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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 557948073    2 VTQIRNQSKASGSGLCEGDEVVSINGNPCADLTYPEVIKLMESITDSLQMLIK 54
Cdd:cd10820    26 VAKIRKKSKAALAGLCEGDELLSINGKPCADLSHSEAMDLIDSSGDTLQLLIK 78

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 557948073    2 VTQIRNQSKASGSGLCEGDEVVSINGNPCADLTYPEVIKLMESITDSLQMLIK 54
Cdd:cd10820    26 VAKIRKKSKAALAGLCEGDELLSINGKPCADLSHSEAMDLIDSSGDTLQLLIK 78

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

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 557948073      2 VTQIRNQSKASGSGLCEGDEVVSINGNPCADLTYPEVIKLMESITDSLQMLIKRPS 57
Cdd:smart00228   30 VSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTVLRGG 85

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073   736 SSSSQPVTPvSPvwSPGVAPTQPPAFPTSNPSKGTVVSSIKIAQPSypPARPASTLNVAGPFKG---PQAAVASQN---Y 809
Cdd:pfam05109  482 TSGASPVTP-SP--SPRDNGTESKAPDMTSPTSAVTTPTPNATSPT--PAVTTPTPNATSPTLGktsPTSAVTTPTpnaT 556

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073   810 TPKPTVSTPTVNAVQP--GAVGPSNELPGMSGRGAqlfakrqsrmekyvvdSDTVQAHAARAQSPTPSLPASwKYSSNVR 887
Cdd:pfam05109  557 SPTPAVTTPTPNATIPtlGKTSPTSAVTTPTPNAT----------------SPTVGETSPQANTTNHTLGGT-SSTPVVT 619

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073   888 APPPVAYNPIHSPSYPLAALKSQPSAAQPSkmGKKKGKKPLNALDVMKHQPyqlnasLFTFQPPDAKDGLPQKSSVKVNS 967
Cdd:pfam05109  620 SPPKNATSAVTTGQHNITSSSTSSMSLRPS--SISETLSPSTSDNSTSHMP------LLTSAHPTGGENITQVTPASTST 691

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 557948073   968 ALAMKQALPPRPVNAASPTNVQASSVYSVPAYT-----SPPSffaEASSPVSASPVPVGIPT 1024
Cdd:pfam05109  692 HHVSTSSPAPRPGTTSQASGPGNSSTSTKPGEVnvtkgTPPK---NATSPQAPSGQKTAVPT 750

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 557948073    2 VTQIRNQSKASGSGLCEGDEVVSINGNPCADLTYPEVIKLMESITDSLQMLIK 54
Cdd:cd10820    26 VAKIRKKSKAALAGLCEGDELLSINGKPCADLSHSEAMDLIDSSGDTLQLLIK 78

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

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 557948073      2 VTQIRNQSKASGSGLCEGDEVVSINGNPCADLTYPEVIKLMESITDSLQMLIKRPS 57
Cdd:smart00228   30 VSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTVLRGG 85

PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form domain-swapping dimers; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 557948073    2 VTQIRNQSKASGSG-LCEGDEVVSINGNPCADLTYPEVIKLMESITDSLQMLIKRP 56
Cdd:cd06728    24 VKEITPDSLAAKDGnLQEGDIILKINGTPVENLSLSEAKKLIEKSKDKLQLVVLRD 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 557948073    9 SKASGSGLCEGDEVVSINGNPCADLTYPEVIKLMESITDSLQMLIKR 55
Cdd:cd06753    33 GKAAQANLRPGDVILAINGESTEGMTHLEAQNKIKAATGSLSLTLER 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 557948073    2 VTQIRNQSKASGSGLCEGDEVVSINGNPCADLTYPEVIKLMESI-TDSLQM 51
Cdd:cd06712    25 VASVDPGSCAAEAGLKEGDYIVSVGGVDCKWSKHSEVVKLLKSAgEEGLEL 75

PDZ domain 5 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 5 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. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ 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 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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 557948073   10 KASGSGLCEGDEVVSINGNPCADLTYPEVIKLMESITDSLQMLIKR 55
Cdd:cd06761    40 RESMGKLTAGDEIVSINGTPVSAMSYQETCHLMQNLPKSLTLEVQK 85

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 557948073    2 VTQIRNQSKASGSG-LCEGDEVVSINGNPCADlTYPEVIKLMESITDSLQMLIKR 55
Cdd:cd06750    29 ISKIEEGGKAASVGkLQVGDEVVNINGVPLSG-SRQEAIQLVKGSHKTLKLVVRR 82

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 557948073   11 ASGSGLC-EGDEVVSINGNPCADLTYPEVIKLMESITDSLQMLIKRP 56
Cdd:cd06695    44 AAESGLIqEGDVILAVNGEPLKGLSYQEVLSLLRGAPPEVTLLLCRP 90

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073  799 GPQAAVASQNYTPKPTVSTPTVNAVQPGAVGPSNELPGMSGRGAQLFAKRQSRMEkyvvdSDTVQAHAARAQSPTPSLPA 878
Cdd:PRK12323  373 GPATAAAAPVAQPAPAAAAPAAAAPAPAAPPAAPAAAPAAAAAARAVAAAPARRS-----PAPEALAAARQASARGPGGA 447

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073  879 SWKYSSNVRAPPPVAYNPIHSPSYPLAALKSQPSAAQPSKMGKKKGKKPlnaldvmkhQPYQLNASLFTFQPPDAKDGLP 958
Cdd:PRK12323  448 PAPAPAPAAAPAAAARPAAAGPRPVAAAAAAAPARAAPAAAPAPADDDP---------PPWEELPPEFASPAPAQPDAAP 518

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 557948073  959 QKSSVKVNSALAMKQALPPRPVNAASPTNVQASSVYSVPAYTSPP 1003
Cdd:PRK12323  519 AGWVAESIPDPATADPDDAFETLAPAPAAAPAPRAAAATEPVVAP 563

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073   736 SSSSQPVTPvSPvwSPGVAPTQPPAFPTSNPSKGTVVSSIKIAQPSypPARPASTLNVAGPFKG---PQAAVASQN---Y 809
Cdd:pfam05109  482 TSGASPVTP-SP--SPRDNGTESKAPDMTSPTSAVTTPTPNATSPT--PAVTTPTPNATSPTLGktsPTSAVTTPTpnaT 556

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073   810 TPKPTVSTPTVNAVQP--GAVGPSNELPGMSGRGAqlfakrqsrmekyvvdSDTVQAHAARAQSPTPSLPASwKYSSNVR 887
Cdd:pfam05109  557 SPTPAVTTPTPNATIPtlGKTSPTSAVTTPTPNAT----------------SPTVGETSPQANTTNHTLGGT-SSTPVVT 619

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073   888 APPPVAYNPIHSPSYPLAALKSQPSAAQPSkmGKKKGKKPLNALDVMKHQPyqlnasLFTFQPPDAKDGLPQKSSVKVNS 967
Cdd:pfam05109  620 SPPKNATSAVTTGQHNITSSSTSSMSLRPS--SISETLSPSTSDNSTSHMP------LLTSAHPTGGENITQVTPASTST 691

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 557948073   968 ALAMKQALPPRPVNAASPTNVQASSVYSVPAYT-----SPPSffaEASSPVSASPVPVGIPT 1024
Cdd:pfam05109  692 HHVSTSSPAPRPGTTSQASGPGNSSTSTKPGEVnvtkgTPPK---NATSPQAPSGQKTAVPT 750

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 557948073   11 ASGSGLCEGDEVVSINGNPCADLTYPEVIKLMESITDSLQMLIKR 55
Cdd:cd06765    30 AKEGSLTVGDRIIAINGIALDNKSLSECEALLRSCRDSLSLSLMK 74

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073   736 SSSSQPVTPVSPVWSPGVAP--TQPPAFPTSNPSKGTVVSSIKIAQPSYPPArPASTLNVAgPFKGPQAAVASQNyTPKP 813
Cdd:pfam03154  193 QAATAGPTPSAPSVPPQGSPatSQPPNQTQSTAAPHTLIQQTPTLHPQRLPS-PHPPLQPM-TQPPPPSQVSPQP-LPQP 269

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073   814 TVSTPTVNAVQPGAVGPSN-ELPGMSGRGAQLFAKRQSRMEKYVVDSDTVQAHAARAQSPTPSLPASwkyssnvraPPPV 892
Cdd:pfam03154  270 SLHGQMPPMPHSLQTGPSHmQHPVPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTPPSQSQLQS---------QQPP 340

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073   893 AYNPIHSPSYPLAALKSQPSAAQPSKMGKKKGKKPLNaldVMKHQPYQLNASLftfQPPDAKDGLPQKSSVKVNSA---- 968
Cdd:pfam03154  341 REQPLPPAPLSMPHIKPPPTTPIPQLPNPQSHKHPPH---LSGPSPFQMNSNL---PPPPALKPLSSLSTHHPPSAhppp 414

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557948073   969 ---LAMKQALPPRPvnaASPTNVQASSVYSVPAYTSPPSFFAEASSPVSASPVPVGIPTSPKQESASSSyfvaprPKFSA 1045
Cdd:pfam03154  415 lqlMPQSQQLPPPP---AQPPVLTQSQSLPPPAASHPPTSGLHQVPSQSPFPQHPFVPGGPPPITPPSG------PPTST 485

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 557948073  1046 KKSGVTIQESGRSLSLPGRSVPPPISTSpwvyQPTYSYSSKPTDGLEKANKRPTPWEAAAKSP 1108
Cdd:pfam03154  486 SSAMPGIQPPSSASVSSSGPVPAAVSCP----LPPVQIKEEALDEAEEPESPPPPPRSPSPEP 544