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.
'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
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) .
The ASGPR's mediate the endocytosis of plasma glycoproteins to which the
terminal sialic acid residue in their carbohydrate moieties has been
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 , 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
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
Mannan-binding proteins (MBP) (also known as mannose-binding proteins).
MBP's bind mannose and N-acetyl-D-glucosamine in a calcium-dependent
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.
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 <PDOC00955>) 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 <PDOC00988>), a CTL
domain, 2 VWFC domains (see <PDOC00928), and a CTCK (see <PDOC00912>).
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
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
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.
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