PLAT/LH2 domain of polycystin-1 like proteins. Polycystins are a large family of membrane proteins composed of multiple domains, present in fish, invertebrates, mammals, and humans that are widely expressed in various cell types and whose biological functions remain poorly defined. In human, mutations in polycystin-1 (PKD1) and polycystin-2 (PKD2) have been shown to be the cause for autosomal dominant polycystic kidney disease (ADPKD). The generally proposed function of PLAT/LH2 domains is to mediate interaction with lipids or membrane bound proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389  742 FHYLIQVYTGYRRSAATTAKVVITLYGSEGRSEPHHLCDPQKTVFERGGLDVFLLTTWTSLGNLHSLRLWHDNSGVSPSW 821
Cdd:cd01752      1 YLYLVTVFTGWRRGAGTTAKVTITLYGAEGESEPHHLRDPEKPIFERGSVDSFLLTTPFPLGELQSIRLWHDNSGLSPSW 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1370468389  822 YVSQVIVCDMAVKRKWHFLCNCWLAVDLGDCELDRVF 858
Cdd:cd01752     81 YLSRVIVRDLQTGKKWFFLCNDWLSVEEGDGTVERTF 117

C-type lectin (CTL)/C-type lectin-like (CTLD) domain; CLECT: C-type lectin (CTL)/C-type lectin-like (CTLD) domain; protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. This group is chiefly comprised of eukaryotic CTLDs, but contains some, as yet functionally uncharacterized, bacterial CTLDs. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces, including CaCO3 and ice. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. For example: mannose-binding lectin and lung surfactant proteins A and D bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, and apoptotic cells) and mediate functions associated with killing and phagocytosis; P (platlet)-, E (endothelial)-, and L (leukocyte)- selectins (sels) mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. Several CTLDs bind to protein ligands, and only some of these binding interactions are Ca2+-dependent; including the CTLDs of Coagulation Factors IX/X (IX/X) and Von Willebrand Factor (VWF) binding proteins, and natural killer cell receptors. C-type lectins, such as lithostathine, and some type II antifreeze glycoproteins function in a Ca2+-independent manner to bind inorganic surfaces. Many proteins in this group contain a single CTLD; these CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers, from which ligand-binding sites project in different orientations. Various vertebrate type 1 transmembrane proteins including macrophage mannose receptor, endo180, phospholipase A2 receptor, and dendritic and epithelial cell receptor (DEC205) have extracellular domains containing 8 or more CTLDs; these CTLDs remain in the parent model. In some members (IX/X and VWF binding proteins), a loop extends to the adjoining domain to form a loop-swapped dimer. A similar conformation is seen in the macrophage mannose receptor CRD4's putative non-sugar bound form of the domain in the acid environment of the endosome. Lineage specific expansions of CTLDs have occurred in several animal lineages including Drosophila melanogaster and Caenorhabditis elegans; these CTLDs also remain in the parent model.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389   33 NCYQLNRFQCSFEEAQHYCHVQRGFLAHIWNKEVQDLIRDYLEEGK--KWWIGQNVMPLKKH-------QDNKYPDVAAN 103
Cdd:cd00037      1 SCYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSSssDVWIGLNDLSSEGTwkwsdgsPLVDYTNWAPG 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1370468389  104 GPPKPLS--CTYLSRNfirisSKG----DKCLLKYYFICQ 137
Cdd:cd00037     81 EPNPGGSedCVVLSSS-----SDGkwndVSCSSKLPFICE 115

PLAT/LH2 domain of polycystin-1 like proteins. Polycystins are a large family of membrane proteins composed of multiple domains, present in fish, invertebrates, mammals, and humans that are widely expressed in various cell types and whose biological functions remain poorly defined. In human, mutations in polycystin-1 (PKD1) and polycystin-2 (PKD2) have been shown to be the cause for autosomal dominant polycystic kidney disease (ADPKD). The generally proposed function of PLAT/LH2 domains is to mediate interaction with lipids or membrane bound proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389  742 FHYLIQVYTGYRRSAATTAKVVITLYGSEGRSEPHHLCDPQKTVFERGGLDVFLLTTWTSLGNLHSLRLWHDNSGVSPSW 821
Cdd:cd01752      1 YLYLVTVFTGWRRGAGTTAKVTITLYGAEGESEPHHLRDPEKPIFERGSVDSFLLTTPFPLGELQSIRLWHDNSGLSPSW 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1370468389  822 YVSQVIVCDMAVKRKWHFLCNCWLAVDLGDCELDRVF 858
Cdd:cd01752     81 YLSRVIVRDLQTGKKWFFLCNDWLSVEEGDGTVERTF 117

PLAT/LH2 domain; This domain is found in a variety of membrane or lipid associated proteins. It is called the PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain or LH2 (Lipoxygenase homology) domain. The known structure of pancreatic lipase shows this domain binds to procolipase pfam01114, which mediates membrane association. So it appears possible that this domain mediates membrane attachment via other protein binding partners. The structure of this domain is known for many members of the family and is composed of a beta sandwich.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389  744 YLIQVYTGYRRSAATTAKVVITLYGSEGRS--EPHHLCDPQktvFERGGLDVFLLTTWTSLGNLHSLRLWHDNSGVSPSW 821
Cdd:pfam01477    1 YQVKVVTGDELGAGTDADVYISLYGKVGESaqLEITLDNPD---FERGAEDSFEIDTDWDVGAILKINLHWDNNGLSDEW 77

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1370468389  822 YVSQVIVC-DMAVKRKWHFLCNCWLAVDLgDCELDRVF 858
Cdd:pfam01477   78 FLKSITVEvPGETGGKYTFPCNSWVYGSK-KYKETRVF 114

C-type lectin (CTL)/C-type lectin-like (CTLD) domain; CLECT: C-type lectin (CTL)/C-type lectin-like (CTLD) domain; protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. This group is chiefly comprised of eukaryotic CTLDs, but contains some, as yet functionally uncharacterized, bacterial CTLDs. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces, including CaCO3 and ice. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. For example: mannose-binding lectin and lung surfactant proteins A and D bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, and apoptotic cells) and mediate functions associated with killing and phagocytosis; P (platlet)-, E (endothelial)-, and L (leukocyte)- selectins (sels) mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. Several CTLDs bind to protein ligands, and only some of these binding interactions are Ca2+-dependent; including the CTLDs of Coagulation Factors IX/X (IX/X) and Von Willebrand Factor (VWF) binding proteins, and natural killer cell receptors. C-type lectins, such as lithostathine, and some type II antifreeze glycoproteins function in a Ca2+-independent manner to bind inorganic surfaces. Many proteins in this group contain a single CTLD; these CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers, from which ligand-binding sites project in different orientations. Various vertebrate type 1 transmembrane proteins including macrophage mannose receptor, endo180, phospholipase A2 receptor, and dendritic and epithelial cell receptor (DEC205) have extracellular domains containing 8 or more CTLDs; these CTLDs remain in the parent model. In some members (IX/X and VWF binding proteins), a loop extends to the adjoining domain to form a loop-swapped dimer. A similar conformation is seen in the macrophage mannose receptor CRD4's putative non-sugar bound form of the domain in the acid environment of the endosome. Lineage specific expansions of CTLDs have occurred in several animal lineages including Drosophila melanogaster and Caenorhabditis elegans; these CTLDs also remain in the parent model.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389   33 NCYQLNRFQCSFEEAQHYCHVQRGFLAHIWNKEVQDLIRDYLEEGK--KWWIGQNVMPLKKH-------QDNKYPDVAAN 103
Cdd:cd00037      1 SCYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSSssDVWIGLNDLSSEGTwkwsdgsPLVDYTNWAPG 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1370468389  104 GPPKPLS--CTYLSRNfirisSKG----DKCLLKYYFICQ 137
Cdd:cd00037     81 EPNPGGSedCVVLSSS-----SDGkwndVSCSSKLPFICE 115

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1370468389  633 QCYYWEIHNQT---WSSAGCQVGpQSTILRTQCLCNHLTFFA 671
Cdd:pfam01825    2 QCVFWDFTNSTtgrWSTEGCTTV-SLNDTHTVCSCNHLTSFA 42

Polycystin cation channel protein; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389 1554 LVGFPVLLATVQLWNLLRHSPRLRVISRTLSRAWDEVVGFLLIILILLTGYAIAFNLLFGCSISDYRTFFSSAVTVVGLL 1633
Cdd:PLN03223  1294 LSGINIILLLGRILKLMDFQPRLGVITRTLWLAGADLMHFFVIFGMVFVGYAFIGHVIFGNASVHFSDMTDSINSLFENL 1373

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370468389 1634 MG-ISHQEEVF----ALDPVLGTFLILTSVILMVLVVINLFVSAILMAFGkERKSLKKEAALIDTllqKLSNLLGISW 1706
Cdd:PLN03223  1374 LGdITYFNEDLknltGLQFVVGMIYFYSYNIFVFMILFNFLLAIICDAFG-EVKANAAETVSVHT---ELFPMLRDKW 1447

Lectin C-type domain; This family includes both long and short form C-type

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389   43 SFEEAQHYCHVQRGFLAHIWNKEVQDLIRDYLEE-GKKWWIGQNVMPLKKhqDNKYPD-----------VAANGPPKPlS 110
Cdd:pfam00059    3 TWDEAREACRKLGGHLVSINSAEELDFLSSTLKKsNKYFWIGLTDRKNEG--TWKWVDgspvnytnwapEPNNNGENE-D 79

                           90       100
                   ....*....|....*....|....*...
gi 1370468389  111 CTYLSRNFIRISSKGdkCLLKYYFICQT 138
Cdd:pfam00059   80 CVELSSSSGKWNDEN--CNSKNPFVCEK 105

PLAT/LH2 domain of polycystin-1 like proteins. Polycystins are a large family of membrane proteins composed of multiple domains, present in fish, invertebrates, mammals, and humans that are widely expressed in various cell types and whose biological functions remain poorly defined. In human, mutations in polycystin-1 (PKD1) and polycystin-2 (PKD2) have been shown to be the cause for autosomal dominant polycystic kidney disease (ADPKD). The generally proposed function of PLAT/LH2 domains is to mediate interaction with lipids or membrane bound proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389  742 FHYLIQVYTGYRRSAATTAKVVITLYGSEGRSEPHHLCDPQKTVFERGGLDVFLLTTWTSLGNLHSLRLWHDNSGVSPSW 821
Cdd:cd01752      1 YLYLVTVFTGWRRGAGTTAKVTITLYGAEGESEPHHLRDPEKPIFERGSVDSFLLTTPFPLGELQSIRLWHDNSGLSPSW 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1370468389  822 YVSQVIVCDMAVKRKWHFLCNCWLAVDLGDCELDRVF 858
Cdd:cd01752     81 YLSRVIVRDLQTGKKWFFLCNDWLSVEEGDGTVERTF 117

Polycystin cation channel; This family contains the cation channel region from group II of Transient receptor potential (TRP) channels, the TRPP subfamily, including PKD1, PKD2, PKD2L and mucolipin proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389 1466 IISQVIYYLLVCYYAFIQGCQLKQQKWRFFTGKRNILDTSIILISFILLGLDMKSISLHKKNMARYRDDQDRFISFYEAV 1545
Cdd:pfam08016   11 LLCEIVFVVFFLYFVVEEILKIRKHRPSYLRSVWNLLDLAIVILSVVLIVLNIYRDFLADRLIKSVEASPVTFIDFDRVA 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389 1546 KVNSAATHLVGFPVLLATVQLWNLLRHSPRLRVISRTLSRAWDEVVGFLLIILILLTGYAIAFNLLFGCSISDYRTFFSS 1625
Cdd:pfam08016   91 QLDNLYRIILAFLVFLTWLKLFKVLRFNKTMSLFTKTLSRAWKDLAGFALMFVIFFFAYAQFGYLLFGTQAPNFSNFVKS 170

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1370468389 1626 AVTVVGLLMGISHQEEVFALDPVLGTFLILTSVILMVLVVINLFVSAILMAF 1677
Cdd:pfam08016  171 ILTLFRTILGDFGYNEIFSGNRVLGPLLFLTFVFLVIFILLNLFLAIINDSY 222

PLAT (Polycystin-1, Lipoxygenase, Alpha-Toxin) domain or LH2 (Lipoxygenase homology 2) domain. It consists of an eight stranded beta-barrel. The domain can be found in various domain architectures, in case of lipoxygenases, alpha toxin, lipases and polycystin, but also as a single domain or as repeats.The putative function of this domain is to facilitate access to sequestered membrane or micelle bound substrates.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389  743 HYLIQVYTGYRRSAATTAKVVITLYGSEGRSEPHhLCDPQKTVFERGGLDVFLLTTWTSLGNLHSLRLWHDNSGVSPSWY 822
Cdd:cd00113      2 RYTVTIKTGDKKGAGTDSNISLALYGENGNSSDI-PILDGPGSFERGSTDTFQIDLKLDIGDITKVYLRRDGSGLSDGWY 80

                           90       100
                   ....*....|....*....|...
gi 1370468389  823 VSQVIVCDMAVKRKWHFLCNCWL 845
Cdd:cd00113     81 CESITVQALGTKKVYTFPVNRWV 103

C-type lectin (CTL)/C-type lectin-like (CTLD) domain; CLECT: C-type lectin (CTL)/C-type lectin-like (CTLD) domain; protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. This group is chiefly comprised of eukaryotic CTLDs, but contains some, as yet functionally uncharacterized, bacterial CTLDs. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces, including CaCO3 and ice. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. For example: mannose-binding lectin and lung surfactant proteins A and D bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, and apoptotic cells) and mediate functions associated with killing and phagocytosis; P (platlet)-, E (endothelial)-, and L (leukocyte)- selectins (sels) mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. Several CTLDs bind to protein ligands, and only some of these binding interactions are Ca2+-dependent; including the CTLDs of Coagulation Factors IX/X (IX/X) and Von Willebrand Factor (VWF) binding proteins, and natural killer cell receptors. C-type lectins, such as lithostathine, and some type II antifreeze glycoproteins function in a Ca2+-independent manner to bind inorganic surfaces. Many proteins in this group contain a single CTLD; these CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers, from which ligand-binding sites project in different orientations. Various vertebrate type 1 transmembrane proteins including macrophage mannose receptor, endo180, phospholipase A2 receptor, and dendritic and epithelial cell receptor (DEC205) have extracellular domains containing 8 or more CTLDs; these CTLDs remain in the parent model. In some members (IX/X and VWF binding proteins), a loop extends to the adjoining domain to form a loop-swapped dimer. A similar conformation is seen in the macrophage mannose receptor CRD4's putative non-sugar bound form of the domain in the acid environment of the endosome. Lineage specific expansions of CTLDs have occurred in several animal lineages including Drosophila melanogaster and Caenorhabditis elegans; these CTLDs also remain in the parent model.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389   33 NCYQLNRFQCSFEEAQHYCHVQRGFLAHIWNKEVQDLIRDYLEEGK--KWWIGQNVMPLKKH-------QDNKYPDVAAN 103
Cdd:cd00037      1 SCYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSSssDVWIGLNDLSSEGTwkwsdgsPLVDYTNWAPG 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1370468389  104 GPPKPLS--CTYLSRNfirisSKG----DKCLLKYYFICQ 137
Cdd:cd00037     81 EPNPGGSedCVVLSSS-----SDGkwndVSCSSKLPFICE 115

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1370468389  633 QCYYWEIHNQT---WSSAGCQVGpQSTILRTQCLCNHLTFFA 671
Cdd:pfam01825    2 QCVFWDFTNSTtgrWSTEGCTTV-SLNDTHTVCSCNHLTSFA 42

C-type lectin (CTL) or carbohydrate-recognition domain (CRD); Many of these domains function as calcium-dependent carbohydrate binding modules.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389    31 QNNCYQLNRFQCSFEEAQHYCHVQRGFLAHIWNKEVQDLIRDYLEEGKK---WWIGQNVMPLKKH-------QDNKYPDV 100
Cdd:smart00034    9 GGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLLKNSGSsdyYWIGLSDPDSNGSwqwsdgsGPVSYSNW 88

                            90       100       110
                    ....*....|....*....|....*....|....*...
gi 1370468389   101 AANGPPKPL-SCTYLSRNFIRISSKGdkCLLKYYFICQ 137
Cdd:smart00034   89 APGEPNNSSgDCVVLSTSGGKWNDVS--CTSKLPFVCE 124

C-type lectin-like domain (CTLD) of the type found in natural killer cell receptors (NKRs); CLECT_NK_receptors_like: C-type lectin-like domain (CTLD) of the type found in natural killer cell receptors (NKRs), including proteins similar to oxidized low density lipoprotein (OxLDL) receptor (LOX-1), CD94, CD69, NKG2-A and -D, osteoclast inhibitory lectin (OCIL), dendritic cell-associated C-type lectin-1 (dectin-1), human myeloid inhibitory C-type lectin-like receptor (MICL), mast cell-associated functional antigen (MAFA), killer cell lectin-like receptors: subfamily F, member 1 (KLRF1) and subfamily B, member 1 (KLRB1), and lys49 receptors. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. NKRs are variously associated with activation or inhibition of natural killer (NK) cells. Activating NKRs stimulate cytolysis by NK cells of virally infected or transformed cells; inhibitory NKRs block cytolysis upon recognition of markers of healthy self cells. Most Lys49 receptors are inhibitory; some are stimulatory. OCIL inhibits NK cell function via binding to the receptor NKRP1D. Murine OCIL in addition to inhibiting NK cell function inhibits osteoclast differentiation. MAFA clusters with the type I Fc epsilon receptor (FcepsilonRI) and inhibits the mast cells secretory response to FcepsilonRI stimulus. CD72 is a negative regulator of B cell receptor signaling. NKG2D is an activating receptor for stress-induced antigens; human NKG2D ligands include the stress induced MHC-I homologs, MICA, MICB, and ULBP family of glycoproteins Several NKRs have a carbohydrate-binding capacity which is not mediated through calcium ions (e.g. OCIL binds a range of high molecular weight sulfated glycosaminoglycans including dextran sulfate, fucoidan, and gamma-carrageenan sugars). Dectin-1 binds fungal beta-glucans and in involved in the innate immune responses to fungal pathogens. MAFA binds saccharides having terminal alpha-D mannose residues in a calcium-dependent manner. LOX-1 is the major receptor for OxLDL in endothelial cells and thought to play a role in the pathology of atherosclerosis. Some NKRs exist as homodimers (e.g.Lys49, NKG2D, CD69, LOX-1) and some as heterodimers (e.g. CD94/NKG2A). Dectin-1 can function as a monomer in vitro.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389   31 QNNCYQLNRFQCSFEEAQHYCHVQRGFLAHIWNKEVQDLIRDYLEEgKKWWIGqnvmpLKKHQDNK----------YPDV 100
Cdd:cd03593      9 GNKCYYFSMEKKTWNESKEACSSKNSSLLKIDDEEELEFLQSQIGS-SSYWIG-----LSREKSEKpwkwidgsplNNLF 82

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1370468389  101 AANGPPKPLSCTYLSRNfiRISSkgDKCLLKYYFICQ 137
Cdd:cd03593     83 NIRGSTKSGNCAYLSST--GIYS--EDCSTKKRWICE 115

C-type lectin-like protein; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389   11 LYIRTSIILGSELNSPAPHGQ--NNCYQLNRFQCSFEEAQHYCHVQRGFLAHIWNKEVQDLIRDYLeEGKKWWIGQNVMP 88
Cdd:PHA03097    32 LSCKLSPGDRSGLNCRSGWVGynNKCYTFSENITNKHLAIERCADMDGILTLIDDQKEVLFVSRYK-GGQDLWIGIEKKK 110

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1370468389   89 LKKHQDNKYPDVAanGPPKPLSCTYLSRNFIrISSkgdKCLLKYYFIC 136
Cdd:PHA03097   111 GDDDDREVLDKVV--KPPKSGKCAYLKDKTI-ISS---NCNATKGWIC 152

Ion transport protein; This family contains sodium, potassium and calcium ion channels. This family is 6 transmembrane helices in which the last two helices flank a loop which determines ion selectivity. In some sub-families (e.g. Na channels) the domain is repeated four times, whereas in others (e.g. K channels) the protein forms as a tetramer in the membrane.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389 1491 KWRFFTGKRNILDTSIILISFILLGLDMKSISLhkknmaryrddqdrfisfyeAVKVNSAathlvgFPVLLatvqLWNLL 1570
Cdd:pfam00520   60 KKRYFRSPWNILDFVVVLPSLISLVLSSVGSLS--------------------GLRVLRL------LRLLR----LLRLI 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370468389 1571 RHSPRLRVISRTLSRAWDEVVGFLLIILILLTGYAIAFNLLFGCS----------ISDYRTFFSSAVTVVGLLMGIS--- 1637
Cdd:pfam00520  110 RRLEGLRTLVNSLIRSLKSLGNLLLLLLLFLFIFAIIGYQLFGGKlktwenpdngRTNFDNFPNAFLWLFQTMTTEGwgd 189

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1370468389 1638 -HQEEVFALDPVLGTFLILTSVILMVLVVINLFVSAILMAFGKERKSLK 1685
Cdd:pfam00520  190 iMYDTIDGKGEFWAYIYFVSFIILGGFLLLNLFIAVIIDNFQELTERTE 238