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 2217294334  213 MSYRRISAVEPKTALPFNRFLPNKSRQPSYVPAPLRKKKPDKHEDNRRSW-----ASPVYTEADGTFSR----------S 277
Cdd:pfam15949    1 MLARRTSSSEPKSSVPFNQFLPNKSNQSAYVPAPLRKKRAEKEEDIRRSWstrtqPSKVAYPPRQFVQRlfqkvsddlgS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334  278 KSMSDVSAEDV-QNLRQLRYEEMQKIKSQLKEQDQKWQDDLAKWKDRRKSYTSDLQKKKEEREEIEKQALEKS----KRS 352
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 2217294334  353 SKTFKEMLQD 362
Cdd:pfam15949  161 SKTFKEMVEE 170

LIM is a small protein-protein interaction domain, containing two zinc fingers; LIM domains are identified in a diverse group of proteins with wide variety of biological functions, including gene expression regulation, cell fate determination, cytoskeleton organization, tumor formation and development. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes. They perform their functions through interactions with other protein partners. LIM domains are 50-60 amino acids in size and share two characteristic highly conserved zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. The consensus sequence of LIM domain has been defined as C-x(2)-C-x(16,23)-H-x(2)-[CH]-x(2)-C-x(2)-C-x(16,21)-C-x(2,3)-[CHD] (where X denotes any amino acid).

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334 1216 CSYCNN-ILGKgaaMIIESLGLCYHLHCFKCVACECDLGGSSSGaevrIRNHQLYCNDCY 1274
Cdd:cd08368      1 CAGCGKpIEGR---ELLRALGKKWHPECFKCAECGKPLGGDSFY----EKDGKPYCEKCY 53

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334  832 ERKRQERWQK-EQDRLLQEKYQ--REQEKLR--EEWQRAKQ-EAERENSKYLDEELMVLSSN------SMSLTTREPSLA 899
Cdd:pfam17380  286 ERQQQEKFEKmEQERLRQEKEEkaREVERRRklEEAEKARQaEMDRQAAIYAEQERMAMEREreleriRQEERKRELERI 365

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334  900 TWEATWSEGSKSSDREGTRageEERRQPQEEVVHEDQGKKPQDQLVIERERKWEQQLQEEQEQKRLQAEAEEQKRPAEEQ 979
Cdd:pfam17380  366 RQEEIAMEISRMRELERLQ---MERQQKNERVRQELEAARKVKILEEERQRKIQQQKVEMEQIRAEQEEARQREVRRLEE 442

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334  980 KRQAEIERetsVRIYQYRRPVDSYDIPKTEEASSgflpgdRNKSRSTTELDDYSTNKNGNNKYLDQ-----IGNMTSSQR 1054
Cdd:pfam17380  443 ERAREMER---VRLEEQERQQQVERLRQQEEERK------RKKLELEKEKRDRKRAEEQRRKILEKeleerKQAMIEEER 513

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217294334 1055 RSK------KEQVPSGAELERQQILQEMRKRTPLHNDNSWIRQRSASVNKEPVSLPGIMRRGESL 1113
Cdd:pfam17380  514 KRKllekemEERQKAIYEEERRREAEEERRKQQEMEERRRIQEQMRKATEERSRLEAMEREREMM 578

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 2217294334  213 MSYRRISAVEPKTALPFNRFLPNKSRQPSYVPAPLRKKKPDKHEDNRRSW-----ASPVYTEADGTFSR----------S 277
Cdd:pfam15949    1 MLARRTSSSEPKSSVPFNQFLPNKSNQSAYVPAPLRKKRAEKEEDIRRSWstrtqPSKVAYPPRQFVQRlfqkvsddlgS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334  278 KSMSDVSAEDV-QNLRQLRYEEMQKIKSQLKEQDQKWQDDLAKWKDRRKSYTSDLQKKKEEREEIEKQALEKS----KRS 352
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 2217294334  353 SKTFKEMLQD 362
Cdd:pfam15949  161 SKTFKEMVEE 170

LIM is a small protein-protein interaction domain, containing two zinc fingers; LIM domains are identified in a diverse group of proteins with wide variety of biological functions, including gene expression regulation, cell fate determination, cytoskeleton organization, tumor formation and development. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes. They perform their functions through interactions with other protein partners. LIM domains are 50-60 amino acids in size and share two characteristic highly conserved zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. The consensus sequence of LIM domain has been defined as C-x(2)-C-x(16,23)-H-x(2)-[CH]-x(2)-C-x(2)-C-x(16,21)-C-x(2,3)-[CHD] (where X denotes any amino acid).

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334 1216 CSYCNN-ILGKgaaMIIESLGLCYHLHCFKCVACECDLGGSSSGaevrIRNHQLYCNDCY 1274
Cdd:cd08368      1 CAGCGKpIEGR---ELLRALGKKWHPECFKCAECGKPLGGDSFY----EKDGKPYCEKCY 53

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
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217294334   630 FGFTI---KWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETG-HLVMDVRR 698
Cdd:smart00228   14 LGFSLvggKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVE---GLTHLEAVDLLKKAGgKVTLTVLR 83

PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334  617 RISINQTPGKSLdfGFTIKWDIP---GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLV 693
Cdd:cd06741      3 KVNLVVEDGQSL--GLMIRGGAEyglGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFL---DITHDEAVKILKSSKHLI 77

                   ....*..
gi 2217294334  694 MDVRRYG 700
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 2217294334  616 MRISINQTPGKSLDFGFTIKWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLVMD 695
Cdd:COG3975    471 LKLVYEDAPSLKPSLGLRVSADGGGLVVTSVLWGSPAYKAGLSAGDELLAIDGLRVT---ADNLDDALAAYKPGDPIELL 547

                   ....*.
gi 2217294334  696 VRRYGK 701
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 2217294334  829 QEEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEELMVLS 885
Cdd:cd16269    217 LEEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLKEQERALESKLKEQEALLE 273

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334  830 EEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEE-LMVLSSNSMSLTTREPSLATWEATWSEG 908
Cdd:PTZ00121  1525 DEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDkNMALRKAEEAKKAEEARIEEVMKLYEEE 1604

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334  909 SKSSDREGTRAGEEERRQPQEEVVHEDQGKKPQDQLVIERERKWEQQLQEEQEQKRLQAE-----AEEQKRPAEEQKRQA 983
Cdd:PTZ00121  1605 KKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAeeakkAEEDKKKAEEAKKAE 1684

                   ....*
gi 2217294334  984 EIERE 988
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 2217294334  213 MSYRRISAVEPKTALPFNRFLPNKSRQPSYVPAPLRKKKPDKHEDNRRSW-----ASPVYTEADGTFSR----------S 277
Cdd:pfam15949    1 MLARRTSSSEPKSSVPFNQFLPNKSNQSAYVPAPLRKKRAEKEEDIRRSWstrtqPSKVAYPPRQFVQRlfqkvsddlgS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334  278 KSMSDVSAEDV-QNLRQLRYEEMQKIKSQLKEQDQKWQDDLAKWKDRRKSYTSDLQKKKEEREEIEKQALEKS----KRS 352
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 2217294334  353 SKTFKEMLQD 362
Cdd:pfam15949  161 SKTFKEMVEE 170

calponin homology (CH) domain found in LIM domain only protein 7 and similar proteins; This family includes LIM domain only protein 7 (LMO-7) and LIM and calponin homology domains-containing protein 1 (LIMCH1), and similar proteins. LMO-7, also called F-box only protein 20, or LOMP, is a transcription regulator for expression of many Emery-Dreifuss muscular dystrophy (EDMD)-relevant genes. It binds to alpha-actinin and AF6/afadin at adherens junctions for epithelial cell-cell adhesion. LIMCH1 acts as an actin stress fiber-associated protein that activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. It positively regulates actin stress fiber assembly and stabilizes focal adhesions, and therefore negatively regulates cell spreading and cell migration. Members of this family contain a single copy of the CH domain at the N-terminus. CH domains are actin filament (F-actin) binding motifs.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217294334   42 DNINVFLKACEQIGLKEAQLFHPGDLQDLSNRVT---VKQEETDRRVKNVLITLYWLGRKAQ 100
Cdd:cd21208     58 DNLNLFLKACEDLGLKDSQLFDPTDLQDLSNRRIathVRKKEDERRLKNVAITLYWLGRAAR 119

LIM is a small protein-protein interaction domain, containing two zinc fingers; LIM domains are identified in a diverse group of proteins with wide variety of biological functions, including gene expression regulation, cell fate determination, cytoskeleton organization, tumor formation and development. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes. They perform their functions through interactions with other protein partners. LIM domains are 50-60 amino acids in size and share two characteristic highly conserved zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. The consensus sequence of LIM domain has been defined as C-x(2)-C-x(16,23)-H-x(2)-[CH]-x(2)-C-x(2)-C-x(16,21)-C-x(2,3)-[CHD] (where X denotes any amino acid).

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334 1216 CSYCNN-ILGKgaaMIIESLGLCYHLHCFKCVACECDLGGSSSGaevrIRNHQLYCNDCY 1274
Cdd:cd08368      1 CAGCGKpIEGR---ELLRALGKKWHPECFKCAECGKPLGGDSFY----EKDGKPYCEKCY 53

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
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217294334   630 FGFTI---KWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETG-HLVMDVRR 698
Cdd:smart00228   14 LGFSLvggKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVE---GLTHLEAVDLLKKAGgKVTLTVLR 83

PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217294334  617 RISINQTPGKSLdfGFTIKWDIP---GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLV 693
Cdd:cd06741      3 KVNLVVEDGQSL--GLMIRGGAEyglGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFL---DITHDEAVKILKSSKHLI 77

                   ....*..
gi 2217294334  694 MDVRRYG 700
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 2217294334  620 INQTPGKSLDFGFTI---KWDIPGIFVASVEAGSPAEFS-QLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETG-HLVM 694
Cdd:cd00136      2 VTLEKDPGGGLGFSIrggKDGGGGIFVSRVEPGGPAARDgRLRVGDRILEVNGVSLE---GLTHEEAVELLKSAGgEVTL 78

                   ...
gi 2217294334  695 DVR 697
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 2217294334  639 PGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLVMDVR 697
Cdd:cd06738     27 PGIFISNVKPGSLAEEVGLEVGDQIVEVNGTSFT---NVDHKEAVMALKSSRHLTITVR 82

calponin homology (CH) domain superfamily; CH domains are actin filament (F-actin) binding motifs, which may be present as a single copy or in tandem repeats (which increase binding affinity). They either function as autonomous actin binding motifs or serve a regulatory function. CH domains are found in cytoskeletal and signal transduction proteins, including actin-binding proteins like spectrin, alpha-actinin, dystrophin, utrophin, and fimbrin, as well as proteins essential for regulation of cell shape (cortexillins), and signaling proteins (Vav).

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2217294334   41 TDNINVFLKACEQIGLKEAQLFHPGDLQDlsnrvtvkqeetDRRVKNVLITLYWLGR 97
Cdd:cd00014     59 RENINLFLNACKKLGLPELDLFEPEDLYE------------KGNLKKVLGTLWALAL 103

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217294334  629 DFGFTIKWDIPgIFVASVEAGSPAEFSQLQVDDEIIAINNTkfsynDSKeW---EEAMAKAQETG 690
Cdd:cd06712     12 GFGFTLRGDSP-VQVASVDPGSCAAEAGLKEGDYIVSVGGV-----DCK-WskhSEVVKLLKSAG 69

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 2217294334  630 FGFTIKWD--IPGIFVASVEAGSPAEFSQLQVDDEIIAINNTkfsyN-DSKEWEEAMAKAQETGH----LVMD 695
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 2217294334  620 INQTPGKSlDFGFTIKwdipGIFVASVEAGSPAEFSQLQVDDEIIAIN 667
Cdd:cd10822     23 IDQDPSKN-PFSYTDK----GIYVTRVSEGGPAEKAGLQVGDKILQVN 65

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 2217294334  829 QEEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEELMVLS 885
Cdd:cd16269    217 LEEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLKEQERALESKLKEQEALLE 273

The third LIM domain of actin binding LIM (abLIM) proteins; The third LIM domain of actin binding LIM (abLIM) proteins: Three homologous members of the abLIM protein family have been identified; abLIM-1, abLIM-2 and abLIM-3. The N-terminal of abLIM consists of four tandem repeats of LIM domains and the C-terminal of acting binding LIM protein is a villin headpiece domain, which has strong actin binding activity. The abLIM-1, which is expressed in retina, brain, and muscle tissue, has been indicated to function as a tumor suppressor. AbLIM-2 and -3, mainly expressed in muscle and neuronal tissue, bind to F-actin strongly. They may serve as a scaffold for signaling modules of the actin cytoskeleton and thereby modulate transcription. It has shown that LIM domains of abLIMs interact with STARS (striated muscle activator of Rho signaling), which directly binds actin and stimulates serum-response factor (SRF)-dependent transcription. All LIM domains are 50-60 amino acids in size and share two characteristic highly conserved zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2217294334 1216 CSYCNNILGKGAAMIieSLGLCYHLHCFKCVACECDLGGSSSGaevriRNHQLYCNDCY 1274
Cdd:cd09329      1 CAGCGQEIKNGQALL--ALDKQWHVWCFKCKECGKVLTGEYMG-----KDGKPYCERDY 52

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 2217294334  632 FTIKWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTkfSYNDSKEWEEAMAKAQETGHLVMDVRR 698
Cdd:TIGR02037  355 LRLKGDVKGVVVTKVVSGSPAARAGLQPGDVILSVNQQ--PVSSVAELRKVLARAKKGGRVALLILR 419

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

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2217294334  630 FGFTIKWDIPgIFVASVEAGSPAEFSQLQVDDEIIAINN 668
Cdd:cd06711     12 FGFTICDDSP-VRVQAVDPGGPAEQAGLQQGDTVLQING 49

calponin homology (CH) domain found in Drosophila melanogaster muscle-specific protein 20 (dMP20) and similar domains; This subfamily contains Drosophila melanogaster muscle-specific protein 20 (dMP20), Echinococcus granulosus myophilin, Dictyostelium discoideum Rac guanine nucleotide exchange factor B (also called Trix), and similar proteins. dMP20 is present only in the synchronous muscles of D. melanogaster. It may be involved in the system linking the nerve impulse with the contraction or the relaxation process. Trix is involved in the regulation of the late steps of the endocytic pathway. dMP20 contains a single copy of the CH domain, while Trix (triple CH-domain array exchange factor) contains three, two type 3 CH domains which are included in this model, and one type 1 CH domain that is not included in this subfamily, but is part of the superfamily. CH domains are actin filament (F-actin) binding motifs.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2217294334   43 NINVFLKACEQIGLKEAQLFHPGDLQDLSNrvtvkqeetdrrVKNVLITLYWLGR 97
Cdd:cd21207     65 NIENFLTACKGYGVPKTDLFQTVDLYEKKN------------IPQVTNCLFALGR 107

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 2217294334  630 FGFTIKWDIPGIfVASVEAGSPAEFSQLQVDDEIIAINNT---KFSYND 675
Cdd:cd06710     12 YGFTISGQAPCV-LSCVVRGSPADVAGLKAGDQILAVNGInvsKASHED 59

calponin homology (CH) domain found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as scaffold proteins, and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the CH domain, an actin-binding domain which is present as a single copy in VAV proteins.

                           10        20        30
                   ....*....|....*....|....*....|..
gi 2217294334   42 DNINVFLKAC-EQIGLKEAQLFHPGDLQDLSN 72
Cdd:cd21201     72 KNIRTFLQACrTVFGLRSADLFEPEDLYDVTN 103

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217294334  640 GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSynDSKEWEEAMAKAQETGHLVMDVRRYGK 701
Cdd:COG0265    202 GVLVARVEPGSPAAKAGLRPGDVILAVDGKPVT--SARDLQRLLASLKPGDTVTLTVLRGGK 261

The third LIM domain of Zyxin-like family; The third LIM domain of Zyxin like family: This family includes Ajuba, Limd1, WTIP, Zyxin, LPP, and Trip6 LIM proteins. Members of Zyxin family contain three tandem C-terminal LIM domains, and a proline-rich N-terminal region. Zyxin proteins are detected primarily in focal adhesion plaques. They function as scaffolds, participating in the assembly of multiple interactions and signal transduction networks, which regulate cell adhesion, spreading, and motility. They can also shuffle into nucleus. In nucleus, zyxin proteins affect gene transcription by interaction with a variety of nuclear proteins, including several transcription factors, playing regulating roles in cell proliferation, differentiation and apoptosis. As in other LIM domains, this domain family is 50-60 amino acids in size and shares two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217294334 1216 CSYCNN-IL---GKGAAMIIESLGLCYHLHCFKCVACECDLggsSSGAEVR----IRNHqLYCNDC 1273
Cdd:cd09357      1 CSVCGEpIMpepGQDETVRIVALDRSFHVNCYKCEDCGMLL---SSEDEGQgcypLDGH-LLCKSC 62

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 2217294334  618 ISINQTPGKSLdfGFTI---KWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSYNDSKEWEEAMAKAQEtghLVM 694
Cdd:cd06752      3 VVLKRPPGEQL--GFNIrggKASGLGIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTARE---IQM 77

                   ....*
gi 2217294334  695 DVRRY 699
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 2217294334  630 FGFTIKWDIPgIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSYNDSKE 678
Cdd:cd23069     13 YGLTVSGDNP-VFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLE 60

PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange factor 6, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Rap guanine nucleotide exchange factor 2 (RapGEF2, also named RA-GEF-1, PDZ-GEF1, CNrasGEF and nRapGEP) and Rap guanine nucleotide exchange factor 6 (RapGEF6, also named RA-GEF-2 and PDZ-GEF2). RapGEF2 and RapGEF6 constitute a subfamily of guanine nucleotide exchange factors (GEFs) for RAP small GTPases that is characterized by the possession of the PDZ and Ras/Rap-associating domains. They activate Rap small GTPases, by catalyzing the release of GDP from the inactive GDP-bound forms, thereby accelerating GTP loading to yield the active GTP-bound forms. The PDZ domain of RapGEF6 (also known as PDZ-GEF2) binds junctional adhesion molecule A (JAM-A). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RapGEF2 and RapGEF6 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2217294334  640 GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFsynDSKEWEEAMAKAQETGHLVMDVR 697
Cdd:cd06755     27 GIFVSKVEKGSKAAEAGLKRGDQILEVNGQNF---ENITLKKALEILRNNTHLSITVK 81

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 2217294334  637 DIPGIFVASVEAGSPAEFS-QLQVDDEIIAINNTKFSYNDSKEWEEAMakaQETGHLV 693
Cdd:cd06791     29 ELSGIFVKSIIPGSAADQDgRIQVNDQIIAVDGVNLQGFTNQEAVEVL---RNTGQVV 83

The second LIM domain of LIMK1 (LIM domain Kinase 1); The second LIM domain of LIMK1 (LIM domain Kinase 1): LIMK1 belongs to the LIMK protein family, which comprises LIMK1 and LIMK2. LIMK contains two LIM domains, a PDZ domain, and a kinase domain. LIMK is involved in the regulation of actin polymerization and microtubule disassembly. LIMK influences architecture of the actin cytoskeleton by regulating the activity of the cofilin family proteins cofilin1, cofilin2, and destrin. The mechanism of the activation is to phosphorylates cofilin on serine 3 and inactivates its actin-severing activity, and altering the rate of actin depolymerization. LIMKs can function in both cytoplasm and nucleus. Both LIMK1 and LIMK2 can act in the nucleus to suppress Rac/Cdc42-dependent cyclin D1 expression. LIMK1 is expressed in all tissues and is localized to focal adhesions in the cell. LIMK1 can form homodimers upon binding of HSP90 and is activated by Rho effector Rho kinase and MAPKAPK2. LIMK1 is important for normal central nervous system development, and its deletion has been implicated in the development of the human genetic disorder Williams syndrome. Moreover, LIMK1 up-regulates the promoter activity of urokinase type plasminogen activator and induces its mRNA and protein expression in breast cancer cells. The LIM domains have been shown to play an important role in regulating kinase activity and likely also contribute to LIMK function by acting as sites of protein-to-protein interactions. All LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2217294334 1216 CSYCNNILGKGAAMIIESLGlcYHLHCFKCVACECDLGGSSSGAEVriRNHQLYCNDCY 1274
Cdd:cd09464      1 CHGCSETITTGLVMVAGEQK--YHPECFSCLRCGAFIGDGDTYALV--EHSKLYCGHCY 55

permuted PDZ domain of Deg/high-temperature requirement factor A (HtrA) family of housekeeping serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Deg/HtrA-type serine proteases that participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. Typically, these proteases have an N-terminal serine protease domain and at least one C-terminal PDZ domain that recognizes substrates, and in some cases activates the protease function. An exception is yeast Nma11p which has two protease domains and four PDZ domains; its N-terminal half is comprised of a protease domain, followed by two PDZ domains, and its C-terminal half has a similar domain arrangement. HtrA-type proteases include the human HtrA1-4 and MBTPS2, tricorn protease, DegS, DegP and C-terminal processing peptidase, cyanobacterial serine proteases Hhoa, HhoB, and HtrA, and yeast Nma11p. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-termini of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This Deg/HtrA family PDZ domain is a circularly permuted PDZ domain which places beta-strand A at the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217294334  640 GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSynDSKEWEEAMAKAQETGHLVMDVRRYGK 701
Cdd:cd06779     26 GVLVAEVIPGSPAAKAGLKEGDVILSVNGKPVT--SFNDLRAALDTKKPGDSLNLTILRDGK 85

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217294334  617 RISINQTPGKSLdfGFTI-------KWDiPGIFVASVEAGSPAEFS-QLQVDDEIIAINNT 669
Cdd:cd06694      4 IVTLKKDPQKGL--GFTIvggensgSLD-LGIFVKSIIPGGPADKDgRIKPGDRIIAINGQ 61