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 119587547    49 CYKVIyfhdtSRRLNFEEAKEACRRDGGQLVSIESEDEQKLIEKFIENLLPSDgDFWIGLRRREEKQSnstacqdlYAWT 128
Cdd:smart00034  12 CYKFS-----TEKKTWEDAQAFCQSLGGHLASIHSEAENDFVASLLKNSGSSD-YYWIGLSDPDSNGS--------WQWS 77

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 119587547   129 DGS-ISQFRNWYVDEPSCGSEVCVVMYHqpsapagiggpYMFQWNDDRCNMKNNFICK 185
Cdd:smart00034  78 DGSgPVSYSNWAPGEPNNSSGDCVVLST-----------SGGKWNDVSCTSKLPFVCE 124

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 119587547  49 CYKVIyfhdtSRRLNFEEAKEACRRDGGQLVSIESEDEQKLIEKFIENllPSDGDFWIGLRRREEKQSnstacqdlYAWT 128
Cdd:cd00037    2 CYKFS-----TEKLTWEEAQEYCRSLGGHLASIHSEEENDFLASLLKK--SSSSDVWIGLNDLSSEGT--------WKWS 66

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 119587547 129 DGS-ISQFRNWYVDEP-SCGSEVCVVMYHQPSapagiggpymFQWNDDRCNMKNNFICKY 186
Cdd:cd00037   67 DGSpLVDYTNWAPGEPnPGGSEDCVVLSSSSD----------GKWNDVSCSSKLPFICEK 116

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 119587547  49 CYKviYFhdtSRRLNFEEAKEACRR--DGGQLVSIESEDEQKLIEKFIENLLPSDGDFWIGLRRREEKQSnstacqdlYA 126
Cdd:cd03594   12 CYG--YF---RQPLSWSDAELFCQKygPGAHLASIHSPAEAAAIASLISSYQKAYQPVWIGLHDPQQSRG--------WE 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119587547 127 WTDGSISQFRNWYVDEPSCGSEVCVVMyhqpSAPAGiggpymFQ-WNDDRCNMKNNFICKY 186
Cdd:cd03594   79 WSDGSKLDYRSWDRNPPYARGGYCAEL----SRSTG------FLkWNDANCEERNPFICKY 129

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119587547   61 RLNFEEAKEACRRDGGQLVSIESEDEQklieKFIENLLPSDG-DFWIGLRRREEKQSNStacqdlyaWTDGSISQFRNWY 139
Cdd:pfam00059   1 SKTWDEAREACRKLGGHLVSINSAEEL----DFLSSTLKKSNkYFWIGLTDRKNEGTWK--------WVDGSPVNYTNWA 68

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 119587547  140 VDEPSCG-SEVCVVMYHQPSapagiggpymfQWNDDRCNMKNNFICKY 186
Cdd:pfam00059  69 PEPNNNGeNEDCVELSSSSG-----------KWNDENCNSKNPFVCEK 105

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 119587547  49 CYKViyfhdTSRRLNFEEAKEACRRDGGQLVSIESEDEQKLIEKFIENLLPS----DGDFWIGLRRReekqsnSTACQDL 124
Cdd:cd03600    6 CYTL-----HPQKLTFLEAQRSCIELGGNLATVRSGEEADVVSLLLAAGPGRhgrgSLRLWIGLQRE------PRQCSDP 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 119587547 125 ------YAW-TDGSISQFRNWyVDEP--SCGSEVCVVMyhqpSAPAGIGGPymFQWNDDRCNMK-NNFICKYS 187
Cdd:cd03600   75 slplrgFSWvTGDQDTDFSNW-LQEPagTCTSPRCVAL----SAAGSTPDN--LKWKDGPCSARaDGYLCKFS 140

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 119587547  54 YFHDTSRRLNFEEAKEACRRDGGQLVSIESEDEQKLIEKFIEnllPSDGDFWIGLRRRE-EKQsnstacqdlYAWTDGSI 132
Cdd:cd03591    3 IFVTNGEEKNFDDAQKLCSEAGGTLAMPRNAAENAAIASYVK---KGNTYAFIGITDLEtEGQ---------FVYLDGGP 70

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 119587547 133 SQFRNWYVDEPS--CGSEVCVVMYHqpsapagiGGpymfQWNDDRCNMKNNFICKY 186
Cdd:cd03591   71 LTYTNWKPGEPNnaGGGEDCVEMYT--------SG----KWNDVACNLTRLFVCEF 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 119587547  58 TSRRLNFEEAKEACRRDGGQLVSIESEDEQklieKFIENLLPSDGDFWIGLRRREEKQSnstacqdlYAWTDGSISQFRN 137
Cdd:cd03603    6 VDGGMTWEAAQTLAESLGGHLVTINSAEEN----DWLLSNFGGYGASWIGASDAATEGT--------WKWSDGEESTYTN 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 119587547 138 WYVDEPscgsevcvvmYHQPSAPAGIGGPYMF-----QWND 173
Cdd:cd03603   74 WGSGEP----------HNNGGGNEDYAAINHFpgisgKWND 104

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 119587547  49 CYKVIyfhdtSRRLNFEEAKEACRR-DGGQLVSIESEDEQKLIEKFIENLLPSDgdFWIGLRRREEKQSNSTAcqdlyaW 127
Cdd:cd03598    3 CYRFV-----KSPRTFRDAQVICRRcYRGNLASIHSFAFNYRVQRLVSTLNQAQ--VWIGGIITGKGRCRRFS------W 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 119587547 128 TDGSISQFRNWYVDEPSCGSEVCVVMYHQpsapagiGGpymfQWNDDRCNMKNNFICKY 186
Cdd:cd03598   70 VDGSVWNYAYWAPGQPGNRRGHCVELCTR-------GG----HWRRAHCKLRRPFICSY 117

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 119587547  41 CRGGTQ--RPCYKViyfhDTSRRlNFEEAKEACRRDGGQLVSIESEDEQKLIEKFIENLLPSDGDFWIGLrrreekqsNS 118
Cdd:cd03596    1 CLKGTKihKKCYLV----SEETK-HYHEASEDCIARGGTLATPRDSDENDALRDYVKASVPGNWEVWLGI--------ND 67

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119587547 119 TACQDLYAWTDGSISQFRNW---YVDEPSCG-SEVCVVMyhqpsAPAGIGgpymfQWNDDRCNMKNNFICKY 186
Cdd:cd03596   68 MVAEGKWVDVNGSPISYFNWereITAQPDGGkRENCVAL-----SSSAQG-----KWFDEDCRREKPYVCEF 129

Link_domain_HAPLN_module_2; this link domain is found in the second link module of proteins similar to the vertebrate HAPLN (hyaluronan/HA and proteoglycan binding link) protein family which includes cartilage link protein. The link domain is a HA-binding domain. HAPLNs contain two contiguous link modules. Both link modules of cartilage link protein are involved in interaction with HA. In cartilage, a chondroitin sulfate proteoglycan core protein (CSPG) aggrecan forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Aggregates with other CSPGs substituting for aggregan may contribute to the structural integrity of many different tissues. Members of the vertebrate HAPLN gene family are physically linked adjacent to CSPG genes.

                         10        20
                 ....*....|....*....|....*.
gi 119587547  53 IYFHDTSRRLNFEEAKEACRRDGGQL 78
Cdd:cd03519    2 VFYLLHPGKLTFSEAVAACQRDGAQI 27