CD201 PROCR (protein C receptor, endothelial [EPCR]), EPCR (endothelial cell protein C receptor)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Liver
Endothelium
Heart
Lung
Skin
Trophoblast
50 / 50

Expression
CD201 is highly expressed on the endothelium of large vessels, on arteries and veins in the heart and lung, intensely in capillaries in the lung and skin, but not in all endothelium of small vessels of the liver and kidney.  Expression is much higher on large vessels particularly arteries.  Expression is also in giant trophoblast cells at the foeto-maternal boundary express CD201. 

Structure
MOLECULAR FAMILY NAME: Belongs to the CD1/MHC family.

CD201 is a single-pass type-1 221 aa transmembrane glycoprotein.  It contains a 15 aa N-terminal signal sequence, an extracellular domain which contains 4 potential N-glycosylation sites and 4 cys residues, a 25 aa C-terminal transmembrane domain and a 3 aa short cytoplasmic domain.   It is homologous to the MHC class I/CD1 family of proteins which features a deep hydrophobic groove involved in antigen presentations formed by 2 α helices (α1 and α2) that overlie an 8 stranded β-pleated sheet.  The structure of CD201 resembles that of CD1d but lacks the a3 domain of MHC and is replaced in the endothelial cell protein C receptor by a transmembrane region followed by a short cytosolic tail.and does not associate with β2-microglobulin.  The CD201 groove is occupied by a tightly bound phospholipid whose presence is important for interaction with protein C even though the protein C binding site does not involve the groove and is distal from the cell membrane.  It is speculated that the phospholipid is required to maintain the structure of CD201.  A soluble form of CD201 that retains its ligand binding capacity is constitutively shed into plasma.  Susceptibility to cleavage is conferred by genetic polymorphism in exon 4 of the CD201 gene.  Thrombin and IL-1 have been shown to induce shedding of CD201 and the accumulation of soluble CD201.

MOLECULAR MASS
Cell Type Unreduced Reduced
50 kDa

POST-TRANSCRIPTIONAL MODIFICATION

A soluble form exists probably released by a metalloprotease

POST-TRANSLATIONAL MODIFICATION

CD201 is a N-glycosylated glycoprotein.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD201

CD201 binds protein C, proteinase 3 and an unidentified phospholipid.

Function
CD201 is an endothelial cell receptor for protein C which is involved in the regulation of coagulation and preventing tissue injury during inflammation and Gram-negative sepsis and binds binds protein C in a calcium-dependent manner.  The presence of CD201 provides a five-fold enhancement of the thrombin-thrombomodulin mediated activation of protein C on endothelial surfaces.  CD201 and PAR1 mediate the anti-inflammatory activities of protein C including the downregulation of P53 and inhibition of endothelial cell apoptosis.  Furthermore, the CD201 proteinase 3 complex can bind Mac-1 on activated neutrophils and inhibits tight adhesion of neutrophils to endothelium.  Plasma soluble CD201 inhibits protein C activation in vitro which suggests it may promote thrombosis in vivo.

  CD201 is a vitamin K-dependent serine protease zymogen and is activated when thrombin, the terminal enzyme of the coagulation system, binds to an endothelial cell surface protein, thrombomodulin.  CD201 is downregulated by exposure of endothelium to TNF.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD201 IN INTACT ANIMAL

Mutations and deficiency of protein C leads to life-threating venous thromboembolism and myocardial infraction.  Patients expressing aberrant CD201 have an increased risk of venous and possibly arterial thrombosis.  Null mice exhibit early embryonic lethality as well as with late fetal loss during pregnancy in the presence of autoantibodies to CD201.  There is evidence that CD201 inhibits the coagulopathy and inflammatory response to E. coli.  CD201 is activated and plays a major role in blood coagulation pathway and may prevent the lethal effects of gram-negative sepsis.  A soluble form of CD201 circulates in plasma and inhibits activated protein C anti-coagulant activity.  A large increase in plasma concentration of soluble CD201 occurs during sepsis and lupus erythematosus.  In lupus, vascular dysfunction is associated with increased levels of soluble CD201


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD201: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD201: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene10544Q9UNN8
Antibodies

Revised June 25, 2008


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