.12e-11

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  820 DVHLRRMESGFGFRILGGDEPGQ---PILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAarNGQV 896
Cdd:cd06676      1 TITLERGSDGLGFSIVGGFGSPHgdlPIYVKTVFEKGAAAEDGRLKRGDQILAVNGESLEGVTHEEAVNILKKT--KGTV 78


                   ....
gi 1034657569  897 NLTV 900
Cdd:cd06676     79 TLTV 82

Unstructured region on MAGI; MAGI_u3 is a region of natively unstructured but highly conserved sequence on a subset, of higher eukaryote, membrane-associated guanylate kinase with WW and PDZ domain-containing proteins. The function is not known.

Pssm-ID: 435496 Cd Length: 60 Bit Score: 61.44 E-value: 1.14e-11

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                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034657569  198 NVTDQILPGATPSAEGKRKRNKSVSNMEKASIEPPEEEEEERPvvNGNGVVVTPESSEHEDK 259
Cdd:pfam16663    1 NVTDALLPGLRGSKQSTPKRTKSYNDMQNAGIVPPEEEEEEDP--PEMNSSFTAESSEHDDH 60

PDZ domain 4 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 4 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. 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 PDZ4 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.

Pssm-ID: 467216 [Multi-domain] Cd Length: 84 Bit Score: 61.86 E-value: 1.17e-11

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569 1198 GFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd06734     13 GFGFVIISSVNKKSGSKIGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKDSGLSVTL 80

PDZ domain 4 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467174 [Multi-domain] Cd Length: 99 Bit Score: 62.36 E-value: 1.25e-11

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gi 1034657569  959 QTSDVVIHRKENEGFGFVIISSLNRPEsgsTITVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIK 1038
Cdd:cd06686      6 ETTEVILRGDPLKGFGIQLQGGVFATE---TLSSPPLISFIEPDSPAERCGVLQVGDRVLSINGIPTEDRTLEEANQLLR 82

                           90
                   ....*....|
gi 1034657569 1039 DAGLSVTLRI 1048
Cdd:cd06686     83 DSASKVTLEI 92

PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the first PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family 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.

Pssm-ID: 467269 [Multi-domain] Cd Length: 84 Bit Score: 61.68 E-value: 1.61e-11

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gi 1034657569 1189 TVDMEKGAKG-FGFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIkSGGRRVRLLL 1267
Cdd:cd10833      3 TVTVEKSPDGsLGFSVRGGSEHGLGIFVSKVEEGSAAERAG-LCVGDKITEVNGVSLENITMSSAVKVL-TGSNRLRMVV 80


                   ..
gi 1034657569 1268 KR 1269
Cdd:cd10833     81 RR 82

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 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 3 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). 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 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.

Pssm-ID: 467240 [Multi-domain] Cd Length: 87 Bit Score: 61.52 E-value: 2.01e-11

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gi 1034657569  470 TLKKSNM--GFGFTIIGG-DEP--DEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSV 538
Cdd:cd06759      4 VLMKGAGgkGLGFSIVGGrDSPrgPMGIYVKTIFPGGAAAEDGRLKEGDEILEVNGESLQGLTHQEAIQKFKQI 77

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.

Pssm-ID: 467193 [Multi-domain] Cd Length: 86 Bit Score: 61.54 E-value: 2.09e-11

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gi 1034657569  972 GFGFVIISSLNRP----ESGSTITvphkigRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLR 1047
Cdd:cd06709     11 GLGFNIVGGTDQPyipnDSGIYVA------KIKEDGAAAIDGRLQEGDKILEINGQSLENLTHQDAVELFRNAGEDVKLK 84


                   ..
gi 1034657569 1048 II 1049
Cdd:cd06709     85 VQ 86

PDZ domain 6 of PDZ domain containing 2 (PDZD2), PDZ domain 3 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 6 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the third PDZ domain (PDZ3) 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 PDZ6 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.

Pssm-ID: 467243 [Multi-domain] Cd Length: 86 Bit Score: 61.51 E-value: 2.12e-11

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gi 1034657569  821 VHLRRME-SGFGFRILGG-DEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHaARNGQVNL 898
Cdd:cd06762      4 VVLHKEEgSGLGFSLAGGsDLENKSITVHRVFPSGLAAQEGTIQKGDRILSINGKSLKGVTHGDALSVLKQ-ARLPKVAV 82


                   ....
gi 1034657569  899 TVRR 902
Cdd:cd06762     83 VVIR 86

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.

Pssm-ID: 467168 [Multi-domain] Cd Length: 89 Bit Score: 61.21 E-value: 3.08e-11

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gi 1034657569  820 DVHLRRMESG-FGFRILGGDEP---GQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAarNGQ 895
Cdd:cd06680      2 DITLRRSSSGsLGFSIVGGYEEshgNQPFFVKSIVPGTPAYNDGRLKCGDIILAVNGVSTVGMSHAALVPLLKEQ--RGR 79


                   ....*
gi 1034657569  896 VNLTV 900
Cdd:cd06680     80 VTLTV 84

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.

Pssm-ID: 467217 [Multi-domain] Cd Length: 84 Bit Score: 60.67 E-value: 3.55e-11

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gi 1034657569  820 DVHLRRMESGFGFRILGGDEPGQ-PILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMhhaaRNG--QV 896
Cdd:cd06735      3 SVELERGPKGFGFSIRGGREYNNmPLYVLRLAEDGPAQRDGRLRVGDQILEINGESTQGMTHAQAIELI----RSGgsVV 78


                   ....*.
gi 1034657569  897 NLTVRR 902
Cdd:cd06735     79 RLLLRR 84

PDZ domain 4 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 4 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 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.

Pssm-ID: 467185 [Multi-domain] Cd Length: 98 Bit Score: 61.09 E-value: 3.63e-11

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gi 1034657569  472 KKSNMGFGFTIIGG---------DEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQ 542
Cdd:cd06701     11 KEPGEKLGISIRGGakghagnplDPTDEGIFISKINPDGAAARDGRLKVGQRILEVNGQSLLGATHQEAVRILRSV--GD 88

                           90
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gi 1034657569  543 SVNLVLCRGY 552
Cdd:cd06701     89 TLTLLVCDGY 98

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.

Pssm-ID: 467180 [Multi-domain] Cd Length: 92 Bit Score: 60.87 E-value: 4.21e-11

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gi 1034657569  959 QTSDVVIHRKENEGFGFVIISSLNRPESGSTITVPhkigRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIK 1038
Cdd:cd06694      1 EIVIVTLKKDPQKGLGFTIVGGENSGSLDLGIFVK----SIIPGGPADKDGRIKPGDRIIAINGQSLEGKTHHAAVEIIQ 76

                           90
                   ....*....|...
gi 1034657569 1039 DAGLSVTLrIIPQ 1051
Cdd:cd06694     77 NAPDKVEL-IISQ 88

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.

Pssm-ID: 467193 [Multi-domain] Cd Length: 86 Bit Score: 60.38 E-value: 4.98e-11

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gi 1034657569  470 TLKKSNMGFGFTIIGG-DEP----DEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSvpIGQSV 544
Cdd:cd06709      4 TLKRGPSGLGFNIVGGtDQPyipnDSGIYVAKIKEDGAAAIDGRLQEGDKILEINGQSLENLTHQDAVELFRN--AGEDV 81


                   ..
gi 1034657569  545 NL 546
Cdd:cd06709     82 KL 83

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.

Pssm-ID: 467254 [Multi-domain] Cd Length: 87 Bit Score: 60.30 E-value: 5.11e-11

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gi 1034657569  817 KELDVHLRRMESGFGFRILGGDEPGQP---ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARN 893
Cdd:cd06792      1 DVFEVELSKKDGSLGISVTGGINTSVRhggIYVKSLVPGGAAEQDGRIQKGDRLLEVNGVSLEGVTHKQAVECLKNAGQV 80


                   ....*....
gi 1034657569  894 gqVNLTVRR 902
Cdd:cd06792     81 --VTLVLER 87

PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight junction (PATJ, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 12 of MUPP1, PDZ domain 10 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 PDZ12 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

Pssm-ID: 467163 [Multi-domain] Cd Length: 86 Bit Score: 60.07 E-value: 5.38e-11

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gi 1034657569 1189 TVDMEKGAKG-FGFSIRGGREYKMD---LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIK 1257
Cdd:cd06675      2 TVEIKRGPQDsLGISIAGGVGSPLGdvpVFIAMIQPNGVAAQTGKLKVGDRIVSINGQSTDGLTHSEAVNLLK 74

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and 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. 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 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.

Pssm-ID: 467239 [Multi-domain] Cd Length: 88 Bit Score: 60.44 E-value: 5.52e-11

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gi 1034657569  821 VHLRRMESGFGFRILGG---DEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAArnGQVN 897
Cdd:cd06758      5 MHLLKEKGGLGIQITGGkgsKRGDIGIFVAGVEEGGSADRDGRLKKGDELLMINGQSLIGLSHQEAVAILRSSA--SPVQ 82


                   ....*.
gi 1034657569  898 LTVRRK 903
Cdd:cd06758     83 LVIASK 88

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.

Pssm-ID: 467257 [Multi-domain] Cd Length: 91 Bit Score: 60.06 E-value: 6.59e-11

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gi 1034657569 1189 TVDMEKGAKGFGFSIRGGrEYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLL 1267
Cdd:cd06795      4 KIVLHKGSTGLGFNIVGG-EDGEGIFISFILAGGPADLSGELRRGDQILSVNGVDLRNATHEQAAAALKNAGQTVTIIA 81

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This tamalin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467197 [Multi-domain] Cd Length: 91 Bit Score: 59.94 E-value: 6.87e-11

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gi 1034657569  963 VVIHRKENEGFGFVIisslnrpesgSTITVPHK----------IGRIIDGSPADRCAkLKVGDRILAVNGQSIINMPHAD 1032
Cdd:cd06713      6 IILEKQDNETFGFEI----------QTYGLHHKnsnevemctyVCRVHEDSPAYLAG-LTAGDVILSVNGVSVEGASHQE 74


                   ....*....
gi 1034657569 1033 IVKLIKDAG 1041
Cdd:cd06713     75 IVELIRSSG 83

PDZ domain 2 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 2 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. 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 PDZ2 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.

Pssm-ID: 467214 [Multi-domain] Cd Length: 82 Bit Score: 59.88 E-value: 6.91e-11

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gi 1034657569  466 FLSTTLKKSNMGFGFTIigGDEPdeFLQ-VKSVIpDGPAAQdGKMEtGDVIVYINEVCVLGHTHADVVKLFQSVPIGQSV 544
Cdd:cd06732      3 LVTVPIVKGPMGFGFTI--ADSP--QGQrVKQIL-DPQRCR-GLQE-GDLIVEINGQNVQNLSHAQVVDVLKECPKGSEV 75


                   ....*..
gi 1034657569  545 NLVLCRG 551
Cdd:cd06732     76 TLLVQRG 82

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.

Pssm-ID: 467168 [Multi-domain] Cd Length: 89 Bit Score: 60.05 E-value: 7.47e-11

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gi 1034657569  962 DVVIHRKENEGFGFVIISSLNrpesGSTITVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:cd06680      2 DITLRRSSSGSLGFSIVGGYE----ESHGNQPFFVKSIVPGTPAYNDGRLKCGDIILAVNGVSTVGMSHAALVPLLKEQR 77


                   ....*....
gi 1034657569 1042 LSVTLRIIP 1050
Cdd:cd06680     78 GRVTLTVVS 86

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467273 [Multi-domain] Cd Length: 80 Bit Score: 59.67 E-value: 8.19e-11

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gi 1034657569  472 KKSNMGFGFTIIGGDEPDEfLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPiGQsVNLVLC 549
Cdd:cd23060      6 KPANGGLGFSLVGGEGGSG-IFVKSISPGGVADRDGRLQVGDRLLQVNGESVIGLSHSKAVNILRKAK-GT-VQLTVS 80

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

Pssm-ID: 467623 [Multi-domain] Cd Length: 88 Bit Score: 59.80 E-value: 8.39e-11

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gi 1034657569  999 IIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIK-DAGLSVTLRI 1048
Cdd:cd06782     21 PIPGGPAEK-AGIKPGDVIVAVDGESVRGMSLDEVVKLLRgPKGTKVKLTI 70

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467196 [Multi-domain] Cd Length: 78 Bit Score: 59.52 E-value: 8.69e-11

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gi 1034657569  470 TLKKSNMGFGFTIiGGDEPdefLQVKSVIPDGPAAQDGKMEtGDVIVYINEVCVLGHTHADVVKLFQSVP 539
Cdd:cd06712      5 HLTKEEGGFGFTL-RGDSP---VQVASVDPGSCAAEAGLKE-GDYIVSVGGVDCKWSKHSEVVKLLKSAG 69

PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467169 [Multi-domain] Cd Length: 89 Bit Score: 59.55 E-value: 9.64e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1189 TVDMEKGAKGFGFSIRGGREYKMDLY----VLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVR 1264
Cdd:cd06681      4 EVTLEKEGNSFGFVIRGGAHEDRNKSrpltVTHVRPGGPADREGTIKPGDRLLSVDGISLHGATHAEAMSILKQCGQEAT 83


                   ..
gi 1034657569 1265 LL 1266
Cdd:cd06681     84 LL 85

PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467169 [Multi-domain] Cd Length: 89 Bit Score: 59.55 E-value: 9.73e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569  817 KELDVHLRRMESGFGFRILGG--DEPGQ--PILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLM 887
Cdd:cd06681      1 KTVEVTLEKEGNSFGFVIRGGahEDRNKsrPLTVTHVRPGGPADREGTIKPGDRLLSVDGISLHGATHAEAMSIL 75

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467249 [Multi-domain] Cd Length: 80 Bit Score: 58.99 E-value: 1.11e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569  649 TIVKGAQGFGF---TIADSPtGQRVKQIlDiQGCP----GLCEGDLIVEINQQNVQNLSHTEVVDILKDCpiGSETSLI 720
Cdd:cd06768      4 HLVKGPEGYGFnlhAEKGRP-GHFIREV-D-PGSPaeraGLKDGDRLVEVNGENVEGESHEQVVEKIKAS--GNQVTLL 77

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.

Pssm-ID: 467222 [Multi-domain] Cd Length: 82 Bit Score: 58.91 E-value: 1.23e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569 1198 GFGFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKsGGRRVRLLLK 1268
Cdd:cd06740     14 GLGFSIRGGAEHGVGIYVSLVEPGSLAEKEG-LRVGDQILRVNDVSFEKVTHAEAVKILR-VSKKLVLSVR 82

guanylate kinase; Provisional

Pssm-ID: 237809 Cd Length: 206 Bit Score: 62.83 E-value: 1.28e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569  138 VPCTTRPHKEGEVPGVDYIFITVEDFMELEKSGALLESGTYEDNYYGTPKPPAEPA 193
Cdd:PRK14738    44 VTATTRPKRPGEIDGVDYHFVTPEEFREMISQNELLEWAEVYGNYYGVPKAPVRQA 99

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

Pssm-ID: 440556 [Multi-domain] Cd Length: 341 Bit Score: 64.51 E-value: 1.41e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1177 SDYRQPQDFDYFTVDMEKGAKGFG--FSIRGGReykmdLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIE 1254
Cdd:COG0793     40 SYYLDPEEYEDFQESTSGEFGGLGaeLGEEDGK-----VVVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVK 113

                           90       100
                   ....*....|....*....|..
gi 1034657569 1255 LIKSG-GRRVRLLLKRGTGQVP 1275
Cdd:COG0793    114 LLRGKaGTKVTLTIKRPGEGEP 135

PDZ domain 2 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 2 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. 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 PDZ2 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.

Pssm-ID: 467214 [Multi-domain] Cd Length: 82 Bit Score: 58.72 E-value: 1.71e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1186 DYFTVDMEKGAKGFGFSIR---GGREYKMDLyvlrlaeDGPaiRNGRMRVGDQIIEINGESTRDMTHARAIELIKS--GG 1260
Cdd:cd06732      2 ELVTVPIVKGPMGFGFTIAdspQGQRVKQIL-------DPQ--RCRGLQEGDLIVEINGQNVQNLSHAQVVDVLKEcpKG 72

                           90
                   ....*....|
gi 1034657569 1261 RRVRLLLKRG 1270
Cdd:cd06732     73 SEVTLLVQRG 82

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467226 [Multi-domain] Cd Length: 75 Bit Score: 58.44 E-value: 1.90e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVIisslnrpeSGSTitvPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd06744      1 TVRVYRGNGSFGFTL--------RGHA---PVYIESVDPGSAAER-AGLKPGDRILFLNGLDVRNCSHDKVVSLLQGSGS 68


                   ....
gi 1034657569 1043 SVTL 1046
Cdd:cd06744     69 MPTL 72

PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight junction (PATJ, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 12 of MUPP1, PDZ domain 10 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 PDZ12 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

Pssm-ID: 467163 [Multi-domain] Cd Length: 86 Bit Score: 58.53 E-value: 1.97e-10

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVIISSLnrpesGSTI-TVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:cd06675      3 VEIKRGPQDSLGISIAGGV-----GSPLgDVPVFIAMIQPNGVAAQTGKLKVGDRIVSINGQSTDGLTHSEAVNLLKNAS 77


                   ....*...
gi 1034657569 1042 LSVTLRII 1049
Cdd:cd06675     78 GTIILQVV 85

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and 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. 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 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.

Pssm-ID: 467239 [Multi-domain] Cd Length: 88 Bit Score: 58.52 E-value: 2.12e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  968 KENEGFGFVIISSLNRPESGSTITVPHkigrIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLR 1047
Cdd:cd06758      9 KEKGGLGIQITGGKGSKRGDIGIFVAG----VEEGGSADRDGRLKKGDELLMINGQSLIGLSHQEAVAILRSSASPVQLV 84


                   .
gi 1034657569 1048 I 1048
Cdd:cd06758     85 I 85

PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNPO2, SYNPO2L, and related domains. SYNPO2 (also known as genethonin-2, myopodin) is a cytoskeleton adaptor protein. It participates in chaperone-assisted selective autophagy (CASA), a mechanism for the disposal of misfolded and damaged proteins and provides a link between the CASA chaperone complex and a membrane-tethering and fusion machinery that generates autophagosome membranes. The SYNPO2 PPxY motif binds CASA cochaperone BCL2-associated athanogene 3 (BAG3) and the SYNPO2 PDZ domain binds vacuolar protein sorting 18 homolog (VPS18). There are three isoforms of SYNPO2, which possess an amino-terminal PDZ domain (SYNPO2a, b, c); the short isoform SYNPO2d, lacks the PDZ 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 SYNPO2-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.

Pssm-ID: 467264 [Multi-domain] Cd Length: 78 Bit Score: 58.09 E-value: 2.25e-10

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1189 TVDMEKGAKgFGFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLK 1268
Cdd:cd10820      1 CVTLTGGAP-WGFRLQGGSEQKKPLQVAKIRKKSKAALAG-LCEGDELLSINGKPCADLSHSEAMDLIDSSGDTLQLLIK 78

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467273 [Multi-domain] Cd Length: 80 Bit Score: 58.13 E-value: 2.75e-10

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034657569  829 GFGFRILGGDEpGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAarNGQVNLTV 900
Cdd:cd23060     11 GLGFSLVGGEG-GSGIFVKSISPGGVADRDGRLQVGDRLLQVNGESVIGLSHSKAVNILRKA--KGTVQLTV 79

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and 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. 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 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.

Pssm-ID: 467239 [Multi-domain] Cd Length: 88 Bit Score: 58.13 E-value: 2.90e-10

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1190 VDMEKGAKGFGFSIRGGREYKMD---LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLL 1266
Cdd:cd06758      5 MHLLKEKGGLGIQITGGKGSKRGdigIFVAGVEEGGSADRDGRLKKGDELLMINGQSLIGLSHQEAVAILRSSASPVQLV 84


                   ...
gi 1034657569 1267 LKR 1269
Cdd:cd06758     85 IAS 87

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.

Pssm-ID: 467284 [Multi-domain] Cd Length: 92 Bit Score: 58.27 E-value: 3.01e-10

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034657569  470 TLKKS-NMGFGFTIIGGD---EPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVP 539
Cdd:cd23071      6 TLKRDpKRGFGFVIVGGEntgKLDLGIFIASIIPGGPAEKDGRIKPGGRLISLNNISLEGVTFNTAVKILQNSP 79

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.

Pssm-ID: 467271 [Multi-domain] Cd Length: 93 Bit Score: 58.42 E-value: 3.22e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  646 MTLTIVKGAQGFGFTIA--DSPTGQR----VKQILdiqgcPG--------LCEGDLIVEINQQNVQNLSHTEVVDILKDC 711
Cdd:cd23058      6 LHIQLKKGPEGLGFSITsrDNPTGGSgpiyIKNIL-----PKgaaiqdgrLKAGDRLLEVNGVDVTGKTQEEVVSLLRST 80

                           90
                   ....*....|..
gi 1034657569  712 PIGSETSLIIHR 723
Cdd:cd23058     81 KLGGTVSLVVSR 92

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.

Pssm-ID: 467271 [Multi-domain] Cd Length: 93 Bit Score: 58.04 E-value: 3.28e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1187 YFTVDMEKGAKGFGFSIRGgREYKMD----LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS--GG 1260
Cdd:cd23058      5 KLHIQLKKGPEGLGFSITS-RDNPTGgsgpIYIKNILPKGAAIQDGRLKAGDRLLEVNGVDVTGKTQEEVVSLLRStkLG 83


                   ....*....
gi 1034657569 1261 RRVRLLLKR 1269
Cdd:cd23058     84 GTVSLVVSR 92

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467273 [Multi-domain] Cd Length: 80 Bit Score: 57.36 E-value: 4.70e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVIISSlnrpESGSTITVPhkigRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd23060      2 IELEKPANGGLGFSLVGG----EGGSGIFVK----SISPGGVADRDGRLQVGDRLLQVNGESVIGLSHSKAVNILRKAKG 73


                   ....*.
gi 1034657569 1043 SVTLRI 1048
Cdd:cd23060     74 TVQLTV 79

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467196 [Multi-domain] Cd Length: 78 Bit Score: 57.21 E-value: 5.09e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569  647 TLTIVKGAQGFGFTI-ADSPTgqRVKQIldIQGCP----GLCEGDLIVEINQQNVQNLSHTEVVDILKDCP 712
Cdd:cd06712      3 TVHLTKEEGGFGFTLrGDSPV--QVASV--DPGSCaaeaGLKEGDYIVSVGGVDCKWSKHSEVVKLLKSAG 69

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.

Pssm-ID: 467285 [Multi-domain] Cd Length: 92 Bit Score: 57.50 E-value: 6.09e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  471 LKKS-NMGFGFTIIGGDEP---DEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPigQSVNL 546
Cdd:cd23072      7 LKKDaKYGLGFQIVGGEKSgrlDLGIFISSITPGGPADLDGRLKPGDRLISVNDVSLEGLSHDAAVEILQNAP--EDVTL 84


                   ..
gi 1034657569  547 VL 548
Cdd:cd23072     85 VV 86

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.

Pssm-ID: 467253 [Multi-domain] Cd Length: 89 Bit Score: 57.24 E-value: 6.46e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  471 LKKSNMGFGFTIIG---GDEPDE----FlqVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQS 543
Cdd:cd06791      7 LVKDEQGLGITIAGyvgEKASGElsgiF--VKSIIPGSAADQDGRIQVNDQIIAVDGVNLQGFTNQEAVEVLRNT--GQV 82


                   ....*..
gi 1034657569  544 VNLVLCR 550
Cdd:cd06791     83 VHLTLAR 89

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.

Pssm-ID: 467162 [Multi-domain] Cd Length: 87 Bit Score: 56.91 E-value: 8.65e-10

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1185 FDYFTVDMEKGA-KGFGFSIRGgREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRV 1263
Cdd:cd06674      1 YDIFTVELQKKPgRGLGLSIVG-KRNDTGVFVSDIVKGGAADADGRLMQGDQILSVNGEDVRNASQEAAAALLKCAQGKV 79


                   ....*.
gi 1034657569 1264 RLLLKR 1269
Cdd:cd06674     80 RLEVGR 85

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.

Pssm-ID: 467257 [Multi-domain] Cd Length: 91 Bit Score: 56.98 E-value: 9.44e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  821 VHLRRMESGFGFRILGGDEpGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTH 880
Cdd:cd06795      5 IVLHKGSTGLGFNIVGGED-GEGIFISFILAGGPADLSGELRRGDQILSVNGVDLRNATH 63

PDZ domain of afadin (AFDN), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of afadin (AFDN, also known as ALL1-fused gene from chromosome 6 protein (AF6) and MLLT4), and related domains. AFDN belongs to the adhesion system, probably together with the E-cadherin-catenin system, that plays a role in the organization of homotypic, interneuronal, and heterotypic cell-cell adherens junctions. The AFDN PDZ domain interaction partners include poliovirus receptor-related protein PRR2/nectin, the junctional adhesion molecule (JAM), the breakpoint-cluster-region protein (BCR), connexin36 (Cx36), and a subset of Eph-related receptor tyrosine kinases; it can also bind low molecular weight ligands, in competition with a natural peptide ligand. Other AFDN-binding proteins have been identified. 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 AFDN 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.

Pssm-ID: 467251 [Multi-domain] Cd Length: 89 Bit Score: 56.53 E-value: 1.04e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1189 TVDMEKGAKGFGFSI---RGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd06789      5 TVTLKKVGNGMGLSIvaaKGAGQDKLGIYIKSVVKGGAADLDGRLQAGDQLLSVDGHSLVGLSQERAAELMTKTGSVVTL 84

Guanylate kinase;

Pssm-ID: 395500 Cd Length: 182 Bit Score: 59.32 E-value: 1.05e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1034657569  138 VPCTTRPHKEGEVPGVDYIFITVEDFMELEKSGALLESGTYEDNYYGT 185
Cdd:pfam00625   34 VPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYGT 81

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

Pssm-ID: 238122 [Multi-domain] Cd Length: 31 Bit Score: 54.84 E-value: 1.12e-09

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                   ....*....|....*....|....*....|.
gi 1034657569  305 PDNWEMAYTEKGEVYFIDHNTKTTSWLDPRL 335
Cdd:cd00201      1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467283 [Multi-domain] Cd Length: 93 Bit Score: 56.65 E-value: 1.19e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVI---------ISSLNrpesGSTITVPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADI 1033
Cdd:cd23070      2 VVTIVKSETGFGFNVrgqvseggqLRSIN----GELYAPLQHVSAVLEGGAADK-AGVRKGDRILEVNGVNVEGATHKQV 76

                           90
                   ....*....|....*..
gi 1034657569 1034 VKLIKDAGLSVTLRIIP 1050
Cdd:cd23070     77 VDLIKSGGDELTLTVIS 93

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.

Pssm-ID: 467285 [Multi-domain] Cd Length: 92 Bit Score: 56.73 E-value: 1.24e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569  826 MESGFGFRILGGDEPGQP---ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHA 890
Cdd:cd23072     11 AKYGLGFQIVGGEKSGRLdlgIFISSITPGGPADLDGRLKPGDRLISVNDVSLEGLSHDAAVEILQNA 78

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

Pssm-ID: 459800 [Multi-domain] Cd Length: 30 Bit Score: 54.43 E-value: 1.26e-09

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gi 1034657569  304 LPDNWEMAYTEKGEVYFIDHNTKTTSWLDP 333
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30

PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ6 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.

Pssm-ID: 467171 [Multi-domain] Cd Length: 85 Bit Score: 56.16 E-value: 1.39e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLL 1267
Cdd:cd06683      4 YTVELKRYGGPLGITISGTEEPFDPIVISGLTEGGLAERTGAIHVGDRILAINGESLRGKPLSEAIHLLQNAGDTVTLKI 83


                   ..
gi 1034657569 1268 KR 1269
Cdd:cd06683     84 SR 85

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.

Pssm-ID: 467177 [Multi-domain] Cd Length: 88 Bit Score: 56.15 E-value: 1.67e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1034657569  999 IIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:cd06690     37 LVPDSPAARDGRLRLGDRILAVNGTSLVGADYQSAMDLIRTSG 79

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. 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 Lin-7-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.

Pssm-ID: 467258 [Multi-domain] Cd Length: 86 Bit Score: 55.91 E-value: 1.73e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVIISslnrpesGSTITVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd06796      4 VVELPKTEEGLGFNVMG-------GKEQNSPIYISRIIPGGVADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQG 76


                   ....
gi 1034657569 1043 SVTL 1046
Cdd:cd06796     77 SVKL 80

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.

Pssm-ID: 467159 [Multi-domain] Cd Length: 96 Bit Score: 56.17 E-value: 1.95e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVII---SSLNRPESGSTITVPHkIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKD 1039
Cdd:cd06671      5 VELWREPGKSLGISIVggrVMGSRLSNGEEIRGIF-IKHVLEDSPAGRNGTLKTGDRILEVNGVDLRNATHEEAVEAIRN 83


                   ....*..
gi 1034657569 1040 AGLSVTL 1046
Cdd:cd06671     84 AGNPVVF 90

PDZ domain 4 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 4 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 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

Pssm-ID: 467156 [Multi-domain] Cd Length: 88 Bit Score: 55.77 E-value: 1.98e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034657569  494 VKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPIgqSVNLVLCR 550
Cdd:cd06668     34 IRSILPEGPVGRNGKLFSGDELLEVNGIQLLGLSHKEVVSILKELPP--PVRLVCCR 88

PDZ domain 4 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 4 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 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.

Pssm-ID: 467182 [Multi-domain] Cd Length: 85 Bit Score: 55.78 E-value: 2.00e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVIIsslnrpesGSTITVPHKIGRIIDgSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd06696      6 VTLTKSEKGSLGFTVT--------KGKDDNGCYIHDIVQ-DPAKSDGRLRPGDRLIMVNGVDVTNMSHTEAVSLLRAAPK 76


                   ....*.
gi 1034657569 1043 SVTLRI 1048
Cdd:cd06696     77 EVTLVL 82

PDZ domain 4 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 4 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 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.

Pssm-ID: 467185 [Multi-domain] Cd Length: 98 Bit Score: 56.08 E-value: 2.13e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVIISSLNrpESGSTITVPHK----IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIK 1038
Cdd:cd06701      7 LTIVKEPGEKLGISIRGGAK--GHAGNPLDPTDegifISKINPDGAAARDGRLKVGQRILEVNGQSLLGATHQEAVRILR 84


                   ....*...
gi 1034657569 1039 DAGLSVTL 1046
Cdd:cd06701     85 SVGDTLTL 92

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467194 [Multi-domain] Cd Length: 76 Bit Score: 55.33 E-value: 2.36e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034657569  971 EGFGFVIisslnrpeSGSTITVPHKIGRiidGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLI 1037
Cdd:cd06710     10 AGYGFTI--------SGQAPCVLSCVVR---GSPADV-AGLKAGDQILAVNGINVSKASHEDVVKLI 64

PDZ domain 2 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 2 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 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.

Pssm-ID: 467166 [Multi-domain] Cd Length: 82 Bit Score: 55.33 E-value: 2.43e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034657569 1213 LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLKR 1269
Cdd:cd06678     26 VFILDLLEGGLAARDGRLKSDDRVLAINGQDLRHGTPEQAAQIIQASGERVHFVVSR 82

PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ6 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.

Pssm-ID: 467171 [Multi-domain] Cd Length: 85 Bit Score: 55.39 E-value: 2.66e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569  993 PHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRI 1048
Cdd:cd06683     28 PIVISGLTEGGLAERTGAIHVGDRILAINGESLRGKPLSEAIHLLQNAGDTVTLKI 83

PDZ domain 6 of PDZ domain containing 2 (PDZD2), PDZ domain 3 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 6 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the third PDZ domain (PDZ3) 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 PDZ6 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.

Pssm-ID: 467243 [Multi-domain] Cd Length: 86 Bit Score: 55.34 E-value: 2.71e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034657569  472 KKSNMGFGFTIIGG-DEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKL 534
Cdd:cd06762      8 KEEGSGLGFSLAGGsDLENKSITVHRVFPSGLAAQEGTIQKGDRILSINGKSLKGVTHGDALSV 71

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). 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 shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467232 [Multi-domain] Cd Length: 82 Bit Score: 55.04 E-value: 2.88e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1187 YFTVDMEKGAKgFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGeSTRDMTHARAIELIKSGGRRVRLL 1266
Cdd:cd06750      2 LIEVQLQGGAP-WGFTLKGGLEHGEPLVISKIEEGGKAASVGKLQVGDEVVNING-VPLSGSRQEAIQLVKGSHKTLKLV 79


                   ...
gi 1034657569 1267 LKR 1269
Cdd:cd06750     80 VRR 82

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

Pssm-ID: 197736 [Multi-domain] Cd Length: 33 Bit Score: 53.37 E-value: 3.43e-09

                            10        20        30
                    ....*....|....*....|....*....|...
gi 1034657569   303 PLPDNWEMAYTEKGEVYFIDHNTKTTSWLDPRL 335
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33

PDZ domain 4 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 4 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. 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 PDZ4 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.

Pssm-ID: 467216 [Multi-domain] Cd Length: 84 Bit Score: 54.93 E-value: 3.48e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  820 DVHLRRMES-GFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARngQVNL 898
Cdd:cd06734      3 DVTLTRRENeGFGFVIISSVNKKSGSKIGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKDSGL--SVTL 80


                   ..
gi 1034657569  899 TV 900
Cdd:cd06734     81 TI 82

PDZ domain of the microtubule-associated serine-threonine (MAST) protein kinase family; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinases, including MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. The PDZ domain gives the MAST family the capacity to scaffold its own kinase activity. These kinases are implicated in the inhibition of neurite outgrowth and regeneration in cultured cells. Their binding partners include microtubules, beta2-syntrophin, TNF receptor-associated factor 6 (TRAF6), cAMP-regulated phosphoprotein (ARPP-16), and PTEN. This family also includes Caenorhabditis elegans KIN-4 MAST kinase, a key longevity factor acting through binding PTEN phosphatase, and Drosophila Drop out which regulates dynein-dependent transport during embryonic development. 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 MAST-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.

Pssm-ID: 467189 [Multi-domain] Cd Length: 93 Bit Score: 55.33 E-value: 3.83e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1193 EKGAKGFGFSIRGGREY--KMDLY-----VLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd06705      8 KKGPRGFGFTLRAIRVYigDSDVYtvhhlVTAVEEGSPAYEAG-LRPGDLITHVNGEPVQGLLHTQVVQLILKGGNKVSI 86

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.

Pssm-ID: 467257 [Multi-domain] Cd Length: 91 Bit Score: 55.05 E-value: 4.12e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENeGFGFVIISSlnrpESGSTITVPHkigrIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd06795      5 IVLHKGST-GLGFNIVGG----EDGEGIFISF----ILAGGPADLSGELRRGDQILSVNGVDLRNATHEQAAAALKNAGQ 75


                   ....
gi 1034657569 1043 SVTL 1046
Cdd:cd06795     76 TVTI 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.

Pssm-ID: 467234 [Multi-domain] Cd Length: 83 Bit Score: 54.63 E-value: 4.32e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569 1200 GFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06752     14 GFNIRGGKASGLGIFISKVIPDSDAHRLG-LKEGDQILSVNGVDFEDIEHSEAVKVLKT 71

PDZ domain 0 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 0 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. 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 PDZ0 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.

Pssm-ID: 467212 [Multi-domain] Cd Length: 85 Bit Score: 54.90 E-value: 4.43e-09

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gi 1034657569  829 GFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHH 889
Cdd:cd06730     14 ELNLEIRGGAENGQFPYLGEVKEDKVVYKSGKLHPGELLLEVNGTPVSGLTLRDVLAVIKH 74

PDZ domain of afadin (AFDN), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of afadin (AFDN, also known as ALL1-fused gene from chromosome 6 protein (AF6) and MLLT4), and related domains. AFDN belongs to the adhesion system, probably together with the E-cadherin-catenin system, that plays a role in the organization of homotypic, interneuronal, and heterotypic cell-cell adherens junctions. The AFDN PDZ domain interaction partners include poliovirus receptor-related protein PRR2/nectin, the junctional adhesion molecule (JAM), the breakpoint-cluster-region protein (BCR), connexin36 (Cx36), and a subset of Eph-related receptor tyrosine kinases; it can also bind low molecular weight ligands, in competition with a natural peptide ligand. Other AFDN-binding proteins have been identified. 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 AFDN 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.

Pssm-ID: 467251 [Multi-domain] Cd Length: 89 Bit Score: 54.99 E-value: 4.74e-09

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gi 1034657569  821 VHLRRMESGFGFRILGGDEPGQP---ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMhhaARNGQ-V 896
Cdd:cd06789      6 VTLKKVGNGMGLSIVAAKGAGQDklgIYIKSVVKGGAADLDGRLQAGDQLLSVDGHSLVGLSQERAAELM---TKTGSvV 82


                   ....*..
gi 1034657569  897 NLTVRRK 903
Cdd:cd06789     83 TLEVAKQ 89

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.

Pssm-ID: 467179 [Multi-domain] Cd Length: 88 Bit Score: 54.53 E-value: 6.16e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1196 AKGFGFSIRGG------REYkmDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIK--SGGRRVRLLL 1267
Cdd:cd06692      7 SKGLGIKIIGGyrentgEEF--GIFIKRILPGGLAATDGRLKEGDLILEVNGESLQGVTNERAVSILRsaSASNHMSLLI 84


                   ...
gi 1034657569 1268 KRG 1270
Cdd:cd06692     85 ARD 87

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.

Pssm-ID: 467188 [Multi-domain] Cd Length: 87 Bit Score: 54.21 E-value: 6.74e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRkENEGFGFVIISSlnrpeSGSTitvPHK-------IGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVK 1035
Cdd:cd06704      3 ITIER-QTGGLGISIAGG-----KGST---PYKgddegifISRVTEGGPAAK-AGVRVGDKLLEVNGVDLVDADHHEAVE 72

                           90
                   ....*....|....
gi 1034657569 1036 LIKDAGLSVTLRII 1049
Cdd:cd06704     73 ALKNSGNTVTMVVL 86

PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467169 [Multi-domain] Cd Length: 89 Bit Score: 54.16 E-value: 6.78e-09

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gi 1034657569  470 TLKKSNMGFGFTIIGG--DEPDEF--LQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQsvPIGQSVN 545
Cdd:cd06681      6 TLEKEGNSFGFVIRGGahEDRNKSrpLTVTHVRPGGPADREGTIKPGDRLLSVDGISLHGATHAEAMSILK--QCGQEAT 83


                   ..
gi 1034657569  546 LV 547
Cdd:cd06681     84 LL 85

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.

Pssm-ID: 467164 [Multi-domain] Cd Length: 83 Bit Score: 53.88 E-value: 8.00e-09

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gi 1034657569  468 STTLKKSNMGFGFTIIGG-DEP--DEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKL 534
Cdd:cd06676      1 TITLERGSDGLGFSIVGGfGSPhgDLPIYVKTVFEKGAAAEDGRLKRGDQILAVNGESLEGVTHEEAVNI 70

PDZ domain 4 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 4 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 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.

Pssm-ID: 467185 [Multi-domain] Cd Length: 98 Bit Score: 54.54 E-value: 8.49e-09

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gi 1034657569 1182 PQDFDYFTVDMEKGAKgFGFSIRGG-REY------KMD--LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARA 1252
Cdd:cd06701      1 PPGLQELTIVKEPGEK-LGISIRGGaKGHagnpldPTDegIFISKINPDGAAARDGRLKVGQRILEVNGQSLLGATHQEA 79

                           90
                   ....*....|....*
gi 1034657569 1253 IELIKSGGRRVRLLL 1267
Cdd:cd06701     80 VRILRSVGDTLTLLV 94

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 3 (MAST3); PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST3, and related domains. MAST3 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST3 plays a critical role in regulating the immune response of inflammatory bowel disease (IBD), and is involved in the process of cytoskeleton organization, intracellular signal transduction and peptidyl-serine phosphorylation. MAST3 also promotes the proliferation and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis. Binding partners of MAST3 include cAMP-regulated phosphoprotein (ARPP-16) and the tumor suppressor 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 MAST3 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.

Pssm-ID: 467288 [Multi-domain] Cd Length: 94 Bit Score: 54.27 E-value: 9.17e-09

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gi 1034657569  963 VVIHrKENEGFGFVIISSLNRPESGSTITVPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd23075      5 IIIH-SSGKKYGFTLRAIRVYMGDSDVYTVHHMVWSVEDGSPAQE-AGLRAGDLITHINGESVLGLVHMDVVELLLKSGN 82

                           90
                   ....*....|
gi 1034657569 1043 SVTLRIIPQE 1052
Cdd:cd23075     83 KVSLRTTALE 92

PDZ domain of membrane palmitoylated proteins (MPPs), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1-7 (also known as MAGUK p55 subfamily members 1-7), and related domains. MPPs comprise a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). MPPs form diverse protein complexes at the cell membranes, which are involved in a wide range of cellular processes, including establishing proper cell structure, polarity and cell adhesion. MPPs have only one PDZ 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 MPP1-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.

Pssm-ID: 467208 [Multi-domain] Cd Length: 80 Bit Score: 53.81 E-value: 9.17e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034657569  987 GSTITVPHK---IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRIIP 1050
Cdd:cd06726     14 GATIKMEEDsviVARILHGGMAHRSGLLHVGDEILEINGIPVSGKTVDELQKLLSSLSGSVTFKLIP 80

PDZ domain 1 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. 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 PDZRN4-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.

Pssm-ID: 467199 [Multi-domain] Cd Length: 92 Bit Score: 53.94 E-value: 9.44e-09

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gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGREYKMD--------LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06715      3 FTVVLHRENGSLGFNIIGGRPCENNqegsssegIYVSKIVENGPAADEGGLQVHDRIIEVNGKDLSKATHEEAVEAFRT 81

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467262 [Multi-domain] Cd Length: 83 Bit Score: 53.35 E-value: 1.11e-08

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gi 1034657569  821 VHLRRME-SGFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARngQVNLT 899
Cdd:cd06801      3 VRVVKQDvGGLGISIKGGAEHKMPILISKIFKGQAADQTGQLFVGDAILSVNGENLEDATHDEAVQALKNAGD--EVTLT 80


                   ..
gi 1034657569  900 VR 901
Cdd:cd06801     81 VK 82

PDZ domain 1 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. 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 INAD-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.

Pssm-ID: 467276 [Multi-domain] Cd Length: 87 Bit Score: 53.67 E-value: 1.19e-08

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gi 1034657569 1190 VDMEKGAK-GFGFSIRGGREYKMD------LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRR 1262
Cdd:cd23063      2 VVIEKTEKkSFGICIVRGEVKVSPntkttgIFIKGIIPDSPAHKCGRLKVGDRILSVNGNDVRNSTEQAAIDLIKEADFK 81


                   ...
gi 1034657569 1263 VRL 1265
Cdd:cd23063     82 IVL 84

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.

Pssm-ID: 467164 [Multi-domain] Cd Length: 83 Bit Score: 53.50 E-value: 1.19e-08

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gi 1034657569  971 EGFGFVIISSLNRPESGSTITVPhkigRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRII 1049
Cdd:cd06676      9 DGLGFSIVGGFGSPHGDLPIYVK----TVFEKGAAAEDGRLKRGDQILAVNGESLEGVTHEEAVNILKKTKGTVTLTVL 83

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

Pssm-ID: 436067 [Multi-domain] Cd Length: 54 Bit Score: 52.53 E-value: 1.21e-08

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gi 1034657569  996 IGRIIDGSPADRcAKLKVGDRILAVNGQSIINMphADIVKLIK-DAGLSVTLRI 1048
Cdd:pfam17820    2 VTAVVPGSPAER-AGLRVGDVILAVNGKPVRSL--EDVARLLQgSAGESVTLTV 52

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.

Pssm-ID: 467254 [Multi-domain] Cd Length: 87 Bit Score: 53.37 E-value: 1.29e-08

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gi 1034657569  967 RKENEGFGFVIISSLNRpesgstiTVPHkiGRI-----IDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:cd06792      8 SKKDGSLGISVTGGINT-------SVRH--GGIyvkslVPGGAAEQDGRIQKGDRLLEVNGVSLEGVTHKQAVECLKNAG 78


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gi 1034657569 1042 LSVTL 1046
Cdd:cd06792     79 QVVTL 83

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.

Pssm-ID: 467206 [Multi-domain] Cd Length: 89 Bit Score: 53.47 E-value: 1.46e-08

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gi 1034657569  970 NEGFGFVIISSLNRPESGSTITVphKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRI 1048
Cdd:cd06723     10 NSGLGFSIAGGTDNPHIGDDPSI--YITKIIPGGAAAADGRLRVNDIILRVNDVDVRNVTHSVAVEALKEAGSIVRLYV 86

PDZ domain 3 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of the Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa and can also form homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the third PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family 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.

Pssm-ID: 467233 [Multi-domain] Cd Length: 89 Bit Score: 53.59 E-value: 1.46e-08

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gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGREYKMDLYVL--RLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06751      2 LTVELSKMKQSLGISISGGIESKVQPVVKieKIFPGGAAALSGNLKAGYELVSVDGESLQQVTHQQAVDIIRR 74

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 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 PDLIM-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.

Pssm-ID: 467235 [Multi-domain] Cd Length: 79 Bit Score: 52.92 E-value: 1.69e-08

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gi 1034657569  993 PHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG--LSVTLR 1047
Cdd:cd06753     23 PLTISRVTPGGKAAQ-ANLRPGDVILAINGESTEGMTHLEAQNKIKAATgsLSLTLE 78

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467196 [Multi-domain] Cd Length: 78 Bit Score: 52.59 E-value: 2.03e-08

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gi 1034657569 1189 TVDMEKGAKGFGFSIRGGREYKmdlyVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGG 1260
Cdd:cd06712      3 TVHLTKEEGGFGFTLRGDSPVQ----VASVDPGSCAAEAG-LKEGDYIVSVGGVDCKWSKHSEVVKLLKSAG 69

PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS3, and related domains. RGS3 down-regulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. It downregulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. In Eph/ephrin signaling, RGS3 binds via its PDZ domain to the cytoplasmic C terminus of Eph receptor tyrosine kinase EphB. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467195 [Multi-domain] Cd Length: 77 Bit Score: 52.39 E-value: 2.17e-08

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gi 1034657569  648 LTIVKGAQGFGFTI-ADSPTgqRVkQILDiQGCP----GLCEGDLIVEINQQNVQNLSHTEVVDILKDCPigSETSLIIH 722
Cdd:cd06711      3 ITIQRGKDGFGFTIcDDSPV--RV-QAVD-PGGPaeqaGLQQGDTVLQINGQPVERSKCVELAHAIRNCP--SEIILLVW 76


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gi 1034657569  723 R 723
Cdd:cd06711     77 R 77

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

Pssm-ID: 467623 [Multi-domain] Cd Length: 88 Bit Score: 52.87 E-value: 2.18e-08

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gi 1034657569 1213 LYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKsG--GRRVRLLLKRGTGQVP 1275
Cdd:cd06782     16 LVVVSPIPGGPAEKAG-IKPGDVIVAVDGESVRGMSLDEVVKLLR-GpkGTKVKLTIRRGGEGEP 78

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 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 3 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). 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 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.

Pssm-ID: 467240 [Multi-domain] Cd Length: 87 Bit Score: 52.66 E-value: 2.40e-08

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gi 1034657569  829 GFGFRILGG-DEPGQP--ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIdLMHHAARNGQVNLTVR 901
Cdd:cd06759     13 GLGFSIVGGrDSPRGPmgIYVKTIFPGGAAAEDGRLKEGDEILEVNGESLQGLTHQEAI-QKFKQIKKGLVVLTVR 87

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467226 [Multi-domain] Cd Length: 75 Bit Score: 52.28 E-value: 2.84e-08

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gi 1034657569 1189 TVDMEKGAKGFGFSIRGgreyKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGG 1260
Cdd:cd06744      1 TVRVYRGNGSFGFTLRG----HAPVYIESVDPGSAAERAG-LKPGDRILFLNGLDVRNCSHDKVVSLLQGSG 67

PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and GIPC3 (also known as C19orf64) constitute the GIPC family. These proteins contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc1 and Gipc2 genes have been linked to cancer, while mutations in the Gipc3 gene cause nonsyndromic hearing loss. 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 GIPC 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.

Pssm-ID: 467191 [Multi-domain] Cd Length: 89 Bit Score: 52.62 E-value: 3.09e-08

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gi 1034657569  648 LTIVKGAQGFGFTIADSPTG----QRVKQILDIQGCPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCPIGSETSL 719
Cdd:cd06707      7 IEVTKSEDALGLTITDNGAGyafiKRIKEGSIMDKVPAICVGDHIEKINGESLVGCRHYEVARMLKEIPIGETFTL 82

PDZ domain 1 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 1 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 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.

Pssm-ID: 467165 [Multi-domain] Cd Length: 89 Bit Score: 52.25 E-value: 3.40e-08

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gi 1034657569 1200 GFSIRGGREYK-MDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLKR 1269
Cdd:cd06677     18 GISIVGGNDTPlINIVIQEVYRDGVIARDGRLLPGDQILEVNGVDISNVTHSQARSVLRQPCPVLRLTVLR 88

PDZ domain 6 of PDZ domain containing 2 (PDZD2), PDZ domain 3 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 6 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the third PDZ domain (PDZ3) 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 PDZ6 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.

Pssm-ID: 467243 [Multi-domain] Cd Length: 86 Bit Score: 51.88 E-value: 4.09e-08

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gi 1034657569 1187 YFTVDMEKGAKGFGFSIRGGREYKM-DLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06762      2 HVVVLHKEEGSGLGFSLAGGSDLENkSITVHRVFPSGLAAQEGTIQKGDRILSINGKSLKGVTHGDALSVLKQ 74

PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GOPC and related domains. GOPC, also known as PIST (PDZ domain protein interacting specifically with TC10), FIG (fused in glioblastoma), and CAL (CFTR-associated ligand), regulates the trafficking of a wide array of proteins, including small GTPases, receptors, and cell surface molecules such as cadherin 23 and CFTR. It may regulate CFTR chloride currents and acid-sensing ASIC3 currents by modulating cell surface expression of both channels, and may play a role in autophagy. Interaction partners of the GOPC PDZ domains include: FZD5, FZD8, ASIC3, CFTR, MUC3, ARFRP1, Ggamma13, neuroligin, and Stargazin. 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 GOPC-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.

Pssm-ID: 467261 [Multi-domain] Cd Length: 83 Bit Score: 51.99 E-value: 4.16e-08

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gi 1034657569 1189 TVDMEKG-AKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELI 1256
Cdd:cd06800      2 KVLLSKEpHEGLGISITGGKEHGVPILISEIHEGQPADRCGGLYVGDAILSVNGIDLRDAKHKEAVTIL 70

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. 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 Zasp52-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.

Pssm-ID: 467281 [Multi-domain] Cd Length: 82 Bit Score: 51.76 E-value: 4.52e-08

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gi 1034657569  820 DVHLRRMESG--FGFRILGGDEPGQPILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLMHHAArnGQVN 897
Cdd:cd23068      1 NIRLRRDDSNtpWGFRLQGGADFGQPLSIQKVNPGSPADKAG-LRRGDVILRINGTDTSNLTHKQAQDLIKRAG--NDLQ 77


                   ....*
gi 1034657569  898 LTVRR 902
Cdd:cd23068     78 LTVQR 82

PDZ domain of connector enhancer of kinase suppressor of ras 1 (CNK1), CNK2, CNK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CNK1 (also known as connector enhancer of KSR 1 (CNKSR1), CNK homolog protein 1, connector enhancer of KSR-like), CNK2 (also known as CNKSR2, CNK homolog protein 2), and CNK3 (also known as CNKSR3, CNK homolog protein 3, CNKSR family member 3, maguin-like). CNK proteins modulate Ras-mediated signaling, acting downstream of Ras as a scaffold for the Raf/MEK/ERK kinase cascade. They also modulate signaling mediated via Rho family small GTPases, through interactions with various guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), and modulate the insulin signaling pathway through interactions with the Arf guanine nucleotide exchange factors. CNK proteins also regulate cell proliferation and migration by acting as scaffolds for the PI3K/Akt and JNK signaling cascades. CNK2 plays a role in the molecular processes that govern morphology of the postsynaptic density (PSD), and influences subcellular localization of the regulatory NCK-interacting kinase TNIK. TNIK binds a region of CNK2 including the PDZ and the DUF domain; this region also binds the kinase MINK1. CNK2 may also influence the membrane localization of MINK1. CNK3 plays a part in transepithelial sodium transport; it coordinates assembly of an epithelial sodium channel (ENaC)-regulatory 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 CNK1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467230 [Multi-domain] Cd Length: 81 Bit Score: 51.84 E-value: 4.68e-08

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gi 1034657569  961 SDVVIHRKENEGFGFVIISSLNRPesgstitvpHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKD- 1039
Cdd:cd06748      2 LVQLTNKKPEEGLGLEIKSTYNGL---------HVITGTKENSPADRCGKIHAGDEVIQVNYQTVVGWQLKNLVRALREd 72


                   ....*....
gi 1034657569 1040 -AGLSVTLR 1047
Cdd:cd06748     73 pHGVTLTLK 81

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

Pssm-ID: 436067 [Multi-domain] Cd Length: 54 Bit Score: 50.60 E-value: 4.83e-08

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gi 1034657569 1214 YVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIeLIKSGGRRVRLLLKR 1269
Cdd:pfam17820    1 VVTAVVPGSPAERAG-LRVGDVILAVNGKPVRSLEDVARL-LQGSAGESVTLTVRR 54

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467196 [Multi-domain] Cd Length: 78 Bit Score: 51.43 E-value: 5.08e-08

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gi 1034657569  965 IH-RKENEGFGFVIisslnRPESgstitvPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL- 1042
Cdd:cd06712      4 VHlTKEEGGFGFTL-----RGDS------PVQVASVDPGSCAAE-AGLKEGDYIVSVGGVDCKWSKHSEVVKLLKSAGEe 71


                   ....*..
gi 1034657569 1043 SVTLRII 1049
Cdd:cd06712     72 GLELQVV 78

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.

Pssm-ID: 467253 [Multi-domain] Cd Length: 89 Bit Score: 51.85 E-value: 5.43e-08

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gi 1034657569  820 DVHLRRMESGFGFRILG-------GDEPGqpILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAar 892
Cdd:cd06791      4 EVELVKDEQGLGITIAGyvgekasGELSG--IFVKSIIPGSAADQDGRIQVNDQIIAVDGVNLQGFTNQEAVEVLRNT-- 79

                           90
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gi 1034657569  893 nGQ-VNLTVRR 902
Cdd:cd06791     80 -GQvVHLTLAR 89

PDZ domain 6 of PDZ domain containing 2 (PDZD2), PDZ domain 3 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 6 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the third PDZ domain (PDZ3) 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 PDZ6 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.

Pssm-ID: 467243 [Multi-domain] Cd Length: 86 Bit Score: 51.49 E-value: 5.48e-08

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gi 1034657569  963 VVIHRKENEGFGFVII--SSLNRPEsgstITVpHkigRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDA 1040
Cdd:cd06762      4 VVLHKEEGSGLGFSLAggSDLENKS----ITV-H---RVFPSGLAAQEGTIQKGDRILSINGKSLKGVTHGDALSVLKQA 75

PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. 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 Dlg5-like family PSZ2 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.

Pssm-ID: 467246 [Multi-domain] Cd Length: 77 Bit Score: 51.58 E-value: 5.49e-08

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gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRIIPQ 1051
Cdd:cd06765     20 ISRIVPGSPAAKEGSLTVGDRIIAINGIALDNKSLSECEALLRSCRDSLSLSLMKV 75

PDZ domain 2 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 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.

Pssm-ID: 467207 [Multi-domain] Cd Length: 85 Bit Score: 51.50 E-value: 5.62e-08

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gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRII 1049
Cdd:cd06724     32 VTKIIEGGAAQKDGRLQVGDKLLAVNDVSLEEVTHEEAVAALKNTSDVVYLKVA 85

PDZ domain 2 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 2 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 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.

Pssm-ID: 467223 [Multi-domain] Cd Length: 84 Bit Score: 51.50 E-value: 5.71e-08

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gi 1034657569 1002 GSPADRCAkLKVGDRILAVNGQSIINMPHADIVKLIK 1038
Cdd:cd06741     36 GSVAENAG-LKVGDQILEVNGRSFLDITHDEAVKILK 71

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.

Pssm-ID: 467209 [Multi-domain] Cd Length: 87 Bit Score: 51.51 E-value: 5.79e-08

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gi 1034657569 1189 TVDMEKGAK-GFGFSIRGGRE------YKMDLYVLRLAEDGPAirNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGR 1261
Cdd:cd06727      2 TVTLHRAPGfGFGIAVSGGRDnphfqsGDTSIVISDVLKGGPA--EGKLQENDRVVSVNGVSMENVEHSFAVQILRKCGK 79


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gi 1034657569 1262 RVRLLLKR 1269
Cdd:cd06727     80 TANITVKR 87

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.

Pssm-ID: 467193 [Multi-domain] Cd Length: 86 Bit Score: 51.52 E-value: 6.02e-08

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gi 1034657569  823 LRRMESGFGFRILGG-DEPGQP----ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARNgqVN 897
Cdd:cd06709      5 LKRGPSGLGFNIVGGtDQPYIPndsgIYVAKIKEDGAAAIDGRLQEGDKILEINGQSLENLTHQDAVELFRNAGED--VK 82


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gi 1034657569  898 LTVR 901
Cdd:cd06709     83 LKVQ 86

PDZ domain of tyrosine-protein phosphatase non-receptor type 3 (PTPN3), tyrosine-protein phosphatase non-receptor type 4 (PTNP4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PTPN3, PTPN4 and related domains. PTPN3 (also known as protein-tyrosine phosphatase H1, PTP-H1) has a tumor-suppressive or a tumor-promoting role in many cancers. It serves as a specific phosphatase for the MAP kinase p38gamma; the two interact via their PDZ domains and cooperate to promote Ras-induced oncogenesis. Interaction partners of the PTPN3 PDZ domain include p38gamma and human papillomavirus E6 oncoprotein. PTPN4 (also known as protein-tyrosine phosphatase MEG1) plays a role in immunity, learning, synaptic plasticity or cell homeostasis. p38gamma is also an interaction partner of the PTPN4 PDZ domain: PTPN4 regulates neuronal cell homeostasis by protecting neurons against apoptosis; binding of the C terminus of p38gamma to the PDZ domain of PTPN4, antagonizes the catalytic autoinhibition of PTPN4, leading to cell apoptosis. Other interaction partners of the PTPN4 PDZ domain include glutamate receptor subunit GluN2A, and RABV strain G protein, among others. 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 PTPN3-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.

Pssm-ID: 467190 [Multi-domain] Cd Length: 90 Bit Score: 51.54 E-value: 6.05e-08

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gi 1034657569 1199 FGFSIRGGREYKMDLYVLRLAEDGPAIR-NGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06706     16 FGFNVKGGVDQKMPVIVSRVAPGTPADLcIPRLNEGDQVLLINGRDISEHTHDQVVMFIKA 76

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467249 [Multi-domain] Cd Length: 80 Bit Score: 51.29 E-value: 6.35e-08

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gi 1034657569  470 TLKKSNMGFGFTI-IGGDEPDEFlqVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNLVL 548
Cdd:cd06768      4 HLVKGPEGYGFNLhAEKGRPGHF--IREVDPGSPAERAG-LKDGDRLVEVNGENVEGESHEQVVEKIKAS--GNQVTLLV 78


                   .
gi 1034657569  549 C 549
Cdd:cd06768     79 V 79

PDZ domain 9 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 9 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 PDZ9 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 PDZ9 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.

Pssm-ID: 467263 [Multi-domain] Cd Length: 79 Bit Score: 51.20 E-value: 7.38e-08

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gi 1034657569  963 VVIHRKENEGFGFVIisSLNRPESGSTITvphkigRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd10817      1 HVELPKDQGGLGIAI--SEEDTENGIVIK------SLTEGGPAAKDGRLKVGDQILAVDDESVVGCPYEKAISLLKTAKG 72


                   ....*.
gi 1034657569 1043 SVTLRI 1048
Cdd:cd10817     73 TVKLTV 78

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. 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 Par6-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.

Pssm-ID: 467202 [Multi-domain] Cd Length: 84 Bit Score: 51.03 E-value: 8.41e-08

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gi 1034657569 1192 MEKGAKGFGFSIRGG--REYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMT 1248
Cdd:cd06718      6 IKPPGKPLGFYIRDGngVERVPGIFISRLVLGSLADSTGLLAVGDEILEVNGVEVTGKS 64

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.

Pssm-ID: 467237 [Multi-domain] Cd Length: 83 Bit Score: 51.11 E-value: 8.79e-08

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gi 1034657569 1199 FGFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06755     14 LHFSLLGGSEKGFGIFVSKVEKGSKAAEAG-LKRGDQILEVNGQNFENITLKKALEILRN 72

PDZ domain 5 of multi-PDZ-domain protein 1 (MUPP1), 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 5 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 PDZ5 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

Pssm-ID: 467157 [Multi-domain] Cd Length: 98 Bit Score: 51.46 E-value: 9.14e-08

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gi 1034657569  821 VHLRRMESGFGFRILGGDEPGQP----ILIGAVIAMGSADRDGRLHPGDELVYVDGIPV 875
Cdd:cd06669     11 IELEKGDRGLGFSILDYQDPLDPsetvIVIRSLVPGGVAEQDGRLLPGDRLVFVNDVSL 69

guanylate kinase; Provisional

Pssm-ID: 173199 Cd Length: 186 Bit Score: 53.84 E-value: 9.27e-08

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gi 1034657569  134 YLRTVPCTTRPHKEGEVPGVDYIFITVEDFMELEKSGALLESGTYEDNYYGTPKPPAEPA 193
Cdd:PRK14737    31 FLFSISCTTRAPRPGDEEGKTYFFLTIEEFKKGIADGEFLEWAEVHDNYYGTPKAFIEDA 90

PDZ domain 4 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 4 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. 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 PDZ4 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.

Pssm-ID: 467216 [Multi-domain] Cd Length: 84 Bit Score: 51.08 E-value: 9.35e-08

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gi 1034657569  469 TTLKKSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNLVL 548
Cdd:cd06734      5 TLTRRENEGFGFVIISSVNKKSGSKIGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKDS--GLSVTLTI 82

PDZ domain 2 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 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.

Pssm-ID: 467187 [Multi-domain] Cd Length: 92 Bit Score: 51.11 E-value: 9.75e-08

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gi 1034657569  968 KENEGFGFVIisslnrpeSGSTITVPHK-------IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDA 1040
Cdd:cd06703      9 RDGKGLGFSI--------AGGKGSTPFRdgdegifISRITEGGAADRDGKLQVGDRVLSINGVDVTEARHDQAVALLTSS 80


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gi 1034657569 1041 GLSVTL 1046
Cdd:cd06703     81 SPTITL 86

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467249 [Multi-domain] Cd Length: 80 Bit Score: 50.90 E-value: 9.86e-08

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gi 1034657569  821 VHLRRMESGFGFRILGG-DEPGQpiLIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLMHhaARNGQVNLT 899
Cdd:cd06768      3 CHLVKGPEGYGFNLHAEkGRPGH--FIREVDPGSPAERAG-LKDGDRLVEVNGENVEGESHEQVVEKIK--ASGNQVTLL 77


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gi 1034657569  900 V 900
Cdd:cd06768     78 V 78

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.

Pssm-ID: 467206 [Multi-domain] Cd Length: 89 Bit Score: 51.16 E-value: 1.01e-07

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gi 1034657569  819 LDVHLRRMESGFGFRILGG-DEPGQP----ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARn 893
Cdd:cd06723      2 EEITLERGNSGLGFSIAGGtDNPHIGddpsIYITKIIPGGAAAADGRLRVNDIILRVNDVDVRNVTHSVAVEALKEAGS- 80

                           90
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gi 1034657569  894 gQVNLTVRRK 903
Cdd:cd06723     81 -IVRLYVKRR 89

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467283 [Multi-domain] Cd Length: 93 Bit Score: 51.25 E-value: 1.03e-07

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gi 1034657569  821 VHLRRMESGFGFRILGG-DEPGQ----------PI-LIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLM 887
Cdd:cd23070      3 VTIVKSETGFGFNVRGQvSEGGQlrsingelyaPLqHVSAVLEGGAADKAG-VRKGDRILEVNGVNVEGATHKQVVDLI 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.

Pssm-ID: 467285 [Multi-domain] Cd Length: 92 Bit Score: 50.95 E-value: 1.04e-07

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gi 1034657569 1189 TVDMEKGAK-GFGFSIRGGREY-KMDL--YVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVR 1264
Cdd:cd23072      4 LVNLKKDAKyGLGFQIVGGEKSgRLDLgiFISSITPGGPADLDGRLKPGDRLISVNDVSLEGLSHDAAVEILQNAPEDVT 83


                   ...
gi 1034657569 1265 LLL 1267
Cdd:cd23072     84 LVV 86

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.

Pssm-ID: 467257 [Multi-domain] Cd Length: 91 Bit Score: 50.82 E-value: 1.16e-07

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gi 1034657569  470 TLKKSNMGFGFTIIGGDEpDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNLVlc 549
Cdd:cd06795      6 VLHKGSTGLGFNIVGGED-GEGIFISFILAGGPADLSGELRRGDQILSVNGVDLRNATHEQAAAALKNA--GQTVTII-- 80

                           90
                   ....*....|.
gi 1034657569  550 rgypLPFDPED 560
Cdd:cd06795     81 ----AQYKPEE 87

PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ6 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.

Pssm-ID: 467171 [Multi-domain] Cd Length: 85 Bit Score: 50.77 E-value: 1.17e-07

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gi 1034657569  821 VHLRRMESGFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAarNGQVNLTV 900
Cdd:cd06683      6 VELKRYGGPLGITISGTEEPFDPIVISGLTEGGLAERTGAIHVGDRILAINGESLRGKPLSEAIHLLQNA--GDTVTLKI 83


                   ..
gi 1034657569  901 RR 902
Cdd:cd06683     84 SR 85

PDZ domain of tax1-binding protein 3 (TAX1BP3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of TAX1BP3, and related domains. TAX1BP3 (also known as glutaminase-interacting protein 3, tax interaction protein 1, TIP-1, tax-interacting protein 1) may regulate a number of protein-protein interactions by competing for PDZ domain binding sites. TAX1BP3 binds beta-catenin and may act as an inhibitor of the Wnt signaling pathway. It competes with LIN7A (also known as Lin-7A or LIN-7A) for inward rectifier potassium channel 4 (KCNJ4) binding, and thereby promotes KCNJ4 internalization. It may play a role in the Rho signaling pathway, and in the activation of CDC42 by the viral protein HPV16 E6. Binding partners of the TAX1BP3 PDZ domain include beta-catenin, KCNJ4, glutaminase liver isoform (GLS2), rho guanine nucleotide exchange factor 16 (ARHGEF16), rhotekin, and CDK5 regulatory subunit-associated protein 3 (also known as LAPZ). 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 TAX1BP3-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.

Pssm-ID: 467265 [Multi-domain] Cd Length: 94 Bit Score: 50.80 E-value: 1.34e-07

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gi 1034657569 1200 GFSIRGG----------REYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLKR 1269
Cdd:cd10822     16 GFSIGGGidqdpsknpfSYTDKGIYVTRVSEGGPAEKAG-LQVGDKILQVNGWDMTMVTHKQAVKRLTKKKPVLRMLVTR 94

PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP3, MPP4, and MPP7, and related domains. MPP3 (also known as MAGUK p55 subfamily member 3, erythrocyte membrane protein p55, or EMP55), MPP4 (also known as MAGUK p55 subfamily member 4 or Discs large homolog 6), and MPP7 (also known as MAGUK p55 subfamily member 7) are membrane-associated guanylate kinase (MAGUK)-like proteins. MPP3 is part of a cell adhesion protein complex including tumor suppressor CADM1 and actin-binding protein 4.1B. Participation in the Crumbs cell polarity complex has also been demonstrated for MPP7 in epithelial cells, and for MPP3 and MPP4 in the retina. MPP4 is needed for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Binding partners of the MPP3 PDZ domain include nectin-3, serotonin 5-hydroxytryptamine, 5-HT(2C) receptor, and a cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1); fragments of MPP4 having the PDZ domain bind CRB (PDZ-SH3-GUK) and GABA transporter GAT1 (PDZ-SH3). 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 MPP1-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.

Pssm-ID: 467260 [Multi-domain] Cd Length: 81 Bit Score: 50.32 E-value: 1.37e-07

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gi 1034657569  838 DEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHA 890
Cdd:cd06799     19 DEKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANS 71

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.

Pssm-ID: 467284 [Multi-domain] Cd Length: 92 Bit Score: 50.57 E-value: 1.43e-07

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gi 1034657569  821 VHLRR-MESGFGFRILGGDEPGQ---PILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLM 887
Cdd:cd23071      5 VTLKRdPKRGFGFVIVGGENTGKldlGIFIASIIPGGPAEKDGRIKPGGRLISLNNISLEGVTFNTAVKIL 75

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467282 [Multi-domain] Cd Length: 76 Bit Score: 50.08 E-value: 1.52e-07

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gi 1034657569 1189 TVDMEKGAKGFGFSIRGGREykmdLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSG 1259
Cdd:cd23069      3 CVVIQRDENGYGLTVSGDNP----VFVQSVKEGGAAYRAG-VQEGDRIIKVNGTLVTHSNHLEVVKLIKSG 68

PDZ domain of PICK1 (protein interacting with C-kinase 1) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PICK1, and related domains. PICK1 (also known as PRKCA-binding protein and protein kinase C-alpha-binding protein) plays a key role in regulating trafficking of binding partners by altering either their subcellular targeting and/or surface expression. PICK1 plays a role in synaptic plasticity by regulating the trafficking and internalization of amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors; the PICK1-PDZ domain binds the AMPA receptor subunits. The PICK1 PDZ domain also binds glutamate transporters, Eph receptors, metabotropic glutamate receptors, and ASICs (acid-sensing ion channels), among others. Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes. 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 PICK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467205 [Multi-domain] Cd Length: 84 Bit Score: 50.11 E-value: 1.66e-07

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gi 1034657569 1189 TVDMEKGAKGF-GFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTH---ARAIELIKS 1258
Cdd:cd06722      2 TVTLKKDAQNLiGISIGGGAPYCPCLYIVQVFDNTPAAKDGTLAAGDEIVGVNGKSVKGKTKvevAKMIQAVKG 75

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. 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 Zasp52-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.

Pssm-ID: 467281 [Multi-domain] Cd Length: 82 Bit Score: 50.22 E-value: 1.83e-07

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gi 1034657569  996 IGRIIDGSPADRCAkLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRI 1048
Cdd:cd23068     29 IQKVNPGSPADKAG-LRRGDVILRINGTDTSNLTHKQAQDLIKRAGNDLQLTV 80

PDZ domain 2 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 2 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. 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 PDZ2 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.

Pssm-ID: 467214 [Multi-domain] Cd Length: 82 Bit Score: 49.86 E-value: 1.90e-07

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gi 1034657569  968 KENEGFGFVIISSLNRPesgstitvphKIGRIIDGSpadRCAKLKVGDRILAVNGQSIINMPHADIVKLIKD 1039
Cdd:cd06732     10 KGPMGFGFTIADSPQGQ----------RVKQILDPQ---RCRGLQEGDLIVEINGQNVQNLSHAQVVDVLKE 68

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.

Pssm-ID: 467244 [Multi-domain] Cd Length: 86 Bit Score: 49.92 E-value: 2.07e-07

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gi 1034657569  645 LMTLTIVKGAQGFGFTI---ADSPTGQR---VKQIL---DIQGCPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCPIGS 715
Cdd:cd06763      1 AVTVELEKGSAGLGFSLeggKGSPLGDRpltIKRIFkggAAEQSGVLQVGDEILQINGTSLQGLTRFEAWNIIKSLPEGP 80


                   ....*..
gi 1034657569  716 eTSLIIH 722
Cdd:cd06763     81 -VTLLIR 86

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467282 [Multi-domain] Cd Length: 76 Bit Score: 49.70 E-value: 2.38e-07

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gi 1034657569  963 VVIHRKENeGFGFVIisslnrpeSGSTITVPHKIGriiDGSPAdRCAKLKVGDRILAVNGQSIINMPHADIVKLIKdAGL 1042
Cdd:cd23069      4 VVIQRDEN-GYGLTV--------SGDNPVFVQSVK---EGGAA-YRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIK-SGS 69


                   ....
gi 1034657569 1043 SVTL 1046
Cdd:cd23069     70 YVAL 73

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

Pssm-ID: 467155 [Multi-domain] Cd Length: 80 Bit Score: 49.59 E-value: 2.42e-07

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gi 1034657569  477 GFGFTIIGGDEPDefLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNLVLCR 550
Cdd:cd06667     11 GLGFGIVGGKSTG--VVVKTILPGGVADRDGRLRSGDHILQIGDTNLRGMGSEQVAQVLRQC--GSHVRLVVAR 80

PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNPO2, SYNPO2L, and related domains. SYNPO2 (also known as genethonin-2, myopodin) is a cytoskeleton adaptor protein. It participates in chaperone-assisted selective autophagy (CASA), a mechanism for the disposal of misfolded and damaged proteins and provides a link between the CASA chaperone complex and a membrane-tethering and fusion machinery that generates autophagosome membranes. The SYNPO2 PPxY motif binds CASA cochaperone BCL2-associated athanogene 3 (BAG3) and the SYNPO2 PDZ domain binds vacuolar protein sorting 18 homolog (VPS18). There are three isoforms of SYNPO2, which possess an amino-terminal PDZ domain (SYNPO2a, b, c); the short isoform SYNPO2d, lacks the PDZ 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 SYNPO2-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.

Pssm-ID: 467264 [Multi-domain] Cd Length: 78 Bit Score: 49.61 E-value: 2.53e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569  830 FGFRILGGDEPGQPILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLM 887
Cdd:cd10820     10 WGFRLQGGSEQKKPLQVAKIRKKSKAALAG-LCEGDELLSINGKPCADLSHSEAMDLI 66

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

Pssm-ID: 395476 [Multi-domain] Cd Length: 81 Bit Score: 49.59 E-value: 2.61e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034657569  477 GFGFTI-IGGDEPDEFLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKlfQSVPIGQSVNLVL 548
Cdd:pfam00595   11 GLGFSLkGGSDQGDPGIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVL--ALKGSGGKVTLTI 80

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

Pssm-ID: 467155 [Multi-domain] Cd Length: 80 Bit Score: 49.59 E-value: 2.80e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  821 VHLRRMESGFGFRILGGDEPGqpILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAArnGQVNLTV 900
Cdd:cd06667      3 IELVNDGSGLGFGIVGGKSTG--VVVKTILPGGVADRDGRLRSGDHILQIGDTNLRGMGSEQVAQVLRQCG--SHVRLVV 78


                   ..
gi 1034657569  901 RR 902
Cdd:cd06667     79 AR 80

PDZ domain 2 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. 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 harmonin 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.

Pssm-ID: 467220 [Multi-domain] Cd Length: 82 Bit Score: 49.24 E-value: 3.27e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034657569 1195 GAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06738     11 GTRGLGCSISSGPTQKPGIFISNVKPGSLAEEVG-LEVGDQIVEVNGTSFTNVDHKEAVMALKS 73

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.

Pssm-ID: 467161 [Multi-domain] Cd Length: 86 Bit Score: 49.60 E-value: 3.39e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  817 KELDVHLRRMESGFGFRILGG-DEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAArnGQ 895
Cdd:cd06673      2 RETTIEINKGKKGLGLSIVGGsDTLLGAIIIHEVYEDGAAAKDGRLWAGDQILEVNGEDLRKATHDEAINVLRQTP--QK 79


                   ....*..
gi 1034657569  896 VNLTVRR 902
Cdd:cd06673     80 VRLLVYR 86

PDZ domain of membrane palmitoylated proteins (MPPs), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1-7 (also known as MAGUK p55 subfamily members 1-7), and related domains. MPPs comprise a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). MPPs form diverse protein complexes at the cell membranes, which are involved in a wide range of cellular processes, including establishing proper cell structure, polarity and cell adhesion. MPPs have only one PDZ 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 MPP1-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.

Pssm-ID: 467208 [Multi-domain] Cd Length: 80 Bit Score: 49.19 E-value: 3.45e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  841 GQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAArnGQVNLTV 900
Cdd:cd06726     21 EDSVIVARILHGGMAHRSGLLHVGDEILEINGIPVSGKTVDELQKLLSSLS--GSVTFKL 78

PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP3, MPP4, and MPP7, and related domains. MPP3 (also known as MAGUK p55 subfamily member 3, erythrocyte membrane protein p55, or EMP55), MPP4 (also known as MAGUK p55 subfamily member 4 or Discs large homolog 6), and MPP7 (also known as MAGUK p55 subfamily member 7) are membrane-associated guanylate kinase (MAGUK)-like proteins. MPP3 is part of a cell adhesion protein complex including tumor suppressor CADM1 and actin-binding protein 4.1B. Participation in the Crumbs cell polarity complex has also been demonstrated for MPP7 in epithelial cells, and for MPP3 and MPP4 in the retina. MPP4 is needed for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Binding partners of the MPP3 PDZ domain include nectin-3, serotonin 5-hydroxytryptamine, 5-HT(2C) receptor, and a cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1); fragments of MPP4 having the PDZ domain bind CRB (PDZ-SH3-GUK) and GABA transporter GAT1 (PDZ-SH3). 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 MPP1-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.

Pssm-ID: 467260 [Multi-domain] Cd Length: 81 Bit Score: 49.16 E-value: 3.74e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRIIP 1050
Cdd:cd06799     27 VARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANSQGPITFKLIP 81

PDZ domain 5 of multi-PDZ-domain protein 1 (MUPP1), 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 5 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 PDZ5 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

Pssm-ID: 467157 [Multi-domain] Cd Length: 98 Bit Score: 49.53 E-value: 3.79e-07

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gi 1034657569  471 LKKSNMGFGFTIIGGDEP----DEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPIGqSVNL 546
Cdd:cd06669     13 LEKGDRGLGFSILDYQDPldpsETVIVIRSLVPGGVAEQDGRLLPGDRLVFVNDVSLENASLDEAVQALKSAPPG-TVRI 91


                   ....*....
gi 1034657569  547 VLCRgyPLP 555
Cdd:cd06669     92 GVAK--PLP 98

PDZ domain 1 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. 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 PDZRN4-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.

Pssm-ID: 467199 [Multi-domain] Cd Length: 92 Bit Score: 49.31 E-value: 3.92e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRkENEGFGFVIIS---SLNRPESGST--ITVphkiGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLI 1037
Cdd:cd06715      5 VVLHR-ENGSLGFNIIGgrpCENNQEGSSSegIYV----SKIVENGPAADEGGLQVHDRIIEVNGKDLSKATHEEAVEAF 79


                   ...
gi 1034657569 1038 KDA 1040
Cdd:cd06715     80 RTA 82

PDZ domain 2 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 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.

Pssm-ID: 467187 [Multi-domain] Cd Length: 92 Bit Score: 49.57 E-value: 4.01e-07

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gi 1034657569  467 LSTTLKKSNMGFGFTIIGGDEP------DEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPI 540
Cdd:cd06703      3 ITTTLIRDGKGLGFSIAGGKGStpfrdgDEGIFISRITEGGAADRDGKLQVGDRVLSINGVDVTEARHDQAVALLTSSSP 82

                           90
                   ....*....|
gi 1034657569  541 GqsVNLVLCR 550
Cdd:cd06703     83 T--ITLVVER 90

PDZ domain 4 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467174 [Multi-domain] Cd Length: 99 Bit Score: 49.65 E-value: 4.32e-07

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gi 1034657569 1197 KGFGFSIRGG---REYKMDLYVLRLAE-DGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd06686     18 KGFGIQLQGGvfaTETLSSPPLISFIEpDSPAERCGVLQVGDRVLSINGIPTEDRTLEEANQLLRDSASKVTL 90

PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467181 [Multi-domain] Cd Length: 90 Bit Score: 49.18 E-value: 4.42e-07

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gi 1034657569  967 RKENEGFGFVIISSLNRPES--GSTITvphKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSV 1044
Cdd:cd06695      7 TKGSSGLGFSFLGGENNSPEdpFSGLV---RIKKLFPGQPAAESGLIQEGDVILAVNGEPLKGLSYQEVLSLLRGAPPEV 83


                   ....
gi 1034657569 1045 TLRI 1048
Cdd:cd06695     84 TLLL 87

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467194 [Multi-domain] Cd Length: 76 Bit Score: 48.78 E-value: 4.55e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569  647 TLTIVKGAQGFGFTIAdsptGQRvKQILD--IQGCP----GLCEGDLIVEINQQNVQNLSHTEVVDILKDC 711
Cdd:cd06710      2 TVEIARGRAGYGFTIS----GQA-PCVLScvVRGSPadvaGLKAGDQILAVNGINVSKASHEDVVKLIGKC 67

PDZ domain of the microtubule-associated serine-threonine (MAST) protein kinase family; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinases, including MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. The PDZ domain gives the MAST family the capacity to scaffold its own kinase activity. These kinases are implicated in the inhibition of neurite outgrowth and regeneration in cultured cells. Their binding partners include microtubules, beta2-syntrophin, TNF receptor-associated factor 6 (TRAF6), cAMP-regulated phosphoprotein (ARPP-16), and PTEN. This family also includes Caenorhabditis elegans KIN-4 MAST kinase, a key longevity factor acting through binding PTEN phosphatase, and Drosophila Drop out which regulates dynein-dependent transport during embryonic development. 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 MAST-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.

Pssm-ID: 467189 [Multi-domain] Cd Length: 93 Bit Score: 49.16 E-value: 4.65e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHrKENEGFGFVIISSlnRPESGST--ITVPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDA 1040
Cdd:cd06705      5 IVIK-KGPRGFGFTLRAI--RVYIGDSdvYTVHHLVTAVEEGSPAYE-AGLRPGDLITHVNGEPVQGLLHTQVVQLILKG 80

                           90
                   ....*....|..
gi 1034657569 1041 GLSVTLRIIPQE 1052
Cdd:cd06705     81 GNKVSIRATPLE 92

PDZ domain of membrane palmitoylated protein 6 (MPP6), MPP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP6, MPP2, and related domains. MPP6 (also known as MAGUK p55 subfamily member, Protein associated with Lin-7, 2 (PALS2), Veli-associated MAGUK 1, and VAM-1) is a membrane-associated guanylate kinase (MAGUK)-like protein. MPP6 is a regulator of Lin-7 expression and localization. MPP6 is also known to bind cell-adhesion protein, nectin-like molecule-2 (Necl-2), and localize to the basolateral plasma membrane in mammalian epithelial cells. MPP2 (also known as MAGUK p55 subfamily member 2) is a postsynaptic protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density. Other members of this family include the Drosophila Vari protein, an essential basolateral septate junction protein which interacts with the cell-adhesion protein neurexin IV. 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 MPP6-MPP2-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.

Pssm-ID: 467268 [Multi-domain] Cd Length: 78 Bit Score: 48.76 E-value: 4.83e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVIisslnRPESGSTItvphkIGRIIDGSPADRCAKLKVGDRILAVNGQSIINmPhADIVKLIKDAGL 1042
Cdd:cd10832      3 VGIRKNPGEPLGVTV-----RLEEGELV-----IARILHGGMIDRQGLLHVGDIIKEVNGVPVGS-P-EQLQEMLKNASG 70


                   ....*...
gi 1034657569 1043 SVTLRIIP 1050
Cdd:cd10832     71 SVTLKILP 78

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.

Pssm-ID: 467250 [Multi-domain] Cd Length: 75 Bit Score: 48.78 E-value: 4.99e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569 1189 TVDMEKGAK-GFGFSIRGGREykmdLYVLRLAEDGPAIrnGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06769      1 TVEIQRDAVlGFGFVAGSERP----VVVRSVTPGGPSE--GKLLPGDQILKINNEPVEDLPRERVIDLIRE 65

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. 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 Lin-7-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.

Pssm-ID: 467258 [Multi-domain] Cd Length: 86 Bit Score: 48.97 E-value: 5.20e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034657569  471 LKKSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQS 537
Cdd:cd06796      7 LPKTEEGLGFNVMGGKEQNSPIYISRIIPGGVADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKA 73

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467282 [Multi-domain] Cd Length: 76 Bit Score: 48.54 E-value: 5.31e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569  470 TLKKSNMGFGFTIiGGDEPdefLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQSvpiGQSVNLVL 548
Cdd:cd23069      5 VIQRDENGYGLTV-SGDNP---VFVQSVKEGGAAYRAG-VQEGDRIIKVNGTLVTHSNHLEVVKLIKS---GSYVALTL 75

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

Pssm-ID: 440556 [Multi-domain] Cd Length: 341 Bit Score: 53.34 E-value: 5.53e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569  477 GFGFTIiggDEPDEFLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQSvPIGQSVNLVLCRG 551
Cdd:COG0793     61 GLGAEL---GEEDGKVVVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRG-KAGTKVTLTIKRP 130

PDZ domain 3 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of the Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa and can also form homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the third PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family 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.

Pssm-ID: 467233 [Multi-domain] Cd Length: 89 Bit Score: 48.97 E-value: 5.91e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569  818 ELDVHLRRMESGFGFRILGG-DEPGQPIL-IGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARN 893
Cdd:cd06751      1 LLTVELSKMKQSLGISISGGiESKVQPVVkIEKIFPGGAAALSGNLKAGYELVSVDGESLQQVTHQQAVDIIRRAYSN 78

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.

Pssm-ID: 467184 [Multi-domain] Cd Length: 89 Bit Score: 48.84 E-value: 6.22e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1198 GFGFSIRGG--REYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTH--ARAI 1253
Cdd:cd06698     12 GLGLSIVGGinRPEGPMVFIQEVIPGGDCYKDGRLRPGDQLVSINKESLIGVTLeeAKSI 71

PDZ domain 3 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 3 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 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.

Pssm-ID: 467167 [Multi-domain] Cd Length: 88 Bit Score: 48.79 E-value: 6.54e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034657569 1200 GFSIRGGR---EYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06679     14 GISVAGGRgsrRGDLPIYVTNVQPDGCLGRDGRIKKGDVLLSINGISLTNLSHSEAVAVLKA 75

PDZ domain 9 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 9 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 PDZ9 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 PDZ9 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.

Pssm-ID: 467263 [Multi-domain] Cd Length: 79 Bit Score: 48.50 E-value: 6.73e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  821 VHLRRMESGFGFRILGGD-EPGqpILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAarNGQVNLT 899
Cdd:cd10817      2 VELPKDQGGLGIAISEEDtENG--IVIKSLTEGGPAAKDGRLKVGDQILAVDDESVVGCPYEKAISLLKTA--KGTVKLT 77


                   ..
gi 1034657569  900 VR 901
Cdd:cd10817     78 VS 79

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

Pssm-ID: 395476 [Multi-domain] Cd Length: 81 Bit Score: 48.05 E-value: 8.04e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  647 TLTIVKGAQG-FGFTIA----DSPTGQRVKQILdiQGCP----GLCEGDLIVEINQQNVQNLSHTEVVDILKdcPIGSET 717
Cdd:pfam00595    1 QVTLEKDGRGgLGFSLKggsdQGDPGIFVSEVL--PGGAaeagGLKVGDRILSINGQDVENMTHEEAVLALK--GSGGKV 76


                   ....
gi 1034657569  718 SLII 721
Cdd:pfam00595   77 TLTI 80

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.

Pssm-ID: 467209 [Multi-domain] Cd Length: 87 Bit Score: 48.42 E-value: 8.09e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  469 TTLKKSNMGFGFTIIGG-DEP-----DEFLQVKSVIPDGPAaqDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQ 542
Cdd:cd06727      4 TLHRAPGFGFGIAVSGGrDNPhfqsgDTSIVISDVLKGGPA--EGKLQENDRVVSVNGVSMENVEHSFAVQILRKC--GK 79


                   ....*...
gi 1034657569  543 SVNLVLCR 550
Cdd:cd06727     80 TANITVKR 87

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

Pssm-ID: 440513 [Multi-domain] Cd Length: 349 Bit Score: 53.17 E-value: 8.11e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034657569  973 FGFVIISSLNRPeSGSTITVPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMphADIVKLIKD-AGLSVTLRI 1048
Cdd:COG0750    110 LAIVLFAVLFMT-VGVPVLTPPVVGEVVPGSPAAK-AGLQPGDRIVAINGQPVTSW--DDLVDIIRAsPGKPLTLTV 182

PDZ domain of MYO18A protein, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MYO18 protein and related domains. MYO18 (also known as myosin XVIIIA, KIAA0216, MysPDZ), a member of the myosin superfamily, is involved in regulating cell protrusion and migration, and Golgi trafficking and morphology, and is required for myoblast adhesion and muscle integrity. The MYO18A/MRCK/LRAP35a complex regulates actomyosin retrograde flow in cell protrusion and migration; the PtdIns(4)P/GOLPH3/MYO18A/F-actin complex is a hub for signals that regulate Golgi trafficking function. The MYO18A PDZ domain binds p190Rho-guanine nucleotide exchange factor (p190RhoGEF), Golgin45, and leucine repeat adaptor protein 1 (Lurap1, also known as Lrap35a). 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 MYO18-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467229 [Multi-domain] Cd Length: 90 Bit Score: 48.08 E-value: 1.06e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  962 DVVIHRKENEGFGFviisSLNR---PESGSTITVPHKigRII-----DGSPADRCAKLKVGDRILAVNGQSIINMPHADI 1033
Cdd:cd06747      1 EITLKRQPTGDFGF----SLRRgtiVERGPDDGQELK--RTVhfaepGAGTKNLATGLLPGDRLIEVNGVNVENASRDEI 74

                           90
                   ....*....|....*
gi 1034657569 1034 VKLIKDAGLSVTLRI 1048
Cdd:cd06747     75 IEMIRKSGDTVTLKV 89

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

Pssm-ID: 395476 [Multi-domain] Cd Length: 81 Bit Score: 47.66 E-value: 1.08e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569  828 SGFGFRILGG-DEPGQPILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLMHHAarNGQVNLTVR 901
Cdd:pfam00595   10 GGLGFSLKGGsDQGDPGIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGS--GGKVTLTIL 81

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.

Pssm-ID: 467250 [Multi-domain] Cd Length: 75 Bit Score: 47.63 E-value: 1.09e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  962 DVVIHRKENEGFGFVIISSLnrpesgstitvPHKIGRIIDGSPADrcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:cd06769      1 TVEIQRDAVLGFGFVAGSER-----------PVVVRSVTPGGPSE--GKLLPGDQILKINNEPVEDLPRERVIDLIRECK 67


                   ....*...
gi 1034657569 1042 LSVTLRII 1049
Cdd:cd06769     68 DSIVLTVL 75

PDZ domain 9 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 9 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 PDZ9 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 PDZ9 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.

Pssm-ID: 467263 [Multi-domain] Cd Length: 79 Bit Score: 47.73 E-value: 1.21e-06

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gi 1034657569 1189 TVDMEKGAKGFGFSIRGGrEYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd10817      1 HVELPKDQGGLGIAISEE-DTENGIVIKSLTEGGPAAKDGRLKVGDQILAVDDESVVGCPYEKAISLLKTAKGTVKL 76

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.

Pssm-ID: 467244 [Multi-domain] Cd Length: 86 Bit Score: 47.99 E-value: 1.26e-06

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gi 1034657569  819 LDVHLRRMESGFGFRILGG-DEP--GQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTH 880
Cdd:cd06763      2 VTVELEKGSAGLGFSLEGGkGSPlgDRPLTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLTR 66

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467228 [Multi-domain] Cd Length: 101 Bit Score: 48.36 E-value: 1.31e-06

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gi 1034657569  815 DYKELDVHLRRMESGFGFrILGGDEPGQPIL-------------IGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHR 881
Cdd:cd06746      3 IIDPRTVVLQKGDKGFGF-VLRGAKAVGPILeftptpafpalqyLESVDPGGVADKAG-LKKGDFLLEINGEDVVKASHE 80

                           90
                   ....*....|....*....
gi 1034657569  882 YVIDLMHHAarNGQVNLTV 900
Cdd:cd06746     81 QVVNLIRQS--GNTLVLKV 97

PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight junction (PATJ, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 12 of MUPP1, PDZ domain 10 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 PDZ12 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

Pssm-ID: 467163 [Multi-domain] Cd Length: 86 Bit Score: 47.74 E-value: 1.34e-06

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gi 1034657569  472 KKSNMGFGFTIIGG------DEPdefLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKL 534
Cdd:cd06675      7 RGPQDSLGISIAGGvgsplgDVP---VFIAMIQPNGVAAQTGKLKVGDRIVSINGQSTDGLTHSEAVNL 72

PDZ domain 1 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 1 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. 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 PDZ1 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.

Pssm-ID: 467213 [Multi-domain] Cd Length: 85 Bit Score: 47.59 E-value: 1.37e-06

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gi 1034657569  967 RKENEGFGFVIISSLNRPESgstitvpHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKL 1036
Cdd:cd06731      7 KKSARGFGFTIIGGDEPDEF-------LQIKSVVPDGPAALDGKLRTGDVLVSVNDTCVLGYTHADVVKL 69

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.

Pssm-ID: 467179 [Multi-domain] Cd Length: 88 Bit Score: 47.60 E-value: 1.38e-06

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gi 1034657569  821 VHLRRMESGFGFRILGGDEPGQP----ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARNGQV 896
Cdd:cd06692      1 IEFSDCSKGLGIKIIGGYRENTGeefgIFIKRILPGGLAATDGRLKEGDLILEVNGESLQGVTNERAVSILRSASASNHM 80


                   ....*.
gi 1034657569  897 NLTVRR 902
Cdd:cd06692     81 SLLIAR 86

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467226 [Multi-domain] Cd Length: 75 Bit Score: 47.27 E-value: 1.39e-06

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gi 1034657569  821 VHLRRMESGFGFrILGGDepgQPILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLMH 888
Cdd:cd06744      2 VRVYRGNGSFGF-TLRGH---APVYIESVDPGSAAERAG-LKPGDRILFLNGLDVRNCSHDKVVSLLQ 64

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.

Pssm-ID: 467162 [Multi-domain] Cd Length: 87 Bit Score: 47.66 E-value: 1.46e-06

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gi 1034657569  962 DVVIHRKENEGFGFVIISSLNrpESGSTITvphkigRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:cd06674      5 TVELQKKPGRGLGLSIVGKRN--DTGVFVS------DIVKGGAADADGRLMQGDQILSVNGEDVRNASQEAAAALLKCAQ 76


                   ....*..
gi 1034657569 1042 LSVTLRI 1048
Cdd:cd06674     77 GKVRLEV 83

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

Pssm-ID: 467623 [Multi-domain] Cd Length: 88 Bit Score: 47.48 E-value: 1.51e-06

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gi 1034657569  487 EPDEFLQVKSVIPDGPAAQDGKMEtGDVIVYINEVCVLGHTHADVVKLFQSvPIGQSVNLVLCRG 551
Cdd:cd06782     11 DDDGYLVVVSPIPGGPAEKAGIKP-GDVIVAVDGESVRGMSLDEVVKLLRG-PKGTKVKLTIRRG 73

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.

Pssm-ID: 467284 [Multi-domain] Cd Length: 92 Bit Score: 47.87 E-value: 1.53e-06

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gi 1034657569  963 VVIHRKENEGFGFVIISSLNRPESGSTITvphkIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd23071      5 VTLKRDPKRGFGFVIVGGENTGKLDLGIF----IASIIPGGPAEKDGRIKPGGRLISLNNISLEGVTFNTAVKILQNSPD 80

                           90
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gi 1034657569 1043 SVTLrIIPQEE 1053
Cdd:cd23071     81 EVEL-IISQPK 90

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). 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 shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467232 [Multi-domain] Cd Length: 82 Bit Score: 47.33 E-value: 1.72e-06

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gi 1034657569  831 GFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGkTHRYVIDLMHHAARNgqVNLTVRR 902
Cdd:cd06750     14 GFTLKGGLEHGEPLVISKIEEGGKAASVGKLQVGDEVVNINGVPLSG-SRQEAIQLVKGSHKT--LKLVVRR 82

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.

Pssm-ID: 467284 [Multi-domain] Cd Length: 92 Bit Score: 47.49 E-value: 2.08e-06

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gi 1034657569 1196 AKGFGFSIRGGrEY--KMDL--YVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLL 1267
Cdd:cd23071     12 KRGFGFVIVGG-ENtgKLDLgiFIASIIPGGPAEKDGRIKPGGRLISLNNISLEGVTFNTAVKILQNSPDEVELII 86

PDZ domain of membrane palmitoylated protein1 (MPP1), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1, and related domains. MPP1 (also known as MAGUK p55 subfamily member 1, erythrocyte membrane protein p55, EMP55) is a membrane-associated guanylate kinase (MAGUK)-like protein which forms a complex with protein 4.1 and glycophorin C (GPC) at the cytoplasmic face of the plasma membrane; this complex is essential for cytoskeleton-membrane linkage in erythrocytes and many non-erythroid cells, and participates in the determination of membrane stability and cell shape. MPP1, by interacting with various scaffold proteins and cytoskeletal proteins in the postsynaptic density, also plays an important role in organizing synaptic and non-synaptic structures. MPP1 is also a component of the Crumbs protein complex in the mammalian retina and may link the Usher protein network and the Crumbs protein complex. The MPP1 PDZ domain binding partners include GPC, ABCC4, and CADM1/Necl-2/SynCAM1. 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 MPP1-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.

Pssm-ID: 467266 [Multi-domain] Cd Length: 81 Bit Score: 47.17 E-value: 2.11e-06

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gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRIIP 1050
Cdd:cd10830     27 VARILHGGMIHRQGSLHVGDEILEINGKSVTNHSVDQLQKMLKETKGMVSLKVIP 81

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. 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 harmonin 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.

Pssm-ID: 467219 [Multi-domain] Cd Length: 85 Bit Score: 47.25 E-value: 2.17e-06

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gi 1034657569  817 KELDVHL-RRMESGFGFRILGGDEPGQPILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLM 887
Cdd:cd06737      1 KLRLVRLdRRGPESLGFSVRGGLEHGCGLFVSHVSPGSQADNKG-LRVGDEIVRINGYSISQCTHEEVINLI 71

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.

Pssm-ID: 467253 [Multi-domain] Cd Length: 89 Bit Score: 47.23 E-value: 2.18e-06

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gi 1034657569  968 KENEGFGFVIISSLNRPESG--STITVPHkigrIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVT 1045
Cdd:cd06791      9 KDEQGLGITIAGYVGEKASGelSGIFVKS----IIPGSAADQDGRIQVNDQIIAVDGVNLQGFTNQEAVEVLRNTGQVVH 84


                   ....
gi 1034657569 1046 LRII 1049
Cdd:cd06791     85 LTLA 88

PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. 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 PDZRN4-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.

Pssm-ID: 467200 [Multi-domain] Cd Length: 88 Bit Score: 47.27 E-value: 2.36e-06

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gi 1034657569 1212 DLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHarAIELIKSGGRRVRLLLKR 1269
Cdd:cd06716     32 GIYVSEVDPNSIAAKDGRIREGDQILQINGVDVQNREE--AIALLSEEEKSITLLVAR 87

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.

Pssm-ID: 467161 [Multi-domain] Cd Length: 86 Bit Score: 46.90 E-value: 2.67e-06

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gi 1034657569  473 KSNMGFGFTIIGG-DEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPigQSVNLVLCR 550
Cdd:cd06673     10 KGKKGLGLSIVGGsDTLLGAIIIHEVYEDGAAAKDGRLWAGDQILEVNGEDLRKATHDEAINVLRQTP--QKVRLLVYR 86

PDZ domain 4 of PDZ domain containing 2 (PDZD2), PDZ domain 2 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 4 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the second PDZ domain (PDZ2) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). 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 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.

Pssm-ID: 467241 [Multi-domain] Cd Length: 90 Bit Score: 46.88 E-value: 2.69e-06

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gi 1034657569  962 DVVIHRKENEGFGfVIISSLNRPESGSTITVPHkigrIIDGSPADRCAKLKVGDRILAVNGQSIINM 1028
Cdd:cd06760      6 EVTLNKEPGVGLG-IGLCCLPLENDIPGIFIHH----LSPGSVAHMDGRLRRGDQILEINGTSLRNV 67

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

Pssm-ID: 467155 [Multi-domain] Cd Length: 80 Bit Score: 46.51 E-value: 2.88e-06

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gi 1034657569 1198 GFGFSIRGGREYKMdlYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLKR 1269
Cdd:cd06667     11 GLGFGIVGGKSTGV--VVKTILPGGVADRDGRLRSGDHILQIGDTNLRGMGSEQVAQVLRQCGSHVRLVVAR 80

PDZ domain 2 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 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.

Pssm-ID: 467207 [Multi-domain] Cd Length: 85 Bit Score: 46.88 E-value: 3.06e-06

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gi 1034657569  470 TLKKSNMGFGFTIIGGD-----EPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSvpIGQSV 544
Cdd:cd06724      3 KLVKGPKGLGFSIAGGVgnqhiPGDNGIYVTKIIEGGAAQKDGRLQVGDKLLAVNDVSLEEVTHEEAVAALKN--TSDVV 80


                   ....
gi 1034657569  545 NLVL 548
Cdd:cd06724     81 YLKV 84

PDZ domain 3 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 3 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 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.

Pssm-ID: 467167 [Multi-domain] Cd Length: 88 Bit Score: 46.48 E-value: 3.38e-06

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gi 1034657569  469 TTLKKSNMGFGFTIIGG------DEPdefLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPIGQ 542
Cdd:cd06679      4 TIKKEPSESLGISVAGGrgsrrgDLP---IYVTNVQPDGCLGRDGRIKKGDVLLSINGISLTNLSHSEAVAVLKASAASS 80


                   ....
gi 1034657569  543 SVNL 546
Cdd:cd06679     81 SIVL 84

PDZ domain 3 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 3 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 Par-3 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 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.

Pssm-ID: 467272 [Multi-domain] Cd Length: 103 Bit Score: 46.89 E-value: 3.56e-06

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gi 1034657569  844 ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARN-----GQVNLTVRRK 903
Cdd:cd23059     39 IFIKSIIHGGAASKDGRLRVNDQLIAVNGESLLGLTNSEAMETLRRAMSTegnirGMIQLVVARR 103

PDZ domain 4 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 4 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 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

Pssm-ID: 467156 [Multi-domain] Cd Length: 88 Bit Score: 46.52 E-value: 3.57e-06

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gi 1034657569 1196 AKGFGFSIRG--GREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLKR 1269
Cdd:cd06668     13 SSGLGISLEGtvDVEVRGHHYIRSILPEGPVGRNGKLFSGDELLEVNGIQLLGLSHKEVVSILKELPPPVRLVCCR 88

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 3 (MAST3); PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST3, and related domains. MAST3 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST3 plays a critical role in regulating the immune response of inflammatory bowel disease (IBD), and is involved in the process of cytoskeleton organization, intracellular signal transduction and peptidyl-serine phosphorylation. MAST3 also promotes the proliferation and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis. Binding partners of MAST3 include cAMP-regulated phosphoprotein (ARPP-16) and the tumor suppressor 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 MAST3 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.

Pssm-ID: 467288 [Multi-domain] Cd Length: 94 Bit Score: 46.56 E-value: 4.11e-06

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gi 1034657569 1192 MEKGAKGFGFSIRGGREY--KMDLYVLR----LAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd23075      7 IHSSGKKYGFTLRAIRVYmgDSDVYTVHhmvwSVEDGSPAQEAGLRAGDLITHINGESVLGLVHMDVVELLLKSGNKVSL 86

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.

Pssm-ID: 467250 [Multi-domain] Cd Length: 75 Bit Score: 45.70 E-value: 5.13e-06

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gi 1034657569  472 KKSNMGFGFTIiGGDEPdefLQVKSVIPDGPAaqDGKMETGDVIVYINEVCV 523
Cdd:cd06769      6 RDAVLGFGFVA-GSERP---VVVRSVTPGGPS--EGKLLPGDQILKINNEPV 51

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.

Pssm-ID: 467186 [Multi-domain] Cd Length: 89 Bit Score: 46.10 E-value: 5.20e-06

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gi 1034657569 1190 VDMEKGAKGFGFSIRGGREY--------KMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGR 1261
Cdd:cd06702      3 IHLVKAGGPLGLSIVGGSDHsshpfgvdEPGIFISKVIPDGAAAKSG-LRIGDRILSVNGKDLRHATHQEAVSALLSPGQ 81


                   ....*...
gi 1034657569 1262 RVRLLLKR 1269
Cdd:cd06702     82 EIKLLVRH 89

PDZ domain 1 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 1 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 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.

Pssm-ID: 467176 [Multi-domain] Cd Length: 102 Bit Score: 46.47 E-value: 5.31e-06

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gi 1034657569 1189 TVDMEKGA-KGFGFSIRGGREY---KMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGES-TRDMTHARAIELIKSGGRRV 1263
Cdd:cd06689     17 YIELEKPEsGGLGFSVVGLKSEnrgELGIFVQEIQPGSVAARDGRLKENDQILAINGQPlDQSISHQQAIAILQQAKGSV 96


                   ....*.
gi 1034657569 1264 RLLLKR 1269
Cdd:cd06689     97 ELVVAR 102

PDZ domain 7 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467173 [Multi-domain] Cd Length: 85 Bit Score: 46.09 E-value: 5.34e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGReYKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLL 1267
Cdd:cd06685      6 VTLYKDSDTEDFGFSVSDGL-YEKGVYVNAIRPGGPADLSG-LQPYDRILQVNHVRTRDFDCCLVVPLIAESGDKLELVV 83


                   ..
gi 1034657569 1268 KR 1269
Cdd:cd06685     84 SR 85

PDZ domain of afadin (AFDN), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of afadin (AFDN, also known as ALL1-fused gene from chromosome 6 protein (AF6) and MLLT4), and related domains. AFDN belongs to the adhesion system, probably together with the E-cadherin-catenin system, that plays a role in the organization of homotypic, interneuronal, and heterotypic cell-cell adherens junctions. The AFDN PDZ domain interaction partners include poliovirus receptor-related protein PRR2/nectin, the junctional adhesion molecule (JAM), the breakpoint-cluster-region protein (BCR), connexin36 (Cx36), and a subset of Eph-related receptor tyrosine kinases; it can also bind low molecular weight ligands, in competition with a natural peptide ligand. Other AFDN-binding proteins have been identified. 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 AFDN 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.

Pssm-ID: 467251 [Multi-domain] Cd Length: 89 Bit Score: 46.13 E-value: 5.46e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  470 TLKKSNMGFGFTIIG--GDEPDEF-LQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNL 546
Cdd:cd06789      7 TLKKVGNGMGLSIVAakGAGQDKLgIYIKSVVKGGAADLDGRLQAGDQLLSVDGHSLVGLSQERAAELMTKT--GSVVTL 84

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467196 [Multi-domain] Cd Length: 78 Bit Score: 45.65 E-value: 5.46e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  820 DVHLRRMESGFGFRILGgdepGQPILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLMhHAARNGQVNLT 899
Cdd:cd06712      3 TVHLTKEEGGFGFTLRG----DSPVQVASVDPGSCAAEAG-LKEGDYIVSVGGVDCKWSKHSEVVKLL-KSAGEEGLELQ 76


                   .
gi 1034657569  900 V 900
Cdd:cd06712     77 V 77

PDZ domain 4 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 4 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. 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 PDZ4 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.

Pssm-ID: 467216 [Multi-domain] Cd Length: 84 Bit Score: 46.07 E-value: 5.51e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034657569  655 QGFGFTIADSPTGQRVKQILDIQ-GCPG-----LCEGDLIVEINQQNVQNLSHTEVVDILKD 710
Cdd:cd06734     12 EGFGFVIISSVNKKSGSKIGRIIpGSPAdrcgqLKVGDRILAVNGISILNLSHGDIVNLIKD 73

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

Pssm-ID: 440556 [Multi-domain] Cd Length: 341 Bit Score: 50.25 E-value: 5.61e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  812 SGPDYKELDVHLRRMESGFGFRIlgGDEPGQpILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLMHHAA 891
Cdd:COG0793     44 DPEEYEDFQESTSGEFGGLGAEL--GEEDGK-VVVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGKA 119

                           90
                   ....*....|..
gi 1034657569  892 rNGQVNLTVRRK 903
Cdd:COG0793    120 -GTKVTLTIKRP 130

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

Pssm-ID: 467623 [Multi-domain] Cd Length: 88 Bit Score: 45.94 E-value: 5.83e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034657569  835 LGGDEPGQPILIgAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLMhhaaR---NGQVNLTVRRK 903
Cdd:cd06782      8 IGKDDDGYLVVV-SPIPGGPAEKAG-IKPGDVIVAVDGESVRGMSLDEVVKLL----RgpkGTKVKLTIRRG 73

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467226 [Multi-domain] Cd Length: 75 Bit Score: 45.73 E-value: 5.94e-06

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  468 STTLKKSNMGFGFTIiGGDEPdefLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNLV 547
Cdd:cd06744      1 TVRVYRGNGSFGFTL-RGHAP---VYIESVDPGSAAERAG-LKPGDRILFLNGLDVRNCSHDKVVSLLQGS--GSMPTLV 73


                   ..
gi 1034657569  548 LC 549
Cdd:cd06744     74 VE 75

permuted PDZ domain of Deg/high-temperature requirement factor A (HtrA) family of housekeeping serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Deg/HtrA-type serine proteases that participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. Typically, these proteases have an N-terminal serine protease domain and at least one C-terminal PDZ domain that recognizes substrates, and in some cases activates the protease function. An exception is yeast Nma11p which has two protease domains and four PDZ domains; its N-terminal half is comprised of a protease domain, followed by two PDZ domains, and its C-terminal half has a similar domain arrangement. HtrA-type proteases include the human HtrA1-4 and MBTPS2, tricorn protease, DegS, DegP and C-terminal processing peptidase, cyanobacterial serine proteases Hhoa, HhoB, and HtrA, and yeast Nma11p. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-termini of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This Deg/HtrA family PDZ domain is a circularly permuted PDZ domain which places beta-strand A at the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467621 [Multi-domain] Cd Length: 91 Bit Score: 46.13 E-value: 6.00e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1034657569  996 IGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRII 1049
Cdd:cd06779     29 VAEVIPGSPAAK-AGLKEGDVILSVNGKPVTSFNDLRAALDTKKPGDSLNLTIL 81

PDZ domain 4 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 4 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 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

Pssm-ID: 467156 [Multi-domain] Cd Length: 88 Bit Score: 45.75 E-value: 6.87e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1034657569  994 HKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTL 1046
Cdd:cd06668     32 HYIRSILPEGPVGRNGKLFSGDELLEVNGIQLLGLSHKEVVSILKELPPPVRL 84

PDZ domain of ARHGAP21 and ARHGAP23, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGAP21, ARHGAP23, and related domains. This subfamily includes the GAPs (GTPase activating proteins): ARHGAP21 (Rho GTPase-activating protein 21; also known as Rho GTPase-activating protein 10, Rho-type GTPase-activating protein 21) and ARHGAP23 (Rho GTPase-activating protein 23; also known as Rho-type GTPase-activating protein 23). GAPs deactivate Rho GTPases by accelerating GTP hydrolysis. ARHGAP21/23 interact with a planar cell polarity (PCP) protein Pk1 to regulate a lateral signaling pathway in migrating cells. The ARHGAP21 PDZ domain binds claudin-2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGAP21-23-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467238 [Multi-domain] Cd Length: 109 Bit Score: 46.30 E-value: 7.41e-06

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1189 TVDMEKGAKGFGFSIR--------------------GGREYK-------MD-LYVLRLAEDGPAIRNGrMRVGDQIIEIN 1240
Cdd:cd06756      3 TVTLQRTSQGFGFTLRhfivyppesavheslkdeenGNRGGKqrsrlepMDtIFVKQVKEGGPAHQAG-LCTGDRIVKVN 81

                           90
                   ....*....|....*..
gi 1034657569 1241 GESTRDMTHARAIELIK 1257
Cdd:cd06756     82 GESVIGKTYSQVIALIQ 98

PDZ domain 2 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 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.

Pssm-ID: 467187 [Multi-domain] Cd Length: 92 Bit Score: 45.71 E-value: 7.58e-06

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  823 LRRMESGFGFRILGG--------DEPGqpILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARng 894
Cdd:cd06703      7 LIRDGKGLGFSIAGGkgstpfrdGDEG--IFISRITEGGAADRDGKLQVGDRVLSINGVDVTEARHDQAVALLTSSSP-- 82


                   ....*....
gi 1034657569  895 QVNLTVRRK 903
Cdd:cd06703     83 TITLVVERE 91

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. 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 RIM-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.

Pssm-ID: 467198 [Multi-domain] Cd Length: 95 Bit Score: 46.01 E-value: 7.83e-06

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gi 1034657569  827 ESGFGFRILGGD--EPGQpilIGAVIAM----GSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAarNGQVNLTV 900
Cdd:cd06714     20 GNGLGLKVVGGKmtESGR---LGAYVTKvkpgSVADTVGHLREGDEVLEWNGISLQGKTFEEVQDIISQS--KGEVELVV 94


                   .
gi 1034657569  901 R 901
Cdd:cd06714     95 S 95

PDZ domain 1 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 1 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 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.

Pssm-ID: 467165 [Multi-domain] Cd Length: 89 Bit Score: 45.70 E-value: 7.90e-06

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gi 1034657569  831 GFRILGG-DEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAArnGQVNLTVRR 902
Cdd:cd06677     18 GISIVGGnDTPLINIVIQEVYRDGVIARDGRLLPGDQILEVNGVDISNVTHSQARSVLRQPC--PVLRLTVLR 88

PDZ domain 3 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 3 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 Par-3 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 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.

Pssm-ID: 467272 [Multi-domain] Cd Length: 103 Bit Score: 46.12 E-value: 8.47e-06

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gi 1034657569 1193 EKGAKGFGFSIRG-----GREYKMDL--YVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIK-----SGG 1260
Cdd:cd23059     12 DTGSAGLGVSVKGktskeDNGGKADLgiFIKSIIHGGAASKDGRLRVNDQLIAVNGESLLGLTNSEAMETLRramstEGN 91

                           90
                   ....*....|.
gi 1034657569 1261 RR--VRLLLKR 1269
Cdd:cd23059     92 IRgmIQLVVAR 102

PDZ domain 4 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 4 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 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.

Pssm-ID: 467182 [Multi-domain] Cd Length: 85 Bit Score: 45.38 E-value: 9.17e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  818 ELDVHLRRMESG-FGFRILGGDEPGQpILIGAVIAmGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARngQV 896
Cdd:cd06696      3 ELEVTLTKSEKGsLGFTVTKGKDDNG-CYIHDIVQ-DPAKSDGRLRPGDRLIMVNGVDVTNMSHTEAVSLLRAAPK--EV 78


                   ....*.
gi 1034657569  897 NLTVRR 902
Cdd:cd06696     79 TLVLGR 84

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467194 [Multi-domain] Cd Length: 76 Bit Score: 44.93 E-value: 9.66e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569  821 VHLRRMESGFGFRILGGdepgQPILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDL 886
Cdd:cd06710      3 VEIARGRAGYGFTISGQ----APCVLSCVVRGSPADVAG-LKAGDQILAVNGINVSKASHEDVVKL 63

PDZ domain 8 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 7 of protein-associated tight junction (PATJ), PDZ domain 2 of Drosophila melanogaster inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 8 of MUPP1, PDZ domain 7 of PATJ, and PDZ domain 2 of Drosophila melanogaster INAD, 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. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C. 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 PDZ8 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.

Pssm-ID: 467160 [Multi-domain] Cd Length: 84 Bit Score: 45.36 E-value: 1.01e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569  821 VHLRRMESGFGFRILGG-DEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTH 880
Cdd:cd06672      4 IELEKGSSGLGLSLAGNkDRSRMSVFVVGIDPDGAAGKDGRIQVGDELLEINGQVLYGRSH 64

PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and GIPC3 (also known as C19orf64) constitute the GIPC family. These proteins contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc1 and Gipc2 genes have been linked to cancer, while mutations in the Gipc3 gene cause nonsyndromic hearing loss. 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 GIPC 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.

Pssm-ID: 467191 [Multi-domain] Cd Length: 89 Bit Score: 45.30 E-value: 1.12e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKD--AGLSVTLRII 1049
Cdd:cd06707     30 IKRIKEGSIMDKVPAICVGDHIEKINGESLVGCRHYEVARMLKEipIGETFTLRLV 85

PDZ domain 3 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467172 [Multi-domain] Cd Length: 87 Bit Score: 45.32 E-value: 1.13e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVT-LRIIP 1050
Cdd:cd06684     32 IDSIKPASIADRCGALHVGDHILSIDGTSVEHCSLAEATQLLASNSGDQVkLEILP 87

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.

Pssm-ID: 467209 [Multi-domain] Cd Length: 87 Bit Score: 44.96 E-value: 1.21e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  647 TLTIVKgAQGFGFTIA-----DSP---TGQRVKQILD-IQGCPG---LCEGDLIVEINQQNVQNLSHTEVVDILKDCpiG 714
Cdd:cd06727      2 TVTLHR-APGFGFGIAvsggrDNPhfqSGDTSIVISDvLKGGPAegkLQENDRVVSVNGVSMENVEHSFAVQILRKC--G 78


                   ....*....
gi 1034657569  715 SETSLIIHR 723
Cdd:cd06727     79 KTANITVKR 87

PDZ domain of the microtubule-associated serine-threonine (MAST) protein kinase family; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinases, including MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. The PDZ domain gives the MAST family the capacity to scaffold its own kinase activity. These kinases are implicated in the inhibition of neurite outgrowth and regeneration in cultured cells. Their binding partners include microtubules, beta2-syntrophin, TNF receptor-associated factor 6 (TRAF6), cAMP-regulated phosphoprotein (ARPP-16), and PTEN. This family also includes Caenorhabditis elegans KIN-4 MAST kinase, a key longevity factor acting through binding PTEN phosphatase, and Drosophila Drop out which regulates dynein-dependent transport during embryonic development. 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 MAST-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.

Pssm-ID: 467189 [Multi-domain] Cd Length: 93 Bit Score: 45.31 E-value: 1.23e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569  647 TLTIVKGAQGFGFTI---------ADSPTGQRVKQILDiQGCP----GLCEGDLIVEINQQNVQNLSHTEVVD-ILKD 710
Cdd:cd06705      4 PIVIKKGPRGFGFTLrairvyigdSDVYTVHHLVTAVE-EGSPayeaGLRPGDLITHVNGEPVQGLLHTQVVQlILKG 80

PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467181 [Multi-domain] Cd Length: 90 Bit Score: 44.94 E-value: 1.28e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  649 TIVKGAQGFGFTIA---DSPTGQRVKQILDIQGC-PG--------LCEGDLIVEINQQNVQNLSHTEVVDILKDCPigSE 716
Cdd:cd06695      5 KLTKGSSGLGFSFLggeNNSPEDPFSGLVRIKKLfPGqpaaesglIQEGDVILAVNGEPLKGLSYQEVLSLLRGAP--PE 82


                   ....*..
gi 1034657569  717 TSLIIHR 723
Cdd:cd06695     83 VTLLLCR 89

PDZ domain 5 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family domain PDZ5 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.

Pssm-ID: 467170 [Multi-domain] Cd Length: 85 Bit Score: 45.03 E-value: 1.30e-05

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gi 1034657569  962 DVVIHRKENEGFGFVIISSLNRPESGSTItvphkIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAG 1041
Cdd:cd06682      2 HVKLPKRSGVGLGITISAPKNRKPGDPLI-----ISDVKKGSVAHRTGTLEPGDKLLAIDNIRLDNCSMEDAAQILQQAE 76


                   ....*..
gi 1034657569 1042 LSVTLRI 1048
Cdd:cd06682     77 DIVKLKI 83

PDZ domain of PICK1 (protein interacting with C-kinase 1) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PICK1, and related domains. PICK1 (also known as PRKCA-binding protein and protein kinase C-alpha-binding protein) plays a key role in regulating trafficking of binding partners by altering either their subcellular targeting and/or surface expression. PICK1 plays a role in synaptic plasticity by regulating the trafficking and internalization of amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors; the PICK1-PDZ domain binds the AMPA receptor subunits. The PICK1 PDZ domain also binds glutamate transporters, Eph receptors, metabotropic glutamate receptors, and ASICs (acid-sensing ion channels), among others. Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes. 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 PICK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467205 [Multi-domain] Cd Length: 84 Bit Score: 44.71 E-value: 1.32e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034657569  468 STTLKKSNMGF-GFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSV 538
Cdd:cd06722      2 TVTLKKDAQNLiGISIGGGAPYCPCLYIVQVFDNTPAAKDGTLAAGDEIVGVNGKSVKGKTKVEVAKMIQAV 73

PDZ domain of densin, erbin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of densin, erbin, and related domains. Densin (also known as leucine-rich repeat-containing protein 7, LRRC7, densin-180, protein LAP1) and erbin (also known as densin-180-like protein, Erbb2-interacting protein, protein LAP2) belong to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play roles in the maintenance of cell shape and apical-basal polarity. Densin and erbin are components of the excitatory postsynaptic compartment and are regulators of dendritic morphology and postsynaptic structure. The densin PDZ domain binds CaV1.3 alpha1 subunit, delta-catenin, and MAGUIN-1. Binding partners of the erbin PDZ domain include ErbB receptor tyrosine kinase ErbB2, HTLV-1 Tax1, Cav1.3 Ca2+channels, and constituents of the cadherin:catenin cell adhesion complex, in particular delta-catenin, p0071 and ARVCF. The erbin PDZ domain binds Smad3, a transductor of the TGFbeta pathway, possibly by a novel interface of binding. Erbin and two other LAP proteins (scribble and lano) redundantly regulate epithelial polarity and apical adhesion 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 densin and erbin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467231 [Multi-domain] Cd Length: 87 Bit Score: 45.01 E-value: 1.37e-05

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gi 1034657569  968 KENEGFGFVIISSLN------RPE-SGSTITvphkigRIIDGSPADRCakLKVGDRILAVNGQSIINMPHADIVKLIKDA 1040
Cdd:cd06749      6 EKNPGLGFSISGGIGsqgnpfRPDdDGIFVT------KVQPDGPASKL--LQPGDKILEVNGYDFVNIEHGQAVSLLKSF 77


                   ....*...
gi 1034657569 1041 GLSVTLRI 1048
Cdd:cd06749     78 QNTVDLVV 85

PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP5, Drosophila Stardust, and related domains. MPP5 (also known as MAGUK p55 subfamily member 1, protein associated with Lin-7 1 or PALS1) and Drosophila Stardust are membrane-associated guanylate kinase (MAGUK)-like proteins that serve as signaling and scaffolding proteins, linking different proteins critical to the formation and maintenance of tight junctions (TJ) and apical-basal polarity. Apical-basal polarity determinants cluster in complexes; in particular, the Crumbs complex (Crb, MPP5, and PATJ) and the PAR/aPKC-complex (PAR-3, PAR-6, aPKC) determine the apical plasma membrane domain. Within the Crumbs complex, Crb is stabilized in the plasma membrane by MPP5, which in turn recruits PATJ and Lin-7 to the complex. MPP5 also links the Crumbs complex with the PAR/aPKC-complex. The Drosophila homolog of the Crumbs complex is the (CRB)-Stardust (Sdt)-Discs Lost (Dlt) complex. MPP5 also acts as an interaction partner for SARS-CoV envelope protein E, which results in delayed formation of TJs and dysregulation 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 MPP5-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.

Pssm-ID: 467259 [Multi-domain] Cd Length: 79 Bit Score: 44.64 E-value: 1.43e-05

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gi 1034657569  841 GQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLM 887
Cdd:cd06798     20 GDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIRGKDVNEVCDLL 66

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.

Pssm-ID: 467193 [Multi-domain] Cd Length: 86 Bit Score: 44.59 E-value: 1.55e-05

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gi 1034657569  647 TLTIVKGAQGFGFTI---ADSP-----TGQRVKQI-----LDIQGcpGLCEGDLIVEINQQNVQNLSHTEVVDILKDcpI 713
Cdd:cd06709      2 EITLKRGPSGLGFNIvggTDQPyipndSGIYVAKIkedgaAAIDG--RLQEGDKILEINGQSLENLTHQDAVELFRN--A 77


                   ....*...
gi 1034657569  714 GSETSLII 721
Cdd:cd06709     78 GEDVKLKV 85

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. 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 Par6-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.

Pssm-ID: 467202 [Multi-domain] Cd Length: 84 Bit Score: 44.48 E-value: 1.57e-05

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gi 1034657569  830 FGFRILGGD--EPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMhhaARNGQVNLTVRR 902
Cdd:cd06718     13 LGFYIRDGNgvERVPGIFISRLVLGSLADSTGLLAVGDEILEVNGVEVTGKSLDDVTDMM---VAPTRLIITVKP 84

permuted PDZ domain of Deg/high-temperature requirement factor A (HtrA) family of housekeeping serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Deg/HtrA-type serine proteases that participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. Typically, these proteases have an N-terminal serine protease domain and at least one C-terminal PDZ domain that recognizes substrates, and in some cases activates the protease function. An exception is yeast Nma11p which has two protease domains and four PDZ domains; its N-terminal half is comprised of a protease domain, followed by two PDZ domains, and its C-terminal half has a similar domain arrangement. HtrA-type proteases include the human HtrA1-4 and MBTPS2, tricorn protease, DegS, DegP and C-terminal processing peptidase, cyanobacterial serine proteases Hhoa, HhoB, and HtrA, and yeast Nma11p. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-termini of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This Deg/HtrA family PDZ domain is a circularly permuted PDZ domain which places beta-strand A at the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467621 [Multi-domain] Cd Length: 91 Bit Score: 44.98 E-value: 1.63e-05

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gi 1034657569  492 LQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGhtHADVVKLFQSVPIGQSVNLVLCRG 551
Cdd:cd06779     27 VLVAEVIPGSPAAKAG-LKEGDVILSVNGKPVTS--FNDLRAALDTKKPGDSLNLTILRD 83

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 1; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinase MAST1, and related domains. MAST1 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. MAST1 functions as a scaffold protein to link the dystrophin/utrophin network with microfilaments via syntrophin, and it has been identified as a main driver of cisplatin resistance in human 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 MAST1 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

Pssm-ID: 467286 [Multi-domain] Cd Length: 95 Bit Score: 45.02 E-value: 1.88e-05

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gi 1034657569 1190 VDMEKGAKGFGFSIRGGREY--KMDLY-----VLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRR 1262
Cdd:cd23073      5 ITIQRSGKKYGFTLRAIRVYmgDSDVYsvhhiVWHVEEGGPAQEAG-LCAGDLITHVNGEPVHGMVHPEVVELILKSGNK 83


                   .
gi 1034657569 1263 V 1263
Cdd:cd23073     84 V 84

PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CASK, Caenorhabditis elegans Lin-2, and related domains. CASK and Lin-2 are membrane-associated guanylate kinase (MAGUK)-like proteins. CASK (also known as Calcium/calmodulin-dependent protein kinase, CAKI, and Camguk) has a role in synaptic transmembrane protein anchoring and ion channel trafficking. CASK may regulate transmembrane proteins that bind calcium, calmodulin, or nucleotides; it regulates the Drosophila ether a go-go (eag) potassium channel, and also regulates autophosphorylation of CaMKII. CASK binding partners include the transcription factor TBR1, and cell-surface proteins, including amyloid precursor protein, neurexins, and syndecans. Lin-2, as a component of the CLin-10-Lin-2-Lin-7 complex, plays a role in controlling the basolateral localization of the EGF receptor Let-23; this complex also associates with the neuron-specific motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor 2B along microtubules. CASK may also function in targeting or scaffolding of the protein parkin which is selectively truncated by a Parkinson's disease-causing mutation; the C-terminus of parkin functions as a class II PDZ-binding motif that binds CASK. 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 MPP6-MPP2-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.

Pssm-ID: 467267 [Multi-domain] Cd Length: 81 Bit Score: 44.40 E-value: 1.95e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569  980 SLNRPESGSTItvphkIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRIIP 1050
Cdd:cd10831     16 TLKMNEDGRCI-----VARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREARGSITFKIVP 81

PDZ domain 4 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 4 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 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.

Pssm-ID: 467182 [Multi-domain] Cd Length: 85 Bit Score: 44.22 E-value: 1.97e-05

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gi 1034657569  646 MTLTIVKGAQG-FGFTIA--DSPTGQRVKQILDIqgcPGLCE-----GDLIVEINQQNVQNLSHTEVVDILKDCPigSET 717
Cdd:cd06696      4 LEVTLTKSEKGsLGFTVTkgKDDNGCYIHDIVQD---PAKSDgrlrpGDRLIMVNGVDVTNMSHTEAVSLLRAAP--KEV 78


                   ....*..
gi 1034657569  718 SLIIHRG 724
Cdd:cd06696     79 TLVLGRA 85

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.

Pssm-ID: 467244 [Multi-domain] Cd Length: 86 Bit Score: 44.53 E-value: 2.03e-05

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gi 1034657569  470 TLKKSNMGFGFTIIGG------DEPdefLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPIGqS 543
Cdd:cd06763      5 ELEKGSAGLGFSLEGGkgsplgDRP---LTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLTRFEAWNIIKSLPEG-P 80


                   ....*.
gi 1034657569  544 VNLVLC 549
Cdd:cd06763     81 VTLLIR 86

PDZ domain 6 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 6 of multi-PDZ-domain protein 1 (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 PDZ6 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 PDZ6 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

Pssm-ID: 467158 [Multi-domain] Cd Length: 87 Bit Score: 44.55 E-value: 2.04e-05

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gi 1034657569  470 TLKKSNMGFGFTIiGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHA 529
Cdd:cd06670      8 TIVKGNSSLGITV-SADKDGNGCIVKSIIHGGAVSRDGRISVGDFIVSINNESLRNVTNA 66

PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. 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 Dlg5-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.

Pssm-ID: 467248 [Multi-domain] Cd Length: 82 Bit Score: 44.24 E-value: 2.12e-05

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gi 1034657569 1190 VDMEKGAKGFGFSIRGGReyKMDLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMT--HARAI 1253
Cdd:cd06767      6 VSIEKGSEPLGISIVSGE--NGGIFVSSVTEGSLAHQAG-LEYGDQLLEVNGINLRNATeqQAALI 68

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. 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 harmonin 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.

Pssm-ID: 467219 [Multi-domain] Cd Length: 85 Bit Score: 44.17 E-value: 2.24e-05

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gi 1034657569  967 RKENEGFGFVIISSLnrpESGSTITVPHkigrIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGlSVTL 1046
Cdd:cd06737      9 RRGPESLGFSVRGGL---EHGCGLFVSH----VSPGSQADN-KGLRVGDEIVRINGYSISQCTHEEVINLIKTKK-TVSL 79


                   ..
gi 1034657569 1047 RI 1048
Cdd:cd06737     80 KV 81

PDZ domain of afadin (AFDN), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of afadin (AFDN, also known as ALL1-fused gene from chromosome 6 protein (AF6) and MLLT4), and related domains. AFDN belongs to the adhesion system, probably together with the E-cadherin-catenin system, that plays a role in the organization of homotypic, interneuronal, and heterotypic cell-cell adherens junctions. The AFDN PDZ domain interaction partners include poliovirus receptor-related protein PRR2/nectin, the junctional adhesion molecule (JAM), the breakpoint-cluster-region protein (BCR), connexin36 (Cx36), and a subset of Eph-related receptor tyrosine kinases; it can also bind low molecular weight ligands, in competition with a natural peptide ligand. Other AFDN-binding proteins have been identified. 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 AFDN 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.

Pssm-ID: 467251 [Multi-domain] Cd Length: 89 Bit Score: 44.20 E-value: 2.43e-05

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gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRIIPQ 1051
Cdd:cd06789     34 IKSVVKGGAADLDGRLQAGDQLLSVDGHSLVGLSQERAAELMTKTGSVVTLEVAKQ 89

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.

Pssm-ID: 467234 [Multi-domain] Cd Length: 83 Bit Score: 44.23 E-value: 2.47e-05

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gi 1034657569  963 VVIHRKENEGFGFVIISSlnrPESGSTITvphkIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDA-G 1041
Cdd:cd06752      3 VVLKRPPGEQLGFNIRGG---KASGLGIF----ISKVIPDSDAHR-LGLKEGDQILSVNGVDFEDIEHSEAVKVLKTArE 74


                   ....*....
gi 1034657569 1042 LSVTLRIIP 1050
Cdd:cd06752     75 IQMRVRYFP 83

circularly permuted PDZ domains of Escherichia coli Regulator of sigma-E protease (RseP) and related domains; Permuted PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ResP (also known as Site-2 protease RseP, and YaeL), and related domains. RseP is involved in the regulation of an extracytoplasmic stress response through the cleavage of membrane-spanning anti-stress-response transcription factor (anti-sigmE) protein RseA; it cleaves the peptide bond between the critical alanine and cysteine in the transmembrane region of RseA, releasing the cytoplasmic domain of RseA with its associated sigmaE. RseP contains two tandem-arranged periplasmic PDZ domains (PDZ-N/PDZ1 and PDZ-C/PDZ2) which act to negatively regulate protease action on intact RseA; they serve as a size-exclusion filter which prevents the access of an intact RseA into the active site of RseP. PDZ domains usually bind in sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This RseP family PDZ domain is a circularly permuted PDZ domain which places both beta-strands A and B at the C-terminus. Another permutation exists in the PDZ superfamily which places beta-strand A at the C-terminus.

Pssm-ID: 467638 [Multi-domain] Cd Length: 83 Bit Score: 44.10 E-value: 2.51e-05

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gi 1034657569  995 KIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPhaDIVKLIKD-AGLSVTLRI 1048
Cdd:cd23081      2 VVGEVVANSPAAE-AGLKPGDRILKIDGQKVRTWE--DIVRIVREnPGKPLTLKI 53

PDZ domain 0 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 0 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. 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 PDZ0 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.

Pssm-ID: 467212 [Multi-domain] Cd Length: 85 Bit Score: 44.11 E-value: 2.53e-05

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gi 1034657569 1198 GFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd06730     14 ELNLEIRGGAENGQFPYLGEVKEDKVVYKSGKLHPGELLLEVNGTPVSGLTLRDVLAVIKHCKEPVRL 81

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 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 PDLIM-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.

Pssm-ID: 467235 [Multi-domain] Cd Length: 79 Bit Score: 43.67 E-value: 2.66e-05

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gi 1034657569  830 FGFRILGGDEPGQPILIGAVIAMGSADRDGrLHPGDELVYVDGIPvagkTHryviDLMHHAARN------GQVNLTVRR 902
Cdd:cd06753     10 WGFRLQGGKDFNQPLTISRVTPGGKAAQAN-LRPGDVILAINGES----TE----GMTHLEAQNkikaatGSLSLTLER 79

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 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 3 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). 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 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.

Pssm-ID: 467240 [Multi-domain] Cd Length: 87 Bit Score: 44.19 E-value: 2.73e-05

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gi 1034657569  647 TLTIVKGA--QGFGFTI---ADSPTGQ---RVKQILdiqgcPG--------LCEGDLIVEINQQNVQNLSHTEVVDILK 709
Cdd:cd06759      2 TIVLMKGAggKGLGFSIvggRDSPRGPmgiYVKTIF-----PGgaaaedgrLKEGDEILEVNGESLQGLTHQEAIQKFK 75

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 440035 [Multi-domain] Cd Length: 274 Bit Score: 47.84 E-value: 2.74e-05

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gi 1034657569  996 IGRIIDGSPADRcAKLKVGDRILAVNGQSIINMphADIVKLI--KDAGLSVTLRII 1049
Cdd:COG0265    205 VARVEPGSPAAK-AGLRPGDVILAVDGKPVTSA--RDLQRLLasLKPGDTVTLTVL 257

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.

Pssm-ID: 467209 [Multi-domain] Cd Length: 87 Bit Score: 44.19 E-value: 2.87e-05

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gi 1034657569  829 GFGFRILGG-DEP----GQP-ILIGAVIAMGSADrdGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARNgqVNLTVRR 902
Cdd:cd06727     12 GFGIAVSGGrDNPhfqsGDTsIVISDVLKGGPAE--GKLQENDRVVSVNGVSMENVEHSFAVQILRKCGKT--ANITVKR 87

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.

Pssm-ID: 467244 [Multi-domain] Cd Length: 86 Bit Score: 43.76 E-value: 2.91e-05

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gi 1034657569  993 PHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIK 1038
Cdd:cd06763     29 PLTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLTRFEAWNIIK 74

PDZ domain 5 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 5 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 PDZ5 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.

Pssm-ID: 467183 [Multi-domain] Cd Length: 87 Bit Score: 43.87 E-value: 2.98e-05

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gi 1034657569  470 TLKKSNMGFGFTIIGG-DEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVP 539
Cdd:cd06697      7 TLTCHPGQLGLKLTGGsDSKYQVIYVLEIVPGSAAAEEGSLQPLDIIHYINGVSTQGMTLEDAVRALEASL 77

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.

Pssm-ID: 467285 [Multi-domain] Cd Length: 92 Bit Score: 44.02 E-value: 3.05e-05

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gi 1034657569  972 GFGFVIISSlnrpESGSTITVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRI 1048
Cdd:cd23072     14 GLGFQIVGG----EKSGRLDLGIFISSITPGGPADLDGRLKPGDRLISVNDVSLEGLSHDAAVEILQNAPEDVTLVV 86

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 4 (MAST4); PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST4, and related domains. MAST4 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST4 is a component of the AICD-MAST4-FOXO1-RTKN2 neuroprotective pathway; MAST4 phosphorylation of forkhead box protein O1 (FOXO1) regulates rhotekin 2 (RTKN2) expression. As this pathway is repressed in Alzheimer's Disease (AD), MAST4 may play a role in preventing AD pathogenesis. 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 MAST4 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.

Pssm-ID: 467289 [Multi-domain] Cd Length: 95 Bit Score: 44.25 E-value: 3.33e-05

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gi 1034657569 1190 VDMEKGAKGFGFSIRGGREY--KMDLY-----VLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRR 1262
Cdd:cd23076      5 IVIHSSGKNYGFTIRAIRVYvgDSDIYtvhhiVWNVEEGSPACQAG-LKAGDLITHINGEPVHGLVHTEVIELLLKSGNK 83


                   ....
gi 1034657569 1263 VRLL 1266
Cdd:cd23076     84 VSIT 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.

Pssm-ID: 467186 [Multi-domain] Cd Length: 89 Bit Score: 43.78 E-value: 3.60e-05

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gi 1034657569  996 IGRIIDGSPADRCAkLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRI 1048
Cdd:cd06702     36 ISKVIPDGAAAKSG-LRIGDRILSVNGKDLRHATHQEAVSALLSPGQEIKLLV 87

PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GOPC and related domains. GOPC, also known as PIST (PDZ domain protein interacting specifically with TC10), FIG (fused in glioblastoma), and CAL (CFTR-associated ligand), regulates the trafficking of a wide array of proteins, including small GTPases, receptors, and cell surface molecules such as cadherin 23 and CFTR. It may regulate CFTR chloride currents and acid-sensing ASIC3 currents by modulating cell surface expression of both channels, and may play a role in autophagy. Interaction partners of the GOPC PDZ domains include: FZD5, FZD8, ASIC3, CFTR, MUC3, ARFRP1, Ggamma13, neuroligin, and Stargazin. 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 GOPC-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.

Pssm-ID: 467261 [Multi-domain] Cd Length: 83 Bit Score: 43.51 E-value: 3.76e-05

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gi 1034657569  827 ESGFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMhhAARNGQVNLTV 900
Cdd:cd06800     10 HEGLGISITGGKEHGVPILISEIHEGQPADRCGGLYVGDAILSVNGIDLRDAKHKEAVTIL--SQQRGEITLEV 81

PDZ domain of PDZ domain-containing protein GIPC3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC3, and related domains. GIPC3 (also known as C19orf64) belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc3 gene cause nonsyndromic hearing loss. 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 GIPC3 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.

Pssm-ID: 467292 [Multi-domain] Cd Length: 89 Bit Score: 43.75 E-value: 3.97e-05

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gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKD--AGLSVTLRII 1049
Cdd:cd23079     30 IKRIKEGSIIDRIKAVCVGDHIEAINDQSIVGCRHYEVAKMLRElpKSQPFTLRLV 85

PDZ domain of tyrosine-protein phosphatase non-receptor type 3 (PTPN3), tyrosine-protein phosphatase non-receptor type 4 (PTNP4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PTPN3, PTPN4 and related domains. PTPN3 (also known as protein-tyrosine phosphatase H1, PTP-H1) has a tumor-suppressive or a tumor-promoting role in many cancers. It serves as a specific phosphatase for the MAP kinase p38gamma; the two interact via their PDZ domains and cooperate to promote Ras-induced oncogenesis. Interaction partners of the PTPN3 PDZ domain include p38gamma and human papillomavirus E6 oncoprotein. PTPN4 (also known as protein-tyrosine phosphatase MEG1) plays a role in immunity, learning, synaptic plasticity or cell homeostasis. p38gamma is also an interaction partner of the PTPN4 PDZ domain: PTPN4 regulates neuronal cell homeostasis by protecting neurons against apoptosis; binding of the C terminus of p38gamma to the PDZ domain of PTPN4, antagonizes the catalytic autoinhibition of PTPN4, leading to cell apoptosis. Other interaction partners of the PTPN4 PDZ domain include glutamate receptor subunit GluN2A, and RABV strain G protein, among others. 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 PTPN3-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.

Pssm-ID: 467190 [Multi-domain] Cd Length: 90 Bit Score: 43.84 E-value: 4.08e-05

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gi 1034657569  963 VVIHRK--ENEGFGFVIisslnrpESGSTITVPHKIGRIIDGSPADRCA-KLKVGDRILAVNGQSIINMPHADIVKLIKD 1039
Cdd:cd06706      4 VLIRMKpdENGRFGFNV-------KGGVDQKMPVIVSRVAPGTPADLCIpRLNEGDQVLLINGRDISEHTHDQVVMFIKA 76


                   .
gi 1034657569 1040 A 1040
Cdd:cd06706     77 S 77

PDZ domain 2 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking, and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2) which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins, APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 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 APBA1,3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467255 [Multi-domain] Cd Length: 78 Bit Score: 43.16 E-value: 4.30e-05

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gi 1034657569  962 DVVIHRKE-NEGFGFV----IISSLNRpesgstitvphkigriidGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKL 1036
Cdd:cd06793      4 TVLIRRPDlKYQLGFSvqngIICSLLR------------------GGIAER-GGVRVGHRIIEINGQSVVATPHEKIVQL 64

                           90
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gi 1034657569 1037 IKDAGLSVTLRIIP 1050
Cdd:cd06793     65 LSNSVGEIHMKTMP 78

PDZ domain 1 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 1 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP) and related domains; Drosophila bazooka PDZ1 belongs to a different PDZ family. 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: Par-3 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 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.

Pssm-ID: 467178 [Multi-domain] Cd Length: 98 Bit Score: 43.76 E-value: 4.49e-05

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gi 1034657569 1206 GREykMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARA 1252
Cdd:cd06691     30 GRT--LGLLIRGIEEGSRAERDGRFQENDCIVEINGVDLIDKSFEQA 74

PDZ domain of PDZ domain-containing protein GIPC3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC3, and related domains. GIPC3 (also known as C19orf64) belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc3 gene cause nonsyndromic hearing loss. 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 GIPC3 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.

Pssm-ID: 467292 [Multi-domain] Cd Length: 89 Bit Score: 43.37 E-value: 4.59e-05

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gi 1034657569  642 QAELMTLTIVKGAQGFGFTIADSPTG----QRVKQILDIQGCPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCPIGSET 717
Cdd:cd23079      1 RGETKEVEVTKTEDALGLTITDNGAGyafiKRIKEGSIIDRIKAVCVGDHIEAINDQSIVGCRHYEVAKMLRELPKSQPF 80


                   ..
gi 1034657569  718 SL 719
Cdd:cd23079     81 TL 82

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. 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 Zasp52-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.

Pssm-ID: 467281 [Multi-domain] Cd Length: 82 Bit Score: 43.29 E-value: 4.60e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034657569  474 SNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNLVLCR 550
Cdd:cd23068      9 SNTPWGFRLQGGADFGQPLSIQKVNPGSPADKAG-LRRGDVILRINGTDTSNLTHKQAQDLIKRA--GNDLQLTVQR 82

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.

Pssm-ID: 467254 [Multi-domain] Cd Length: 87 Bit Score: 43.35 E-value: 4.69e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  644 ELMTLTIVKGAQGFGFTIADSP-TGQR-----VKQILdiqgcPG--------LCEGDLIVEINQQNVQNLSHTEVVDILK 709
Cdd:cd06792      1 DVFEVELSKKDGSLGISVTGGInTSVRhggiyVKSLV-----PGgaaeqdgrIQKGDRLLEVNGVSLEGVTHKQAVECLK 75

                           90
                   ....*....|....
gi 1034657569  710 DCPigSETSLIIHR 723
Cdd:cd06792     76 NAG--QVVTLVLER 87

Stage IV sporulation protein SpoIVB, serine protease, degrades SpoIIQ, SpoIVFA [Cell cycle control, cell division, chromosome partitioning, Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 444534 [Multi-domain] Cd Length: 438 Bit Score: 47.53 E-value: 5.01e-05

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gi 1034657569 1220 EDG----PAiRNGRMRVGDQIIEINGESTRDMTH-ARAIELIKSGGRRVRLLLKRG 1270
Cdd:COG5832    145 EDGkkysPA-KDAGIQVGDIILKINGQKIKSAEEvAELINKAGKAGKPLKLTVKRG 199

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.

Pssm-ID: 467210 [Multi-domain] Cd Length: 79 Bit Score: 42.98 E-value: 5.04e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1188 FTVDMEKGAKGFGFSIRGGreYKmdLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELI-KSGGrRVRLL 1266
Cdd:cd06728      1 LKVTLTKSRKNDEYGLRLG--SR--IFVKEITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKLIeKSKD-KLQLV 75


                   ...
gi 1034657569 1267 LKR 1269
Cdd:cd06728     76 VLR 78

PDZ domain 4 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 4 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 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.

Pssm-ID: 467185 [Multi-domain] Cd Length: 98 Bit Score: 43.75 E-value: 5.16e-05

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gi 1034657569  830 FGFRILGG--DEPGQP-------ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIdlmhHAARNGQVNLTV 900
Cdd:cd06701     17 LGISIRGGakGHAGNPldptdegIFISKINPDGAAARDGRLKVGQRILEVNGQSLLGATHQEAV----RILRSVGDTLTL 92


                   ....*...
gi 1034657569  901 rrkVLCGG 908
Cdd:cd06701     93 ---LVCDG 97

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467283 [Multi-domain] Cd Length: 93 Bit Score: 43.55 E-value: 5.35e-05

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gi 1034657569  470 TLKKSNMGFGFTI------------IGGDEPDEFLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQS 537
Cdd:cd23070      4 TIVKSETGFGFNVrgqvseggqlrsINGELYAPLQHVSAVLEGGAADKAG-VRKGDRILEVNGVNVEGATHKQVVDLIKS 82

circularly permuted first PDZ domain (PDZ1) of Escherichia coli periplasmic serine endoprotease DegP and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Escherichia coli DegP (also known as heat shock protein DegP and Protease Do) and related domains. DegP belongs to the HtrA family of housekeeping proteases. It acts as a protease, degrading transiently denatured and unfolded or misfolded proteins which accumulate in the periplasm following heat shock or other stress conditions, and as a molecular chaperone at low temperatures. DegP has two PDZ domains in addition to the protease domain; its PDZ1 domain is responsible for identifying the distinct substrate sequences that affect degradation (degron) of the substrate sequence, and its PDZ2 domain is responsible for combining with other DegP monomers to form a stable oligomer structure. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This DegP family PDZ domain 1 is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467630 [Multi-domain] Cd Length: 91 Bit Score: 43.24 E-value: 5.35e-05

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gi 1034657569  996 IGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPH-ADIVKLIKdAGLSVTLRII 1049
Cdd:cd10839     29 VAQVLPDSPAAK-AGLKAGDVILSLNGKPITSSADlRNRVATTK-PGTKVELKIL 81

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). 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 shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467232 [Multi-domain] Cd Length: 82 Bit Score: 43.09 E-value: 5.44e-05

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gi 1034657569  479 GFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEV 521
Cdd:cd06750     14 GFTLKGGLEHGEPLVISKIEEGGKAASVGKLQVGDEVVNINGV 56

PDZ domain 6 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 6 of multi-PDZ-domain protein 1 (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 PDZ6 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 PDZ6 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

Pssm-ID: 467158 [Multi-domain] Cd Length: 87 Bit Score: 43.01 E-value: 5.59e-05

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gi 1034657569 1189 TVDMEKGAKGFGFSIrGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMT--HARAI 1253
Cdd:cd06670      6 TITIVKGNSSLGITV-SADKDGNGCIVKSIIHGGAVSRDGRISVGDFIVSINNESLRNVTnaQARAI 71

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and 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. 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 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.

Pssm-ID: 467239 [Multi-domain] Cd Length: 88 Bit Score: 43.11 E-value: 6.15e-05

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gi 1034657569  471 LKKSNMGFGFTIIGG---DEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSvpIGQSVNLV 547
Cdd:cd06758      7 LLKEKGGLGIQITGGkgsKRGDIGIFVAGVEEGGSADRDGRLKKGDELLMINGQSLIGLSHQEAVAILRS--SASPVQLV 84


                   ...
gi 1034657569  548 LCR 550
Cdd:cd06758     85 IAS 87

PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. 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 PDZRN4-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.

Pssm-ID: 467200 [Multi-domain] Cd Length: 88 Bit Score: 43.03 E-value: 6.43e-05

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gi 1034657569  470 TLKKSNMG--FGFTII--GGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVlgHTHADVVKLFQSVpiGQSVN 545
Cdd:cd06716      7 TLKRSNSQekLGLTLCyrTDDEEDTGIYVSEVDPNSIAAKDGRIREGDQILQINGVDV--QNREEAIALLSEE--EKSIT 82


                   ....*
gi 1034657569  546 LVLCR 550
Cdd:cd06716     83 LLVAR 87

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

Pssm-ID: 197736 [Multi-domain] Cd Length: 33 Bit Score: 41.43 E-value: 6.61e-05

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gi 1034657569   350 LPYGWEKIDDPIYGTYYVDHINRRTQFENPVL 381
Cdd:smart00456    2 LPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 2; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST2 (also known as microtubule-associated serine/threonine kinase-205 kD, MAST205) , and related domains. MAST2 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST2 may function to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Binding partners of MAST2 include beta2-syntrophin, TNF receptor-associated factor 6 (TRAF6), cAMP-regulated phosphoprotein (ARPP-16), Na+/H+ exchanger NHE3 (SLC9A3) and PTEN. MAST2 is also associated with microtubules of the spermatid manchette. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAST2 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467287 [Multi-domain] Cd Length: 93 Bit Score: 43.08 E-value: 6.62e-05

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gi 1034657569 1192 MEKGAKGFGFSIRGGREY--KMDLY-----VLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVR 1264
Cdd:cd23074      7 IHRAGKKYGFTLRAIRVYmgDSDVYtvhhmVWHVEDGGPASEAG-LRQGDLITHVNGEPVHGLVHTEVVELILKSGNKVS 85


                   .
gi 1034657569 1265 L 1265
Cdd:cd23074     86 I 86

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.

Pssm-ID: 467179 [Multi-domain] Cd Length: 88 Bit Score: 42.98 E-value: 7.00e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569  477 GFGFTIIGG---DEPDEF-LQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPIGQSVNLVLCRG 551
Cdd:cd06692      9 GLGIKIIGGyreNTGEEFgIFIKRILPGGLAATDGRLKEGDLILEVNGESLQGVTNERAVSILRSASASNHMSLLIARD 87

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.

Pssm-ID: 467250 [Multi-domain] Cd Length: 75 Bit Score: 42.62 E-value: 7.38e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  820 DVHLRR-MESGFGFrILGGDepgQPILIGAVIAMGSADrdGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARngQVNL 898
Cdd:cd06769      1 TVEIQRdAVLGFGF-VAGSE---RPVVVRSVTPGGPSE--GKLLPGDQILKINNEPVEDLPRERVIDLIRECKD--SIVL 72


                   ..
gi 1034657569  899 TV 900
Cdd:cd06769     73 TV 74

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 2; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST2 (also known as microtubule-associated serine/threonine kinase-205 kD, MAST205) , and related domains. MAST2 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST2 may function to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Binding partners of MAST2 include beta2-syntrophin, TNF receptor-associated factor 6 (TRAF6), cAMP-regulated phosphoprotein (ARPP-16), Na+/H+ exchanger NHE3 (SLC9A3) and PTEN. MAST2 is also associated with microtubules of the spermatid manchette. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAST2 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467287 [Multi-domain] Cd Length: 93 Bit Score: 43.08 E-value: 7.44e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKeNEGFGFVIISSLNRPESGSTITVPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd23074      5 IIIHRA-GKKYGFTLRAIRVYMGDSDVYTVHHMVWHVEDGGPASE-AGLRQGDLITHVNGEPVHGLVHTEVVELILKSGN 82

                           90
                   ....*....|
gi 1034657569 1043 SVTLRIIPQE 1052
Cdd:cd23074     83 KVSISTTPLE 92

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

Pssm-ID: 459800 [Multi-domain] Cd Length: 30 Bit Score: 40.95 E-value: 7.99e-05

                           10        20        30
                   ....*....|....*....|....*....|
gi 1034657569  350 LPYGWEKIDDPIYGTYYVDHINRRTQFENP 379
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

Pssm-ID: 238122 [Multi-domain] Cd Length: 31 Bit Score: 40.97 E-value: 8.16e-05

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1034657569  351 PYGWEKIDDPIYGTYYVDHINRRTQFENPVL 381
Cdd:cd00201      1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

PDZ domain of ARHGAP21 and ARHGAP23, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGAP21, ARHGAP23, and related domains. This subfamily includes the GAPs (GTPase activating proteins): ARHGAP21 (Rho GTPase-activating protein 21; also known as Rho GTPase-activating protein 10, Rho-type GTPase-activating protein 21) and ARHGAP23 (Rho GTPase-activating protein 23; also known as Rho-type GTPase-activating protein 23). GAPs deactivate Rho GTPases by accelerating GTP hydrolysis. ARHGAP21/23 interact with a planar cell polarity (PCP) protein Pk1 to regulate a lateral signaling pathway in migrating cells. The ARHGAP21 PDZ domain binds claudin-2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGAP21-23-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467238 [Multi-domain] Cd Length: 109 Bit Score: 43.22 E-value: 8.32e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  468 STTLKKSNMGFGFTI----------------------------IGGDEPDEFLQVKSVIPDGPAAQDGkMETGDVIVYIN 519
Cdd:cd06756      3 TVTLQRTSQGFGFTLrhfivyppesavheslkdeengnrggkqRSRLEPMDTIFVKQVKEGGPAHQAG-LCTGDRIVKVN 81

                           90
                   ....*....|....*..
gi 1034657569  520 EVCVLGHTHADVVKLFQ 536
Cdd:cd06756     82 GESVIGKTYSQVIALIQ 98

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.

Pssm-ID: 467184 [Multi-domain] Cd Length: 89 Bit Score: 42.68 E-value: 8.82e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569  827 ESGFGFRILGG-DEPGQP-ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTH 880
Cdd:cd06698     10 STGLGLSIVGGiNRPEGPmVFIQEVIPGGDCYKDGRLRPGDQLVSINKESLIGVTL 65

PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and GIPC3 (also known as C19orf64) constitute the GIPC family. These proteins contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc1 and Gipc2 genes have been linked to cancer, while mutations in the Gipc3 gene cause nonsyndromic hearing loss. 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 GIPC 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.

Pssm-ID: 467191 [Multi-domain] Cd Length: 89 Bit Score: 42.22 E-value: 1.10e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  463 KGTFLSTTLKKSNMGFGFTIIggDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPIGQ 542
Cdd:cd06707      1 KGQPKEIEVTKSEDALGLTIT--DNGAGYAFIKRIKEGSIMDKVPAICVGDHIEKINGESLVGCRHYEVARMLKEIPIGE 78


                   ....*...
gi 1034657569  543 SVNLVLCR 550
Cdd:cd06707     79 TFTLRLVE 86

PDZ domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of whirlin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short 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 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

Pssm-ID: 467224 [Multi-domain] Cd Length: 91 Bit Score: 42.34 E-value: 1.12e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569 1189 TVDMEKGAKGFGFSIRGGREYKMDL-YVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELI 1256
Cdd:cd06742      3 LVRIKKTKPTLGIAIEGGANTKQPLpRVINIQRGGSAHNCGGLKVGHVILEVNGTSLRGLEHREAARLI 71

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.

Pssm-ID: 467164 [Multi-domain] Cd Length: 83 Bit Score: 42.33 E-value: 1.13e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569  647 TLTIVKGAQGFGFTI---ADSPTGQ---RVKQILDiQGCPG----LCEGDLIVEINQQNVQNLSHTEVVDILKDC 711
Cdd:cd06676      1 TITLERGSDGLGFSIvggFGSPHGDlpiYVKTVFE-KGAAAedgrLKRGDQILAVNGESLEGVTHEEAVNILKKT 74

PDZ domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of whirlin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short 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 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

Pssm-ID: 467224 [Multi-domain] Cd Length: 91 Bit Score: 42.34 E-value: 1.20e-04

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                   ....*....|....*....|....*....|....*....|....*.
gi 1034657569  995 KIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDA 1040
Cdd:cd06742     29 RVINIQRGGSAHNCGGLKVGHVILEVNGTSLRGLEHREAARLIAEA 74

PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the first PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family 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.

Pssm-ID: 467269 [Multi-domain] Cd Length: 84 Bit Score: 42.04 E-value: 1.21e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569   15 VHESVIGRNPEGQLGFELKGGAENGQFPYLGEVKPGKVAYESGskLVSEELLLEVN 70
Cdd:cd10833      1 IHTVTVEKSPDGSLGFSVRGGSEHGLGIFVSKVEEGSAAERAG--LCVGDKITEVN 54

PDZ domain 4 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 4 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 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

Pssm-ID: 467156 [Multi-domain] Cd Length: 88 Bit Score: 42.28 E-value: 1.22e-04

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                   ....*....|....*....|....*....|....*....|..
gi 1034657569  846 IGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLM 887
Cdd:cd06668     34 IRSILPEGPVGRNGKLFSGDELLEVNGIQLLGLSHKEVVSIL 75

PDZ domain 1 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467175 [Multi-domain] Cd Length: 83 Bit Score: 42.01 E-value: 1.24e-04

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gi 1034657569  963 VVIHRKENEGFGFVI---ISSLNRPesgstitvphKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKD 1039
Cdd:cd06687      3 VELIKKEGSTLGLTVsggIDKDGKP----------RVSNLRPGGIAARSDQLNVGDYIKSVNGIRTTKLRHDEIISLLKN 72


                   ....*....
gi 1034657569 1040 AGLSVTLRI 1048
Cdd:cd06687     73 VGERVVLEV 81

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467228 [Multi-domain] Cd Length: 101 Bit Score: 42.58 E-value: 1.35e-04

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gi 1034657569  470 TLKKSNMGFGFTIIGG---DEPDEF--------LQ-VKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLfqs 537
Cdd:cd06746     10 VLQKGDKGFGFVLRGAkavGPILEFtptpafpaLQyLESVDPGGVADKAG-LKKGDFLLEINGEDVVKASHEQVVNL--- 85

                           90
                   ....*....|
gi 1034657569  538 vpIGQSVNLV 547
Cdd:cd06746     86 --IRQSGNTL 93

PDZ domain 1 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 1 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 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.

Pssm-ID: 467176 [Multi-domain] Cd Length: 102 Bit Score: 42.62 E-value: 1.45e-04

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gi 1034657569  965 IHRKENEGFGF--VIISSLNRPESGstITVPhkigRIIDGSPADRCAKLKVGDRILAVNGQSI-INMPHADIVKLIKDAG 1041
Cdd:cd06689     20 LEKPESGGLGFsvVGLKSENRGELG--IFVQ----EIQPGSVAARDGRLKENDQILAINGQPLdQSISHQQAIAILQQAK 93


                   ....*
gi 1034657569 1042 LSVTL 1046
Cdd:cd06689     94 GSVEL 98

PDZ domain 4 of PDZ domain containing 2 (PDZD2), PDZ domain 2 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 4 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the second PDZ domain (PDZ2) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). 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 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.

Pssm-ID: 467241 [Multi-domain] Cd Length: 90 Bit Score: 41.87 E-value: 1.49e-04

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gi 1034657569 1213 LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMT 1248
Cdd:cd06760     33 IFIHHLSPGSVAHMDGRLRRGDQILEINGTSLRNVT 68

PDZ domain of tyrosine-protein phosphatase non-receptor type 3 (PTPN3), tyrosine-protein phosphatase non-receptor type 4 (PTNP4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PTPN3, PTPN4 and related domains. PTPN3 (also known as protein-tyrosine phosphatase H1, PTP-H1) has a tumor-suppressive or a tumor-promoting role in many cancers. It serves as a specific phosphatase for the MAP kinase p38gamma; the two interact via their PDZ domains and cooperate to promote Ras-induced oncogenesis. Interaction partners of the PTPN3 PDZ domain include p38gamma and human papillomavirus E6 oncoprotein. PTPN4 (also known as protein-tyrosine phosphatase MEG1) plays a role in immunity, learning, synaptic plasticity or cell homeostasis. p38gamma is also an interaction partner of the PTPN4 PDZ domain: PTPN4 regulates neuronal cell homeostasis by protecting neurons against apoptosis; binding of the C terminus of p38gamma to the PDZ domain of PTPN4, antagonizes the catalytic autoinhibition of PTPN4, leading to cell apoptosis. Other interaction partners of the PTPN4 PDZ domain include glutamate receptor subunit GluN2A, and RABV strain G protein, among others. 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 PTPN3-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.

Pssm-ID: 467190 [Multi-domain] Cd Length: 90 Bit Score: 41.91 E-value: 1.50e-04

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gi 1034657569  821 VHLRRMESG-FGFRILGGDEPGQPILIGAVIAMGSADR-DGRLHPGDELVYVDGIPVAGKTHRYVIdLMHHAARN---GQ 895
Cdd:cd06706      6 IRMKPDENGrFGFNVKGGVDQKMPVIVSRVAPGTPADLcIPRLNEGDQVLLINGRDISEHTHDQVV-MFIKASRErhsGE 84


                   ....*.
gi 1034657569  896 VNLTVR 901
Cdd:cd06706     85 LVLLVR 90

PDZ domain 4 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. 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 INAD-like 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.

Pssm-ID: 467278 [Multi-domain] Cd Length: 82 Bit Score: 41.73 E-value: 1.51e-04

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gi 1034657569 1189 TVDMEKGAKGFGFSIRGGREY-KMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELI-KSGGRRVRL 1265
Cdd:cd23065      1 TIELKTDKSPLGVSVVGGKNHvTTGCIITHIYPNSIVAADKRLKVFDQILDINGTKVHVMTTLKVHQLFhKTYEKAVTL 79

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467273 [Multi-domain] Cd Length: 80 Bit Score: 41.57 E-value: 1.53e-04

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gi 1034657569   24 PEGQLGFELKGGaENGQFPYLGEVKPGKVAYESGSKLVSEELLlEVNETPVAGLTIRDVLAVIKHCKDPLRL 95
Cdd:cd23060      8 ANGGLGFSLVGG-EGGSGIFVKSISPGGVADRDGRLQVGDRLL-QVNGESVIGLSHSKAVNILRKAKGTVQL 77

PDZ domain of the microtubule-associated serine-threonine (MAST) protein kinase family; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinases, including MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. The PDZ domain gives the MAST family the capacity to scaffold its own kinase activity. These kinases are implicated in the inhibition of neurite outgrowth and regeneration in cultured cells. Their binding partners include microtubules, beta2-syntrophin, TNF receptor-associated factor 6 (TRAF6), cAMP-regulated phosphoprotein (ARPP-16), and PTEN. This family also includes Caenorhabditis elegans KIN-4 MAST kinase, a key longevity factor acting through binding PTEN phosphatase, and Drosophila Drop out which regulates dynein-dependent transport during embryonic development. 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 MAST-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.

Pssm-ID: 467189 [Multi-domain] Cd Length: 93 Bit Score: 42.23 E-value: 1.58e-04

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gi 1034657569  470 TLKKSNMGFGFTI------IGgdEPDEF-LQ--VKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLfqsvpI 540
Cdd:cd06705      6 VIKKGPRGFGFTLrairvyIG--DSDVYtVHhlVTAVEEGSPAYEAG-LRPGDLITHVNGEPVQGLLHTQVVQL-----I 77

                           90
                   ....*....|....
gi 1034657569  541 GQSVNLVLCRGYPL 554
Cdd:cd06705     78 LKGGNKVSIRATPL 91

PDZ domain 5 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 5 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 PDZ5 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.

Pssm-ID: 467183 [Multi-domain] Cd Length: 87 Bit Score: 41.94 E-value: 1.64e-04

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gi 1034657569   25 EGQLGFELKGGAENG-QFPYLGEVKPGKVAYESGSkLVSEELLLEVNETPVAGLTIRDVLAVIKHCKDPLRLK 96
Cdd:cd06697     12 PGQLGLKLTGGSDSKyQVIYVLEIVPGSAAAEEGS-LQPLDIIHYINGVSTQGMTLEDAVRALEASLPTVVLK 83

PDZ domain of tax1-binding protein 3 (TAX1BP3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of TAX1BP3, and related domains. TAX1BP3 (also known as glutaminase-interacting protein 3, tax interaction protein 1, TIP-1, tax-interacting protein 1) may regulate a number of protein-protein interactions by competing for PDZ domain binding sites. TAX1BP3 binds beta-catenin and may act as an inhibitor of the Wnt signaling pathway. It competes with LIN7A (also known as Lin-7A or LIN-7A) for inward rectifier potassium channel 4 (KCNJ4) binding, and thereby promotes KCNJ4 internalization. It may play a role in the Rho signaling pathway, and in the activation of CDC42 by the viral protein HPV16 E6. Binding partners of the TAX1BP3 PDZ domain include beta-catenin, KCNJ4, glutaminase liver isoform (GLS2), rho guanine nucleotide exchange factor 16 (ARHGEF16), rhotekin, and CDK5 regulatory subunit-associated protein 3 (also known as LAPZ). 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 TAX1BP3-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.

Pssm-ID: 467265 [Multi-domain] Cd Length: 94 Bit Score: 41.94 E-value: 1.72e-04

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gi 1034657569  966 HRKENEGFGFVIISSLNRPESGSTITVPHK---IGRIIDGSPADRCAkLKVGDRILAVNGQSIINMPHADIVKLIK 1038
Cdd:cd10822      8 RQGENLILGFSIGGGIDQDPSKNPFSYTDKgiyVTRVSEGGPAEKAG-LQVGDKILQVNGWDMTMVTHKQAVKRLT 82

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.

Pssm-ID: 467186 [Multi-domain] Cd Length: 89 Bit Score: 41.86 E-value: 1.72e-04

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gi 1034657569  820 DVHLRRMESGFGFRILGG----------DEPGqpILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIdlMHH 889
Cdd:cd06702      2 EIHLVKAGGPLGLSIVGGsdhsshpfgvDEPG--IFISKVIPDGAAAKSG-LRIGDRILSVNGKDLRHATHQEAV--SAL 76

                           90
                   ....*....|...
gi 1034657569  890 AARNGQVNLTVRR 902
Cdd:cd06702     77 LSPGQEIKLLVRH 89

PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNPO2, SYNPO2L, and related domains. SYNPO2 (also known as genethonin-2, myopodin) is a cytoskeleton adaptor protein. It participates in chaperone-assisted selective autophagy (CASA), a mechanism for the disposal of misfolded and damaged proteins and provides a link between the CASA chaperone complex and a membrane-tethering and fusion machinery that generates autophagosome membranes. The SYNPO2 PPxY motif binds CASA cochaperone BCL2-associated athanogene 3 (BAG3) and the SYNPO2 PDZ domain binds vacuolar protein sorting 18 homolog (VPS18). There are three isoforms of SYNPO2, which possess an amino-terminal PDZ domain (SYNPO2a, b, c); the short isoform SYNPO2d, lacks the PDZ 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 SYNPO2-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.

Pssm-ID: 467264 [Multi-domain] Cd Length: 78 Bit Score: 41.53 E-value: 1.72e-04

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gi 1034657569  983 RPESGSTITVPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRI 1048
Cdd:cd10820     13 RLQGGSEQKKPLQVAKIRKKSKAAL-AGLCEGDELLSINGKPCADLSHSEAMDLIDSSGDTLQLLI 77

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

Pssm-ID: 467226 [Multi-domain] Cd Length: 75 Bit Score: 41.49 E-value: 1.85e-04

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gi 1034657569  647 TLTIVKGAQGFGFTIA-DSPTgqRVKQILDiqGCP----GLCEGDLIVEINQQNVQNLSHTEVVDILKDCpiGSETSLII 721
Cdd:cd06744      1 TVRVYRGNGSFGFTLRgHAPV--YIESVDP--GSAaeraGLKPGDRILFLNGLDVRNCSHDKVVSLLQGS--GSMPTLVV 74

PDZ domain 1 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. 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 INAD-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.

Pssm-ID: 467276 [Multi-domain] Cd Length: 87 Bit Score: 41.73 E-value: 1.87e-04

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gi 1034657569  472 KKSNMGFGFTIIGG---DEPDEFLQ---VKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKL 534
Cdd:cd23063      6 KTEKKSFGICIVRGevkVSPNTKTTgifIKGIIPDSPAHKCGRLKVGDRILSVNGNDVRNSTEQAAIDL 74

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]

Pssm-ID: 273938 [Multi-domain] Cd Length: 428 Bit Score: 45.68 E-value: 1.91e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  996 IGRIIDGSPADRcAKLKVGDRILAVNGQSIINMphADIVKLIKDA--GLSVTLRII----PQE---EL-NSPTSAPSSEK 1065
Cdd:TIGR02037  261 VAQVLPGSPAEK-AGLKAGDVITSVNGKPISSF--ADLRRAIGTLkpGKKVTLGILrkgkEKTitvTLgASPEEQASSSN 337

                           90
                   ....*....|
gi 1034657569 1066 QSPMAQQSPL 1075
Cdd:TIGR02037  338 PFLGLTVANL 347

PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS3, and related domains. RGS3 down-regulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. It downregulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. In Eph/ephrin signaling, RGS3 binds via its PDZ domain to the cytoplasmic C terminus of Eph receptor tyrosine kinase EphB. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467195 [Multi-domain] Cd Length: 77 Bit Score: 41.22 E-value: 1.93e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569  972 GFGFVIISslnrpesgstiTVPHKIGRIIDGSPADRCAkLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTL 1046
Cdd:cd06711     11 GFGFTICD-----------DSPVRVQAVDPGGPAEQAG-LQQGDTVLQINGQPVERSKCVELAHAIRNCPSEIIL 73

PDZ domain 1 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467175 [Multi-domain] Cd Length: 83 Bit Score: 41.63 E-value: 2.03e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034657569 1192 MEKGAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd06687      6 IKKEGSTLGLTVSGGIDKDGKPRVSNLRPGGIAARSDQLNVGDYIKSVNGIRTTKLRHDEIISLLKNVGERVVL 79

PDZ domain of PDZ domain-containing protein GIPC2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC2, and related domains. GIPC2 belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc2 gene have been linked to cancer. 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 GIPC2 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.

Pssm-ID: 467291 Cd Length: 93 Bit Score: 41.82 E-value: 2.03e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKD--AGLSVTLRII 1049
Cdd:cd23078     32 IKRIKDGSVIDSVKTICVGDHIECINGENIVGWRHYEVAKKLKElkKEELFTLKLI 87

PDZ domain 3 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 3 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 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.

Pssm-ID: 467167 [Multi-domain] Cd Length: 88 Bit Score: 41.47 E-value: 2.28e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  647 TLTIVKGA-QGFGFTIA---DSPTGQRVKQILDIQ--GCPG----LCEGDLIVEINQQNVQNLSHTEVVDILKDCPIGSE 716
Cdd:cd06679      2 TVTIKKEPsESLGISVAggrGSRRGDLPIYVTNVQpdGCLGrdgrIKKGDVLLSINGISLTNLSHSEAVAVLKASAASSS 81


                   ...
gi 1034657569  717 TSL 719
Cdd:cd06679     82 IVL 84

PDZ domain 1 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 1 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 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.

Pssm-ID: 467176 [Multi-domain] Cd Length: 102 Bit Score: 41.85 E-value: 2.44e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569  829 GFGFRILGGDEP---GQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVA-GKTHRYVIDLMHHAArnGQVNLTVRR 902
Cdd:cd06689     27 GLGFSVVGLKSEnrgELGIFVQEIQPGSVAARDGRLKENDQILAINGQPLDqSISHQQAIAILQQAK--GSVELVVAR 102

PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ6 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.

Pssm-ID: 467171 [Multi-domain] Cd Length: 85 Bit Score: 41.14 E-value: 2.46e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034657569  479 GFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNLVLCR 550
Cdd:cd06683     16 GITISGTEEPFDPIVISGLTEGGLAERTGAIHVGDRILAINGESLRGKPLSEAIHLLQNA--GDTVTLKISR 85

PDZ domain 0 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 0 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. 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 PDZ0 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.

Pssm-ID: 467212 [Multi-domain] Cd Length: 85 Bit Score: 41.42 E-value: 2.49e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569  477 GFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKL 534
Cdd:cd06730     14 ELNLEIRGGAENGQFPYLGEVKEDKVVYKSGKLHPGELLLEVNGTPVSGLTLRDVLAV 71

PDZ domain 5 of multi-PDZ-domain protein 1 (MUPP1), 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 5 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 PDZ5 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

Pssm-ID: 467157 [Multi-domain] Cd Length: 98 Bit Score: 41.45 E-value: 2.73e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1190 VDMEKGAKGFGFSIrggREYK--MD----LYVLR-LAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGR- 1261
Cdd:cd06669     11 IELEKGDRGLGFSI---LDYQdpLDpsetVIVIRsLVPGGVAEQDGRLLPGDRLVFVNDVSLENASLDEAVQALKSAPPg 87


                   ....
gi 1034657569 1262 RVRL 1265
Cdd:cd06669     88 TVRI 91

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. 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 Par6-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.

Pssm-ID: 467202 [Multi-domain] Cd Length: 84 Bit Score: 41.01 E-value: 2.79e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  963 VVIHRKENEGFGFVIiSSLNRPESGSTITvphkIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLI-KDAG 1041
Cdd:cd06718      3 VELIKPPGKPLGFYI-RDGNGVERVPGIF----ISRLVLGSLADSTGLLAVGDEILEVNGVEVTGKSLDDVTDMMvAPTR 77


                   ....*.
gi 1034657569 1042 LSVTLR 1047
Cdd:cd06718     78 LIITVK 83

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. 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 harmonin 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.

Pssm-ID: 467219 [Multi-domain] Cd Length: 85 Bit Score: 41.09 E-value: 2.97e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569  472 KKSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQS 537
Cdd:cd06737      9 RRGPESLGFSVRGGLEHGCGLFVSHVSPGSQADNKG-LRVGDEIVRINGYSISQCTHEEVINLIKT 73

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.

Pssm-ID: 467186 [Multi-domain] Cd Length: 89 Bit Score: 41.09 E-value: 3.09e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034657569  470 TLKKSNMGFGFTIIGG----------DEPDEFlqVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVK 533
Cdd:cd06702      4 HLVKAGGPLGLSIVGGsdhsshpfgvDEPGIF--ISKVIPDGAAAKSG-LRIGDRILSVNGKDLRHATHQEAVS 74

PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNPO2, SYNPO2L, and related domains. SYNPO2 (also known as genethonin-2, myopodin) is a cytoskeleton adaptor protein. It participates in chaperone-assisted selective autophagy (CASA), a mechanism for the disposal of misfolded and damaged proteins and provides a link between the CASA chaperone complex and a membrane-tethering and fusion machinery that generates autophagosome membranes. The SYNPO2 PPxY motif binds CASA cochaperone BCL2-associated athanogene 3 (BAG3) and the SYNPO2 PDZ domain binds vacuolar protein sorting 18 homolog (VPS18). There are three isoforms of SYNPO2, which possess an amino-terminal PDZ domain (SYNPO2a, b, c); the short isoform SYNPO2d, lacks the PDZ 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 SYNPO2-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.

Pssm-ID: 467264 [Multi-domain] Cd Length: 78 Bit Score: 40.76 E-value: 3.16e-04

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gi 1034657569  681 GLCEGDLIVEINQQNVQNLSHTEVVDIL 708
Cdd:cd10820     39 GLCEGDELLSINGKPCADLSHSEAMDLI 66

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467228 [Multi-domain] Cd Length: 101 Bit Score: 41.43 E-value: 3.18e-04

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gi 1034657569   19 VIGRNPEGqLGFELKGGAENGQ---------FP---YLGEVKPGKVAYESGSKlvSEELLLEVNETPVAGLTIRDVLAVI 86
Cdd:cd06746     10 VLQKGDKG-FGFVLRGAKAVGPileftptpaFPalqYLESVDPGGVADKAGLK--KGDFLLEINGEDVVKASHEQVVNLI 86

                           90
                   ....*....|..
gi 1034657569   87 KHCKDPLRLKCV 98
Cdd:cd06746     87 RQSGNTLVLKVV 98

Predicted secreted protein YlbL, contains PDZ domain [Signal transduction mechanisms];

Pssm-ID: 442703 [Multi-domain] Cd Length: 344 Bit Score: 44.80 E-value: 3.21e-04

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1034657569  999 IIDGSPADRcaKLKVGDRILAVNGQSIINMphADIVKLIKD--AGLSVTLRI 1048
Cdd:COG3480    145 VLEGSPADG--VLQPGDVITAVDGKPVTTA--EDLRDALAAkkPGDTVTLTV 192

PDZ domain 8 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 7 of protein-associated tight junction (PATJ), PDZ domain 2 of Drosophila melanogaster inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 8 of MUPP1, PDZ domain 7 of PATJ, and PDZ domain 2 of Drosophila melanogaster INAD, 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. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C. 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 PDZ8 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.

Pssm-ID: 467160 [Multi-domain] Cd Length: 84 Bit Score: 40.74 E-value: 3.57e-04

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gi 1034657569  494 VKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPigQSVNLVLCR 550
Cdd:cd06672     30 VVGIDPDGAAGKDGRIQVGDELLEINGQVLYGRSHLNASAIIKSAP--SKVKIVFLR 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.

Pssm-ID: 467250 [Multi-domain] Cd Length: 75 Bit Score: 40.31 E-value: 3.65e-04

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gi 1034657569  647 TLTIVKGAQ-GFGFTIadspTGQRVKQILDI-QGCPG---LCEGDLIVEINQQNVQNLSHTEVVDILKDCP 712
Cdd:cd06769      1 TVEIQRDAVlGFGFVA----GSERPVVVRSVtPGGPSegkLLPGDQILKINNEPVEDLPRERVIDLIRECK 67

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.

Pssm-ID: 467188 [Multi-domain] Cd Length: 87 Bit Score: 40.72 E-value: 3.67e-04

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gi 1034657569  470 TLKKSNMGFGFTIIGGD------EPDEFLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQS 543
Cdd:cd06704      4 TIERQTGGLGISIAGGKgstpykGDDEGIFISRVTEGGPAAKAG-VRVGDKLLEVNGVDLVDADHHEAVEALKNS--GNT 80


                   ....*..
gi 1034657569  544 VNLVLCR 550
Cdd:cd06704     81 VTMVVLR 87

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.

Pssm-ID: 467206 [Multi-domain] Cd Length: 89 Bit Score: 40.76 E-value: 3.69e-04

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gi 1034657569  647 TLTIVKGAQGFGFTIA---DSP-----TGQRVKQIldIQGCPGLCEG-----DLIVEINQQNVQNLSHTEVVDILKDCpi 713
Cdd:cd06723      3 EITLERGNSGLGFSIAggtDNPhigddPSIYITKI--IPGGAAAADGrlrvnDIILRVNDVDVRNVTHSVAVEALKEA-- 78

                           90
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gi 1034657569  714 GSETSLIIHR 723
Cdd:cd06723     79 GSIVRLYVKR 88

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.

Pssm-ID: 467271 [Multi-domain] Cd Length: 93 Bit Score: 41.09 E-value: 3.91e-04

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gi 1034657569  963 VVIH-RKENEGFGFVIISSLNrPESGSTitvPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDA- 1040
Cdd:cd23058      6 LHIQlKKGPEGLGFSITSRDN-PTGGSG---PIYIKNILPKGAAIQDGRLKAGDRLLEVNGVDVTGKTQEEVVSLLRSTk 81

                           90
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gi 1034657569 1041 -GLSVTLRIIPQ 1051
Cdd:cd23058     82 lGGTVSLVVSRQ 93

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467262 [Multi-domain] Cd Length: 83 Bit Score: 40.63 E-value: 3.94e-04

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gi 1034657569  472 KKSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKL 534
Cdd:cd06801      7 KQDVGGLGISIKGGAEHKMPILISKIFKGQAADQTGQLFVGDAILSVNGENLEDATHDEAVQA 69

PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP5, Drosophila Stardust, and related domains. MPP5 (also known as MAGUK p55 subfamily member 1, protein associated with Lin-7 1 or PALS1) and Drosophila Stardust are membrane-associated guanylate kinase (MAGUK)-like proteins that serve as signaling and scaffolding proteins, linking different proteins critical to the formation and maintenance of tight junctions (TJ) and apical-basal polarity. Apical-basal polarity determinants cluster in complexes; in particular, the Crumbs complex (Crb, MPP5, and PATJ) and the PAR/aPKC-complex (PAR-3, PAR-6, aPKC) determine the apical plasma membrane domain. Within the Crumbs complex, Crb is stabilized in the plasma membrane by MPP5, which in turn recruits PATJ and Lin-7 to the complex. MPP5 also links the Crumbs complex with the PAR/aPKC-complex. The Drosophila homolog of the Crumbs complex is the (CRB)-Stardust (Sdt)-Discs Lost (Dlt) complex. MPP5 also acts as an interaction partner for SARS-CoV envelope protein E, which results in delayed formation of TJs and dysregulation 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 MPP5-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.

Pssm-ID: 467259 [Multi-domain] Cd Length: 79 Bit Score: 40.41 E-value: 4.08e-04

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gi 1034657569  963 VVIHRKENEGFGFVIisslnRPESGSTItvphkIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd06798      2 IVRIEKTREPLGATV-----RNEGDSVI-----ISRIVKGGAAEKSGLLHEGDEILEINGIEIRGKDVNEVCDLLADMHG 71


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gi 1034657569 1043 SVTLRIIP 1050
Cdd:cd06798     72 TLTFLLIP 79

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 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 PDLIM-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.

Pssm-ID: 467235 [Multi-domain] Cd Length: 79 Bit Score: 40.59 E-value: 4.21e-04

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gi 1034657569  681 GLCEGDLIVEINQQNVQNLSHTEVVDILKDCpiGSETSLIIHR 723
Cdd:cd06753     39 NLRPGDVILAINGESTEGMTHLEAQNKIKAA--TGSLSLTLER 79

PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS3, and related domains. RGS3 down-regulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. It downregulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. In Eph/ephrin signaling, RGS3 binds via its PDZ domain to the cytoplasmic C terminus of Eph receptor tyrosine kinase EphB. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467195 [Multi-domain] Cd Length: 77 Bit Score: 40.45 E-value: 4.31e-04

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gi 1034657569  470 TLKKSNMGFGFTIIGgDEPdefLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQSVPiGQSVNLVL 548
Cdd:cd06711      4 TIQRGKDGFGFTICD-DSP---VRVQAVDPGGPAEQAG-LQQGDTVLQINGQPVERSKCVELAHAIRNCP-SEIILLVW 76

PDZ domain 1 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. 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 PDZRN4-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.

Pssm-ID: 467199 [Multi-domain] Cd Length: 92 Bit Score: 40.84 E-value: 4.39e-04

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gi 1034657569  467 LSTTLKKSNMGFGFTIIGG--------DEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSV 538
Cdd:cd06715      3 FTVVLHRENGSLGFNIIGGrpcennqeGSSSEGIYVSKIVENGPAADEGGLQVHDRIIEVNGKDLSKATHEEAVEAFRTA 82


                   ....
gi 1034657569  539 --PI 540
Cdd:cd06715     83 kePI 86

PDZ domain 5 of inactivation no after potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ45 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. 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 INAD-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.

Pssm-ID: 467279 [Multi-domain] Cd Length: 80 Bit Score: 40.56 E-value: 4.43e-04

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gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRI 1048
Cdd:cd23066     26 IADLLPGGYAEIDGKLQKGDIITKFNGDALSGLPFQVCYALFKGANGKISLEV 78

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.

Pssm-ID: 467177 [Multi-domain] Cd Length: 88 Bit Score: 40.74 E-value: 4.48e-04

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gi 1034657569  494 VKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSV 538
Cdd:cd06690     34 IRTLVPDSPAARDGRLRLGDRILAVNGTSLVGADYQSAMDLIRTS 78

PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight junction (PATJ, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 12 of MUPP1, PDZ domain 10 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 PDZ12 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

Pssm-ID: 467163 [Multi-domain] Cd Length: 86 Bit Score: 40.43 E-value: 4.57e-04

                           10        20
                   ....*....|....*....|....*.
gi 1034657569  685 GDLIVEINQQNVQNLSHTEVVDILKD 710
Cdd:cd06675     50 GDRIVSINGQSTDGLTHSEAVNLLKN 75

PDZ domain 4 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. 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 INAD-like 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.

Pssm-ID: 467278 [Multi-domain] Cd Length: 82 Bit Score: 40.58 E-value: 4.57e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569  821 VHLRRMESGFGFRILGG-DEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMH 888
Cdd:cd23065      2 IELKTDKSPLGVSVVGGkNHVTTGCIITHIYPNSIVAADKRLKVFDQILDINGTKVHVMTTLKVHQLFH 70

PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of harmonin isoforms a and b, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. 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 harmonin 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.

Pssm-ID: 467221 [Multi-domain] Cd Length: 94 Bit Score: 40.76 E-value: 4.60e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDA--GLSVTLRII 1049
Cdd:cd06739     32 VSAVYEGGAADKHGGIVKGDQIMMVNGKSLTDVTLAEAEAALQRAmnSGGDWIDLV 87

PDZ domain of MYO18A protein, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MYO18 protein and related domains. MYO18 (also known as myosin XVIIIA, KIAA0216, MysPDZ), a member of the myosin superfamily, is involved in regulating cell protrusion and migration, and Golgi trafficking and morphology, and is required for myoblast adhesion and muscle integrity. The MYO18A/MRCK/LRAP35a complex regulates actomyosin retrograde flow in cell protrusion and migration; the PtdIns(4)P/GOLPH3/MYO18A/F-actin complex is a hub for signals that regulate Golgi trafficking function. The MYO18A PDZ domain binds p190Rho-guanine nucleotide exchange factor (p190RhoGEF), Golgin45, and leucine repeat adaptor protein 1 (Lurap1, also known as Lrap35a). 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 MYO18-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467229 [Multi-domain] Cd Length: 90 Bit Score: 40.76 E-value: 4.64e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569 1196 AKGFGFSIR----------GGREYKMdlyVLRLAEDGPAIRNGRMRV--GDQIIEINGESTRDMTHARAIELIKSGGRRV 1263
Cdd:cd06747      9 TGDFGFSLRrgtivergpdDGQELKR---TVHFAEPGAGTKNLATGLlpGDRLIEVNGVNVENASRDEIIEMIRKSGDTV 85


                   ..
gi 1034657569 1264 RL 1265
Cdd:cd06747     86 TL 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.

Pssm-ID: 467210 [Multi-domain] Cd Length: 79 Bit Score: 40.28 E-value: 4.80e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569  963 VVIHRKENEGFGFVIisslnrpesGSTITVPHkigrIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLI 1037
Cdd:cd06728      4 TLTKSRKNDEYGLRL---------GSRIFVKE----ITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKLI 65

PDZ domain 2 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking, and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2) which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins, APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 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 APBA1,3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467255 [Multi-domain] Cd Length: 78 Bit Score: 40.08 E-value: 4.99e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569 1200 GFSIRGGreykmdlYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06793     17 GFSVQNG-------IICSLLRGGIAERGG-VRVGHRIIEINGQSVVATPHEKIVQLLSN 67

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 440035 [Multi-domain] Cd Length: 274 Bit Score: 43.60 E-value: 5.53e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569 1196 AKGFGFSIRGGreykmdLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLKRG 1270
Cdd:COG0265    192 AEALGLPEPEG------VLVARVEPGSPAAKAG-LRPGDVILAVDGKPVTSARDLQRLLASLKPGDTVTLTVLRG 259

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.

Pssm-ID: 467252 [Multi-domain] Cd Length: 90 Bit Score: 40.48 E-value: 5.72e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569  820 DVHLRRMESGFGFRILG---GDEPGQP---ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRY 882
Cdd:cd06790      4 PVELEKGSEGLGISIIGmgvGADAGLEklgIFVKTVTEGGAAQRDGRIQVNDQIVEVDGISLVGVTQAF 72

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467194 [Multi-domain] Cd Length: 76 Bit Score: 39.92 E-value: 5.76e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569 1189 TVDMEKGAKGFGFSIRGGREYkmdlyVLRLAEDG-PAIRNGrMRVGDQIIEINGESTRDMTHARAIELI 1256
Cdd:cd06710      2 TVEIARGRAGYGFTISGQAPC-----VLSCVVRGsPADVAG-LKAGDQILAVNGINVSKASHEDVVKLI 64

PDZ domain of densin, erbin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of densin, erbin, and related domains. Densin (also known as leucine-rich repeat-containing protein 7, LRRC7, densin-180, protein LAP1) and erbin (also known as densin-180-like protein, Erbb2-interacting protein, protein LAP2) belong to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play roles in the maintenance of cell shape and apical-basal polarity. Densin and erbin are components of the excitatory postsynaptic compartment and are regulators of dendritic morphology and postsynaptic structure. The densin PDZ domain binds CaV1.3 alpha1 subunit, delta-catenin, and MAGUIN-1. Binding partners of the erbin PDZ domain include ErbB receptor tyrosine kinase ErbB2, HTLV-1 Tax1, Cav1.3 Ca2+channels, and constituents of the cadherin:catenin cell adhesion complex, in particular delta-catenin, p0071 and ARVCF. The erbin PDZ domain binds Smad3, a transductor of the TGFbeta pathway, possibly by a novel interface of binding. Erbin and two other LAP proteins (scribble and lano) redundantly regulate epithelial polarity and apical adhesion 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 densin and erbin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467231 [Multi-domain] Cd Length: 87 Bit Score: 40.39 E-value: 5.78e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  829 GFGFRILGG-DEPGQP-------ILIGAVIAMGSADrdGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAARNgqVNLTV 900
Cdd:cd06749     10 GLGFSISGGiGSQGNPfrpdddgIFVTKVQPDGPAS--KLLQPGDKILEVNGYDFVNIEHGQAVSLLKSFQNT--VDLVV 85


                   ..
gi 1034657569  901 RR 902
Cdd:cd06749     86 ER 87

Peptidase family M50;

Pssm-ID: 426630 [Multi-domain] Cd Length: 291 Bit Score: 43.63 E-value: 5.91e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  986 SGSTITVPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPhaDIVKLIKD-AGLSVTLRIIPQEELNSPTSAPSSE 1064
Cdd:pfam02163   87 SGVPPPAPPVIGGVAPGSPAAK-AGLKPGDVILSINGKKITSWQ--DLVEALAKsPGKPITLTVERGGQTLTVTITPKSS 163


                   ...
gi 1034657569 1065 KQS 1067
Cdd:pfam02163  164 EES 166

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 1; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinase MAST1, and related domains. MAST1 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. MAST1 functions as a scaffold protein to link the dystrophin/utrophin network with microfilaments via syntrophin, and it has been identified as a main driver of cisplatin resistance in human 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 MAST1 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

Pssm-ID: 467286 [Multi-domain] Cd Length: 95 Bit Score: 40.40 E-value: 6.30e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  961 SDVVIHRkENEGFGFVIISSLNRPESGSTITVPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDA 1040
Cdd:cd23073      3 SPITIQR-SGKKYGFTLRAIRVYMGDSDVYSVHHIVWHVEEGGPAQE-AGLCAGDLITHVNGEPVHGMVHPEVVELILKS 80

                           90
                   ....*....|..
gi 1034657569 1041 GLSVTLRIIPQE 1052
Cdd:cd23073     81 GNKVAVTTTPFE 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.

Pssm-ID: 467222 [Multi-domain] Cd Length: 82 Bit Score: 40.04 E-value: 6.43e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569  470 TLK--KSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQSV 538
Cdd:cd06740      5 TLKrsKSHEGLGFSIRGGAEHGVGIYVSLVEPGSLAEKEG-LRVGDQILRVNDVSFEKVTHAEAVKILRVS 74

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 440035 [Multi-domain] Cd Length: 274 Bit Score: 43.60 E-value: 6.43e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  492 LQVKSVIPDGPAAQDGkMETGDVIVYINEVCVlgHTHADVVKLFQSVPIGQSVNLVLCRG 551
Cdd:COG0265    203 VLVARVEPGSPAAKAG-LRPGDVILAVDGKPV--TSARDLQRLLASLKPGDTVTLTVLRG 259

PDZ domain of neuronal nitric oxide synthase (nNOS), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of nNOS, and related domains. nNOS produces a key signaling molecule, nitric oxide (NO), which has diverse functions throughout the body and acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. nNOS is concentrated at synaptic junctions in the brain and motor endplates in skeletal muscle. The PDZ domain of neuronal nitric oxide synthase (nNOS) interacts with the PDZ domain of alpha1-syntrophin (in muscle cells) and with the second PDZ domain of Disks large homolog 4 (Dlg4, also known as PSD-95), and nitric oxide synthase 1 adaptor protein NOS1AP in neurons. Dlg4 binds NMDA receptors, and nNOS, forming a complex in neurons. NOS1AP competes with Dgl4 for the nNOS PDZ domain and prevents the coupling of nNos activation with NMDA receptor-mediated calcium influx. 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 nNOS-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.

Pssm-ID: 467192 [Multi-domain] Cd Length: 110 Bit Score: 40.82 E-value: 6.50e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034657569  963 VVIHRKENEGFGFVIISSLNRPesgstitvPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKD 1039
Cdd:cd06708      5 VRLFKRKVGGLGFLVKQRVCKP--------PVIISDLIRGGAAEQSGLVQVGDIILAVNGRPLVDVSYESALEVLRS 73

PDZ domain 1 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467225 [Multi-domain] Cd Length: 76 Bit Score: 39.57 E-value: 7.19e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034657569  657 FGFTI-ADSPTgqrvkQILDIQ-GCP----GLCEGDLIVEINQQNVQNLSHTEVVDILKDCP 712
Cdd:cd06743     11 FGFSIgGSGPC-----YILSVEeGSSahaaGLQPGDQILELDGQDVSSLSCEAIIALARRCP 67

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467194 [Multi-domain] Cd Length: 76 Bit Score: 39.54 E-value: 7.21e-04

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gi 1034657569  471 LKKSNMGFGFTIIGgdepdeflQ----VKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKL 534
Cdd:cd06710      5 IARGRAGYGFTISG--------QapcvLSCVVRGSPADVAG-LKAGDQILAVNGINVSKASHEDVVKL 63

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 4 (MAST4); PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST4, and related domains. MAST4 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST4 is a component of the AICD-MAST4-FOXO1-RTKN2 neuroprotective pathway; MAST4 phosphorylation of forkhead box protein O1 (FOXO1) regulates rhotekin 2 (RTKN2) expression. As this pathway is repressed in Alzheimer's Disease (AD), MAST4 may play a role in preventing AD pathogenesis. 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 MAST4 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.

Pssm-ID: 467289 [Multi-domain] Cd Length: 95 Bit Score: 40.40 E-value: 7.26e-04

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gi 1034657569  963 VVIHrKENEGFGFVIISSLNRPESGSTITVPHKIGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGL 1042
Cdd:cd23076      5 IVIH-SSGKNYGFTIRAIRVYVGDSDIYTVHHIVWNVEEGSPACQ-AGLKAGDLITHINGEPVHGLVHTEVIELLLKSGN 82

                           90
                   ....*....|
gi 1034657569 1043 SVTLRIIPQE 1052
Cdd:cd23076     83 KVSITTTPFE 92

PDZ domain 9 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 9 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 PDZ9 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 PDZ9 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.

Pssm-ID: 467263 [Multi-domain] Cd Length: 79 Bit Score: 39.64 E-value: 7.33e-04

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gi 1034657569  470 TLKKSNMGFGFTIIGGDEPDEFLqVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQS 537
Cdd:cd10817      3 ELPKDQGGLGIAISEEDTENGIV-IKSLTEGGPAAKDGRLKVGDQILAVDDESVVGCPYEKAISLLKT 69

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.

Pssm-ID: 467217 [Multi-domain] Cd Length: 84 Bit Score: 39.87 E-value: 7.52e-04

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gi 1034657569  647 TLTIVKGAQGFGFTI------ADSPTgqRVKQILD---IQGCPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCpiGSET 717
Cdd:cd06735      3 SVELERGPKGFGFSIrggreyNNMPL--YVLRLAEdgpAQRDGRLRVGDQILEINGESTQGMTHAQAIELIRSG--GSVV 78


                   ....*.
gi 1034657569  718 SLIIHR 723
Cdd:cd06735     79 RLLLRR 84

PDZ domain of PDZ domain-containing protein GIPC1; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC1, and related domains. GIPC1 (also known as GIPC, GAIP/RGS19-interacting protein or Tax-interacting protein 2) belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC1 functions as an adaptor molecule for loading PDZ-target cargoes on the MYO6 motor protein. The GIPC1 PDZ domain interacts with a variety of ligands, such as RGS19, NRP1, GLUT1, SEMA4C, SDC4 and IGF1R. 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 GIPC1 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.

Pssm-ID: 467290 [Multi-domain] Cd Length: 94 Bit Score: 40.18 E-value: 7.59e-04

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gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKD--AGLSVTLRII 1049
Cdd:cd23077     32 IKRIKEGSVIDRIQLISVGDMIEAINGQSLLGCRHYEVARLLKElpRGRTFTLKLT 87

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.

Pssm-ID: 467222 [Multi-domain] Cd Length: 82 Bit Score: 39.65 E-value: 7.82e-04

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gi 1034657569  968 KENEGFGFVIisslnrpESGSTitvpHKIGRIID----GSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIK 1038
Cdd:cd06740     10 KSHEGLGFSI-------RGGAE----HGVGIYVSlvepGSLAEK-EGLRVGDQILRVNDVSFEKVTHAEAVKILR 72

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467228 [Multi-domain] Cd Length: 101 Bit Score: 40.27 E-value: 7.86e-04

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gi 1034657569  647 TLTIVKGAQGFGFTI----ADSPTGQRVK-------QILD--IQGCP----GLCEGDLIVEINQQNVQNLSHTEVVDILK 709
Cdd:cd06746      8 TVVLQKGDKGFGFVLrgakAVGPILEFTPtpafpalQYLEsvDPGGVadkaGLKKGDFLLEINGEDVVKASHEQVVNLIR 87

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.

Pssm-ID: 467179 [Multi-domain] Cd Length: 88 Bit Score: 39.90 E-value: 7.91e-04

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gi 1034657569  654 AQGFGFTI-------ADSPTGQRVKQILdiqgcPG--------LCEGDLIVEINQQNVQNLSHTEVVDILKDCPIGSETS 718
Cdd:cd06692      7 SKGLGIKIiggyrenTGEEFGIFIKRIL-----PGglaatdgrLKEGDLILEVNGESLQGVTNERAVSILRSASASNHMS 81


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gi 1034657569  719 LIIHRGG 725
Cdd:cd06692     82 LLIARDE 88

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 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 PDLIM-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.

Pssm-ID: 467235 [Multi-domain] Cd Length: 79 Bit Score: 39.44 E-value: 8.12e-04

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gi 1034657569  478 FGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMEtGDVIVYINEVCVLGHTHADVVKLFQSvpIGQSVNLVLCR 550
Cdd:cd06753     10 WGFRLQGGKDFNQPLTISRVTPGGKAAQANLRP-GDVILAINGESTEGMTHLEAQNKIKA--ATGSLSLTLER 79

PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467181 [Multi-domain] Cd Length: 90 Bit Score: 39.94 E-value: 9.08e-04

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gi 1034657569  819 LDVHLRRMESGFGFRILGG--DEPGQP----ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAAr 892
Cdd:cd06695      2 FEVKLTKGSSGLGFSFLGGenNSPEDPfsglVRIKKLFPGQPAAESGLIQEGDVILAVNGEPLKGLSYQEVLSLLRGAP- 80

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gi 1034657569  893 nGQVNLTVRRK 903
Cdd:cd06695     81 -PEVTLLLCRP 90

PDZ domain 2 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 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.

Pssm-ID: 467207 [Multi-domain] Cd Length: 85 Bit Score: 39.56 E-value: 9.45e-04

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gi 1034657569  820 DVHLRRMESGFGFRILGGDE----PG-QPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTH 880
Cdd:cd06724      1 EIKLVKGPKGLGFSIAGGVGnqhiPGdNGIYVTKIIEGGAAQKDGRLQVGDKLLAVNDVSLEEVTH 66

PDZ domain of neuronal nitric oxide synthase (nNOS), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of nNOS, and related domains. nNOS produces a key signaling molecule, nitric oxide (NO), which has diverse functions throughout the body and acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. nNOS is concentrated at synaptic junctions in the brain and motor endplates in skeletal muscle. The PDZ domain of neuronal nitric oxide synthase (nNOS) interacts with the PDZ domain of alpha1-syntrophin (in muscle cells) and with the second PDZ domain of Disks large homolog 4 (Dlg4, also known as PSD-95), and nitric oxide synthase 1 adaptor protein NOS1AP in neurons. Dlg4 binds NMDA receptors, and nNOS, forming a complex in neurons. NOS1AP competes with Dgl4 for the nNOS PDZ domain and prevents the coupling of nNos activation with NMDA receptor-mediated calcium influx. 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 nNOS-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.

Pssm-ID: 467192 [Multi-domain] Cd Length: 110 Bit Score: 40.44 E-value: 9.49e-04

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gi 1034657569 1198 GFGFSIRGgREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS--GGRRVRLLLK 1268
Cdd:cd06708     14 GLGFLVKQ-RVCKPPVIISDLIRGGAAEQSGLVQVGDIILAVNGRPLVDVSYESALEVLRSipSETPVVLILR 85

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

Pssm-ID: 436067 [Multi-domain] Cd Length: 54 Bit Score: 38.66 E-value: 1.04e-03

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gi 1034657569  845 LIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHryVIDLMHHAArNGQVNLTVRR 902
Cdd:pfam17820    1 VVTAVVPGSPAERAG-LRVGDVILAVNGKPVRSLED--VARLLQGSA-GESVTLTVRR 54

PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. 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 Dlg5-like family PSZ2 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.

Pssm-ID: 467246 [Multi-domain] Cd Length: 77 Bit Score: 39.25 E-value: 1.05e-03

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gi 1034657569  836 GGDEPG----QPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKT 879
Cdd:cd06765      6 GQKDSGisleNGVFISRIVPGSPAAKEGSLTVGDRIIAINGIALDNKS 53

PDZ domain 3 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 3 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 Par-3 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 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.

Pssm-ID: 467272 [Multi-domain] Cd Length: 103 Bit Score: 39.96 E-value: 1.18e-03

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gi 1034657569  494 VKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVV-----KLFQSVPIGQSVNLVLCR 550
Cdd:cd23059     41 IKSIIHGGAASKDGRLRVNDQLIAVNGESLLGLTNSEAMetlrrAMSTEGNIRGMIQLVVAR 102

PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight junction (PATJ, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 12 of MUPP1, PDZ domain 10 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 PDZ12 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

Pssm-ID: 467163 [Multi-domain] Cd Length: 86 Bit Score: 39.27 E-value: 1.19e-03

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gi 1034657569  843 PILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAArnGQVNLTV 900
Cdd:cd06675     29 PVFIAMIQPNGVAAQTGKLKVGDRIVSINGQSTDGLTHSEAVNLLKNAS--GTIILQV 84

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This tamalin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467197 [Multi-domain] Cd Length: 91 Bit Score: 39.53 E-value: 1.19e-03

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gi 1034657569  472 KKSNMGFGFTI-------IGGDEPDEFLQVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQS 537
Cdd:cd06713     10 KQDNETFGFEIqtyglhhKNSNEVEMCTYVCRVHEDSPAYLAG-LTAGDVILSVNGVSVEGASHQEIVELIRS 81

PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. 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 PDZRN4-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.

Pssm-ID: 467200 [Multi-domain] Cd Length: 88 Bit Score: 39.18 E-value: 1.29e-03

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gi 1034657569  962 DVVIHRKENEG-FGFVIISSLNrPESGSTITVphkiGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHAdiVKLIKDA 1040
Cdd:cd06716      5 EVTLKRSNSQEkLGLTLCYRTD-DEEDTGIYV----SEVDPNSIAAKDGRIREGDQILQINGVDVQNREEA--IALLSEE 77


                   ....*.
gi 1034657569 1041 GLSVTL 1046
Cdd:cd06716     78 EKSITL 83

PDZ domain 5 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 5 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 PDZ5 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.

Pssm-ID: 467183 [Multi-domain] Cd Length: 87 Bit Score: 39.25 E-value: 1.34e-03

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gi 1034657569 1192 MEKGAKGFGFSIRGGREYKMD-LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRL 1265
Cdd:cd06697      8 LTCHPGQLGLKLTGGSDSKYQvIYVLEIVPGSAAAEEGSLQPLDIIHYINGVSTQGMTLEDAVRALEASLPTVVL 82

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.

Pssm-ID: 467222 [Multi-domain] Cd Length: 82 Bit Score: 38.88 E-value: 1.42e-03

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gi 1034657569  821 VHLRRMES--GFGFRILGGDEPGQPILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTH 880
Cdd:cd06740      4 VTLKRSKSheGLGFSIRGGAEHGVGIYVSLVEPGSLAEKEG-LRVGDQILRVNDVSFEKVTH 64

PDZ domain 4 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. 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 Dlg5-like 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.

Pssm-ID: 467247 [Multi-domain] Cd Length: 81 Bit Score: 38.91 E-value: 1.44e-03

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gi 1034657569 1186 DYFTVDMEKGAKGFGFSIRGGReyKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARA-IELIK 1257
Cdd:cd06766      1 EPRLVFLKKSQVELGIQLCGGN--LHGIFVEDVEDDSPAKGPDGLVPGDLILEYNSVDMRNKTAEEAyLEMLK 71

PDZ domain 2 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the second PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467270 [Multi-domain] Cd Length: 85 Bit Score: 39.29 E-value: 1.46e-03

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gi 1034657569  996 IGRIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIK 1038
Cdd:cd10834     31 VSKVDPGGLAEQ-NGIKVGDQILAVNGVSFEDITHSKAVEVLK 72

PDZ domain 4 of PDZ domain containing 2 (PDZD2), PDZ domain 2 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 4 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the second PDZ domain (PDZ2) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). 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 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.

Pssm-ID: 467241 [Multi-domain] Cd Length: 90 Bit Score: 39.18 E-value: 1.54e-03

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gi 1034657569  682 LCEGDLIVEINQQNVQNLSHTEVVDILKDCPIGsETSLIIHR 723
Cdd:cd06760     50 LRRGDQILEINGTSLRNVTLNEAYAILSQCKPG-PVTLIISR 90

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 3 (MAST3); PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST3, and related domains. MAST3 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST3 plays a critical role in regulating the immune response of inflammatory bowel disease (IBD), and is involved in the process of cytoskeleton organization, intracellular signal transduction and peptidyl-serine phosphorylation. MAST3 also promotes the proliferation and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis. Binding partners of MAST3 include cAMP-regulated phosphoprotein (ARPP-16) and the tumor suppressor 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 MAST3 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.

Pssm-ID: 467288 [Multi-domain] Cd Length: 94 Bit Score: 39.24 E-value: 1.57e-03

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gi 1034657569  498 IPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQsvpigQSVNLVLCRGYPL 554
Cdd:cd23075     40 VEDGSPAQEAGLRAGDLITHINGESVLGLVHMDVVELLL-----KSGNKVSLRTTAL 91

permuted PDZ domain of Deg/high-temperature requirement factor A (HtrA) family of housekeeping serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Deg/HtrA-type serine proteases that participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. Typically, these proteases have an N-terminal serine protease domain and at least one C-terminal PDZ domain that recognizes substrates, and in some cases activates the protease function. An exception is yeast Nma11p which has two protease domains and four PDZ domains; its N-terminal half is comprised of a protease domain, followed by two PDZ domains, and its C-terminal half has a similar domain arrangement. HtrA-type proteases include the human HtrA1-4 and MBTPS2, tricorn protease, DegS, DegP and C-terminal processing peptidase, cyanobacterial serine proteases Hhoa, HhoB, and HtrA, and yeast Nma11p. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-termini of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This Deg/HtrA family PDZ domain is a circularly permuted PDZ domain which places beta-strand A at the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467621 [Multi-domain] Cd Length: 91 Bit Score: 39.20 E-value: 1.59e-03

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gi 1034657569 1196 AKGFGFSIRGGreykmdLYVLRLAEDGPAIRNGrMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLKRG 1270
Cdd:cd06779     16 AKELGLPVNRG------VLVAEVIPGSPAAKAG-LKEGDVILSVNGKPVTSFNDLRAALDTKKPGDSLNLTILRD 83

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 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 3 of PDZD2, also known as KIAA0300, PIN-1, 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 also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). 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 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.

Pssm-ID: 467240 [Multi-domain] Cd Length: 87 Bit Score: 38.79 E-value: 1.72e-03

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gi 1034657569  972 GFGFVIISSLNRPESGSTITVPhkigRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDA--GLsVTLRI 1048
Cdd:cd06759     13 GLGFSIVGGRDSPRGPMGIYVK----TIFPGGAAAEDGRLKEGDEILEVNGESLQGLTHQEAIQKFKQIkkGL-VVLTV 86

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467273 [Multi-domain] Cd Length: 80 Bit Score: 38.87 E-value: 1.76e-03

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gi 1034657569  652 KGAQGFGFTIADSPTGQRVKQIldiqgCPG--------LCEGDLIVEINQQNVQNLSHTEVVDILKDCP 712
Cdd:cd23060      9 NGGLGFSLVGGEGGSGIFVKSI-----SPGgvadrdgrLQVGDRLLQVNGESVIGLSHSKAVNILRKAK 72

PDZ domain of tyrosine-protein phosphatase non-receptor type 3 (PTPN3), tyrosine-protein phosphatase non-receptor type 4 (PTNP4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PTPN3, PTPN4 and related domains. PTPN3 (also known as protein-tyrosine phosphatase H1, PTP-H1) has a tumor-suppressive or a tumor-promoting role in many cancers. It serves as a specific phosphatase for the MAP kinase p38gamma; the two interact via their PDZ domains and cooperate to promote Ras-induced oncogenesis. Interaction partners of the PTPN3 PDZ domain include p38gamma and human papillomavirus E6 oncoprotein. PTPN4 (also known as protein-tyrosine phosphatase MEG1) plays a role in immunity, learning, synaptic plasticity or cell homeostasis. p38gamma is also an interaction partner of the PTPN4 PDZ domain: PTPN4 regulates neuronal cell homeostasis by protecting neurons against apoptosis; binding of the C terminus of p38gamma to the PDZ domain of PTPN4, antagonizes the catalytic autoinhibition of PTPN4, leading to cell apoptosis. Other interaction partners of the PTPN4 PDZ domain include glutamate receptor subunit GluN2A, and RABV strain G protein, among others. 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 PTPN3-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.

Pssm-ID: 467190 [Multi-domain] Cd Length: 90 Bit Score: 38.83 E-value: 1.77e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034657569  478 FGFTIIGGDEPDEFLQVKSVIPDGPAAQ-DGKMETGDVIVYINEVCVLGHTHADVVKLFQSVPIGQSVNLVL 548
Cdd:cd06706     16 FGFNVKGGVDQKMPVIVSRVAPGTPADLcIPRLNEGDQVLLINGRDISEHTHDQVVMFIKASRERHSGELVL 87

PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNPO2, SYNPO2L, and related domains. SYNPO2 (also known as genethonin-2, myopodin) is a cytoskeleton adaptor protein. It participates in chaperone-assisted selective autophagy (CASA), a mechanism for the disposal of misfolded and damaged proteins and provides a link between the CASA chaperone complex and a membrane-tethering and fusion machinery that generates autophagosome membranes. The SYNPO2 PPxY motif binds CASA cochaperone BCL2-associated athanogene 3 (BAG3) and the SYNPO2 PDZ domain binds vacuolar protein sorting 18 homolog (VPS18). There are three isoforms of SYNPO2, which possess an amino-terminal PDZ domain (SYNPO2a, b, c); the short isoform SYNPO2d, lacks the PDZ 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 SYNPO2-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.

Pssm-ID: 467264 [Multi-domain] Cd Length: 78 Bit Score: 38.44 E-value: 1.87e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  478 FGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMEtGDVIVYINEVCVLGHTHADVVKLFQS 537
Cdd:cd10820     10 WGFRLQGGSEQKKPLQVAKIRKKSKAALAGLCE-GDELLSINGKPCADLSHSEAMDLIDS 68

circularly permuted first PDZ domain (PDZ1) of Saccharomyces cerevisiae pro-apoptotic serine protease Nma111p and related domains; First PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the HtrA-type protease Saccharomyces cerevisiae Nma111p (also known as Ynm3p), and related domains. Nma111p is a nuclear serine protease which mediates apoptosis through proteolysis of the apoptotic inhibitor Bir1p. Nma111p is composed of two protease domains and four PDZ domains; its N-terminal half is comprised of a protease domain, followed by two PDZ domains, and its C-terminal half has a similar domain arrangement. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This ScNma111-like PDZ1 domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation places both beta-strands A and B on the C-terminus.

Pssm-ID: 467625 [Multi-domain] Cd Length: 89 Bit Score: 38.71 E-value: 1.94e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  488 PDE--FLQVKSVIPDGPAaqDGKMETGDVIVYINevcvlGHTHADVVKLF----QSVpiGQSVNLVLCRG 551
Cdd:cd06786     19 PSEtgMLVAETVLPEGPA--DGKLEEGDVLISVN-----GELITQFIRLEeildENV--GKTVELVVQRG 79

PDZ domain 5 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family domain PDZ5 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.

Pssm-ID: 467170 [Multi-domain] Cd Length: 85 Bit Score: 38.87 E-value: 1.96e-03

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1034657569  824 RRMESGFGFRILGGD--EPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPV 875
Cdd:cd06682      7 KRSGVGLGITISAPKnrKPGDPLIISDVKKGSVAHRTGTLEPGDKLLAIDNIRL 60

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467282 [Multi-domain] Cd Length: 76 Bit Score: 38.53 E-value: 1.98e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  821 VHLRRMESGFGFRILGGDepgqPILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTHRYVIDLMhhaARNGQVNLTV 900
Cdd:cd23069      4 VVIQRDENGYGLTVSGDN----PVFVQSVKEGGAAYRAG-VQEGDRIIKVNGTLVTHSNHLEVVKLI---KSGSYVALTL 75

Splicing factor [RNA processing and modification];

Pssm-ID: 227435 [Multi-domain] Cd Length: 590 Bit Score: 42.76 E-value: 2.04e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569  294 KPED---NEEPDPLPDNWEMAYTEKGEVYFIDHNTKTTSWLDPRLAKKAKPPEECKENE 349
Cdd:COG5104     41 KPKEllkGSEEDLDVDPWKECRTADGKVYYYNSITRESRWKIPPERKKVEPIAEQKHDE 99

PDZ domain 3 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 3 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. 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 PDZ3 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.

Pssm-ID: 467215 [Multi-domain] Cd Length: 85 Bit Score: 38.75 E-value: 2.05e-03

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gi 1034657569  645 LMTLTIVKGAQGFGFTI--ADSPTGQ-RVKQILdiqgcPG--------LCEGDLIVEINQQNVQNLSHTEVVDILKDCPI 713
Cdd:cd06733      1 ELTVFLRRQETGFGFRIlgGTEEGSQvSIGAIV-----PGgaadldgrLRTGDELLSVDGVNVVGASHHKVVDLMGNAAR 75

                           90
                   ....*....|
gi 1034657569  714 GSETSLIIHR 723
Cdd:cd06733     76 NGQVNLTVRR 85

PDZ domain 1 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. 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 Dlg5-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.

Pssm-ID: 467245 [Multi-domain] Cd Length: 95 Bit Score: 38.92 E-value: 2.09e-03

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gi 1034657569 1189 TVDMEKG-----AKGFGFSIRGGREYKM-----DLYVLRLaeDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06764      6 TVEFEKVrddmdLKALGFDIAGGVNDPQfpgdcSIFVTKV--DKGSIADGRLRVNDCLLRINDVDLTNKDKKQAIQAVLN 83

                           90
                   ....*....|.
gi 1034657569 1259 GGRRVRLLLKR 1269
Cdd:cd06764     84 GGGVINMVVRR 94

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.

Pssm-ID: 467184 [Multi-domain] Cd Length: 89 Bit Score: 38.82 E-value: 2.13e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569  477 GFGFTIIGG----DEPDEFLQvkSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHAD 530
Cdd:cd06698     12 GLGLSIVGGinrpEGPMVFIQ--EVIPGGDCYKDGRLRPGDQLVSINKESLIGVTLEE 67

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.

Pssm-ID: 467184 [Multi-domain] Cd Length: 89 Bit Score: 38.82 E-value: 2.20e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569  972 GFGFVIISSLNRPEsGSTITvphkIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHAD 1032
Cdd:cd06698     12 GLGLSIVGGINRPE-GPMVF----IQEVIPGGDCYKDGRLRPGDQLVSINKESLIGVTLEE 67

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467249 [Multi-domain] Cd Length: 80 Bit Score: 38.57 E-value: 2.25e-03

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gi 1034657569   29 GFELKGGA-ENGQFpyLGEVKPGKVAYESGskLVSEELLLEVNETPVAGLTIRDVLAVIKHCKDPLRL 95
Cdd:cd06768     13 GFNLHAEKgRPGHF--IREVDPGSPAERAG--LKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTL 76

PDZ domain of membrane palmitoylated proteins (MPPs), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1-7 (also known as MAGUK p55 subfamily members 1-7), and related domains. MPPs comprise a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). MPPs form diverse protein complexes at the cell membranes, which are involved in a wide range of cellular processes, including establishing proper cell structure, polarity and cell adhesion. MPPs have only one PDZ 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 MPP1-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.

Pssm-ID: 467208 [Multi-domain] Cd Length: 80 Bit Score: 38.40 E-value: 2.41e-03

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gi 1034657569 1215 VLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKS 1258
Cdd:cd06726     26 VARILHGGMAHRSGLLHVGDEILEINGIPVSGKTVDELQKLLSS 69

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. 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 Zasp52-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.

Pssm-ID: 467281 [Multi-domain] Cd Length: 82 Bit Score: 38.28 E-value: 2.48e-03

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gi 1034657569  681 GLCEGDLIVEINQQNVQNLSHTEVVDILKDCpiGSETSLIIHR 723
Cdd:cd23068     42 GLRRGDVILRINGTDTSNLTHKQAQDLIKRA--GNDLQLTVQR 82

PDZ domain 1 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. 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 INAD-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.

Pssm-ID: 467276 [Multi-domain] Cd Length: 87 Bit Score: 38.65 E-value: 2.48e-03

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gi 1034657569  828 SGFGFRILGGDEPGQP------ILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHA 890
Cdd:cd23063     10 KSFGICIVRGEVKVSPntkttgIFIKGIIPDSPAHKCGRLKVGDRILSVNGNDVRNSTEQAAIDLIKEA 78

circularly permuted PDZ domain of high-temperature requirement factor A (HtrA) family serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of HtrA family serine proteases including human HtrA1, HtrA2 (mitochondrial), HtrA3, and HtrA4, and related domains. These proteases are key enzymes associated with pregnancy. Their diverse biological functions include cell growth proliferation, migration and apoptosis. They are also implicated in disorders including Alzheimer's, Parkinson's, arthritis and cancer. HtrA1 (also known as high-temperature requirement A serine peptidase 1, L56, and serine protease 11) substrates include extracellular matrix proteins, proteoglycans, and insulin-like growth factor (IGF)-binding proteins. HtrA1 also inhibits signaling by members of the transforming growth factor beta (TGF-beta) family. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This HtrA-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467624 [Multi-domain] Cd Length: 98 Bit Score: 38.63 E-value: 2.52e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569  998 RIIDGSPADRcAKLKVGDRILAVNGQSIINMphADIVKLIK-DAGLSVTLR---------IIPQE 1052
Cdd:cd06785     37 KVIPGSPAQR-AGLKDGDVIISINGKPVKSS--SDVYEAVKsGSSLLVVVRrgnedllltVTPEE 98

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.

Pssm-ID: 467159 [Multi-domain] Cd Length: 96 Bit Score: 38.84 E-value: 2.59e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  472 KKSNMGFGFTIIGGDEPDEFLQ---------VKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVV 532
Cdd:cd06671      9 REPGKSLGISIVGGRVMGSRLSngeeirgifIKHVLEDSPAGRNGTLKTGDRILEVNGVDLRNATHEEAV 78

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.

Pssm-ID: 467210 [Multi-domain] Cd Length: 79 Bit Score: 38.36 E-value: 2.64e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569  467 LSTTLKKSNMGFGFTIIGGDEpdefLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKL 534
Cdd:cd06728      1 LKVTLTKSRKNDEYGLRLGSR----IFVKEITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKL 64

PDZ domain 3 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 3 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 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.

Pssm-ID: 467211 [Multi-domain] Cd Length: 82 Bit Score: 38.32 E-value: 2.68e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569  479 GFTIIGGDEPDEFlqVKSVIPDGPAAQDGkMETGDVIVYINEVCVLGHTHADVVKLFQSVPIGQSVNLV 547
Cdd:cd06729     14 GLRLAGGNDVGIF--VAGVQEGSPAEKQG-LQEGDQILKVNGVDFRNLTREEAVLFLLDLPKGEEVTIL 79

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 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 PDLIM-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.

Pssm-ID: 467235 [Multi-domain] Cd Length: 79 Bit Score: 37.89 E-value: 2.88e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657569   29 GFELKGGAENGQFPYLGEVKPGKVAYESGskLVSEELLLEVNETPVAGLTIRDVLAVIKHCKDPLRLKC 97
Cdd:cd06753     11 GFRLQGGKDFNQPLTISRVTPGGKAAQAN--LRPGDVILAINGESTEGMTHLEAQNKIKAATGSLSLTL 77

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.

Pssm-ID: 467159 [Multi-domain] Cd Length: 96 Bit Score: 38.46 E-value: 2.96e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034657569  648 LTIVKG-AQGFGFTIADSPTGQRVKQILdiQGCPG-----LCEGDLIVEINQQNVQNLSHTEVVDILKDCP 712
Cdd:cd06671     17 ISIVGGrVMGSRLSNGEEIRGIFIKHVL--EDSPAgrngtLKTGDRILEVNGVDLRNATHEEAVEAIRNAG 85

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467282 [Multi-domain] Cd Length: 76 Bit Score: 37.76 E-value: 3.05e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034657569  647 TLTIVKGAQGFGFTIA-DSPTG-QRVKQildiQG---CPGLCEGDLIVEINQQNVQNLSHTEVVDILK 709
Cdd:cd23069      3 CVVIQRDENGYGLTVSgDNPVFvQSVKE----GGaayRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIK 66

PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP3, MPP4, and MPP7, and related domains. MPP3 (also known as MAGUK p55 subfamily member 3, erythrocyte membrane protein p55, or EMP55), MPP4 (also known as MAGUK p55 subfamily member 4 or Discs large homolog 6), and MPP7 (also known as MAGUK p55 subfamily member 7) are membrane-associated guanylate kinase (MAGUK)-like proteins. MPP3 is part of a cell adhesion protein complex including tumor suppressor CADM1 and actin-binding protein 4.1B. Participation in the Crumbs cell polarity complex has also been demonstrated for MPP7 in epithelial cells, and for MPP3 and MPP4 in the retina. MPP4 is needed for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Binding partners of the MPP3 PDZ domain include nectin-3, serotonin 5-hydroxytryptamine, 5-HT(2C) receptor, and a cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1); fragments of MPP4 having the PDZ domain bind CRB (PDZ-SH3-GUK) and GABA transporter GAT1 (PDZ-SH3). 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 MPP1-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.

Pssm-ID: 467260 [Multi-domain] Cd Length: 81 Bit Score: 37.99 E-value: 3.57e-03

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gi 1034657569 1208 EYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELI 1256
Cdd:cd06799     20 EKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQIL 68

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.

Pssm-ID: 467237 [Multi-domain] Cd Length: 83 Bit Score: 38.01 E-value: 3.66e-03

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                   ....*....|....*....|....*....
gi 1034657569  681 GLCEGDLIVEINQQNVQNLSHTEVVDILK 709
Cdd:cd06755     43 GLKRGDQILEVNGQNFENITLKKALEILR 71

Fe-S oxidoreductase, related to NifB/MoaA family [Energy production and conversion];

Pssm-ID: 441232 [Multi-domain] Cd Length: 441 Bit Score: 41.28 E-value: 4.20e-03

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                   ....*....|....*....|....*....|...
gi 1034657569  993 PHKIGRIIDGSPADRcAKLKVGDRILAVNGQSI 1025
Cdd:COG1625      5 GAKISKVEPGSIAEE-LGIEPGDRLLSINGQPI 36

PDZ domain 1 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP 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.

Pssm-ID: 467175 [Multi-domain] Cd Length: 83 Bit Score: 37.78 E-value: 4.48e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569  472 KKSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNL 546
Cdd:cd06687      7 KKEGSTLGLTVSGGIDKDGKPRVSNLRPGGIAARSDQLNVGDYIKSVNGIRTTKLRHDEIISLLKNV--GERVVL 79

Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 227354 [Multi-domain] Cd Length: 872 Bit Score: 41.68 E-value: 4.66e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657569  263 ASGEMPSQPYPAPVYSQPEELKEQMDDTKPTKPEDNEEPDPLpdnWEMAYTEKGEVYFIDHNTKTTSWLDPRLAKKAK-- 340
Cdd:COG5021    350 SIKDLPHQVGSNPFLEAHPEFSELLKNQSRGTTRDFRNKPTG---WSSSIEDLGQFLFSDFLTSSSTYEDLRREQLGRes 426

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1034657569  341 -----------PPEECKENELPYGWEKIDDPIYGTYYVDHINRRTQFENPVLEAK 384
Cdd:COG5021    427 desfyvasnvqQQRASREGPLLSGWKTRLNNLYRFYFVEHRKKTLTKNDSRLGSF 481

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.

Pssm-ID: 467168 [Multi-domain] Cd Length: 89 Bit Score: 37.71 E-value: 4.76e-03

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gi 1034657569   16 HESVIGRNPEGQLGFELKGGAE--NGQFP-YLGEVKPGKVAYESGsKLVSEELLLEVNETPVAGLTIRDVLAVIKHCK 90
Cdd:cd06680      1 KDITLRRSSSGSLGFSIVGGYEesHGNQPfFVKSIVPGTPAYNDG-RLKCGDIILAVNGVSTVGMSHAALVPLLKEQR 77

PDZ domain of MYO18A protein, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MYO18 protein and related domains. MYO18 (also known as myosin XVIIIA, KIAA0216, MysPDZ), a member of the myosin superfamily, is involved in regulating cell protrusion and migration, and Golgi trafficking and morphology, and is required for myoblast adhesion and muscle integrity. The MYO18A/MRCK/LRAP35a complex regulates actomyosin retrograde flow in cell protrusion and migration; the PtdIns(4)P/GOLPH3/MYO18A/F-actin complex is a hub for signals that regulate Golgi trafficking function. The MYO18A PDZ domain binds p190Rho-guanine nucleotide exchange factor (p190RhoGEF), Golgin45, and leucine repeat adaptor protein 1 (Lurap1, also known as Lrap35a). 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 MYO18-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467229 [Multi-domain] Cd Length: 90 Bit Score: 37.68 E-value: 4.94e-03

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                   ....*....|....*....|....*....
gi 1034657569  681 GLCEGDLIVEINQQNVQNLSHTEVVDILK 709
Cdd:cd06747     51 GLLPGDRLIEVNGVNVENASRDEIIEMIR 79

PDZ domain of PDZ domain-containing protein GIPC1; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC1, and related domains. GIPC1 (also known as GIPC, GAIP/RGS19-interacting protein or Tax-interacting protein 2) belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC1 functions as an adaptor molecule for loading PDZ-target cargoes on the MYO6 motor protein. The GIPC1 PDZ domain interacts with a variety of ligands, such as RGS19, NRP1, GLUT1, SEMA4C, SDC4 and IGF1R. 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 GIPC1 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.

Pssm-ID: 467290 [Multi-domain] Cd Length: 94 Bit Score: 37.87 E-value: 5.19e-03

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gi 1034657569  648 LTIVKGAQGFGFTIADSPTG----QRVKQILDIQGCPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCPIGSETSL 719
Cdd:cd23077      9 VEVFKSEDALGLTITDNGAGyafiKRIKEGSVIDRIQLISVGDMIEAINGQSLLGCRHYEVARLLKELPRGRTFTL 84

PDZ domain 3 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 3 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 Par-3 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 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.

Pssm-ID: 467272 [Multi-domain] Cd Length: 103 Bit Score: 38.03 E-value: 5.41e-03

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gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKlikdaglsvTLRIIPQEELNSP 1057
Cdd:cd23059     41 IKSIIHGGAASKDGRLRVNDQLIAVNGESLLGLTNSEAME---------TLRRAMSTEGNIR 93

PDZ domain of MYO18A protein, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MYO18 protein and related domains. MYO18 (also known as myosin XVIIIA, KIAA0216, MysPDZ), a member of the myosin superfamily, is involved in regulating cell protrusion and migration, and Golgi trafficking and morphology, and is required for myoblast adhesion and muscle integrity. The MYO18A/MRCK/LRAP35a complex regulates actomyosin retrograde flow in cell protrusion and migration; the PtdIns(4)P/GOLPH3/MYO18A/F-actin complex is a hub for signals that regulate Golgi trafficking function. The MYO18A PDZ domain binds p190Rho-guanine nucleotide exchange factor (p190RhoGEF), Golgin45, and leucine repeat adaptor protein 1 (Lurap1, also known as Lrap35a). 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 MYO18-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467229 [Multi-domain] Cd Length: 90 Bit Score: 37.68 E-value: 5.45e-03

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gi 1034657569  820 DVHLRRMESG-FGF---------RILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHH 889
Cdd:cd06747      1 EITLKRQPTGdFGFslrrgtiveRGPDDGQELKRTVHFAEPGAGTKNLATGLLPGDRLIEVNGVNVENASRDEIIEMIRK 80

                           90
                   ....*....|..
gi 1034657569  890 AARngQVNLTVR 901
Cdd:cd06747     81 SGD--TVTLKVQ 90

PDZ domain of PDZ domain-containing protein GIPC2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GIPC2, and related domains. GIPC2 belongs to the GIPC family, members of which contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc2 gene have been linked to cancer. 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 GIPC2 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.

Pssm-ID: 467291 Cd Length: 93 Bit Score: 37.59 E-value: 5.46e-03

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gi 1034657569  648 LTIVKGAQGFGFTIADSPTG----QRVKQILDIQGCPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCP 712
Cdd:cd23078      9 VNVYKSEDSLGLTITDNGVGyafiKRIKDGSVIDSVKTICVGDHIECINGENIVGWRHYEVAKKLKELK 77

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.

Pssm-ID: 467237 [Multi-domain] Cd Length: 83 Bit Score: 37.24 E-value: 5.69e-03

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gi 1034657569 1002 GSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIK-DAGLSVTLR 1047
Cdd:cd06755     36 GSKAAE-AGLKRGDQILEVNGQNFENITLKKALEILRnNTHLSITVK 81

PDZ domain of PICK1 (protein interacting with C-kinase 1) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PICK1, and related domains. PICK1 (also known as PRKCA-binding protein and protein kinase C-alpha-binding protein) plays a key role in regulating trafficking of binding partners by altering either their subcellular targeting and/or surface expression. PICK1 plays a role in synaptic plasticity by regulating the trafficking and internalization of amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors; the PICK1-PDZ domain binds the AMPA receptor subunits. The PICK1 PDZ domain also binds glutamate transporters, Eph receptors, metabotropic glutamate receptors, and ASICs (acid-sensing ion channels), among others. Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes. 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 PICK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467205 [Multi-domain] Cd Length: 84 Bit Score: 37.40 E-value: 5.73e-03

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 1034657569  996 IGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRI 1048
Cdd:cd06722     29 IVQVFDNTPAAKDGTLAAGDEIVGVNGKSVKGKTKVEVAKMIQAVKGEVTIHY 81

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. 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 RIM-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.

Pssm-ID: 467198 [Multi-domain] Cd Length: 95 Bit Score: 37.53 E-value: 5.78e-03

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gi 1034657569 1198 GFGFSIRGGREY---KMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLK 1268
Cdd:cd06714     22 GLGLKVVGGKMTesgRLGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFEEVQDIISQSKGEVELVVS 95

PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. 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 Dlg5-like family PSZ2 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.

Pssm-ID: 467246 [Multi-domain] Cd Length: 77 Bit Score: 37.33 E-value: 5.82e-03

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gi 1034657569 1195 GAKGFGFSIRGGreykmdLYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIKSGGRRVRLLLKR 1269
Cdd:cd06765      6 GQKDSGISLENG------VFISRIVPGSPAAKEGSLTVGDRIIAINGIALDNKSLSECEALLRSCRDSLSLSLMK 74

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.

Pssm-ID: 467179 [Multi-domain] Cd Length: 88 Bit Score: 37.59 E-value: 5.93e-03

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gi 1034657569  971 EGFGFVIISSlNRPESGSTITVphKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRII 1049
Cdd:cd06692      8 KGLGIKIIGG-YRENTGEEFGI--FIKRILPGGLAATDGRLKEGDLILEVNGESLQGVTNERAVSILRSASASNHMSLL 83

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

Pssm-ID: 467155 [Multi-domain] Cd Length: 80 Bit Score: 37.26 E-value: 6.17e-03

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gi 1034657569  647 TLTIVKGAQGFGFTIADS-PTGQRVKQILdiqgcPG--------LCEGDLIVEINQQNVQNLSHTEVVDILKDCpiGSET 717
Cdd:cd06667      2 VIELVNDGSGLGFGIVGGkSTGVVVKTIL-----PGgvadrdgrLRSGDHILQIGDTNLRGMGSEQVAQVLRQC--GSHV 74


                   ....*.
gi 1034657569  718 SLIIHR 723
Cdd:cd06667     75 RLVVAR 80

PDZ domain of ARHGAP21 and ARHGAP23, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGAP21, ARHGAP23, and related domains. This subfamily includes the GAPs (GTPase activating proteins): ARHGAP21 (Rho GTPase-activating protein 21; also known as Rho GTPase-activating protein 10, Rho-type GTPase-activating protein 21) and ARHGAP23 (Rho GTPase-activating protein 23; also known as Rho-type GTPase-activating protein 23). GAPs deactivate Rho GTPases by accelerating GTP hydrolysis. ARHGAP21/23 interact with a planar cell polarity (PCP) protein Pk1 to regulate a lateral signaling pathway in migrating cells. The ARHGAP21 PDZ domain binds claudin-2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGAP21-23-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467238 [Multi-domain] Cd Length: 109 Bit Score: 37.82 E-value: 6.30e-03

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gi 1034657569  981 LNRPESGSTITVPHkigrIIDGSPADRcAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRII 1049
Cdd:cd06756     46 RSRLEPMDTIFVKQ----VKEGGPAHQ-AGLCTGDRIVKVNGESVIGKTYSQVIALIQNSDSTLELSVM 109

PDZ domain of densin, erbin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of densin, erbin, and related domains. Densin (also known as leucine-rich repeat-containing protein 7, LRRC7, densin-180, protein LAP1) and erbin (also known as densin-180-like protein, Erbb2-interacting protein, protein LAP2) belong to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play roles in the maintenance of cell shape and apical-basal polarity. Densin and erbin are components of the excitatory postsynaptic compartment and are regulators of dendritic morphology and postsynaptic structure. The densin PDZ domain binds CaV1.3 alpha1 subunit, delta-catenin, and MAGUIN-1. Binding partners of the erbin PDZ domain include ErbB receptor tyrosine kinase ErbB2, HTLV-1 Tax1, Cav1.3 Ca2+channels, and constituents of the cadherin:catenin cell adhesion complex, in particular delta-catenin, p0071 and ARVCF. The erbin PDZ domain binds Smad3, a transductor of the TGFbeta pathway, possibly by a novel interface of binding. Erbin and two other LAP proteins (scribble and lano) redundantly regulate epithelial polarity and apical adhesion 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 densin and erbin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467231 [Multi-domain] Cd Length: 87 Bit Score: 37.31 E-value: 6.48e-03

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gi 1034657569  470 TLKKsNMGFGFTIIGG----------DEPDEFlqVKSVIPDGPAAqdGKMETGDVIVYINEVCVLGHTHADVVKLFQSVp 539
Cdd:cd06749      4 RIEK-NPGLGFSISGGigsqgnpfrpDDDGIF--VTKVQPDGPAS--KLLQPGDKILEVNGYDFVNIEHGQAVSLLKSF- 77

                           90
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gi 1034657569  540 iGQSVNLVLCR 550
Cdd:cd06749     78 -QNTVDLVVER 87

PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. 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 Dlg5-like family PSZ2 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.

Pssm-ID: 467246 [Multi-domain] Cd Length: 77 Bit Score: 36.94 E-value: 6.94e-03

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gi 1034657569  494 VKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSVpiGQSVNLVLCRGYP 553
Cdd:cd06765     20 ISRIVPGSPAAKEGSLTVGDRIIAINGIALDNKSLSECEALLRSC--RDSLSLSLMKVFP 77

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.

Pssm-ID: 467253 [Multi-domain] Cd Length: 89 Bit Score: 37.21 E-value: 7.04e-03

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gi 1034657569  651 VKGAQGFGFTIA--------DSPTGQRVKQIL-----DIQGCpgLCEGDLIVEINQQNVQNLSHTEVVDILK 709
Cdd:cd06791      8 VKDEQGLGITIAgyvgekasGELSGIFVKSIIpgsaaDQDGR--IQVNDQIIAVDGVNLQGFTNQEAVEVLR 77

permuted PDZ domain of Deg/high-temperature requirement factor A (HtrA) family of housekeeping serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Deg/HtrA-type serine proteases that participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. Typically, these proteases have an N-terminal serine protease domain and at least one C-terminal PDZ domain that recognizes substrates, and in some cases activates the protease function. An exception is yeast Nma11p which has two protease domains and four PDZ domains; its N-terminal half is comprised of a protease domain, followed by two PDZ domains, and its C-terminal half has a similar domain arrangement. HtrA-type proteases include the human HtrA1-4 and MBTPS2, tricorn protease, DegS, DegP and C-terminal processing peptidase, cyanobacterial serine proteases Hhoa, HhoB, and HtrA, and yeast Nma11p. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-termini of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This Deg/HtrA family PDZ domain is a circularly permuted PDZ domain which places beta-strand A at the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467621 [Multi-domain] Cd Length: 91 Bit Score: 37.27 E-value: 7.22e-03

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gi 1034657569  680 PGLCEGDLIVEINQQNVQNlsHTEVVDILKDCPIGSETSLIIHRGG 725
Cdd:cd06779     41 AGLKEGDVILSVNGKPVTS--FNDLRAALDTKKPGDSLNLTILRDG 84

circularly permuted second PDZ domain (PDZ2) of Escherichia coli periplasmic serine endoprotease DegP and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Escherichia coli DegP (also known as heat shock protein DegP and Protease Do), and related domains. DegP belongs to the HtrA family of housekeeping proteases. It acts as a protease, degrading transiently denatured and unfolded or misfolded proteins which accumulate in the periplasm following heat shock or other stress conditions, and as a molecular chaperone at low temperatures. DegP has two PDZ domains in addition to the protease domain; its PDZ1 domain is responsible for the identifying the distinct substrate sequences that affect degradation (degron) of the substrate sequence, and its PDZ2 domain is responsible for the combining with other DegP monomers to form a stable oligomer structure. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This DegP family PDZ domain 2 is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

Pssm-ID: 467631 [Multi-domain] Cd Length: 83 Bit Score: 37.22 E-value: 7.23e-03

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gi 1034657569 1002 GSPADRcAKLKVGDRILAVNGQSIINMphADIVKLIKDAGLSVTLRIIPQEE 1053
Cdd:cd23084     28 GSPAAQ-SGLKKGDVIIGVNRQPVKSI--AELRKVLKSKPSAVLLQIKRGDS 76

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.

Pssm-ID: 467188 [Multi-domain] Cd Length: 87 Bit Score: 37.26 E-value: 7.32e-03

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gi 1034657569  819 LDVHLRRMESGFGFRILGG--------DEPGqpILIGAVIAMGSADRDGrLHPGDELVYVDGIPVAGKTH 880
Cdd:cd06704      1 LTITIERQTGGLGISIAGGkgstpykgDDEG--IFISRVTEGGPAAKAG-VRVGDKLLEVNGVDLVDADH 67

PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. 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 PDZRN4-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.

Pssm-ID: 467200 [Multi-domain] Cd Length: 88 Bit Score: 37.25 E-value: 7.45e-03

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gi 1034657569  815 DYKELDVHLRRMESGFGFRIL--GGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHryVIDLMHHAAR 892
Cdd:cd06716      2 EYEEVTLKRSNSQEKLGLTLCyrTDDEEDTGIYVSEVDPNSIAAKDGRIREGDQILQINGVDVQNREE--AIALLSEEEK 79

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gi 1034657569  893 NgqVNLTVRR 902
Cdd:cd06716     80 S--ITLLVAR 87

PDZ domain 1 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as (X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2), which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins such as APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 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 APBA1,2,3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

Pssm-ID: 467203 [Multi-domain] Cd Length: 86 Bit Score: 37.24 E-value: 7.60e-03

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gi 1034657569 1222 GPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIK 1257
Cdd:cd06720     38 GPAARSGKLNIGDQIMSINGTSLVGLPLSTCQAIIK 73

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and 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. 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 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.

Pssm-ID: 467239 [Multi-domain] Cd Length: 88 Bit Score: 36.95 E-value: 7.86e-03

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gi 1034657569  648 LTIVKGAQGFGFTIAD------SPTGQRVKQILD---IQGCPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCP 712
Cdd:cd06758      5 MHLLKEKGGLGIQITGgkgskrGDIGIFVAGVEEggsADRDGRLKKGDELLMINGQSLIGLSHQEAVAILRSSA 78

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This tamalin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

Pssm-ID: 467197 [Multi-domain] Cd Length: 91 Bit Score: 37.22 E-value: 7.95e-03

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gi 1034657569  647 TLTIVKGAQG-FGFTI-------ADSPTGQRVKQILDIQG-----CPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCP 712
Cdd:cd06713      5 TIILEKQDNEtFGFEIqtyglhhKNSNEVEMCTYVCRVHEdspayLAGLTAGDVILSVNGVSVEGASHQEIVELIRSSG 83

PDZ domain 6 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 6 of multi-PDZ-domain protein 1 (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 PDZ6 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 PDZ6 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

Pssm-ID: 467158 [Multi-domain] Cd Length: 87 Bit Score: 36.85 E-value: 8.29e-03

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gi 1034657569  647 TLTIVKGAQGFGFTIADSP--TGQRVKQIldiqgCPG--------LCEGDLIVEINQQNVQNLSHTEVVDILKDC-PIGS 715
Cdd:cd06670      6 TITIVKGNSSLGITVSADKdgNGCIVKSI-----IHGgavsrdgrISVGDFIVSINNESLRNVTNAQARAILRRAsLVGT 80


                   ....
gi 1034657569  716 ETSL 719
Cdd:cd06670     81 DISI 84

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 1; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinase MAST1, and related domains. MAST1 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. MAST1 functions as a scaffold protein to link the dystrophin/utrophin network with microfilaments via syntrophin, and it has been identified as a main driver of cisplatin resistance in human 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 MAST1 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

Pssm-ID: 467286 [Multi-domain] Cd Length: 95 Bit Score: 37.31 E-value: 8.60e-03

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gi 1034657569  681 GLCEGDLIVEINQQNVQNLSHTEVVDIL 708
Cdd:cd23073     50 GLCAGDLITHVNGEPVHGMVHPEVVELI 77

PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of harmonin isoforms a and b, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. 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 harmonin 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.

Pssm-ID: 467221 [Multi-domain] Cd Length: 94 Bit Score: 36.90 E-value: 9.29e-03

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gi 1034657569 1200 GFSIRGGREYKMD--LYVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAIELIK----SGGRRVRL 1265
Cdd:cd06739     15 DLALEGGIDSPLGgkIVVSAVYEGGAADKHGGIVKGDQIMMVNGKSLTDVTLAEAEAALQramnSGGDWIDL 86

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.

Pssm-ID: 467201 [Multi-domain] Cd Length: 87 Bit Score: 36.96 E-value: 9.90e-03

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gi 1034657569  479 GFTIIG--GDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTHADVVKLFQSV 538
Cdd:cd06717     13 GISIVGqsNERGDGGIYVGSIMKGGAVAADGRIEPGDMILQVNDISFENMSNDDAVRVLREA 74