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 1489865995  261 MLTRKIQSWK----------LGTTVPPISFTPGPCSEADLKRWEAIRE-------ASRLRHKKRLMVERLFQKIYGENGS 323
Cdd:pfam15949    1 MLARRTSSSEpkssvpfnqfLPNKSNQSAYVPAPLRKKRAEKEEDIRRswstrtqPSKVAYPPRQFVQRLFQKVSDDLGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489865995  324 KSMSDVSAEDV-QNLRQLRYEEMQKIKSQLKEQDQKWQDDLAKWKDRRKSYTSDLQKKKEEREEIEKQALEKS----KRS 398
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 1489865995  399 SKTFKEMLQD 408
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 1489865995 1235 CSYCNN-ILGKgaaMIIESLGLCYHLHCFKCVACECDLGGSSSGaevrIRNHQLYCNDCY 1293
Cdd:cd08368      1 CAGCGKpIEGR---ELLRALGKKWHPECFKCAECGKPLGGDSFY----EKDGKPYCEKCY 53

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 1489865995  848 QEEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEELMVLS 904
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 1489865995  261 MLTRKIQSWK----------LGTTVPPISFTPGPCSEADLKRWEAIRE-------ASRLRHKKRLMVERLFQKIYGENGS 323
Cdd:pfam15949    1 MLARRTSSSEpkssvpfnqfLPNKSNQSAYVPAPLRKKRAEKEEDIRRswstrtqPSKVAYPPRQFVQRLFQKVSDDLGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489865995  324 KSMSDVSAEDV-QNLRQLRYEEMQKIKSQLKEQDQKWQDDLAKWKDRRKSYTSDLQKKKEEREEIEKQALEKS----KRS 398
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 1489865995  399 SKTFKEMLQD 408
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 1489865995 1235 CSYCNN-ILGKgaaMIIESLGLCYHLHCFKCVACECDLGGSSSGaevrIRNHQLYCNDCY 1293
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 1489865995   676 FGFTI---KWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETG-HLVMDVRR 744
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 1489865995  663 RISINQTPGKSLdfGFTIKWDIP---GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLV 739
Cdd:cd06741      3 KVNLVVEDGQSL--GLMIRGGAEyglGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFL---DITHDEAVKILKSSKHLI 77

                   ....*..
gi 1489865995  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 1489865995  662 MRISINQTPGKSLDFGFTIKWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLVMD 741
Cdd:COG3975    471 LKLVYEDAPSLKPSLGLRVSADGGGLVVTSVLWGSPAYKAGLSAGDELLAIDGLRVT---ADNLDDALAAYKPGDPIELL 547

                   ....*.
gi 1489865995  742 VRRYGK 747
Cdd:COG3975    548 VFRRDE 553

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 1489865995  678 FTIKWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTkfSYNDSKEWEEAMAKAQETGHLVMDVRR 744
Cdd:TIGR02037  355 LRLKGDVKGVVVTKVVSGSPAARAGLQPGDVILSVNQQ--PVSSVAELRKVLARAKKGGRVALLILR 419

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489865995  849 EEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEE-LMVLSSNSMSLTTREPSLATWEATWSEG 927
Cdd:PTZ00121  1525 DEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDkNMALRKAEEAKKAEEARIEEVMKLYEEE 1604

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489865995  928 SKSSDREGTRAGEEERRQPQEEVVHEDQGKKPQDQLVIERERKWEQQLQEEQEQKRLQAE-----AEEQKRPAEEQKRQA 1002
Cdd:PTZ00121  1605 KKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAeeakkAEEDKKKAEEAKKAE 1684

                   ....*
gi 1489865995 1003 EIERE 1007
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 1489865995  261 MLTRKIQSWK----------LGTTVPPISFTPGPCSEADLKRWEAIRE-------ASRLRHKKRLMVERLFQKIYGENGS 323
Cdd:pfam15949    1 MLARRTSSSEpkssvpfnqfLPNKSNQSAYVPAPLRKKRAEKEEDIRRswstrtqPSKVAYPPRQFVQRLFQKVSDDLGS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489865995  324 KSMSDVSAEDV-QNLRQLRYEEMQKIKSQLKEQDQKWQDDLAKWKDRRKSYTSDLQKKKEEREEIEKQALEKS----KRS 398
Cdd:pfam15949   81 KSMSDIRCEEEaQPLSQVRYEELQKIRNQLKEEEDKWQDDLARWKSRRRSASQDLIKKEEERKKIEKLMSGEGgdsnRRK 160

                          170
                   ....*....|
gi 1489865995  399 SKTFKEMLQD 408
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 1489865995 1235 CSYCNN-ILGKgaaMIIESLGLCYHLHCFKCVACECDLGGSSSGaevrIRNHQLYCNDCY 1293
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 1489865995   676 FGFTI---KWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETG-HLVMDVRR 744
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 1489865995  663 RISINQTPGKSLdfGFTIKWDIP---GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETGHLV 739
Cdd:cd06741      3 KVNLVVEDGQSL--GLMIRGGAEyglGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFL---DITHDEAVKILKSSKHLI 77

                   ....*..
gi 1489865995  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 1489865995  666 INQTPGKSLDFGFTI---KWDIPGIFVASVEAGSPAEFS-QLQVDDEIIAINNTKFSyndSKEWEEAMAKAQETG-HLVM 740
Cdd:cd00136      2 VTLEKDPGGGLGFSIrggKDGGGGIFVSRVEPGGPAARDgRLRVGDRILEVNGVSLE---GLTHEEAVELLKSAGgEVTL 78

                   ...
gi 1489865995  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 1489865995  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 1489865995  686 GIFVASVEAGSPAEFSQLQVDDEIIAINNTKF 717
Cdd:cd06729     24 GIFVAGVQEGSPAEKQGLQEGDQILKVNGVDF 55

The first LIM domain of Enigma-like family; The first LIM domain of Enigma-like family: The Enigma LIM domain family is comprised of three members: Enigma, ENH, and Cypher (mouse)/ZASP (human). These subfamily members contain a single PDZ domain at the N-terminus and three LIM domains at the C-terminus. Enigma was initially characterized in humans and is expressed in multiple tissues, such as skeletal muscle, heart, bone, and brain. The third LIM domain specifically interacts with the insulin receptor and the second LIM domain interacts with the receptor tyrosine kinase Ret and the adaptor protein APS. Thus Enigma is implicated in signal transduction processes, such as mitogenic activity, insulin related actin organization, and glucose metabolism. The second member, ENH protein, was first identified in rat brain. It has been shown that ENH interacts with protein kinase D1 (PKD1) via its LIM domains and forms a complex with PKD1 and the alpha1C subunit of cardiac L-type voltage-gated calcium channel in rat neonatal cardiomyocytes. The N-terminal PDZ domain interacts with alpha-actinin at the Z-line. ZASP/Cypher is required for maintenance of Z-line structure during muscle contraction, but not required for Z-line assembly. In heart, Cypher/ZASP plays a structural role through its interaction with cytoskeletal Z-line proteins. In addition, there is increasing evidence that Cypher/ZASP also performs signaling functions. Studies reveal that Cypher/ZASP interacts with and directs PKC to the Z-line, where PKC phosphorylates downstream signaling targets. 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 1489865995 1235 CSYCNNILgKGAAMIieSLGLCYHLHCFKCVACECDLggsSSGAEVRIRNHqLYCNDCY 1293
Cdd:cd09361      1 CAHCNQVI-RGPFLV--ALGRSWHPEEFTCSHCHCSL---AEIGFVEEKGS-LYCELCY 52

PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the first PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489865995  664 ISINQTPGKSLdfGFTIKWDIP---GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFsynDSKEWEEAMAKAQETGHLVM 740
Cdd:cd10833      4 VTVEKSPDGSL--GFSVRGGSEhglGIFVSKVEEGSAAERAGLCVGDKITEVNGVSL---ENITMSSAVKVLTGSNRLRM 78

                   ....*.
gi 1489865995  741 DVRRYG 746
Cdd:cd10833     79 VVRRMG 84

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 1489865995 1235 CSYCNNILGKGAAMIieSLGLCYHLHCFKCVACECDLGGSSSGaevriRNHQLYCNDCY 1293
Cdd:cd09329      1 CAGCGQEIKNGQALL--ALDKQWHVWCFKCKECGKVLTGEYMG-----KDGKPYCERDY 52

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 1489865995  848 QEEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEELMVLS 904
Cdd:cd16269    217 LEEQQRELEQKLEDQERSYEEHLRQLKEKMEEERENLLKEQERALESKLKEQEALLE 273

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 1489865995  847 DQEEERKRQERWQKEQDRLLQEKYQREQEKLREEWQRAKQEAERENSKYLDEEL 900
Cdd:cd16269    223 ELEQKLEDQERSYEEHLRQLKEKMEEERENLLKEQERALESKLKEQEALLEEGF 276

The second LIM domain of Lmx1a and Lmx1b; The second LIM domain of Lmx1a and Lmx1b: Lmx1a and Lmx1b belong to the LHX protein family, which features two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain. Members of LHX family are found in the nucleus and act as transcription factors or cofactors. LHX proteins are critical for the development of specialized cells in multiple tissue types, including the nervous system, skeletal muscle, the heart, the kidneys, and endocrine organs such as the pituitary gland and the pancreas. Mouse Lmx1a is expressed in multiple tissues, including the roof plate of the neural tube, the developing brain, the otic vesicles, the notochord, and the pancreas. In mouse, mutations in Lmx1a result in failure of the roof plate to develop. Lmx1a may act upstream of other roof plate markers such as MafB, Gdf7, Bmp6, and Bmp7. Further characterization of these mice reveals numerous defects including disorganized cerebellum, hippocampus, and cortex; altered pigmentation; female sterility, skeletal defects, and behavioral abnormalities. In the mouse, Lmx1b functions in the developing limbs and eyes, the kidneys, the brain, and in cranial mesenchyme. The disruption of Lmx1b gene results kidney and limb defects. In the brain, Lmx1b is important for generation of mesencephalic dopamine neurons and the differentiation of serotonergic neurons. In the mouse eye, Lmx1b regulates anterior segment (cornea, iris, ciliary body, trabecular meshwork, and lens) development. 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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1489865995 1235 CSYCNNILGKgAAMIIESLGLCYHLHCFKCVACECDLggsSSGAEVRIRNHQLYCNDCY 1293
Cdd:cd09378      1 CSGCLEKIAP-SELVMRALENVYHLRCFCCCVCERQL---QKGDEFVLKEGQLLCKSDY 55

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

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489865995  851 ERKRQERWQK-EQDRLLQEKYQ--REQEKLR--EEWQRAKQ-EAERENSKYLDEELMVLSSN------SMSLTTREPSLA 918
Cdd:pfam17380  286 ERQQQEKFEKmEQERLRQEKEEkaREVERRRklEEAEKARQaEMDRQAAIYAEQERMAMEREreleriRQEERKRELERI 365

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489865995  919 TWEATWSEGSKSSDREGTRageEERRQPQEEVVHEDQGKKPQDQLVIERERKWEQQLQEEQEQKRLQAEAEEQKRPAEEQ 998
Cdd:pfam17380  366 RQEEIAMEISRMRELERLQ---MERQQKNERVRQELEAARKVKILEEERQRKIQQQKVEMEQIRAEQEEARQREVRRLEE 442

                   ....*...
gi 1489865995  999 KRQAEIER 1006
Cdd:pfam17380  443 ERAREMER 450

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1489865995  657 DQFSDMRISINQTPGKsldFGFTIKWDIPGIFVASVEAGSPAEFSQLQVDDEIIAIN 713
Cdd:COG0793     46 EEYEDFQESTSGEFGG---LGAELGEEDGKVVVVSVIPGSPAEKAGIKPGDIILAID 99

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1489865995  686 GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSynDSKEWEEAMAKAQETGHLVMDVRRYGK 747
Cdd:COG0265    202 GVLVARVEPGSPAAKAGLRPGDVILAVDGKPVT--SARDLQRLLASLKPGDTVTLTVLRGGK 261

PDZ domain 1 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 1 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which 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 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
                   ....*....|....*....|....*....|....*....|
gi 1489865995  675 DFGFTIKWDIPgIFVASVEAGSPAEFSQLQVDDEIIAINN 714
Cdd:cd06743     10 AFGFSIGGSGP-CYILSVEEGSSAHAAGLQPGDQILELDG 48

The first LIM domain of Four and a half LIM domains protein (FHL); The first LIM domain of Four and a half LIM domains protein (FHL): LIM-only protein family consists of five members, designated FHL1, FHL2, FHL3, FHL5 and LIMPETin. The first four members are composed of four complete LIM domains arranged in tandem and an N-terminal single zinc finger domain with a consensus sequence equivalent to the C-terminal half of a LIM domain. LIMPETin is an exception, containing six LIM domains. FHL1, 2 and 3 are predominantly expressed in muscle tissues, and FHL5 is highly expressed in male germ cells. FHL proteins exert their roles as transcription co-activators or co-repressors through a wide array of interaction partners. For example, FHL1 binds to Myosin-binding protein C, regulating myosin filament formation and sarcomere assembly. FHL2 has shown to interact with more than 50 different proteins, including receptors, structural proteins, transcription factors and cofactors, signal transducers, splicing factors, DNA replication and repair enzymes, and metabolic enzymes. FHL3 int eracts with many transcription factors, such as CREB, BKLF/KLF3, CtBP2, MyoD, and MZF_1. FHL5 is a tissue-specific coactivator of CREB/CREM family transcription factors. 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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1489865995 1235 CSYCNNILGkgaamiIESLGLCY---HLH--CFKCVACECDLGGSSSGAevriRNHQLYCNDCY 1293
Cdd:cd09343      5 CEECKKKIG------CDSKDLSYkdrHWHegCFKCFKCQRSLVDKPFAA----KDEDLLCTECY 58

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 1489865995  686 GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFsynDSKEWEEAMAKAQETGHLVMDVR 743
Cdd:cd06755     27 GIFVSKVEKGSKAAEAGLKRGDQILEVNGQNF---ENITLKKALEILRNNTHLSITVK 81

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 1489865995  676 FGFTIKWDIPgIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSYNDSKE 724
Cdd:cd23069     13 YGLTVSGDNP-VFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLE 60

The fifth LIM domain of protein LIMPETin; The fifth LIM domain of protein LIMPETin: LIMPETin contains 6 LIM domains at the C-terminal and an N-terminal PET domain. Four of the six LIM domains are highly homologous to the four and half LIM domain protein family and two of them show sequence similarity to the LIM domains of the testin family. Thus, LIMPETin may be the recombinant product of genes coding testin and FHL proteins. In Schistosoma mansoni, where LIMPETin was first identified, LIMPETin is down regulated in sexually mature adult Schistosoma females compared to sexually immature adult females and adult male. Its differential expression indicates that it is a transcription regulator. 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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1489865995 1235 CSYCNNILGKGAamiIESLGLCYHLHCFKCVACECDLGGSSSGAevriRNHQLYCNDCY 1293
Cdd:cd09430      1 CSKCNKIINSGG---VTYKNEPWHRECFTCTNCSKSLAGQRFTS----RDEKPYCADCF 52

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1489865995 1235 CSYCNNILGKGAAMIIESLGlcYHLHCFKCVACECDLGGSSSGAEVriRNHQLYCNDCY 1293
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 1489865995  686 GIFVASVEAGSPAEFSQLQVDDEIIAINNTKFSynDSKEWEEAMAKAQETGHLVMDVRRYGK 747
Cdd:cd06779     26 GVLVAEVIPGSPAAKAGLKEGDVILSVNGKPVT--SFNDLRAALDTKKPGDSLNLTILRDGK 85

The second LIM domain of Prickle; The second LIM domain of Prickle: Prickle contains three C-terminal LIM domains and a N-terminal PET domain. Prickles have been implicated in roles of regulating tissue polarity or planar cell polarity (PCP). PCP establishment requires the conserved Frizzled/Dishevelled PCP pathway. Prickle interacts with Dishevelled, thereby modulating Frizzled/Dishevelled activity and PCP signaling. Two forms of prickles have been identified; namely prickle 1 and prickle 2. Prickle 1 and prickle 2 are differentially expressed. While prickle 1 is expressed in fetal heart and hematological malignancies, prickle 2 is found in fetal brain, adult cartilage, pancreatic islet, and some types of timorous cells. 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 1489865995 1235 CSYCNNILGkgAAMIIESLGLCYHLHCFKCVACECDLGGSssgaEVRIRNHQLYCNDCY 1293
Cdd:cd09418      3 CSACDEIIF--ADECTEAEGRHWHMKHFCCFECECQLGGQ----RYIMREGRPYCCHCF 55

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

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                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1489865995  688 FVASVEAGSPAEFSQLQVDDEIIAINNTKFSynDSKEWEEAMAKAQETgHLVMDVRR 744
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPVR--SLEDVARLLQGSAGE-SVTLTVRR 54

circularly permuted second PDZ domain (PDZ2) of Escherichia coli periplasmic serine endoprotease DegP and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Escherichia coli DegP (also known as heat shock protein DegP and Protease Do), and related domains. DegP belongs to the HtrA family of housekeeping proteases. It acts as a protease, degrading transiently denatured and unfolded or misfolded proteins which accumulate in the periplasm following heat shock or other stress conditions, and as a molecular chaperone at low temperatures. DegP has two PDZ domains in addition to the protease domain; its PDZ1 domain is responsible for the identifying the distinct substrate sequences that affect degradation (degron) of the substrate sequence, and its PDZ2 domain is responsible for the combining with other DegP monomers to form a stable oligomer structure. 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 DegP family PDZ domain 2 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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1489865995  678 FTIKWDIPGIFVASVEAGSPAEFSQLQVDDEIIAINNTKFsyNDSKEweeaMAKAQETGH--LVMDVRRYG 746
Cdd:cd23084     11 VTDEDGGKGVVVTEVDPGSPAAQSGLKKGDVIIGVNRQPV--KSIAE----LRKVLKSKPsaVLLQIKRGD 75

The first LIM domain of actin binding LIM (abLIM) proteins; The first 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
                   ....*....|....*....|....*....|....*..
gi 1489865995 1257 YHLHCFKCVACECDLggSSSGAEVriRNHQLYCNDCY 1293
Cdd:cd09327     20 FHIKCFTCKVCGCDL--AQGGFFV--KEGEYYCTDDY 52