PROCR (Protein C Receptor)
Endothelial protein C receptor gene: role in coagulation, inflammation, and disease susceptibility
Gene Information Card
| Symbol | PROCR |
|---|---|
| Full Name | Protein C Receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 20q11.22 |
| NCBI Gene ID | 10544 ncbi.nlm.nih.gov/gene/10544 |
| Ensembl ID | ENSG00000101200 |
| UniProt ID | Q9UNN8 |
| OMIM ID | 600646 |
| HGNC ID | 9452 |
| Aliases | EPCR, CCD41, bA42O4.2 |
Description
PROCR encodes endothelial protein C receptor (EPCR), a transmembrane glycoprotein primarily expressed on endothelial cells. EPCR binds protein C and activated protein C (APC), enhancing the activation of protein C by the thrombin-thrombomodulin complex. This receptor plays a critical role in anticoagulation, cytoprotection, and anti-inflammatory signaling. Genetic variants in PROCR are associated with altered plasma protein C levels, venous thromboembolism, and other thrombotic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Venous thromboembolism | PROCR variants (e.g., Ser219Gly) alter EPCR shedding or function, reducing APC generation and increasing thrombosis risk | ClinVar, OMIM |
| Thrombophilia due to protein C deficiency | Loss-of-function mutations impair EPCR-mediated protein C activation, leading to hypercoagulable state | OMIM, NCBI |
| Pregnancy loss | PROCR polymorphisms associated with recurrent miscarriage via thrombotic mechanisms | ClinVar, literature |
| Sepsis | EPCR shedding during inflammation reduces APC cytoprotective effects, contributing to organ dysfunction | UniProt, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Liver | 5.6 | Low |
| Kidney | 18.4 | Medium |
| Endothelium | High | High (nTPM not standardized) |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | High | Primary endothelial cells; high EPCR expression |
| EA.hy926 | High | Endothelial cell line; used for functional studies |
| HEK293 | Low | Non-endothelial; low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.655A>G (p.Ser219Gly) | SNP | ~10-15% in Europeans | Increased soluble EPCR levels; reduced membrane-bound EPCR; associated with thrombosis risk |
| c.460C>T (p.Arg154*) | Nonsense | Rare | Loss of function; truncated protein; linked to protein C deficiency |
| c.467G>A (p.Arg156His) | Missense | Rare | Impaired protein C binding; reduced APC generation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce EPCR expression or protein C binding lead to decreased APC generation and increased thrombosis risk.
Gain of Function (GOF)
Not well documented; some variants (e.g., Ser219Gly) increase soluble EPCR but may reduce membrane function, not a classical gain-of-function.
Dominant Negative (DN)
No clear dominant-negative mechanism reported; most variants act via haploinsufficiency or altered function.
View complete mutation data：
Gene Ontology (GO)
| • transmembrane signaling receptor activity (GO:0004888) | • calcium ion binding (GO:0005509) |
| • plasma membrane (GO:0005886) | • blood coagulation (GO:0007596) |
| • integral component of membrane (GO:0016021) | • platelet activation (GO:0030168) |
| • positive regulation of coagulation (GO:0050820) |
Pathways
• Protein C anticoagulant pathway (Reactome: R-HSA-140837)
• Hemostasis (Reactome: R-HSA-109582)
• Thrombin signaling and protease-activated receptors (KEGG: hsa04610)
Protein Summary
Endothelial protein C receptor (EPCR) is a 46 kDa type I transmembrane glycoprotein encoded by PROCR. It consists of an N-terminal extracellular domain homologous to the CD1/MHC class I family, a transmembrane helix, and a short cytoplasmic tail. EPCR binds protein C and activated protein C (APC) with high affinity, localizing them to the endothelial surface and enhancing protein C activation by the thrombin-thrombomodulin complex. Beyond anticoagulation, EPCR mediates APC's cytoprotective effects, including anti-inflammatory and anti-apoptotic signaling via protease-activated receptor 1 (PAR1). Soluble EPCR (sEPCR) is generated by proteolytic shedding and can inhibit APC activity. EPCR is highly expressed on endothelium of large vessels, heart, lung, and kidney, with lower expression in liver and microvasculature.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PROCR Knockout HEK293 Cell Line | EDJ-KQ7086 | Human | 10544 | Details Get a Quote |
| PROCR Knockout HCT 116 Cell Line | EDJ-KQ31924 | Human | 10544 | Details Get a Quote |
| PROCR Knockout HeLa Cell Line | EDJ-KQ31925 | Human | 10544 | Details Get a Quote |
| PROCR Knockout A-549 Cell Line | EDJ-KQ30540 | Human | 10544 | Details Get a Quote |
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