Domain of unknown function (DUF4757); This presumed domain is functionally uncharacterized. This domain family is found in eukaryotes, and is typically between 145 and 166 amino acids in length. The family is found in association with pfam00412. There are two completely conserved residues (W and L) that may be functionally important.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835    9 MSYRRISAVEPKTALPFNRFLPNKSRQPSYVPAPLRKKKPDKHEDNRRSW-----ASPVYTEADGTFSSQFlllqalQTY 83
Cdd:pfam15949    1 MLARRTSSSEPKSSVPFNQFLPNKSNQSAYVPAPLRKKRAEKEEDIRRSWstrtqPSKVAYPPRQFVQRLF------QKV 74

                   ....*.
gi 1370463835   84 SDDILS 89
Cdd:pfam15949   75 SDDLGS 80

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370463835  875 QEEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEELMVLS 931
Cdd:cd16269    217 LEEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLKEQERALESKLKEQEALLE 273

Domain of unknown function (DUF4757); This presumed domain is functionally uncharacterized. This domain family is found in eukaryotes, and is typically between 145 and 166 amino acids in length. The family is found in association with pfam00412. There are two completely conserved residues (W and L) that may be functionally important.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835    9 MSYRRISAVEPKTALPFNRFLPNKSRQPSYVPAPLRKKKPDKHEDNRRSW-----ASPVYTEADGTFSSQFlllqalQTY 83
Cdd:pfam15949    1 MLARRTSSSEPKSSVPFNQFLPNKSNQSAYVPAPLRKKRAEKEEDIRRSWstrtqPSKVAYPPRQFVQRLF------QKV 74

                   ....*.
gi 1370463835   84 SDDILS 89
Cdd:pfam15949   75 SDDLGS 80

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 1370463835  663 RISINQTPGKSLdfGFTIKWDIP---GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLV 739
Cdd:cd06741      3 KVNLVVEDGQSL--GLMIRGGAEyglGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFL---DITHDEAVKILKSSKHLI 77

                   ....*..
gi 1370463835  740 MDVRRYG 746
Cdd:cd06741     78 MTVKDVG 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835  662 MRISINQTPGKSLDFGFTIKWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLVMD 741
Cdd:COG3975    471 LKLVYEDAPSLKPSLGLRVSADGGGLVVTSVLWGSPAYKAGLSAGDELLAIDGLRVT---ADNLDDALAAYKPGDPIELL 547

                   ....*.
gi 1370463835  742 VRRYGK 747
Cdd:COG3975    548 VFRRDE 553

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370463835  875 QEEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEELMVLS 931
Cdd:cd16269    217 LEEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLKEQERALESKLKEQEALLE 273

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835  876 EEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEE-LMVLSSNSMSLTTREPSLATWEATWSEG 954
Cdd:PTZ00121  1525 DEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDkNMALRKAEEAKKAEEARIEEVMKLYEEE 1604

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835  955 SKSSDREGTRAGEEERRQPQEEVVHEDQGKKPQDQLVIERERKWEQQLQEEQEQKRLQAE-----AEEQKRPAEEQKRQA 1029
Cdd:PTZ00121  1605 KKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAeeakkAEEDKKKAEEAKKAE 1684

                   ....*
gi 1370463835 1030 EIERE 1034
Cdd:PTZ00121  1685 EDEKK 1689

Domain of unknown function (DUF4757); This presumed domain is functionally uncharacterized. This domain family is found in eukaryotes, and is typically between 145 and 166 amino acids in length. The family is found in association with pfam00412. There are two completely conserved residues (W and L) that may be functionally important.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835    9 MSYRRISAVEPKTALPFNRFLPNKSRQPSYVPAPLRKKKPDKHEDNRRSW-----ASPVYTEADGTFSSQFlllqalQTY 83
Cdd:pfam15949    1 MLARRTSSSEPKSSVPFNQFLPNKSNQSAYVPAPLRKKRAEKEEDIRRSWstrtqPSKVAYPPRQFVQRLF------QKV 74

                   ....*.
gi 1370463835   84 SDDILS 89
Cdd:pfam15949   75 SDDLGS 80

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 1370463835  663 RISINQTPGKSLdfGFTIKWDIP---GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLV 739
Cdd:cd06741      3 KVNLVVEDGQSL--GLMIRGGAEyglGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFL---DITHDEAVKILKSSKHLI 77

                   ....*..
gi 1370463835  740 MDVRRYG 746
Cdd:cd06741     78 MTVKDVG 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835  666 INQTPGKSLDFGFTI---KWDIPGIFVASVEAGSPAEFS-QLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETG-HLVM 740
Cdd:cd00136      2 VTLEKDPGGGLGFSIrggKDGGGGIFVSRVEPGGPAARDgRLRVGDRILEVNGVSLE---GLTHEEAVELLKSAGgEVTL 78

                   ...
gi 1370463835  741 DVR 743
Cdd:cd00136     79 TVR 81

PDZ domain 2 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370463835  685 PGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLVMDVR 743
Cdd:cd06738     27 PGIFISNVKPGSLAEEVGLEVGDQIVEVNGTSFT---NVDHKEAVMALKSSRHLTITVR 82

PDZ domain 3 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1370463835  686 GIFVASVEAGSPAEFSQLQVDDEIIAINNTKF 717
Cdd:cd06729     24 GIFVAGVQEGSPAEKQGLQEGDQILKVNGVDF 55

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370463835  676 FGFTIKWD--IPGIFVASVEAGSPAEFSQLQVDDEIIAINNTkfsyN-DSKEWEEAMAKAQETGH----LVMD 741
Cdd:cd06768     12 YGFNLHAEkgRPGHFIREVDPGSPAERAGLKDGDRLVEVNGE----NvEGESHEQVVEKIKASGNqvtlLVVD 80

PDZ domain of tax1-binding protein 3 (TAX1BP3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of TAX1BP3, and related domains. TAX1BP3 (also known as glutaminase-interacting protein 3, tax interaction protein 1, TIP-1, tax-interacting protein 1) may regulate a number of protein-protein interactions by competing for PDZ domain binding sites. TAX1BP3 binds beta-catenin and may act as an inhibitor of the Wnt signaling pathway. It competes with LIN7A (also known as Lin-7A or LIN-7A) for inward rectifier potassium channel 4 (KCNJ4) binding, and thereby promotes KCNJ4 internalization. It may play a role in the Rho signaling pathway, and in the activation of CDC42 by the viral protein HPV16 E6. Binding partners of the TAX1BP3 PDZ domain include beta-catenin, KCNJ4, glutaminase liver isoform (GLS2), rho guanine nucleotide exchange factor 16 (ARHGEF16), rhotekin, and CDK5 regulatory subunit-associated protein 3 (also known as LAPZ). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This TAX1BP3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1370463835  666 INQTPGKSlDFGFTIKwdipGIFVASVEAGSPAEFSQLQVDDEIIAIN 713
Cdd:cd10822     23 IDQDPSKN-PFSYTDK----GIYVTRVSEGGPAEKAGLQVGDKILQVN 65

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370463835  678 FTIKWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTkfSYNDSKEWEEAMAKAQETGHLVMDVRR 744
Cdd:TIGR02037  355 LRLKGDVKGVVVTKVVSGSPAARAGLQPGDVILSVNQQ--PVSSVAELRKVLARAKKGGRVALLILR 419

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1370463835  874 DQEEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEEL 927
Cdd:cd16269    223 ELEQKLEDQERSYEEHLRQLKEKMEEERENLLKEQERALESKLKEQEALLEEGF 276

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1370463835  676 FGFTIKWDIPGIfVASVEAGSPAEFSQLQVDDEIIAINNT---KFSYND 721
Cdd:cd06710     12 YGFTISGQAPCV-LSCVVRGSPADVAGLKAGDQILAVNGInvsKASHED 59

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

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1370463835  676 FGFTIKWDIPgIFVASVEAGSPAEFSQLQVDDEIIAINN 714
Cdd:cd06744     11 FGFTLRGHAP-VYIESVDPGSAAERAGLKPGDRILFLNG 48

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370463835  686 GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSynDSKEWEEAMAKAQETGHLVMDVRRYGK 747
Cdd:COG0265    202 GVLVARVEPGSPAAKAGLRPGDVILAVDGKPVT--SARDLQRLLASLKPGDTVTLTVLRGGK 261

PDZ domain of PDZ domain-containing protein 11, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZD11, and related domains. PDZD11 (also known as ATPase-interacting PDZ protein, plasma membrane calcium ATPase-interacting single-PDZ protein, PMCA-interacting single-PDZ protein, PISP) is involved in the dynamic assembly of apical junctions (AJs). It is recruited by PLEKHA7 to AJs to promote the efficient junctional recruitment and stabilization of nectins, and the efficient early phases of assembly of AJs in epithelial cells. The PDZD11 PDZ domain binds nectin-1 and nectin-3. PDZD11 also binds to a PDZ binding motif located in the C-terminal tail of the human sodium-dependent multivitamin transporter, to the cytoplasmic tail of the Menkes copper ATPase ATP7A, and to the cytoplasmic tail of all plasma membrane Ca2+-ATPase b-splice variants. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD11-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835  664 ISINQTPGKSLdfGFTI---KWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSYNDSKEWEEAMAKAQEtghLVM 740
Cdd:cd06752      3 VVLKRPPGEQL--GFNIrggKASGLGIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTARE---IQM 77

                   ....*
gi 1370463835  741 DVRRY 745
Cdd:cd06752     78 RVRYF 82

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1370463835  676 FGFTIKWDIPgIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSYNDSKE 724
Cdd:cd23069     13 YGLTVSGDNP-VFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLE 60

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370463835  683 DIPGIFVASVEAGSPAEFS-QLQVDDEIIAINNTKFSYNDSKEWEEAMakaQETGHLV 739
Cdd:cd06791     29 ELSGIFVKSIIPGSAADQDgRIQVNDQIIAVDGVNLQGFTNQEAVEVL---RNTGQVV 83

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835  876 EEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEE-LMVLSSNSMSLTTREPSLATWEATWSEG 954
Cdd:PTZ00121  1525 DEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDkNMALRKAEEAKKAEEARIEEVMKLYEEE 1604

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835  955 SKSSDREGTRAGEEERRQPQEEVVHEDQGKKPQDQLVIERERKWEQQLQEEQEQKRLQAE-----AEEQKRPAEEQKRQA 1029
Cdd:PTZ00121  1605 KKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAeeakkAEEDKKKAEEAKKAE 1684

                   ....*
gi 1370463835 1030 EIERE 1034
Cdd:PTZ00121  1685 EDEKK 1689

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835  874 DQEEERKRQERWQKEQDRLLQEKYQREQEKLReEWQRAKQEAERENSKyLDEELMvlssnsmslTTREPSLATWEATWSE 953
Cdd:pfam17380  347 ERELERIRQEERKRELERIRQEEIAMEISRMR-ELERLQMERQQKNER-VRQELE---------AARKVKILEEERQRKI 415

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835  954 GSKSSDREGTRAGEEERRQPQEEVVHEDQGKkpqdqlviERERKWEQQLQEEQEQKRLQAEAEEQKRpaeeQKRQAEIER 1033
Cdd:pfam17380  416 QQQKVEMEQIRAEQEEARQREVRRLEEERAR--------EMERVRLEEQERQQQVERLRQQEEERKR----KKLELEKEK 483

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370463835 1034 ETSVRIYQYRRPVDSYDIpktEEASSGFLPGDRNKSRSTTELDDYStnkngNNKYLDQIGNMTSSQRRSKKEQVpsgael 1113
Cdd:pfam17380  484 RDRKRAEEQRRKILEKEL---EERKQAMIEEERKRKLLEKEMEERQ-----KAIYEEERRREAEEERRKQQEME------ 549

                          250
                   ....*....|...
gi 1370463835 1114 ERQQILQEMRKRT 1126
Cdd:pfam17380  550 ERRRIQEQMRKAT 562

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370463835  688 FVASVEAGSPAEFSQLQVDDEIIAINNTKFSynDSKEWEEAMAKAQETgHLVMDVRR 744
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPVR--SLEDVARLLQGSAGE-SVTLTVRR 54

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 1370463835  662 MRISINQTPGKSLDFG---FTIKWDIPGIFVASVEAGSPAEF-SQLQVDDEIIAINNTKFsYNDSKEWEEAMAKAQETGH 737
Cdd:cd06760      5 MEVTLNKEPGVGLGIGlccLPLENDIPGIFIHHLSPGSVAHMdGRLRRGDQILEINGTSL-RNVTLNEAYAILSQCKPGP 83

                   ....*..
gi 1370463835  738 LVMDVRR 744
Cdd:cd06760     84 VTLIISR 90

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

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1370463835  683 DIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFS 718
Cdd:cd06782     12 DDGYLVVVSPIPGGPAEKAGIKPGDVIVAVDGESVR 47