{PDOC00537} {PS00615; C_TYPE_LECTIN_1} {PS50041; C_TYPE_LECTIN_2} {BEGIN} ********************************************** * C-type lectin domain signature and profile * ********************************************** A number of different families of proteins share a conserved domain which was first characterized in some animal lectins and which seem to function as a calcium-dependent carbohydrate-recognition domain [1,2,3]. This domain, which is known as the C-type lectin domain (CTL) or as the carbohydrate-recognition domain (CRD), consists of about 110 to 130 residues. There are four cysteines which are perfectly conserved and involved in two disulfide bonds. A schematic representation of the CTL domain is shown below. +------+ | | xcxxxxcxxxxxxxCxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxCxxxxWxCxxxxCx | | | ************|* +----+ +-------------------------------------------------+ 'C': conserved cysteine involved in a disulfide bond. 'c': optional cysteine involved in a disulfide bond. '*': position of the pattern. The categories of proteins, in which the CTL domain has been found, are listed below. Type-II membrane proteins where the CTL domain is located at the C-terminal extremity of the proteins: - Asialoglycoprotein receptors (ASGPR) (also known as hepatic lectins) [4]. The ASGPR's mediate the endocytosis of plasma glycoproteins to which the terminal sialic acid residue in their carbohydrate moieties has been removed. - Low affinity immunoglobulin epsilon Fc receptor (lymphocyte IgE receptor), which plays an essential role in the regulation of IgE production and in the differentiation of B cells. - Kupffer cell receptor. A receptor with an affinity for galactose and fucose, that could be involved in endocytosis. - A number of proteins expressed on the surface of natural killer T-cells: NKG2, NKR-P1, YE1/88 (Ly-49), CD69 and on B-cells: CD72, LyB-2. The CTL- domain in these proteins is distantly related to other CTL-domains; it is unclear whether they are likely to bind carbohydrates. Proteins that consist of an N-terminal collagenous domain followed by a CTL- domain [5], these proteins are sometimes called 'collectins': - Pulmonary surfactant-associated protein A (SP-A). SP-A is a calcium- dependent protein that binds to surfactant phospholipids and contributes to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung. - Pulmonary surfactant-associated protein D (SP-D). - Conglutinin, a calcium-dependent lectin-like protein which binds to a yeast cell wall extract and to immune complexes through the complement component (iC3b). - Mannan-binding proteins (MBP) (also known as mannose-binding proteins). MBP's bind mannose and N-acetyl-D-glucosamine in a calcium-dependent manner. - Bovine collectin-43 (CL-43). Selectins (or LEC-CAM) [6,7]. Selectins are cell adhesion molecules implicated in the interaction of leukocytes with platelets or vascular endothelium. Structurally, selectins consist of a long extracellular domain, followed by a transmembrane region and a short cytoplasmic domain. The extracellular domain is itself composed of a CTL-domain, followed by an EGF-like domain and a variable number of SCR/Sushi repeats. Known selectins are: - Lymph node homing receptor (also known as L-selectin, leukocyte adhesion molecule-1, (LAM-1), leu-8, gp90-mel, or LECAM-1) - Endothelial leukocyte adhesion molecule 1 (ELAM-1, E-selectin or LECAM-2). The ligand recognized by ELAM-1 is sialyl-Lewis x. - Granule membrane protein 140 (GMP-140, P-selectin, PADGEM, CD62, or LECAM- 3). The ligand recognized by GMP-140 is Lewis x. Large proteoglycans that contain a CTL-domain followed by one copy of a SCR/ Sushi repeat, in their C-terminal section: - Aggrecan (cartilage-specific proteoglycan core protein). This proteoglycan is a major component of the extracellular matrix of cartilagenous tissues where it has a role in the resistance to compression. - Brevican. - Neurocan. - Versican (large fibroblast proteoglycan), a large chondroitin sulfate proteoglycan that may play a role in intercellular signalling. In addition to the CTL and Sushi domains, these proteins also contain, in their N-terminal domain, an Ig-like V-type region, two or four link domains (see ) and up to two EGF-like repeats. Two type-I membrane proteins: - Mannose receptor from macrophages. This protein mediates the endocytosis of glycoproteins by macrophages in several recognition and uptake processes. Its extracellular section consists of a fibronectin type II domain followed by eight tandem repeats of the CTL domain. - 180 Kd secretory phospholipase A2 receptor (PLA2-R). A protein whose structure is highly similar to that of the mannose receptor. - DEC-205 receptor. This protein is used by dendritic cells and thymic epithelial cells to capture and endocytose diverse carbohydrate-binding antigens and direct them to antigen-processing cellular compartiments. DEC- 205 extracellular section consists of a fibronectin type II domain followed by ten tandem repeats of the CTL domain. - Silk moth hemocytin, an humoral lectin which is involved in a self-defence mechanism. It is composed of 2 FA58C domains (see ), a CTL domain, 2 VWFC domains (see ). Various other proteins that uniquely consist of a CTL domain: - Invertebrate soluble galactose-binding lectins. A category to which belong a humoral lectin from a flesh fly; echinoidin, a lectin from the coelomic fluid of a sea urchin; BRA-2 and BRA-3, two lectins from the coelomic fluid of a barnacle, a lectin from the tunicate Polyandrocarpa misakiensis and a newt oviduct lectin. The physiological importance of these lectins is not yet known but they may play an important role in defense mechanisms. - Pancreatic stone protein (PSP) (also known as pancreatic thread protein (PTP), or reg), a protein that might act as an inhibitor of spontaneous calcium carbonate precipitation. - Pancreatitis associated protein (PAP), a protein that might be involved in the control of bacterial proliferation. - Tetranectin, a plasma protein that binds to plasminogen and to isolated kringle 4. - Eosinophil granule major basic protein (MBP), a cytotoxic protein. - A galactose specific lectin from a rattlesnake. - Two subunits of a coagulation factor IX/factor X-binding protein (IX/X-bp), a snake venom anticoagulant protein which binds with factors IX and X in the presence of calcium. - Two subunits of a phospholipase A2 inhibitor from the plasma of a snake (PLI-A and PLI-B). - A lipopolysaccharide-binding protein (LPS-BP) from the hemolymph of a cockroach [8]. - Sea raven antifreeze protein (AFP) [9]. As a signature pattern for this domain, we selected the C-terminal region with its three conserved cysteines. -Consensus pattern: C-[LIVMFYATG]-x(5,12)-[WL]-{T}-[DNSR]-{C}-{LI}-C-x(5,6)- [FYWLIVSTA]-[LIVMSTA]-C [The 3 C's are involved in disulfide bonds] -Sequences known to belong to this class detected by the pattern: ALL, except the distantly related natural killer T-cell and B-cell proteins. -Other sequence(s) detected in Swiss-Prot: 15. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: 2. -Note: All CTL domains have five Trp residues before the second Cys, with the exception of tunicate lectin and cockroach LPS-BP which have Leu. -Expert(s) to contact by email: Drickamer K.; kd@glycob.ox.ac.uk -Last update: April 2006 / Pattern revised. [ 1] Drickamer K. "Two distinct classes of carbohydrate-recognition domains in animal lectins." J. Biol. Chem. 263:9557-9560(1988). PubMed=3290208 [ 2] Drickamer K. "Evolution of Ca(2+)-dependent animal lectins." Prog. Nucleic Acid Res. Mol. Biol. 45:207-232(1993). PubMed=8341801 [ 3] Drickamer K. Curr. Opin. Struct. Biol. 3:393-400(1993). [ 4] Spiess M. "The asialoglycoprotein receptor: a model for endocytic transport receptors." Biochemistry 29:10009-10018(1990). PubMed=2125488 [ 5] Weis W.I., Kahn R., Fourme R., Drickamer K., Hendrickson W.A. "Structure of the calcium-dependent lectin domain from a rat mannose-binding protein determined by MAD phasing." Science 254:1608-1615(1991). PubMed=1721241 [ 6] Siegelman M. "Sweetening the selectin pot." Curr. Biol. 1:125-128(1991). PubMed=15336187 [ 7] Lasky L.A. "Selectins: interpreters of cell-specific carbohydrate information during inflammation." Science 258:964-969(1992). PubMed=1439808 [ 8] Jomori T., Natori S. "Molecular cloning of cDNA for lipopolysaccharide-binding protein from the hemolymph of the American cockroach, Periplaneta americana. Similarity of the protein with animal lectins and its acute phase expression." J. Biol. Chem. 266:13318-13323(1991). PubMed=1712779 [ 9] Ng N.F.L., Hew C.-L. "Structure of an antifreeze polypeptide from the sea raven. Disulfide bonds and similarity to lectin-binding proteins." J. Biol. Chem. 267:16069-16075(1992). PubMed=1644794 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}