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 13929084  30 CVGNECFALFQDPVTFLDASQACQRLQGHLMTVRSSVAADVISLLVSD-----SSMDSRPWIGLQL-PQGCGDPvhLGPL 103
Cdd:cd03600   1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAgpgrhGRGSLRLWIGLQRePRQCSDP--SLPL 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13929084 104 RGFQWVTGDNHTSYSRWARPndqSPPLCG-PLCVTVStATEAAPGEPAWEEKPCENETKGFLCEFYF 169
Cdd:cd03600  79 RGFSWVTGDQDTDFSNWLQE---PAGTCTsPRCVALS-AAGSTPDNLKWKDGPCSARADGYLCKFSF 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        30
                  ....*....|....*....|....*....|....*.
gi 13929084   244 CSVENGGCEYMCNRSANGPRCVCPSGGDLQADGRSC 279
Cdd:pfam14670   1 CSVNNGGCSHLCLNTPGGYTCSCPEGYELQDDGRTC 36

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        30
                  ....*....|....*....|....*....|....*
gi 13929084   288 NELCQHFCVNnsdVPGSYSCMCETGYQLAADGHRC 322
Cdd:pfam14670   5 NGGCSHLCLN---TPGGYTCSCPEGYELQDDGRTC 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 13929084  30 CVGNECFALFQDPVTFLDASQACQRLQGHLMTVRSSVAADVISLLVSD-----SSMDSRPWIGLQL-PQGCGDPvhLGPL 103
Cdd:cd03600   1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAgpgrhGRGSLRLWIGLQRePRQCSDP--SLPL 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13929084 104 RGFQWVTGDNHTSYSRWARPndqSPPLCG-PLCVTVStATEAAPGEPAWEEKPCENETKGFLCEFYF 169
Cdd:cd03600  79 RGFSWVTGDQDTDFSNWLQE---PAGTCTsPRCVALS-AAGSTPDNLKWKDGPCSARADGYLCKFSF 141

Thrombomodulin like fifth domain, EGF-like; Members of this family adopt a fold similar to other EGF domains, with a flat major and a twisted minor beta sheet. Disulphide pairing, however, is not of the usual 1-3, 2-4, 5-6 type; rather 1-2, 3-4, 5-6 pairing is found. Its extended major sheet (strands beta-2 and beta-3 and the connecting loop) projects into thrombin's active site groove. This domain is required for interaction of thrombomodulin with thrombin, and subsequent activation of protein-C.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 13929084   405 MFCNETSCPADCDPNSPSFCQCPEGFILDEGSIC 438
Cdd:pfam09064   1 LHCAEKKCPAVCDPNSGGSCYCPEGFILDDNFVC 34

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        30
                  ....*....|....*....|....*....|....*.
gi 13929084   244 CSVENGGCEYMCNRSANGPRCVCPSGGDLQADGRSC 279
Cdd:pfam14670   1 CSVNNGGCSHLCLNTPGGYTCSCPEGYELQDDGRTC 36

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        30
                  ....*....|....*....|....*....|....*
gi 13929084   288 NELCQHFCVNnsdVPGSYSCMCETGYQLAADGHRC 322
Cdd:pfam14670   5 NGGCSHLCLN---TPGGYTCSCPEGYELQDDGRTC 36

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....
gi 13929084    324 DVDDCKQGpNPCPQ--LCSNTEGGFECRCYDGYE 355
Cdd:smart00179   1 DIDECASG-NPCQNggTCVNTVGSYRCECPPGYT 33

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 13929084  30 CVGNECFALFQDPVTFLDASQACQRLQGHLMTVRSSVAADVISLLVSD-----SSMDSRPWIGLQL-PQGCGDPvhLGPL 103
Cdd:cd03600   1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAgpgrhGRGSLRLWIGLQRePRQCSDP--SLPL 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13929084 104 RGFQWVTGDNHTSYSRWARPndqSPPLCG-PLCVTVStATEAAPGEPAWEEKPCENETKGFLCEFYF 169
Cdd:cd03600  79 RGFSWVTGDQDTDFSNWLQE---PAGTCTsPRCVALS-AAGSTPDNLKWKDGPCSARADGYLCKFSF 141

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 13929084  35 CFALFQDPVTFLDASQACQRLQGHLMTVRSSVAADVISLLVSDSSmDSRPWIGLQLPQGCGdpvhlgplrGFQWVTGDNH 114
Cdd:cd00037   2 CYKFSTEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKKSS-SSDVWIGLNDLSSEG---------TWKWSDGSPL 71

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 13929084 115 TSYSRWARpnDQSPPLCGPLCVTVSTATEAapgepAWEEKPCeNETKGFLCEF 167
Cdd:cd00037  72 VDYTNWAP--GEPNPGGSEDCVVLSSSSDG-----KWNDVSC-SSKLPFICEK 116

Thrombomodulin like fifth domain, EGF-like; Members of this family adopt a fold similar to other EGF domains, with a flat major and a twisted minor beta sheet. Disulphide pairing, however, is not of the usual 1-3, 2-4, 5-6 type; rather 1-2, 3-4, 5-6 pairing is found. Its extended major sheet (strands beta-2 and beta-3 and the connecting loop) projects into thrombin's active site groove. This domain is required for interaction of thrombomodulin with thrombin, and subsequent activation of protein-C.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 13929084   405 MFCNETSCPADCDPNSPSFCQCPEGFILDEGSIC 438
Cdd:pfam09064   1 LHCAEKKCPAVCDPNSGGSCYCPEGFILDDNFVC 34

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        30
                  ....*....|....*....|....*....|....*.
gi 13929084   244 CSVENGGCEYMCNRSANGPRCVCPSGGDLQADGRSC 279
Cdd:pfam14670   1 CSVNNGGCSHLCLNTPGGYTCSCPEGYELQDDGRTC 36

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        30
                  ....*....|....*....|....*....|....*
gi 13929084   288 NELCQHFCVNnsdVPGSYSCMCETGYQLAADGHRC 322
Cdd:pfam14670   5 NGGCSHLCLN---TPGGYTCSCPEGYELQDDGRTC 36

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 13929084  33 NECFALFQDPVTFLDASQACQRL-QGHLMTVRSSVAADVISLLVSDSSMdSRPWIGLQLPQGcgdpvhlGPLRGFQWVTG 111
Cdd:cd03598   1 GRCYRFVKSPRTFRDAQVICRRCyRGNLASIHSFAFNYRVQRLVSTLNQ-AQVWIGGIITGK-------GRCRRFSWVDG 72

                        90       100
                ....*....|....*....|....*....
gi 13929084 112 dNHTSYSRWARpnDQsPPLCGPLCVTVST 140
Cdd:cd03598  73 -SVWNYAYWAP--GQ-PGNRRGHCVELCT 97

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 13929084 324 DVDDCKQGpNPCP--QLCSNTEGGFECRCYDGYEL 356
Cdd:cd00054   1 DIDECASG-NPCQngGTCVNTVGSYRCSCPPGYTG 34

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 13929084   328 CKQGPNPCPQLCSNTEGGFECRCYDGYEL 356
Cdd:pfam14670   1 CSVNNGGCSHLCLNTPGGYTCSCPEGYEL 29