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 34582319  32 SASGACYSLHHATFKRRAAEEACSLRGGTLSTVHSGSEFQAVLLLLRAGPGPgGGSKDLLFWVALERSISQCTQEKEPLR 111
Cdd:cd03600   1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGPGR-HGRGSLRLWIGLQREPRQCSDPSLPLR 79

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34582319 112 GFSWLHPDsedsEDSP-LPWVEEPQRSCTVRKCAALQATRG-VEPAGWKEMRCHLRTDGYLCKYQF 175
Cdd:cd03600  80 GFSWVTGD----QDTDfSNWLQEPAGTCTSPRCVALSAAGStPDNLKWKDGPCSARADGYLCKFSF 141

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 34582319  32 SASGACYSLHHATFKRRAAEEACSLRGGTLSTVHSGSEFQAVLLLLRAGPGPgGGSKDLLFWVALERSISQCTQEKEPLR 111
Cdd:cd03600   1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGPGR-HGRGSLRLWIGLQREPRQCSDPSLPLR 79

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34582319 112 GFSWLHPDsedsEDSP-LPWVEEPQRSCTVRKCAALQATRG-VEPAGWKEMRCHLRTDGYLCKYQF 175
Cdd:cd03600  80 GFSWVTGD----QDTDfSNWLQEPAGTCTSPRCVALSAAGStPDNLKWKDGPCSARADGYLCKFSF 141

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                          10        20
                  ....*....|....*....|....*
gi 34582319   263 CLDHLGDFTCECAVGFELGKDGRSC 287
Cdd:pfam14670  12 CLNTPGGYTCSCPEGYELQDDGRTC 36

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 34582319  32 SASGACYSLHHATFKRRAAEEACSLRGGTLSTVHSGSEFQAVLLLLRAGPGPgGGSKDLLFWVALERSISQCTQEKEPLR 111
Cdd:cd03600   1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGPGR-HGRGSLRLWIGLQREPRQCSDPSLPLR 79

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34582319 112 GFSWLHPDsedsEDSP-LPWVEEPQRSCTVRKCAALQATRG-VEPAGWKEMRCHLRTDGYLCKYQF 175
Cdd:cd03600  80 GFSWVTGD----QDTDfSNWLQEPAGTCTSPRCVALSAAGStPDNLKWKDGPCSARADGYLCKFSF 141

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 34582319     34 SGACYSLHHATFKRRAAEEACSLRGGTLSTVHSGSEFQAVLLLLRAGPGPGggskdlLFWVALersiSQCTQEKEplrgF 113
Cdd:smart00034   9 GGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLLKNSGSSD------YYWIGL----SDPDSNGS----W 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 34582319    114 SWlhpdSEDSEDSPLPWVEEPQRSCTVRKCAALQATRGvepaGWKEMRCHLRTdGYLCK 172
Cdd:smart00034  75 QW----SDGSGPVSYSNWAPGEPNNSSGDCVVLSTSGG----KWNDVSCTSKL-PFVCE 124

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                          10        20
                  ....*....|....*....|....*
gi 34582319   263 CLDHLGDFTCECAVGFELGKDGRSC 287
Cdd:pfam14670  12 CLNTPGGYTCSCPEGYELQDDGRTC 36