DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in dishevelled-like proteins. Dishevelled-like proteins play a key role in the transduction of the Wnt signal from the cell surface to the nucleus, which in turn is an important regulatory pathway for cellular development and growth. They contain an N-terminal DIX domain, a central PDZ domain, and a C-terminal DEP domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 426 TIVKTMAAPDSGLDIRDRMWLKITIPNAFIGSDVVDWLYSHVEGFQDRREARKYACNLLKAGFIRHTVNKITFSEQCYYV 505
Cdd:cd04438     2 GIPRVMRRPDSGLEIKDRMWLKITIPNSFIGSDLVDWLLSHVEGLTDRREARKYASSLLKLGYIRHTVNKITFSEQCYYV 81

                  ...
gi 1176118552 506 FGD 508
Cdd:cd04438    82 FGD 84

Dishevelled specific domain; This domain is specific to the signalling protein dishevelled. The domain is found adjacent to the PDZ domain pfam00595, often in conjunction with DEP (pfam00610) and DIX (pfam00778). Much of it is disordered and yet conserved.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552  93 DQQSVISA-ASDLHPPMPRTVGIGDSRPPSFHPHGGHS-TAGDFDSEVDSTVSSRRgsrrrEKHINRNEVIH-GRHRQGG 169
Cdd:pfam02377   1 DGGSQCTEsPSDLPPPLERTGGIGDSRPPSFHPNAAGSrDGLDNETETESVVSHRR-----DRERRRRREGHdHGPRLNG 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 170 RHEGDR------YESAS-MMSSDIETTSYQDSSDDQSSVsRFSSTTE--GSQLLRGRHRRRRRRPRMPRVQRCSSFSTIT 240
Cdd:pfam02377  76 HSKGERrpdlggYDSSStLMSSELETTSFFDSEDDDSTS-RFSSSTEqsSSSRLLRRHRRRRRKPKMPRMERSSSFSSIT 154

                  ....*.
gi 1176118552 241 ESTMSL 246
Cdd:pfam02377 155 DSTMSL 160

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in dishevelled-like proteins. Dishevelled-like proteins play a key role in the transduction of the Wnt signal from the cell surface to the nucleus, which in turn is an important regulatory pathway for cellular development and growth. They contain an N-terminal DIX domain, a central PDZ domain, and a C-terminal DEP domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 426 TIVKTMAAPDSGLDIRDRMWLKITIPNAFIGSDVVDWLYSHVEGFQDRREARKYACNLLKAGFIRHTVNKITFSEQCYYV 505
Cdd:cd04438     2 GIPRVMRRPDSGLEIKDRMWLKITIPNSFIGSDLVDWLLSHVEGLTDRREARKYASSLLKLGYIRHTVNKITFSEQCYYV 81

                  ...
gi 1176118552 506 FGD 508
Cdd:cd04438    82 FGD 84

DIX domain; The DIX domain is present in Dishevelled and axin. This domain is involved in homo- and hetero-oligomerization. It is involved in the homo- oligomerization of mouse axin. The axin DIX domain also interacts with the dishevelled DIX domain. The DIX domain has also been called the DAX domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1176118552   3 ETKVIYHIDDEDTPYLVKLPKSPTDVTLSDFKNVLNRP-SYKFFFKSMDDDFGVVKEEISDEEMNLPCFNGRVVAWL 78
Cdd:pfam00778   1 ETKVIYYLCDEPVPYRIKIHKPGGQITLGDFKELLPKKgNYRYFFKTLDPEFGTVKEEITDDDDILPLWEGKIVAKV 77

Domain found in Dishevelled, Egl-10, and Pleckstrin; Domain of unknown function present in signalling proteins that contain PH, rasGEF, rhoGEF, rhoGAP, RGS, PDZ domains. DEP domain in Drosophila dishevelled is essential to rescue planar polarity defects and induce JNK signalling (Cell 94, 109-118).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1176118552  434 PDSGLDIRDRMWLKITIPNAFIGSDVVDWLYSHVEgFQDRREARKYACNLLKAGFIRHTV--NKITFS-EQCYYVFGD 508
Cdd:smart00049   1 PETGLKLRDRKYFLKTYPNCFTGSELVDWLMDNLE-IIDREEAVHLGQLLLDEGLIHHVNgpNKHTFKdSKALYRFTT 77

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1176118552 437 GLDIRDRMWLKITIPNAFIGSDVVDWLYSHVEgFQDRREARKYACNLLKAGFIRHTVNKI-TFS-EQCYYVF 506
Cdd:pfam00610   1 GVKLKDRRKHLKTYPNCFTGSEAVDWLMDNLE-IITREEAVELGQLLLDQGLIHHVGDKHgLFKdSYYFYRF 71

Segment polarity protein dishevelled (Dsh) C terminal; This domain family is found in eukaryotes, and is typically between 177 and 207 amino acids in length. The family is found in association with pfam00778, pfam02377, pfam00610, pfam00595. The segment polarity gene dishevelled (dsh) is required for pattern formation of the embryonic segments. It is involved in the determination of body organization through the Wingless pathway (analogous to the Wnt-1 pathway).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 512 NMAALSINEHEGDG---DQDTLGPLPtHQQGISWMSGPPSygyhqmPSYPPPQPIVDAQTPGYAQSF-YSAHSGSQSPH- 586
Cdd:pfam12316   1 NMANLNLNDDDGSSgasDQDTLAPLP-HPGTAPWPMGQFF------PYQYPPPPPYTQFPPYHEDSSsYSGGGGSAGSQh 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 587 -----------SASGSSKRSGGGGGDRGDGDHRSSGGSSSEKSGSSKGKSKSKEREARSVEGSVQLP------------- 642
Cdd:pfam12316  74 segsrssgsnrSGGGGPRKQKEEKAGSKGGSGSESESARRSSQRGIRVPAQGSRGSHASSRSSHSLGgggsrshhslhas 153

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1176118552 643 ----------PMPGAPPIGVP---IGVPIGVPIGvpigapmpggppmpgiammpRPLDQVPENVSASRNSFRMAMG 705
Cdd:pfam12316 154 haggmplayyGPPGLPPPAAApaaSQGPPGAPPG--------------------RELASVPPELTASRQSFQMAMG 209

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in dishevelled-like proteins. Dishevelled-like proteins play a key role in the transduction of the Wnt signal from the cell surface to the nucleus, which in turn is an important regulatory pathway for cellular development and growth. They contain an N-terminal DIX domain, a central PDZ domain, and a C-terminal DEP domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 426 TIVKTMAAPDSGLDIRDRMWLKITIPNAFIGSDVVDWLYSHVEGFQDRREARKYACNLLKAGFIRHTVNKITFSEQCYYV 505
Cdd:cd04438     2 GIPRVMRRPDSGLEIKDRMWLKITIPNSFIGSDLVDWLLSHVEGLTDRREARKYASSLLKLGYIRHTVNKITFSEQCYYV 81

                  ...
gi 1176118552 506 FGD 508
Cdd:cd04438    82 FGD 84

DIX domain; The DIX domain is present in Dishevelled and axin. This domain is involved in homo- and hetero-oligomerization. It is involved in the homo- oligomerization of mouse axin. The axin DIX domain also interacts with the dishevelled DIX domain. The DIX domain has also been called the DAX domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1176118552   3 ETKVIYHIDDEDTPYLVKLPKSPTDVTLSDFKNVLNRP-SYKFFFKSMDDDFGVVKEEISDEEMNLPCFNGRVVAWL 78
Cdd:pfam00778   1 ETKVIYYLCDEPVPYRIKIHKPGGQITLGDFKELLPKKgNYRYFFKTLDPEFGTVKEEITDDDDILPLWEGKIVAKV 77

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 250 TVTLNMEKVNFLGISIVGQSNkrGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREmvhKPGP 329
Cdd:cd00136     1 TVTLEKDPGGGLGFSIRGGKD--GGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKS---AGGE 75

                  ....*.
gi 1176118552 330 ITLTVA 335
Cdd:cd00136    76 VTLTVR 81

Domain found in Dishevelled, Egl-10, and Pleckstrin; Domain of unknown function present in signalling proteins that contain PH, rasGEF, rhoGEF, rhoGAP, RGS, PDZ domains. DEP domain in Drosophila dishevelled is essential to rescue planar polarity defects and induce JNK signalling (Cell 94, 109-118).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1176118552  434 PDSGLDIRDRMWLKITIPNAFIGSDVVDWLYSHVEgFQDRREARKYACNLLKAGFIRHTV--NKITFS-EQCYYVFGD 508
Cdd:smart00049   1 PETGLKLRDRKYFLKTYPNCFTGSELVDWLMDNLE-IIDREEAVHLGQLLLDEGLIHHVNgpNKHTFKdSKALYRFTT 77

PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of human PTPN13, and related domains. PTPN13, also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1), negatively regulates FAS-mediated apoptosis and NGFR-mediated pro-apoptotic signaling, and may also regulate phosphoinositide 3-kinase (PI3K) signaling. It contains 5 PDZ domains; interaction partners of its second PDZ domain (PDZ2) include the Fas receptor (TNFRSF6) and thyroid receptor-interacting protein 6 (TRIP6). The second PDZ (PDZ2) domain, but not PDZ1 or PDZ3, of FRMPD2 binds to GluN2A and GluN2B, two subunits of N-methyl-d-aspartic acid (NMDA) receptors. Other binding partners of the FRMPDZ2 PDZ2 domain include NOD2, and catenin family members, delta catenin (CTNND2), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) and p0071 (also known as plakophilin 4; PKP4). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 247 NIITVTLNmEKVNFLGISIVGQSNKRGD-GGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLRemvH 325
Cdd:cd06792     1 DVFEVELS-KKDGSLGISVTGGINTSVRhGGIYVKSLVPGGAAEQDGRIQKGDRLLEVNGVSLEGVTHKQAVECLK---N 76

                          90
                  ....*....|.
gi 1176118552 326 KPGPITLTVAK 336
Cdd:cd06792    77 AGQVVTLVLER 87

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 248 IITVTLNMEKVNFLGISIVGQSNK-----RGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLRE 322
Cdd:cd23059     5 TFEIPLNDTGSAGLGVSVKGKTSKednggKADLGIFIKSIIHGGAASKDGRLRVNDQLIAVNGESLLGLTNSEAMETLRR 84

                          90
                  ....*....|....*....
gi 1176118552 323 MVH----KPGPITLTVAKC 337
Cdd:cd23059    85 AMStegnIRGMIQLVVARR 103

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 248 IITVTLNMEKvNFLGISIVGqsnKRGDG----GIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLRem 323
Cdd:cd06789     3 IITVTLKKVG-NGMGLSIVA---AKGAGqdklGIYIKSVVKGGAADLDGRLQAGDQLLSVDGHSLVGLSQERAAELMT-- 76

                          90
                  ....*....|....
gi 1176118552 324 vhKPGP-ITLTVAK 336
Cdd:cd06789    77 --KTGSvVTLEVAK 88

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1176118552 261 LGISI---VGQSNKRGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLR 321
Cdd:cd06724    11 LGFSIaggVGNQHIPGDNGIYVTKIIEGGAAQKDGRLQVGDKLLAVNDVSLEEVTHEEAVAALK 74

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1176118552 261 LGISIVG-QSNKRGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREMvhKPGPITLTVA 335
Cdd:cd06759    14 LGFSIVGgRDSPRGPMGIYVKTIFPGGAAAEDGRLKEGDEILEVNGESLQGLTHQEAIQKFKQI--KKGLVVLTVR 87

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1176118552 261 LGISIVGQS--NKRGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREMvhKPGPITLTVAK 336
Cdd:cd06669    20 LGFSILDYQdpLDPSETVIVIRSLVPGGVAEQDGRLLPGDRLVFVNDVSLENASLDEAVQALKSA--PPGTVRIGVAK 95

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 248 IITVTLNMEKVNFLGISIVGQSNKRGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREMvhKP 327
Cdd:cd06760     4 IMEVTLNKEPGVGLGIGLCCLPLENDIPGIFIHHLSPGSVAHMDGRLRRGDQILEINGTSLRNVTLNEAYAILSQC--KP 81

                  ....*....
gi 1176118552 328 GPITLTVAK 336
Cdd:cd06760    82 GPVTLIISR 90

PDZ1 domain of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains. Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This STXBP4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1176118552 261 LGISIVGQSNKRG--DGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLReMVHKPGPITLTVAK 336
Cdd:cd06692    10 LGIKIIGGYRENTgeEFGIFIKRILPGGLAATDGRLKEGDLILEVNGESLQGVTNERAVSILR-SASASNHMSLLIAR 86

PDZ domain of synaptojanin-2-binding protein (SYNJ2BP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNJ2BP, and related domains. SYNJ2BP (also known as mitochondrial outer membrane protein 25, OMP25) regulates endocytosis of activin type 2 receptor kinases through the Ral/RALBP1-dependent pathway and may be involved in suppression of activin-induced signal transduction. Binding partners of the SYNJ2BP PDZ domain include activin type II receptors (ActR-II), and SYNJ2. SYNJ2BP interacts with the PDZ binding motif of the Notch Delta-like ligand 1 (DLL1) and DLL4, promoting Delta-Notch signaling, and inhibiting sprouting angiogenesis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SYNJ2BP-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1176118552 261 LGISIVG---QSNKRGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLR 321
Cdd:cd06709    12 LGFNIVGgtdQPYIPNDSGIYVAKIKEDGAAAIDGRLQEGDKILEINGQSLENLTHQDAVELFR 75

PDZ domain 10 of multi-PDZ-domain protein 1 (MUPP1), domain 8 of PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 10 of MUPP1, PDZ domain 8 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ10 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1176118552 261 LGISIVGQSNKRgDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREmvhKPGPITLTV 334
Cdd:cd06673    15 LGLSIVGGSDTL-LGAIIIHEVYEDGAAAKDGRLWAGDQILEVNGEDLRKATHDEAINVLRQ---TPQKVRLLV 84

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1176118552 261 LGISIVGQSNKRGdggIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREmvhKPGPITLTVA 335
Cdd:cd23060    12 LGFSLVGGEGGSG---IFVKSISPGGVADRDGRLQVGDRLLQVNGESVIGLSHSKAVNILRK---AKGTVQLTVS 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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1176118552 261 LGISIVGQSNkrgdGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLRE 322
Cdd:cd06667    12 LGFGIVGGKS----TGVVVKTILPGGVADRDGRLRSGDHILQIGDTNLRGMGSEQVAQVLRQ 69

PDZ domain 1 of FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of FRMPD2 (also known as PDZ domain-containing protein 4, and related domains. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1176118552 248 IITVTLNMEKVNFLGISIVGQSNK-RGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLR 321
Cdd:cd23071     2 IVCVTLKRDPKRGFGFVIVGGENTgKLDLGIFIASIIPGGPAEKDGRIKPGGRLISLNNISLEGVTFNTAVKILQ 76

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1176118552 261 LGISIVGQSNKRGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREMvhkPGPITLTVAK 336
Cdd:cd06668    16 LGISLEGTVDVEVRGHHYIRSILPEGPVGRNGKLFSGDELLEVNGIQLLGLSHKEVVSILKEL---PPPVRLVCCR 88

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 250 TVTLNmEKVNFLGISIVG-QSNKRGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREmvhKPG 328
Cdd:cd06676     1 TITLE-RGSDGLGFSIVGgFGSPHGDLPIYVKTVFEKGAAAEDGRLKRGDQILAVNGESLEGVTHEEAVNILKK---TKG 76

                  ....*.
gi 1176118552 329 PITLTV 334
Cdd:cd06676    77 TVTLTV 82

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1176118552 261 LGISIVGQSNK-RGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREMvhKPG-PITLTVAK 336
Cdd:cd23058    17 LGFSITSRDNPtGGSGPIYIKNILPKGAAIQDGRLKAGDRLLEVNGVDVTGKTQEEVVSLLRST--KLGgTVSLVVSR 92

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1176118552 261 LGISIVGQSN-------KRGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLRE 322
Cdd:cd06701    17 LGISIRGGAKghagnplDPTDEGIFISKINPDGAAARDGRLKVGQRILEVNGQSLLGATHQEAVRILRS 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 250 TVTLNMEKVNF-LGISIVG-QSNKRGDGGIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREMvhKP 327
Cdd:cd06763     1 AVTVELEKGSAgLGFSLEGgKGSPLGDRPLTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLTRFEAWNIIKSL--PE 78

                  ....*..
gi 1176118552 328 GPITLTV 334
Cdd:cd06763    79 GPVTLLI 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 248 IITVTLNMEKVNFlGISIVGqsnkrGDG---GIYVGSIMKGGAVDLDGRIEPGDMLLQVNDVNFENMSNDDAVRVLREMV 324
Cdd:cd06733     1 ELTVFLRRQETGF-GFRILG-----GTEegsQVSIGAIVPGGAADLDGRLRTGDELLSVDGVNVVGASHHKVVDLMGNAA 74

                          90
                  ....*....|
gi 1176118552 325 HKpGPITLTV 334
Cdd:cd06733    75 RN-GQVNLTV 83

Segment polarity protein dishevelled (Dsh) C terminal; This domain family is found in eukaryotes, and is typically between 177 and 207 amino acids in length. The family is found in association with pfam00778, pfam02377, pfam00610, pfam00595. The segment polarity gene dishevelled (dsh) is required for pattern formation of the embryonic segments. It is involved in the determination of body organization through the Wingless pathway (analogous to the Wnt-1 pathway).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 512 NMAALSINEHEGDG---DQDTLGPLPtHQQGISWMSGPPSygyhqmPSYPPPQPIVDAQTPGYAQSF-YSAHSGSQSPH- 586
Cdd:pfam12316   1 NMANLNLNDDDGSSgasDQDTLAPLP-HPGTAPWPMGQFF------PYQYPPPPPYTQFPPYHEDSSsYSGGGGSAGSQh 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 587 -----------SASGSSKRSGGGGGDRGDGDHRSSGGSSSEKSGSSKGKSKSKEREARSVEGSVQLP------------- 642
Cdd:pfam12316  74 segsrssgsnrSGGGGPRKQKEEKAGSKGGSGSESESARRSSQRGIRVPAQGSRGSHASSRSSHSLGgggsrshhslhas 153

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1176118552 643 ----------PMPGAPPIGVP---IGVPIGVPIGvpigapmpggppmpgiammpRPLDQVPENVSASRNSFRMAMG 705
Cdd:pfam12316 154 haggmplayyGPPGLPPPAAApaaSQGPPGAPPG--------------------RELASVPPELTASRQSFQMAMG 209

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176118552 251 VTLNMEKVN-FLGISIVGQSNKrgdG-GIYVGSIMKGGAVDLDGrIEPGDMLLQVNDVNFENMSNDDAVRVLREMVHkpg 328
Cdd:cd10834     4 VHLYTTSDDyCLGFNIRGGSEY---GlGIYVSKVDPGGLAEQNG-IKVGDQILAVNGVSFEDITHSKAVEVLKSQTH--- 76