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 442615245  45 YRFFRDRISWFEADAVCQFHHANLVTVDNSFQFDATRDLLRELDvNDIVWIGLMRPQNSDRFMWSNSRPLVADTgYWAES 124
Cdd:cd00037    3 YKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSS-SSDVWIGLNDLSSEGTWKWSDGSPLVDYT-NWAPG 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 442615245 125 LPLMDAP-LCAVIDPIRDYRWHALRCGgpETASFLCEM 161
Cdd:cd00037   81 EPNPGGSeDCVVLSSSSDGKWNDVSCS--SKLPFICEK 116

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 442615245  45 YRFFRDRISWFEADAVCQFHHANLVTVDNSFQFDATRDLLRELDvNDIVWIGLMRPQNSDRFMWSNSRPLVADTgYWAES 124
Cdd:cd00037    3 YKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSS-SSDVWIGLNDLSSEGTWKWSDGSPLVDYT-NWAPG 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 442615245 125 LPLMDAP-LCAVIDPIRDYRWHALRCGgpETASFLCEM 161
Cdd:cd00037   81 EPNPGGSeDCVVLSSSSDGKWNDVSCS--SKLPFICEK 116

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442615245   51 RISWFEADAVCQFHHANLVTVDNSfqfdATRDLLRELDVNDIV--WIGLMRPQNSDRFMWSNSRPLVAdTGYWAESLPLM 128
Cdd:pfam00059   1 SKTWDEAREACRKLGGHLVSINSA----EELDFLSSTLKKSNKyfWIGLTDRKNEGTWKWVDGSPVNY-TNWAPEPNNNG 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 442615245  129 DAPLCAVIdPIRDYRWHALRCGGPetASFLCEM 161
Cdd:pfam00059  76 ENEDCVEL-SSSSGKWNDENCNSK--NPFVCEK 105

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 442615245  45 YRFFRDRISWFEADAVCQFHHANLVTVDNSFQFDATRDLLRELDvNDIVWIGLMRPQNSDRFMWSNSRPLVADTgYWAES 124
Cdd:cd00037    3 YKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSS-SSDVWIGLNDLSSEGTWKWSDGSPLVDYT-NWAPG 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 442615245 125 LPLMDAP-LCAVIDPIRDYRWHALRCGgpETASFLCEM 161
Cdd:cd00037   81 EPNPGGSeDCVVLSSSSDGKWNDVSCS--SKLPFICEK 116

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 442615245  42 NVFYrFFRDRISWFEADAVCQFHHANLVTVDNSFQFDATRDLLRELdvNDIVWIGLMRPQNSDRfmWSNSRPLVADtgYW 121
Cdd:cd03602    1 RTFY-LVNESKTWSEAQQYCRENYTDLATVQNQEDNALLSNLSRVS--NSAAWIGLYRDVDSWR--WSDGSESSFR--NW 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 442615245 122 aesLPLMDAP--LCAVIDPIRdyRWHALRCggPETASFLC 159
Cdd:cd03602   74 ---NTFQPFGqgDCATMYSSG--RWYAALC--SALKPFIC 106

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 442615245  34 WTMPQEGlnvFYRFFRDRISWFEADAVCQFHHANLVTVDN----SFqfdatrdLLRELDVNDIVWIGLMRPQNSDRFMWS 109
Cdd:cd03590    5 WKSFQSS---CYFFSTEKKSWEESRQFCEDMGAHLVIINSqeeqEF-------ISKILSGNRSYWIGLSDEETEGEWKWV 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 442615245 110 NSRPLVADTGYWAESLPLMDAPL---CAVIDPiRDYRWHALRCGgpETASFLCEM 161
Cdd:cd03590   75 DGTPLNSSKTFWHPGEPNNWGGGgedCAELVY-DSGGWNDVPCN--LEYRWICEK 126

C-type lectin-like domain (CTLD) of the type found in CEL-1 from Cucumaria echinata and Echinoidin from Anthocidaris crassispina; CLECT_CEL-1_like: C-type lectin-like domain (CTLD) of the type found in CEL-1 from Cucumaria echinata and Echinoidin from Anthocidaris crassispina. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. The CEL-1 CTLD binds three calcium ions and has a high specificity for N-acteylgalactosamine (GalNAc). CEL-1 exhibits strong cytotoxicity which is inhibited by GalNAc. This protein may play a role as a toxin defending against predation. Echinoidin is found in the coelomic fluid of the sea urchin and is specific for GalBeta1-3GalNAc. Echinoidin has a cell adhesive activity towards human cancer cells which is not mediated through the CTLD. Both CEL-1 and Echinoidin are multimeric proteins comprised of multiple dimers linked by disulfide bonds.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442615245  45 YRFFRDRISWFEADAVCQ-F----HHANLVTV----DNSFQFdatrDLLRELDVNDI---VWIGLMRPQNSDRFMWSNSR 112
Cdd:cd03589   13 YRFFGDRLTWEEAELRCRsFsipgLIAHLVSIhsqeENDFVY----DLFESSRGPDTpygLWIGLHDRTSEGPFEWTDGS 88

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 442615245 113 PLvaDTGYWAESLPlMDAPL---CAVI--DPIRDYRWHALRCGgpETASFLCEM 161
Cdd:cd03589   89 PV--DFTKWAGGQP-DNYGGnedCVQMwrRGDAGQSWNDMPCD--AVFPYICKM 137

C-type lectin-like domain (CTLD) of the type found in human thrombomodulin(TM), Endosialin, C14orf27, and C1qR; CLECT_thrombomodulin_like: C-type lectin-like domain (CTLD) of the type found in human thrombomodulin(TM), Endosialin, C14orf27, and C1qR. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. In these thrombomodulin-like proteins the residues involved in coordinating Ca2+ in the classical MBP-A CTLD are not conserved. TM exerts anti-fibrinolytic and anti-inflammatory activity. TM also regulates blood coagulation in the anticoagulant protein C pathway. In this pathway, the procoagulant properties of thrombin (T) are lost when it binds TM. TM also plays a key role in tumor biology. It is expressed on endothelial cells and on several type of tumor cell including squamous cell carcinoma. Loss of TM expression correlates with advanced stage and poor prognosis. Loss of function of TM function may be associated with arterial or venous thrombosis and with late fetal loss. Soluble molecules of TM retaining the CTLD are detected in human plasma and urine where higher levels indicate injury and/or enhanced turnover of the endothelium. C1qR is expressed on endothelial cells and stem cells. It is also expressed on monocots and neutrophils, where it is subject to ectodomain shedding. Soluble forms of C1qR retaining the CTLD is detected in human plasma. C1qR modulates the phagocytosis of apoptotic cells in vivo. C1qR-deficient mice are defective in clearance of apoptotic cells in vivo. The cytoplasmic tail of C1qR, C-terminal to the CTLD of CD93, contains a PDZ binding domain which interacts with the PDZ domain-containing adaptor protein, GIPC. The juxtamembrane region of this tail interacts with the ezrin/radixin/moesin family. Endosialin functions in the growth and progression of abdominal tumors and is expressed in the stroma of several tumors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442615245  45 YRFFRDRISWFEADAVCQFHHANLVTVDNSFQFDATRDLLRELDVNDIV-----WIGLMR--PQNSDR------FMWSNS 111
Cdd:cd03600    7 YTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGPGRHGRgslrlWIGLQRepRQCSDPslplrgFSWVTG 86

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 442615245 112 RPlvaDTGY--W-AESLPLMDAPLCAVIDP----IRDYRWHALRCGGPeTASFLCE 160
Cdd:cd03600   87 DQ---DTDFsnWlQEPAGTCTSPRCVALSAagstPDNLKWKDGPCSAR-ADGYLCK 138