Apx/Shroom domain ASD2; This region is found in the actin binding protein Shroom which mediates apical contriction in epithelial cells and is required for neural tube closure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655  1187 ELAREIVGKDKSLADILDPSVKIKTTMDLMEGIFPKDEYLLEEAQQRRKLlpkvplPRVTEDKKQDPGMPGVVSLATNST 1266
Cdd:pfam08687    1 ELVKELVPKDKSLADILDPKPSRKTTMDLMEGLFPEDTLRAMKPDLGEAY------KKAPSEEGSEEEASGTSSLSSCSA 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655  1267 YYSTSAPKAELLIKMKDL------QEPEEYSAGDLDHDLSVKKQELIDSISRKLQVLREARESLLEDIQANNALGDEVEA 1340
Cdd:pfam08687   75 YYTTSAPKAELLTKMKDLttlpspDQPEEQGEEELDNDLQQKKVELIESLQRKLQVLREEQEALQEEIQANAALGAEVEA 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655  1341 IVKDVCKPNEFDKFRMFIGDLDKVVNLLLSLSGRLARVENALNNLDDNPSPGDRQSLLEKQRVLTQQHEDAKELKENLDR 1420
Cdd:pfam08687  155 LVQEVCKPNELEKYRMFIGDLEKVVSLLLSLSGRLARVENALSSLDSDADAEERQSLLEKRRLLLRQLEDAKELKENLDR 234

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 569011655  1421 RERIVFDILATYLSEENLADYEHFVKMKSALIIEQRELEDKIHLGEEQLKCLFDSL 1476
Cdd:pfam08687  235 RERVVSGILARYLTAEQLQDYRHFVKMKAALLIEQRELDEKIKLGEEQLKALKESL 290

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   25 RLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGFRQEAICLVKGSHKTLKLVV 104
Cdd:cd06750     1 QLIEVQLQGGAPWGFTLKGGLEHGEPLVISKIEEGGKAASVGKLQVGDEVVNINGVPLSGSRQEAIQLVKGSHKTLKLVV 80

                  ..
gi 569011655  105 KR 106
Cdd:cd06750    81 RR 82

Apx/Shroom domain ASD2; This region is found in the actin binding protein Shroom which mediates apical contriction in epithelial cells and is required for neural tube closure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655  1187 ELAREIVGKDKSLADILDPSVKIKTTMDLMEGIFPKDEYLLEEAQQRRKLlpkvplPRVTEDKKQDPGMPGVVSLATNST 1266
Cdd:pfam08687    1 ELVKELVPKDKSLADILDPKPSRKTTMDLMEGLFPEDTLRAMKPDLGEAY------KKAPSEEGSEEEASGTSSLSSCSA 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655  1267 YYSTSAPKAELLIKMKDL------QEPEEYSAGDLDHDLSVKKQELIDSISRKLQVLREARESLLEDIQANNALGDEVEA 1340
Cdd:pfam08687   75 YYTTSAPKAELLTKMKDLttlpspDQPEEQGEEELDNDLQQKKVELIESLQRKLQVLREEQEALQEEIQANAALGAEVEA 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655  1341 IVKDVCKPNEFDKFRMFIGDLDKVVNLLLSLSGRLARVENALNNLDDNPSPGDRQSLLEKQRVLTQQHEDAKELKENLDR 1420
Cdd:pfam08687  155 LVQEVCKPNELEKYRMFIGDLEKVVSLLLSLSGRLARVENALSSLDSDADAEERQSLLEKRRLLLRQLEDAKELKENLDR 234

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 569011655  1421 RERIVFDILATYLSEENLADYEHFVKMKSALIIEQRELEDKIHLGEEQLKCLFDSL 1476
Cdd:pfam08687  235 RERVVSGILARYLTAEQLQDYRHFVKMKAALLIEQRELDEKIKLGEEQLKALKESL 290

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   25 RLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGFRQEAICLVKGSHKTLKLVV 104
Cdd:cd06750     1 QLIEVQLQGGAPWGFTLKGGLEHGEPLVISKIEEGGKAASVGKLQVGDEVVNINGVPLSGSRQEAIQLVKGSHKTLKLVV 80

                  ..
gi 569011655  105 KR 106
Cdd:cd06750    81 RR 82

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655    26 LVEVQLSGGAPWGFTLKGGREHGE-PLVITKIEEGSkAAAVDKLLAGDEIVAINDVSLSGFRQE-AICLVKGSHKTLKLV 103
Cdd:pfam00595    1 QVTLEKDGRGGLGFSLKGGSDQGDpGIFVSEVLPGG-AAEAGGLKVGDRILSINGQDVENMTHEeAVLALKGSGGKVTLT 79

                   ..
gi 569011655   104 VK 105
Cdd:pfam00595   80 IL 81

Apx/Shroom domain ASD2; This region is found in the actin binding protein Shroom which mediates apical contriction in epithelial cells and is required for neural tube closure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655  1187 ELAREIVGKDKSLADILDPSVKIKTTMDLMEGIFPKDEYLLEEAQQRRKLlpkvplPRVTEDKKQDPGMPGVVSLATNST 1266
Cdd:pfam08687    1 ELVKELVPKDKSLADILDPKPSRKTTMDLMEGLFPEDTLRAMKPDLGEAY------KKAPSEEGSEEEASGTSSLSSCSA 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655  1267 YYSTSAPKAELLIKMKDL------QEPEEYSAGDLDHDLSVKKQELIDSISRKLQVLREARESLLEDIQANNALGDEVEA 1340
Cdd:pfam08687   75 YYTTSAPKAELLTKMKDLttlpspDQPEEQGEEELDNDLQQKKVELIESLQRKLQVLREEQEALQEEIQANAALGAEVEA 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655  1341 IVKDVCKPNEFDKFRMFIGDLDKVVNLLLSLSGRLARVENALNNLDDNPSPGDRQSLLEKQRVLTQQHEDAKELKENLDR 1420
Cdd:pfam08687  155 LVQEVCKPNELEKYRMFIGDLEKVVSLLLSLSGRLARVENALSSLDSDADAEERQSLLEKRRLLLRQLEDAKELKENLDR 234

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 569011655  1421 RERIVFDILATYLSEENLADYEHFVKMKSALIIEQRELEDKIHLGEEQLKCLFDSL 1476
Cdd:pfam08687  235 RERVVSGILARYLTAEQLQDYRHFVKMKAALLIEQRELDEKIKLGEEQLKALKESL 290

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   25 RLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGFRQEAICLVKGSHKTLKLVV 104
Cdd:cd06750     1 QLIEVQLQGGAPWGFTLKGGLEHGEPLVISKIEEGGKAASVGKLQVGDEVVNINGVPLSGSRQEAIQLVKGSHKTLKLVV 80

                  ..
gi 569011655  105 KR 106
Cdd:cd06750    81 RR 82

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569011655   29 VQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVdKLLAGDEIVAINDVSLSGF-RQEAICLVKGSHKTLKLVVK 105
Cdd:cd10820     2 VTLTGGAPWGFRLQGGSEQKKPLQVAKIRKKSKAALA-GLCEGDELLSINGKPCADLsHSEAMDLIDSSGDTLQLLIK 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        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655     24 VRLVEVQLSGGaPWGFTLKGGREHGEPLVITKIEEGSkAAAVDKLLAGDEIVAINDVSLSGFRQ-EAICLVKGSHKTLKL 102
Cdd:smart00228    2 PRLVELEKGGG-GLGFSLVGGKDEGGGVVVSSVVPGS-PAAKAGLRVGDVILEVNGTSVEGLTHlEAVDLLKKAGGKVTL 79

                    ....*.
gi 569011655    103 VVKRKS 108
Cdd:smart00228   80 TVLRGG 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655    26 LVEVQLSGGAPWGFTLKGGREHGE-PLVITKIEEGSkAAAVDKLLAGDEIVAINDVSLSGFRQE-AICLVKGSHKTLKLV 103
Cdd:pfam00595    1 QVTLEKDGRGGLGFSLKGGSDQGDpGIFVSEVLPGG-AAEAGGLKVGDRILSINGQDVENMTHEeAVLALKGSGGKVTLT 79

                   ..
gi 569011655   104 VK 105
Cdd:pfam00595   80 IL 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   25 RLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGFR-QEAICLVKGSHKTLKLV 103
Cdd:cd06801     1 RTVRVVKQDVGGLGISIKGGAEHKMPILISKIFKGQAADQTGQLFVGDAILSVNGENLEDAThDEAVQALKNAGDEVTLT 80

                  ..
gi 569011655  104 VK 105
Cdd:cd06801    81 VK 82

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569011655   38 GFTLKGGREHGEPLVITKIEEGSkAAAVDKLLAGDEIVAINDVSLSGFRQEAICLVKGSHKTLKLVVKR 106
Cdd:cd10833    15 GFSVRGGSEHGLGIFVSKVEEGS-AAERAGLCVGDKITEVNGVSLENITMSSAVKVLTGSNRLRMVVRR 82

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569011655   26 LVEVQL-SGGAPWGFTLKGGRE--HGE-PLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGF-RQEAICLVK 94
Cdd:cd06763     1 AVTVELeKGSAGLGFSLEGGKGspLGDrPLTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGLtRFEAWNIIK 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 569011655   38 GFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVAINDVSL 82
Cdd:cd06800    14 GISITGGKEHGVPILISEIHEGQPADRCGGLYVGDAILSVNGIDL 58

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   24 VRLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSkAAAVDKLLAGDEIVAINDVSLSGF-RQEAICLVKgSHKTLKL 102
Cdd:cd06741     1 ERKVNLVVEDGQSLGLMIRGGAEYGLGIYVTGVDPGS-VAENAGLKVGDQILEVNGRSFLDItHDEAVKILK-SSKHLIM 78

                  ....
gi 569011655  103 VVKR 106
Cdd:cd06741    79 TVKD 82

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   25 RLVEVQLS--GGAPwGFTLKGGReHGE-----PLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGF-RQEAICLVKGS 96
Cdd:cd06681     1 KTVEVTLEkeGNSF-GFVIRGGA-HEDrnksrPLTVTHVRPGGPADREGTIKPGDRLLSVDGISLHGAtHAEAMSILKQC 78

                  ....*...
gi 569011655   97 HKTLKLVV 104
Cdd:cd06681    79 GQEATLLI 86

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   29 VQLSGGapwgftlKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGF-RQEAICLVKGSHKTLKLVVKRK 107
Cdd:cd06758    16 IQITGG-------KGSKRGDIGIFVAGVEEGGSADRDGRLKKGDELLMINGQSLIGLsHQEAVAILRSSASPVQLVIASK 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569011655   38 GFTLKGG--REHGE-PLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGF-RQEAICLVKGSHKTLKLVV 104
Cdd:cd06676    12 GFSIVGGfgSPHGDlPIYVKTVFEKGAAAEDGRLKRGDQILAVNGESLEGVtHEEAVNILKKTKGTVTLTV 82

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   26 LVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGFRQ-EAICLVKGSHKTLKLVV 104
Cdd:cd06687     2 VVELIKKEGSTLGLTVSGGIDKDGKPRVSNLRPGGIAARSDQLNVGDYIKSVNGIRTTKLRHdEIISLLKNVGERVVLEV 81

                  .
gi 569011655  105 K 105
Cdd:cd06687    82 E 82

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 569011655   51 LVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGFRQE-AICLVKGSHKTLKLVV 104
Cdd:cd10817    24 IVIKSLTEGGPAAKDGRLKVGDQILAVDDESVVGCPYEkAISLLKTAKGTVKLTV 78

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 569011655   37 WGFTLKGGREHGEPLVITKIEEGSKAAAVdKLLAGDEIVAINDVSLSGFRQ-EAICLVKGsHKTLKLVVK 105
Cdd:cd10834    15 LGFNIRGGSEYGLGIYVSKVDPGGLAEQN-GIKVGDQILAVNGVSFEDITHsKAVEVLKS-QTHLMLTIK 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569011655   32 SGGAPWGFTLKGGREhgEP-----LVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGF-RQEAICLVK 94
Cdd:cd06759     9 AGGKGLGFSIVGGRD--SPrgpmgIYVKTIFPGGAAAEDGRLKEGDEILEVNGESLQGLtHQEAIQKFK 75

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   25 RLVEVQLSGGAP--WGFTLKGGREHG---EPLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGF-RQEAICLVKGSHK 98
Cdd:cd06694     1 EIVIVTLKKDPQkgLGFTIVGGENSGsldLGIFVKSIIPGGPADKDGRIKPGDRIIAINGQSLEGKtHHAAVEIIQNAPD 80

                          90
                  ....*....|..
gi 569011655   99 TLKLVVKRKSDP 110
Cdd:cd06694    81 KVELIISQPKSV 92

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569011655   38 GFTLKGGREHGeplVITK-IEEGSKAAAVDKLLAGDEIVAINDVSLSGFRQEAICLV-KGSHKTLKLVVKR 106
Cdd:cd06667    13 GFGIVGGKSTG---VVVKtILPGGVADRDGRLRSGDHILQIGDTNLRGMGSEQVAQVlRQCGSHVRLVVAR 80

Predicted metalloprotease, contains C-terminal PDZ domain [General function prediction only];

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   23 GVRLVEVQLSGGAPW-GFTLKggrEHGEPLVITKIEEGSkAAAVDKLLAGDEIVAINDVSLSGFRQEAICLVKGSHKTLK 101
Cdd:COG3975   470 GLKLVYEDAPSLKPSlGLRVS---ADGGGLVVTSVLWGS-PAYKAGLSAGDELLAIDGLRVTADNLDDALAAYKPGDPIE 545

                  ....*
gi 569011655  102 LVVKR 106
Cdd:COG3975   546 LLVFR 550

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011655   25 RLVEVQLSGGAPWGFTLKggrEHGEPLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGFRQEAIC-LVKGSHKTLKLV 103
Cdd:cd06726     1 RLVEFEKARDEPLGATIK---MEEDSVIVARILHGGMAHRSGLLHVGDEILEINGIPVSGKTVDELQkLLSSLSGSVTFK 77

                  .
gi 569011655  104 V 104
Cdd:cd06726    78 L 78

PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569011655   50 PLVITKIEegSKAAAVD--KLLAGDEIVAINDVSLSGFRQ-EAICLVKGS--HKTLKLVVKRK 107
Cdd:cd23058    33 PIYIKNIL--PKGAAIQdgRLKAGDRLLEVNGVDVTGKTQeEVVSLLRSTklGGTVSLVVSRQ 93

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569011655   38 GFTLK--GGR--EHGEpLV--ITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGFRQEAIC-LVKGSHKTLKLVVK 105
Cdd:cd06714    22 GLGLKvvGGKmtESGR-LGayVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFEEVQdIISQSKGEVELVVS 95

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569011655   32 SGGAPWGFTLKGG--REHGEPLVITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGFR-QEAICLVKGSHKTLKLVVKR 106
Cdd:cd06682     8 RSGVGLGITISAPknRKPGDPLIISDVKKGSVAHRTGTLEPGDKLLAIDNIRLDNCSmEDAAQILQQAEDIVKLKIRK 85

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

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gi 569011655   25 RLVEVQLSGGAPWGFTLKGGRehGEPL-----VITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGFRQ-EAICLVKGSHK 98
Cdd:cd06675     1 RTVEIKRGPQDSLGISIAGGV--GSPLgdvpvFIAMIQPNGVAAQTGKLKVGDRIVSINGQSTDGLTHsEAVNLLKNASG 78

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gi 569011655   99 TLKLVV 104
Cdd:cd06675    79 TIILQV 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.

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gi 569011655   38 GFTLKGG-REH-GEPL-------VITKIEEGSKAAAVDKLLAGDEIVAINDVSLSGF-RQEAICLVKGSHKTLKLVV 104
Cdd:cd06701    18 GISIRGGaKGHaGNPLdptdegiFISKINPDGAAARDGRLKVGQRILEVNGQSLLGAtHQEAVRILRSVGDTLTLLV 94

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

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gi 569011655   38 GFTLKGG------REHGEPLVITKIEEGSkAAAVDKLLAGDEIVAINDVSLSG-FRQEAICLVKGSHKTLKLVVKR 106
Cdd:cd06704    13 GISIAGGkgstpyKGDDEGIFISRVTEGG-PAAKAGVRVGDKLLEVNGVDLVDaDHHEAVEALKNSGNTVTMVVLR 87