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 119600829   4 KKLFVTNGERMPFSKVKALCAGLQATVAAPKNAEENKAIQDVAKDT---AFLGITDEATEGQFMYLTGRRLTYSNWKKDE 80
Cdd:cd03591    1 EKIFVTNGEEKNFDDAQKLCSEAGGTLAMPRNAAENAAIASYVKKGntyAFIGITDLETEGQFVYLDGGPLTYTNWKPGE 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 119600829  81 PNDHGSGEDCVILLNNGLWNGISCTSSFIAICEF 114
Cdd:cd03591   81 PNNAGGGEDCVEMYTSGKWNDVACNLTRLFVCEF 114

C-type lectin-like domain (CTLD) of the type found in human collectins including lung surfactant proteins A and D, mannose- or mannan binding lectin (MBL), and CL-L1 (collectin liver 1); CLECT_collectin_like: C-type lectin-like domain (CTLD) of the type found in human collectins including lung surfactant proteins A and D, mannose- or mannan binding lectin (MBL), and CL-L1 (collectin liver 1). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. The CTLDs of these collectins bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, or apoptotic cells) and mediate functions associated with killing and phagocytosis. MBPs recognize high mannose oligosaccharides in a calcium dependent manner, bind to a broad range of pathogens, and trigger cell killing by activating the complement pathway. MBP also acts directly as an opsonin. SP-A and SP-D in addition to functioning as host defense components, are components of pulmonary surfactant which play a role in surfactant homeostasis. Pulmonary surfactant is a phospholipid-protein complex which reduces the surface tension within the lungs. SP-A binds the major surfactant lipid: dipalmitoylphosphatidylcholine (DPPC). SP-D binds two minor components of surfactant that contain sugar moieties: glucosylceramide and phosphatidylinositol (PI). MBP and SP-A, -D monomers are homotrimers with an N-terminal collagen region and three CTLDs. Multiple homotrimeric units associate to form supramolecular complexes. MBL deficiency results in an increased susceptibility to a large number of different infections and to inflammatory disease, such as rheumatoid arthritis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119600829   4 KKLFVTNGERMPFSKVKALCAGLQATVAAPKNAEENKAIQDVAKDT---AFLGITDEATEGQFMYLTGRRLTYSNWKKDE 80
Cdd:cd03591    1 EKIFVTNGEEKNFDDAQKLCSEAGGTLAMPRNAAENAAIASYVKKGntyAFIGITDLETEGQFVYLDGGPLTYTNWKPGE 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 119600829  81 PNDHGSGEDCVILLNNGLWNGISCTSSFIAICEF 114
Cdd:cd03591   81 PNNAGGGEDCVEMYTSGKWNDVACNLTRLFVCEF 114

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 119600829     3 GKKLFVTNGERMPFSKVKALCAGLQATVAAPKNAEENKAIQDVAK-----DTAFLGITDEATEGQFMYLTGRRLT-YSNW 76
Cdd:smart00034   9 GGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLLKnsgssDYYWIGLSDPDSNGSWQWSDGSGPVsYSNW 88

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 119600829    77 KKDEPNdhGSGEDCV-ILLNNGLWNGISCTSSFIAICE 113
Cdd:smart00034  89 APGEPN--NSSGDCVvLSTSGGKWNDVSCTSKLPFVCE 124

C-type lectin-like domain (CTLD) of the type found in human collectins including lung surfactant proteins A and D, mannose- or mannan binding lectin (MBL), and CL-L1 (collectin liver 1); CLECT_collectin_like: C-type lectin-like domain (CTLD) of the type found in human collectins including lung surfactant proteins A and D, mannose- or mannan binding lectin (MBL), and CL-L1 (collectin liver 1). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. The CTLDs of these collectins bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, or apoptotic cells) and mediate functions associated with killing and phagocytosis. MBPs recognize high mannose oligosaccharides in a calcium dependent manner, bind to a broad range of pathogens, and trigger cell killing by activating the complement pathway. MBP also acts directly as an opsonin. SP-A and SP-D in addition to functioning as host defense components, are components of pulmonary surfactant which play a role in surfactant homeostasis. Pulmonary surfactant is a phospholipid-protein complex which reduces the surface tension within the lungs. SP-A binds the major surfactant lipid: dipalmitoylphosphatidylcholine (DPPC). SP-D binds two minor components of surfactant that contain sugar moieties: glucosylceramide and phosphatidylinositol (PI). MBP and SP-A, -D monomers are homotrimers with an N-terminal collagen region and three CTLDs. Multiple homotrimeric units associate to form supramolecular complexes. MBL deficiency results in an increased susceptibility to a large number of different infections and to inflammatory disease, such as rheumatoid arthritis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119600829   4 KKLFVTNGERMPFSKVKALCAGLQATVAAPKNAEENKAIQDVAKDT---AFLGITDEATEGQFMYLTGRRLTYSNWKKDE 80
Cdd:cd03591    1 EKIFVTNGEEKNFDDAQKLCSEAGGTLAMPRNAAENAAIASYVKKGntyAFIGITDLETEGQFVYLDGGPLTYTNWKPGE 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 119600829  81 PNDHGSGEDCVILLNNGLWNGISCTSSFIAICEF 114
Cdd:cd03591   81 PNNAGGGEDCVEMYTSGKWNDVACNLTRLFVCEF 114

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 119600829     3 GKKLFVTNGERMPFSKVKALCAGLQATVAAPKNAEENKAIQDVAK-----DTAFLGITDEATEGQFMYLTGRRLT-YSNW 76
Cdd:smart00034   9 GGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLLKnsgssDYYWIGLSDPDSNGSWQWSDGSGPVsYSNW 88

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 119600829    77 KKDEPNdhGSGEDCV-ILLNNGLWNGISCTSSFIAICE 113
Cdd:smart00034  89 APGEPN--NSSGDCVvLSTSGGKWNDVSCTSKLPFVCE 124

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 119600829   3 GKKLFVTNGERMPFSKVKALCAGLQATVAAPKNAEENKAIQDVAKDTA------FLGITDEATEGQFMYLTGRRLTYSNW 76
Cdd:cd03596    8 HKKCYLVSEETKHYHEASEDCIARGGTLATPRDSDENDALRDYVKASVpgnwevWLGINDMVAEGKWVDVNGSPISYFNW 87

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 119600829  77 KKDEPN--DHGSGEDCVIL--LNNGLWNGISCTSSFIAICEF 114
Cdd:cd03596   88 EREITAqpDGGKRENCVALssSAQGKWFDEDCRREKPYVCEF 129

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 119600829   9 TNGERMPFSKVKALCAGLQATVAAPKNAEENKAIQDVAK----DTAFLGITDEATEGQFMYLTGRRLTYSNWKKDEPNDh 84
Cdd:cd03592    5 YSTEKMTFNEAVKYCKSRGTDLVAIQNAEENALLNGFALkynlGYYWIDGNDINNEGTWVDTDKKELEYKNWAPGEPNN- 83

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119600829  85 GSGEDCVILLN--NGLWNGISCTSSFIAICE 113
Cdd:cd03592   84 GRNENCLEIYIkdNGKWNDEPCSKKKSAICY 114

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 119600829   6 LFVTNGerMPFSKVKALCAGLQATVAAPKNAEENKAIQDVAKD--TAFLGITDEATEGQFMYLTGRRLTYSNWKKDEPND 83
Cdd:cd03603    4 KFVDGG--MTWEAAQTLAESLGGHLVTINSAEENDWLLSNFGGygASWIGASDAATEGTWKWSDGEESTYTNWGSGEPHN 81

                         90       100
                 ....*....|....*....|..
gi 119600829  84 HGSGEDCVI-----LLNNGLWN 100
Cdd:cd03603   82 NGGGNEDYAainhfPGISGKWN 103

C-type lectin-like domain (CTLD) of the type found in lectins TC14, TC14-2, TC14-3, and TC14-4 from the budding tunicate Polyandrocarpa misakiensis and PfG6 from the Acorn worm; CLECT_TC14_like: C-type lectin-like domain (CTLD) of the type found in lectins TC14, TC14-2, TC14-3, and TC14-4 from the budding tunicate Polyandrocarpa misakiensis and PfG6 from the Acorn worm. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. TC14 is homodimeric. The CTLD of TC14 binds D-galactose and D-fucose. TC14 is expressed constitutively by multipotent epithelial and mesenchymal cells and plays in role during budding, in inducing the aggregation of undifferentiated mesenchymal cells to give rise to epithelial forming tissue. TC14-2 and TC14-3 shows calcium-dependent galactose binding activity. TC14-3 is a cytostatic factor which blocks cell growth and dedifferentiation of the atrial epithelium during asexual reproduction. It may also act as a differentiation inducing factor. Galactose inhibits the cytostatic activity of TC14-3. The gene for Acorn worm PfG6 is gill-specific; PfG6 may be a secreted protein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119600829  12 ERMPFSKVKALC--AGLQATVAAPKNAEENKAI---QDVAKDTAFLGITD-EATEGQFMYLTGRRL--TYSNWKKDEPND 83
Cdd:cd03601    8 ETMNYAKAGAFCrsRGMRLASLAMRDSEMRDAIlafTLVKGHGYWVGADNlQDGEYDFLWNDGVSLptDSDLWAPNEPSN 87

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119600829  84 HGSGEDCVILLNN-GLWNGISCTSSFIAICE 113
Cdd:cd03601   88 PQSRQLCVQLWSKyNLLDDEYCGRAKRVICE 118

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 119600829  62 QFMYLTGRRLTYSNWKKDEPNdhGSGEDCVILL-NNGLWNGISCTSSFIAICEF 114
Cdd:cd03598   66 RFSWVDGSVWNYAYWAPGQPG--NRRGHCVELCtRGGHWRRAHCKLRRPFICSY 117