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 388453181  30 CVEHDCFALYPGPATFLDASQICNRLRGHLMTVRSSVAADVISLLLSGDRGV----SRRLWIGLQLPPG-CGDPKplGPL 104
Cdd:cd03600    1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGPGRhgrgSLRLWIGLQREPRqCSDPS--LPL 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 388453181 105 RGFEWVTRDSNTSYSRWARLdlnGAPPCG-PLCVAVSAAGATaPGEPVWEEQQCDVKADGFLCEFYF 170
Cdd:cd03600   79 RGFSWVTGDQDTDFSNWLQE---PAGTCTsPRCVALSAAGST-PDNLKWKDGPCSARADGYLCKFSF 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 388453181  244 CSVENGGCEHACNTIAGAPRCLCPAGAALQADGRSC 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 388453181  284 NNLCEHFCVPNpdkPDSYSCMCETGYRLAADQHRC 318
Cdd:pfam14670   5 NGGCSHLCLNT---PGGYTCSCPEGYELQDDGRTC 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 388453181  30 CVEHDCFALYPGPATFLDASQICNRLRGHLMTVRSSVAADVISLLLSGDRGV----SRRLWIGLQLPPG-CGDPKplGPL 104
Cdd:cd03600    1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGPGRhgrgSLRLWIGLQREPRqCSDPS--LPL 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 388453181 105 RGFEWVTRDSNTSYSRWARLdlnGAPPCG-PLCVAVSAAGATaPGEPVWEEQQCDVKADGFLCEFYF 170
Cdd:cd03600   79 RGFSWVTGDQDTDFSNWLQE---PAGTCTsPRCVALSAAGST-PDNLKWKDGPCSARADGYLCKFSF 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 388453181  401 MFCNQTACPADCDPNTRGNCECPDGYILDDGFMC 434
Cdd:pfam09064   1 LHCAEKKCPAVCDPNSGGSCYCPEGFILDDNFVC 34

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388453181   42 PATFLDASQICNRLRGHLMTVRSSVAADVISLLLSGDrgvSRRLWIGLQLPPGCGDpkplgplrgFEWVTrDSNTSYSRW 121
Cdd:pfam00059   1 SKTWDEAREACRKLGGHLVSINSAEELDFLSSTLKKS---NKYFWIGLTDRKNEGT---------WKWVD-GSPVNYTNW 67

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 388453181  122 ARLDLNGAPpcGPLCVAVSAAGATapgepvWEEQQCDVKAdGFLCEF 168
Cdd:pfam00059  68 APEPNNNGE--NEDCVELSSSSGK------WNDENCNSKN-PFVCEK 105

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 388453181  284 NNLCEHFCVPNpdkPDSYSCMCETGYRLAADQHRC 318
Cdd:pfam14670   5 NGGCSHLCLNT---PGGYTCSCPEGYELQDDGRTC 36

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 388453181 436 DIDECENGGYCS--GVCLNLPGTFECICGP 463
Cdd:cd00054    1 DIDECASGNPCQngGTCVNTVGSYRCSCPP 30

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 388453181  320 DVDDCLLVPSPCPQR--CVNKQGGFECHCKPG 349
Cdd:pfam07645   1 DVDECATGTHNCPANtvCVNTIGSFECRCPDG 32

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 388453181  30 CVEHDCFALYPGPATFLDASQICNRLRGHLMTVRSSVAADVISLLLSGDRGV----SRRLWIGLQLPPG-CGDPKplGPL 104
Cdd:cd03600    1 CVSDACYTLHPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGPGRhgrgSLRLWIGLQREPRqCSDPS--LPL 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 388453181 105 RGFEWVTRDSNTSYSRWARLdlnGAPPCG-PLCVAVSAAGATaPGEPVWEEQQCDVKADGFLCEFYF 170
Cdd:cd03600   79 RGFSWVTGDQDTDFSNWLQE---PAGTCTsPRCVALSAAGST-PDNLKWKDGPCSARADGYLCKFSF 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 388453181    25 PGGSQCVEHDCFALYPGPATFLDASQICNRLRGHLMTVRSSVAADVISLLLSgDRGVSRRLWIGLQLPPGCGdpkplgpl 104
Cdd:smart00034   2 PSGWISYGGKCYKFSTEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLLK-NSGSSDYYWIGLSDPDSNG-------- 72

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 388453181   105 rGFEWVTRDSNTSYSRWARLDLNGAppcGPLCVAVSAAGATapgepvWEEQQCDVKAdGFLCE 167
Cdd:smart00034  73 -SWQWSDGSGPVSYSNWAPGEPNNS---SGDCVVLSTSGGK------WNDVSCTSKL-PFVCE 124

C-type lectin-like domain (CTLD) of the type found in Human REG-1 (lithostathine), REG-4, and avian eggshell-specific proteins: ansocalcin, structhiocalcin-1(SCA-1), and -2(SCA-2); CLECT_REG-1_like: C-type lectin-like domain (CTLD) of the type found in Human REG-1 (lithostathine), REG-4, and avian eggshell-specific proteins: ansocalcin, structhiocalcin-1(SCA-1), and -2(SCA-2). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. REG-1 is a proliferating factor which participates in various kinds of tissue regeneration including pancreatic beta-cell regeneration, regeneration of intestinal mucosa, regeneration of motor neurons, and perhaps in tissue regeneration of damaged heart. REG-1 may play a role on the pathophysiology of Alzheimer's disease and in the development of gastric cancers. Its expression is correlated with reduced survival from early-stage colorectal cancer. REG-1 also binds and aggregates several bacterial strains from the intestinal flora and it has been suggested that it is involved in the control of the intestinal bacterial ecosystem. Rat lithostathine has calcium carbonate crystal inhibitor activity in vitro. REG-IV is unregulated in pancreatic, gastric, hepatocellular, and prostrate adenocarcinomas. REG-IV activates the EGF receptor/Akt/AP-1 signaling pathway in colorectal carcinoma. Ansocalcin, SCA-1 and -2 are found at high concentration in the calcified egg shell layer of goose and ostrich, respectively and tend to form aggregates. Ansocalcin nucleates calcite crystal aggregates in vitro.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388453181  35 CFALYPGPATFLDASQICNRLR--GHLMTVRSSVAADVISLLLSGDRGVSRRLWIGLQLPPGCgdpkplgplRGFEWVTR 112
Cdd:cd03594   12 CYGYFRQPLSWSDAELFCQKYGpgAHLASIHSPAEAAAIASLISSYQKAYQPVWIGLHDPQQS---------RGWEWSDG 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 388453181 113 DSnTSYSRWARldlNGAPPCGPLCVAVSAAGATApgepVWEEQQCDVKaDGFLCEF 168
Cdd:cd03594   83 SK-LDYRSWDR---NPPYARGGYCAELSRSTGFL----KWNDANCEER-NPFICKY 129

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 388453181   42 PATFLDASQICNRLRGHLMTVRSSVAADVISLLLSGDrgvSRRLWIGLQLPPGCGDpkplgplrgFEWVTrDSNTSYSRW 121
Cdd:pfam00059   1 SKTWDEAREACRKLGGHLVSINSAEELDFLSSTLKKS---NKYFWIGLTDRKNEGT---------WKWVD-GSPVNYTNW 67

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 388453181  122 ARLDLNGAPpcGPLCVAVSAAGATapgepvWEEQQCDVKAdGFLCEF 168
Cdd:pfam00059  68 APEPNNNGE--NEDCVELSSSSGK------WNDENCNSKN-PFVCEK 105

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 388453181  284 NNLCEHFCVPNpdkPDSYSCMCETGYRLAADQHRC 318
Cdd:pfam14670   5 NGGCSHLCLNT---PGGYTCSCPEGYELQDDGRTC 36

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|...
gi 388453181   320 DVDDCLLvPSPCPQ--RCVNKQGGFECHCKPGY 350
Cdd:smart00179   1 DIDECAS-GNPCQNggTCVNTVGSYRCECPPGY 32

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 388453181 320 DVDDCLLvPSPCP--QRCVNKQGGFECHCKPGY 350
Cdd:cd00054    1 DIDECAS-GNPCQngGTCVNTVGSYRCSCPPGY 32