PROSITE documentation PDOC00537
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{PDOC00537}
{PS00615; C_TYPE_LECTIN_1}
{PS50041; C_TYPE_LECTIN_2}
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* C-type lectin domain signature and profile *
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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 <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
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
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