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 17544698     24 CNYGDIEYDGYCYTFVNQRLLFPDAQTHCATLGGVLVRVRGDQDGRWLAAIAGTEfhATYGNFWIGLQ--LVDGQWEWED 101
Cdd:smart00034   1 CPSGWISYGGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLLKNS--GSSDYYWIGLSdpDSNGSWQWSD 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 17544698    102 AS-TSTYKNWAPGYPFSGYDYVGA-QLSNAKWVTVRSSLMLPFIC 144
Cdd:smart00034  79 GSgPVSYSNWAPGEPNNSSGDCVVlSTSGGKWNDVSCTSKLPFVC 123

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 17544698     24 CNYGDIEYDGYCYTFVNQRLLFPDAQTHCATLGGVLVRVRGDQDGRWLAAIAGTEfhATYGNFWIGLQ--LVDGQWEWED 101
Cdd:smart00034   1 CPSGWISYGGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLLKNS--GSSDYYWIGLSdpDSNGSWQWSD 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 17544698    102 AS-TSTYKNWAPGYPFSGYDYVGA-QLSNAKWVTVRSSLMLPFIC 144
Cdd:smart00034  79 GSgPVSYSNWAPGEPNNSSGDCVVlSTSGGKWNDVSCTSKLPFVC 123

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 17544698  34 YCYTFVNQRLLFPDAQTHCATLGGVLVRVRGDQDGRWLAAIAGTefhATYGNFWIGLQ--LVDGQWEWEDAST-STYKNW 110
Cdd:cd00037   1 SCYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKK---SSSSDVWIGLNdlSSEGTWKWSDGSPlVDYTNW 77

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 17544698 111 APGYPFSGYDYVGAQLS---NAKWVTVRSSLMLPFICYY 146
Cdd:cd00037  78 APGEPNPGGSEDCVVLSsssDGKWNDVSCSSKLPFICEK 116

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698    45 FPDAQTHCATLGGVLVRVRGDQDGRWLAAIAgtefHATYGNFWIGL--QLVDGQWEWEDASTSTYKNWA--PGYPFSGYD 120
Cdd:pfam00059   4 WDEAREACRKLGGHLVSINSAEELDFLSSTL----KKSNKYFWIGLtdRKNEGTWKWVDGSPVNYTNWApePNNNGENED 79

                          90       100
                  ....*....|....*....|....*.
gi 17544698   121 YVGAQLSNAKWVTVRSSLMLPFICYY 146
Cdd:pfam00059  80 CVELSSSSGKWNDENCNSKNPFVCEK 105

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 17544698     24 CNYGDIEYDGYCYTFVNQRLLFPDAQTHCATLGGVLVRVRGDQDGRWLAAIAGTEfhATYGNFWIGLQ--LVDGQWEWED 101
Cdd:smart00034   1 CPSGWISYGGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLLKNS--GSSDYYWIGLSdpDSNGSWQWSD 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 17544698    102 AS-TSTYKNWAPGYPFSGYDYVGA-QLSNAKWVTVRSSLMLPFIC 144
Cdd:smart00034  79 GSgPVSYSNWAPGEPNNSSGDCVVlSTSGGKWNDVSCTSKLPFVC 123

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 17544698  34 YCYTFVNQRLLFPDAQTHCATLGGVLVRVRGDQDGRWLAAIAGTefhATYGNFWIGLQ--LVDGQWEWEDAST-STYKNW 110
Cdd:cd00037   1 SCYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKK---SSSSDVWIGLNdlSSEGTWKWSDGSPlVDYTNW 77

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 17544698 111 APGYPFSGYDYVGAQLS---NAKWVTVRSSLMLPFICYY 146
Cdd:cd00037  78 APGEPNPGGSEDCVVLSsssDGKWNDVSCSSKLPFICEK 116

A bacterial subgroup of the C-type lectin-like (CTLD) domain; a subgroup of bacterial protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins; CLECT_VCBS: A bacterial subgroup of the C-type lectin-like (CTLD) domain; a subgroup of bacterial protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces including CaCO3 and ice. Bacterial CTLDs within this group are functionally uncharacterized. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers from which ligand-binding sites project in different orientations. In some CTLDs a loop extends to the adjoining domain to form a loop-swapped dimer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698  36 YTFVNQRLLFPDAQTHCATLGGVLVRVRGDQDGRWLAAIAGTefhatYGNFWIGLQL--VDGQWEWEDASTSTYKNWAPG 113
Cdd:cd03603   3 YKFVDGGMTWEAAQTLAESLGGHLVTINSAEENDWLLSNFGG-----YGASWIGASDaaTEGTWKWSDGEESTYTNWGSG 77

                        90       100
                ....*....|....*....|....*
gi 17544698 114 YPFS----GYDYVGAQ---LSNAKW 131
Cdd:cd03603  78 EPHNngggNEDYAAINhfpGISGKW 102

C-type lectin (CTL)/C-type lectin-like (CTLD) domain subgroup 1; a subgroup of protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins; CLECT_1: C-type lectin (CTL)/C-type lectin-like (CTLD) domain subgroup 1; a subgroup of protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. 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. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers from which ligand-binding sites project in different orientations. In some CTLDs a loop extends to the adjoining domain to form a loop-swapped dimer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698  36 YTFVNQRLLFPDAQTHCATLGGVLVRVRGDQDGRWLAAIAGTefhaTYGNFWIGLQLVDGQWEWEDASTSTYKNWAPGYP 115
Cdd:cd03602   3 FYLVNESKTWSEAQQYCRENYTDLATVQNQEDNALLSNLSRV----SNSAAWIGLYRDVDSWRWSDGSESSFRNWNTFQP 78

                        90       100       110
                ....*....|....*....|....*....|
gi 17544698 116 FSGYDyVGAQLSNAKWVTVRSSLMLPFICY 145
Cdd:cd03602  79 FGQGD-CATMYSSGRWYAALCSALKPFICY 107

C-type lectin-like domain (CTLD) of the type found in Human REG-1 (lithostathine), REG-4, and avian eggshell-specific proteins: ansocalcin, structhiocalcin-1(SCA-1), and -2(SCA-2); CLECT_REG-1_like: C-type lectin-like domain (CTLD) of the type found in Human REG-1 (lithostathine), REG-4, and avian eggshell-specific proteins: ansocalcin, structhiocalcin-1(SCA-1), and -2(SCA-2). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. REG-1 is a proliferating factor which participates in various kinds of tissue regeneration including pancreatic beta-cell regeneration, regeneration of intestinal mucosa, regeneration of motor neurons, and perhaps in tissue regeneration of damaged heart. REG-1 may play a role on the pathophysiology of Alzheimer's disease and in the development of gastric cancers. Its expression is correlated with reduced survival from early-stage colorectal cancer. REG-1 also binds and aggregates several bacterial strains from the intestinal flora and it has been suggested that it is involved in the control of the intestinal bacterial ecosystem. Rat lithostathine has calcium carbonate crystal inhibitor activity in vitro. REG-IV is unregulated in pancreatic, gastric, hepatocellular, and prostrate adenocarcinomas. REG-IV activates the EGF receptor/Akt/AP-1 signaling pathway in colorectal carcinoma. Ansocalcin, SCA-1 and -2 are found at high concentration in the calcified egg shell layer of goose and ostrich, respectively and tend to form aggregates. Ansocalcin nucleates calcite crystal aggregates in vitro.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698  24 CNYGDIEYDGYCYTFVNQRLLFPDAQTHCATL--GGVLVRVRGDQDGRWLAA-IAGteFHATYGNFWIGLQ--LVDGQWE 98
Cdd:cd03594   1 CPKGWLPYKGNCYGYFRQPLSWSDAELFCQKYgpGAHLASIHSPAEAAAIASlISS--YQKAYQPVWIGLHdpQQSRGWE 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 17544698  99 WEDASTSTYKNWAPGYPFSGYDYVGAQLSN---AKWVTVRSSLMLPFICYY 146
Cdd:cd03594  79 WSDGSKLDYRSWDRNPPYARGGYCAELSRStgfLKWNDANCEERNPFICKY 129

C-type lectin-like domain (CTLD) of the type found in the human proteins, eosinophil major basic protein (EMBP) and prepro major basic protein homolog (MBPH); CLECT_EMBP_like: C-type lectin-like domain (CTLD) of the type found in the human proteins, eosinophil major basic protein (EMBP) and prepro major basic protein homolog (MBPH). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Eosinophils and basophils carry out various functions in allergic, parasitic, and inflammatory diseases. EMBP is stored in eosinophil crystalloid granules and is released upon degranulation. EMBP is also expressed in basophils. The proform of EMBP is expressed in placental X cells and breast tissue and increases significantly during human pregnancy. EMBP has cytotoxic properties and damages bacteria and mammalian cells, in vitro, as well as, helminth parasites. EMBP deposition has been observed in the inflamed tissue of allergy patients in a variety of diseases including asthma, atopic dermatitis, and rhinitis. In addition to its cytotoxic functions, EMBP activates cells and stimulates cytokine production. EMBP has been shown to bind the proteoglycan heparin. The binding site is similar to the carbohydrate binding site of other classical CTLD, such as mannose-binding protein (MBP1), however, heparin binding to EMBP is calcium ion independent. MBPH has reduced potency in cytotoxic and cytostimulatory assays compared with EMBP.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698  33 GYCYTFVNQRLLFPDAQTHCATLggvlvrVRGDqdgrwLAAIAGTEFH---------ATYGNFWIG----LQLVDGQWEW 99
Cdd:cd03598   1 GRCYRFVKSPRTFRDAQVICRRC------YRGN-----LASIHSFAFNyrvqrlvstLNQAQVWIGgiitGKGRCRRFSW 69

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 17544698 100 EDASTSTYKNWAPGYPFSGYDY-VGAQLSNAKWVTVRSSLMLPFICYY 146
Cdd:cd03598  70 VDGSVWNYAYWAPGQPGNRRGHcVELCTRGGHWRRAHCKLRRPFICSY 117

C-type lectin-like domain (CTLD) of the type found in the type 1 transmembrane proteins: P(platlet)-, E(endothelial)-, and L(leukocyte)- selectins (sels); CLECT_selectins_like: C-type lectin-like domain (CTLD) of the type found in the type 1 transmembrane proteins: P(platlet)-, E(endothelial)-, and L(leukocyte)- selectins (sels). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. P- E- and L-sels are cell adhesion receptors that mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. L- sel is expressed constitutively on most leukocytes. P-sel is stored in the Weibel-Palade bodies of endothelial cells and in the alpha granules of platlets. E- sels are present on endothelial cells. Following platelet and/or endothelial cell activation P- sel is rapidly translocated to the cell surface and E-sel expression is induced. The initial step in leukocyte migration involves interactions of selectins with fucosylated, sialylated, and sulfated carbohydrate moieties on target ligands displayed on glycoprotein scaffolds on endothelial cells and leucocytes. A major ligand of P- E- and L-sels is PSGL-1 (P-sel glycoprotein ligand). Interactions of E- and P- sels with tumor cells may promote extravasation of cancer cells. Regulation of L-sel and P-sel function includes proteolytic shedding of the most extracellular portion (containing the CTLD) from the cell surface. Increased levels of the soluble form of P-sel in the plasma have been found in a number of diseases including coronary disease and diabetes. E- and P- sel also play roles in the development of synovial inflammation in inflammatory arthritis. Platelet P-sel, but not endothelial P-sel, plays a role in the inflammatory response and neointimal formation after arterial injury. Selectins may also function as signal-transducing receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698  36 YTFVNQRLLFPDAQTHCATLGGVLVRVRGDQDGRWLAAIAGTEFHATYgnfWIGLQLVDGQWEWEDASTS--TYKNWAPG 113
Cdd:cd03592   3 YHYSTEKMTFNEAVKYCKSRGTDLVAIQNAEENALLNGFALKYNLGYY---WIDGNDINNEGTWVDTDKKelEYKNWAPG 79

                ..
gi 17544698 114 YP 115
Cdd:cd03592  80 EP 81

C-type lectin-like domain (CTLD) of the type found in the tetranectin (TN), cartilage derived C-type lectin (CLECSF1), and stem cell growth factor (SCGF); CLECT_tetranectin_like: C-type lectin-like domain (CTLD) of the type found in the tetranectin (TN), cartilage derived C-type lectin (CLECSF1), and stem cell growth factor (SCGF). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. TN binds to plasminogen and stimulates activation of plasminogen, playing a key role in the regulation of proteolytic processes. The TN CTLD binds two calcium ions. Its calcium free form binds to various kringle-like protein ligands. Two residues involved in the coordination of calcium are critical for the binding of TN to the fourth kringle (K4) domain of plasminogen (Plg K4). TN binds the kringle 1-4 form of angiostatin (AST K1-4). AST K1-4 is a fragment of Plg, commonly found in cancer tissues. TN inhibits the binding of Plg and AST K1-4 to the extracellular matrix (EMC) of endothelial cells and counteracts the antiproliferative effects of AST K1-4 on these cells. TN also binds the tenth kringle domain of apolipoprotein (a). In addition, TN binds fibrin and complex polysaccharides in a Ca2+ dependent manner. The binding site for complex sulfated polysaccharides is N-terminal to the CTLD. TN is homotrimeric; N-terminal to the CTLD is an alpha helical domain responsible for trimerization of monomeric units. TN may modulate angiogenesis through interactions with angiostatin and coagulation through interaction with fibrin. TN may play a role in myogenesis and in bone development. Mice having a deletion in the TN gene exhibit a kyphotic spine abnormality. TN is a useful prognostic marker of certain cancer types. CLECSF1 is expressed in cartilage tissue, which is primarily intracellular matrix (ECM), and is a candidate for organizing ECM. SCGF is strongly expressed in bone marrow and is a cytokine for primitive hematopoietic progenitor cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698 177 HRCYSFIPTLLPYAAAKQKCESIGKTLAIFDDQMQINFVTSVsVSKFSMNYGSFWVGLTKNTADNTFHWADGNVNSLKNW 256
Cdd:cd03596   9 KKCYLVSEETKHYHEASEDCIARGGTLATPRDSDENDALRDY-VKASVPGNWEVWLGINDMVAEGKWVDVNGSPISYFNW 87

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 17544698 257 TPGYPFQ------HQTVVSQQVSNGKWKTSETDTLLPSVC 290
Cdd:cd03596  88 EREITAQpdggkrENCVALSSSAQGKWFDEDCRREKPYVC 127

C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR); CLECT_DC-SIGN_like: C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and the related receptor, DC-SIGN receptor (DC-SIGNR). This group also contains proteins similar to hepatic asialoglycoprotein receptor (ASGP-R) and langerin in human. These proteins are type II membrane proteins with a CTLD ectodomain. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. DC-SIGN is thought to mediate the initial contact between dendritic cells and resting T cells, and may also mediate the rolling of DCs on epithelium. DC-SIGN and DC-SIGNR bind to oligosaccharides present on human tissues, as well as, on pathogens including parasites, bacteria, and viruses. DC-SIGN and DC-SIGNR bind to HIV enhancing viral infection of T cells. DC-SIGN and DC-SIGNR are homotetrameric, and contain four CTLDs stabilized by a coiled coil of alpha helices. The hepatic ASGP-R is an endocytic recycling receptor which binds and internalizes desialylated glycoproteins having a terminal galactose or N-acetylgalactosamine residues on their N-linked carbohydrate chains, via the clathrin-coated pit mediated endocytic pathway, and delivers them to lysosomes for degradation. It has been proposed that glycoproteins bearing terminal Sia (sialic acid) alpha2, 6GalNAc and Sia alpha2, 6Gal are endogenous ligands for ASGP-R and that ASGP-R participates in regulating the relative concentration of serum glycoproteins bearing alpha 2,6-linked Sia. The human ASGP-R is a hetero-oligomer composed of two subunits, both of which are found within this group. Langerin is expressed in a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin induces the formation of Birbeck Granules (BGs) and associates with these BGs following internalization. Langerin binds, in a calcium-dependent manner, to glyco-conjugates containing mannose and related sugars mediating their uptake and degradation. Langerin molecules oligomerize as trimers with three CTLDs held together by a coiled-coil of alpha helices.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698 179 CYSFIPTLLPYAAAKQKCESIGKTLAIFDDQMQINFVTSVSVSKFsmnygSFWVGLTKNTADNTFHWADGNV--NSLKNW 256
Cdd:cd03590  12 CYFFSTEKKSWEESRQFCEDMGAHLVIINSQEEQEFISKILSGNR-----SYWIGLSDEETEGEWKWVDGTPlnSSKTFW 86

                ....*
gi 17544698 257 TPGYP 261
Cdd:cd03590  87 HPGEP 91

C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins; CLECT_CSPGs: C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins (CSPGs) in human and chicken aggrecan, frog brevican, and zebra fish dermacan. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Xenopus brevican is expressed in the notochord and the brain during early embryogenesis. Zebra fish dermacan is expressed in dermal bones and may play a role in dermal bone development. CSPGs do contain LINK domain(s) which bind HA. These LINK domains are considered by one classification system to be a variety of CTLD, but are omitted from this hierarchical classification based on insignificant sequence similarity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698  24 CNYGDIEYDGYCYTFVNQRLLFPDAQTHCATLGGVLVRVRGDQDgrwlaaiagTEFHATYGN--FWIGL--QLVDGQWEW 99
Cdd:cd03588   1 CEEGWDKFQGHCYRHFPDRETWEDAERRCREQQGHLSSIVTPEE---------QEFVNNNAQdyQWIGLndRTIEGDFRW 71

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 17544698 100 EDASTSTYKNWAPGYP----FSGYDYVGAQLSN-AKWVTVRSSLMLPFIC 144
Cdd:cd03588  72 SDGHPLQFENWRPNQPdnffATGEDCVVMIWHEeGEWNDVPCNYHLPFTC 121

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698 176 EHRCYSFIPTLLPYAAAKQKCESIGKTLAIFDDQMQINFVTSVSVSKFsmnygsFWVGLTKNTADNTFHWADGNVnsLKN 255
Cdd:cd03593   9 GNKCYYFSMEKKTWNESKEACSSKNSSLLKIDDEEELEFLQSQIGSSS------YWIGLSREKSEKPWKWIDGSP--LNN 80

                .
gi 17544698 256 W 256
Cdd:cd03593  81 L 81

A bacterial subgroup of the C-type lectin-like (CTLD) domain; a subgroup of bacterial protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins; CLECT_VCBS: A bacterial subgroup of the C-type lectin-like (CTLD) domain; a subgroup of bacterial protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces including CaCO3 and ice. Bacterial CTLDs within this group are functionally uncharacterized. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers from which ligand-binding sites project in different orientations. In some CTLDs a loop extends to the adjoining domain to form a loop-swapped dimer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698 180 YSFIPTLLPYAAAKQKCESIGKTLAIFDDQMQINFVtsvsVSKFSmNYGSFWVGLTKNTADNTFHWADGNVNSLKNWTPG 259
Cdd:cd03603   3 YKFVDGGMTWEAAQTLAESLGGHLVTINSAEENDWL----LSNFG-GYGASWIGASDAATEGTWKWSDGEESTYTNWGSG 77

                ....*..
gi 17544698 260 YPFQHQT 266
Cdd:cd03603  78 EPHNNGG 84

C-type lectin-like domain (CTLD) of the type found in the human type-1A transmembrane proteins chondrolectin (CHODL) and layilin; CLECT_chondrolectin_like: C-type lectin-like domain (CTLD) of the type found in the human type-1A transmembrane proteins chondrolectin (CHODL) and layilin. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. CHODL is predominantly expressed in muscle cells and is associated with T-cell maturation. Various alternatively spliced isoforms have been of CHODL have been identified. The transmembrane form of CHODL is localized in the ER-Golgi apparatus. Layilin is widely expressed in different cell types. The extracellular CTLD of layilin binds hyaluronan (HA), a major constituent of the extracellular matrix (ECM). The cytoplasmic tail of layilin binds various members of the band 4.1/ERM superfamily (talin, radixin, and merlin). The ERM proteins are cytoskeleton-membrane linker molecules which link actin to receptors in the plasma membrane. Layilin co-localizes in with talin in membrane ruffles and may mediate signals from the ECM to the cell cytoskeleton.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698  42 RLLFPDAQTHCATLGGVLVRVRGDQDGRWLAAIAgTEFHATYGNFWIGLQLVDG----------QWEWEDASTSTYKNWA 111
Cdd:cd03595  24 RLNFEEARQACREDGGELLSIESENEQKLIERFI-QTLRASDGDFWIGLRRSSQynvtssacssLYYWLDGSISTFRNWY 102

                ....*....
gi 17544698 112 PGYPFSGYD 120
Cdd:cd03595 103 VDEPSCGSE 111

C-type lectin-like domain (CTLD) of the type found in the type 1 transmembrane proteins: P(platlet)-, E(endothelial)-, and L(leukocyte)- selectins (sels); CLECT_selectins_like: C-type lectin-like domain (CTLD) of the type found in the type 1 transmembrane proteins: P(platlet)-, E(endothelial)-, and L(leukocyte)- selectins (sels). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. P- E- and L-sels are cell adhesion receptors that mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. L- sel is expressed constitutively on most leukocytes. P-sel is stored in the Weibel-Palade bodies of endothelial cells and in the alpha granules of platlets. E- sels are present on endothelial cells. Following platelet and/or endothelial cell activation P- sel is rapidly translocated to the cell surface and E-sel expression is induced. The initial step in leukocyte migration involves interactions of selectins with fucosylated, sialylated, and sulfated carbohydrate moieties on target ligands displayed on glycoprotein scaffolds on endothelial cells and leucocytes. A major ligand of P- E- and L-sels is PSGL-1 (P-sel glycoprotein ligand). Interactions of E- and P- sels with tumor cells may promote extravasation of cancer cells. Regulation of L-sel and P-sel function includes proteolytic shedding of the most extracellular portion (containing the CTLD) from the cell surface. Increased levels of the soluble form of P-sel in the plasma have been found in a number of diseases including coronary disease and diabetes. E- and P- sel also play roles in the development of synovial inflammation in inflammatory arthritis. Platelet P-sel, but not endothelial P-sel, plays a role in the inflammatory response and neointimal formation after arterial injury. Selectins may also function as signal-transducing receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698 189 YAAAKQKCESIGKTLAIFDDQMQINFVTSVSVsKFSMNYgsFWVGLTKNTADNTFHWADGNVNSLKNWTPGYP---FQHQ 265
Cdd:cd03592  12 FNEAVKYCKSRGTDLVAIQNAEENALLNGFAL-KYNLGY--YWIDGNDINNEGTWVDTDKKELEYKNWAPGEPnngRNEN 88

                        90       100
                ....*....|....*....|....*..
gi 17544698 266 TVVSQQVSNGKWKTSETDTLLPSVCSG 292
Cdd:cd03592  89 CLEIYIKDNGKWNDEPCSKKKSAICYT 115

C-type lectin-like domain (CTLD) of the type found in the tetranectin (TN), cartilage derived C-type lectin (CLECSF1), and stem cell growth factor (SCGF); CLECT_tetranectin_like: C-type lectin-like domain (CTLD) of the type found in the tetranectin (TN), cartilage derived C-type lectin (CLECSF1), and stem cell growth factor (SCGF). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. TN binds to plasminogen and stimulates activation of plasminogen, playing a key role in the regulation of proteolytic processes. The TN CTLD binds two calcium ions. Its calcium free form binds to various kringle-like protein ligands. Two residues involved in the coordination of calcium are critical for the binding of TN to the fourth kringle (K4) domain of plasminogen (Plg K4). TN binds the kringle 1-4 form of angiostatin (AST K1-4). AST K1-4 is a fragment of Plg, commonly found in cancer tissues. TN inhibits the binding of Plg and AST K1-4 to the extracellular matrix (EMC) of endothelial cells and counteracts the antiproliferative effects of AST K1-4 on these cells. TN also binds the tenth kringle domain of apolipoprotein (a). In addition, TN binds fibrin and complex polysaccharides in a Ca2+ dependent manner. The binding site for complex sulfated polysaccharides is N-terminal to the CTLD. TN is homotrimeric; N-terminal to the CTLD is an alpha helical domain responsible for trimerization of monomeric units. TN may modulate angiogenesis through interactions with angiostatin and coagulation through interaction with fibrin. TN may play a role in myogenesis and in bone development. Mice having a deletion in the TN gene exhibit a kyphotic spine abnormality. TN is a useful prognostic marker of certain cancer types. CLECSF1 is expressed in cartilage tissue, which is primarily intracellular matrix (ECM), and is a candidate for organizing ECM. SCGF is strongly expressed in bone marrow and is a cytokine for primitive hematopoietic progenitor cells.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17544698  35 CYTFVNQRLLFPDAQTHCATLGGVLVRVRGDQDGRWLAAIAGTEFHATyGNFWIGLQ--LVDGQWEWEDASTSTYKNW-- 110
Cdd:cd03596  11 CYLVSEETKHYHEASEDCIARGGTLATPRDSDENDALRDYVKASVPGN-WEVWLGINdmVAEGKWVDVNGSPISYFNWer 89

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 17544698 111 -APGYPFSGYDY---VGAQLSNAKWVTVRSSLMLPFICYY 146
Cdd:cd03596  90 eITAQPDGGKREncvALSSSAQGKWFDEDCRREKPYVCEF 129