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 62471643  49 SYYVFGQTKVNWYVAYENCRRLQSELVTFETAEEFDAIAAFLNARGDRSeHWTSGNDLGKTGTHYWFSNAQLVTIKRWAP 128
Cdd:cd00037   1 SCYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSSSSD-VWIGLNDLSSEGTWKWSDGSPLVDYTNWAP 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 62471643 129 KQPDNaGGREHCIHLgyiyGYSTEFQLNDRPChnhaSSLFKYICE 173
Cdd:cd00037  80 GEPNP-GGSEDCVVL----SSSSDGKWNDVSC----SSKLPFICE 115

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 62471643  49 SYYVFGQTKVNWYVAYENCRRLQSELVTFETAEEFDAIAAFLNARGDRSeHWTSGNDLGKTGTHYWFSNAQLVTIKRWAP 128
Cdd:cd00037   1 SCYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSSSSD-VWIGLNDLSSEGTWKWSDGSPLVDYTNWAP 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 62471643 129 KQPDNaGGREHCIHLgyiyGYSTEFQLNDRPChnhaSSLFKYICE 173
Cdd:cd00037  80 GEPNP-GGSEDCVVL----SSSSDGKWNDVSC----SSKLPFICE 115

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471643    57 KVNWYVAYENCRRLQSELVTFETAEEFDAIAAFLNARGdrSEHWTSGNDLGKTGTHYWFSNAQlVTIKRWAPKqPDNAGG 136
Cdd:pfam00059   1 SKTWDEAREACRKLGGHLVSINSAEELDFLSSTLKKSN--KYFWIGLTDRKNEGTWKWVDGSP-VNYTNWAPE-PNNNGE 76

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 62471643   137 REHCIHLgyiygYSTEFQLNDRPChnhaSSLFKYICE 173
Cdd:pfam00059  77 NEDCVEL-----SSSSGKWNDENC----NSKNPFVCE 104

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 62471643  49 SYYVFGQTKVNWYVAYENCRRLQSELVTFETAEEFDAIAAFLNARGDRSeHWTSGNDLGKTGTHYWFSNAQLVTIKRWAP 128
Cdd:cd00037   1 SCYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSSSSD-VWIGLNDLSSEGTWKWSDGSPLVDYTNWAP 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 62471643 129 KQPDNaGGREHCIHLgyiyGYSTEFQLNDRPChnhaSSLFKYICE 173
Cdd:cd00037  80 GEPNP-GGSEDCVVL----SSSSDGKWNDVSC----SSKLPFICE 115

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 62471643  47 NESYYVFGQTKVNWYVAYENCRRLQSELVTFETAEEFDAIAAFLNARGDrseHWTSGNDLGKTGTHYWFSNAQL-VTIKR 125
Cdd:cd03590   9 QSSCYFFSTEKKSWEESRQFCEDMGAHLVIINSQEEQEFISKILSGNRS---YWIGLSDEETEGEWKWVDGTPLnSSKTF 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 62471643 126 WAPKQPDNAGGR-EHCIHLGYIYGystefQLNDRPCHNHasslFKYICE 173
Cdd:cd03590  86 WHPGEPNNWGGGgEDCAELVYDSG-----GWNDVPCNLE----YRWICE 125

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471643    57 KVNWYVAYENCRRLQSELVTFETAEEFDAIAAFLNARGdrSEHWTSGNDLGKTGTHYWFSNAQlVTIKRWAPKqPDNAGG 136
Cdd:pfam00059   1 SKTWDEAREACRKLGGHLVSINSAEELDFLSSTLKKSN--KYFWIGLTDRKNEGTWKWVDGSP-VNYTNWAPE-PNNNGE 76

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 62471643   137 REHCIHLgyiygYSTEFQLNDRPChnhaSSLFKYICE 173
Cdd:pfam00059  77 NEDCVEL-----SSSSGKWNDENC----NSKNPFVCE 104

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 62471643  51 YVFGQTKVNWYVAYENCRRLQSELVTFETAEEFDAIAAFLNARGDrSEHWTSGNDLGKTGThyWF-SNAQLVTIKRWAPK 129
Cdd:cd03592   3 YHYSTEKMTFNEAVKYCKSRGTDLVAIQNAEENALLNGFALKYNL-GYYWIDGNDINNEGT--WVdTDKKELEYKNWAPG 79

                        90       100       110
                ....*....|....*....|....*....|...
gi 62471643 130 QPDNaGGREHCIHlGYIYgysTEFQLNDRPCHN 162
Cdd:cd03592  80 EPNN-GRNENCLE-IYIK---DNGKWNDEPCSK 107

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 62471643  60 WYVAYENCRRLQSELVTFETAEEfdaiAAFLNARGDRSEhWTSGNDLGKTGTHYWfSNAQLVTIKRWAPKQPDN--AGGR 137
Cdd:cd03588  22 WEDAERRCREQQGHLSSIVTPEE----QEFVNNNAQDYQ-WIGLNDRTIEGDFRW-SDGHPLQFENWRPNQPDNffATGE 95

                        90       100
                ....*....|....*....|....*.
gi 62471643 138 EHCIHLGYIYGystefQLNDRPCHNH 163
Cdd:cd03588  96 DCVVMIWHEEG-----EWNDVPCNYH 116