Wikipedia

Endothelial protein C receptor

Endothelial protein C receptor (EPCR) also known as activated protein C receptor (APC receptor) is a protein that in humans is encoded by the PROCR gene.[5][6][7] PROCR has also recently been designated CD201 (cluster of differentiation 201).

PROCR
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPROCR, CCCA, CCD41, EPCR, protein C receptor
External IDsOMIM: 600646; MGI: 104596; HomoloGene: 4670; GeneCards: PROCR; OMA:PROCR - orthologs
Orthologs
SpeciesHumanMouse
Entrez

10544

19124

Ensembl

ENSG00000101000

ENSMUSG00000027611

UniProt

Q9UNN8

Q64695

RefSeq (mRNA)

NM_006404

NM_011171

RefSeq (protein)

NP_006395

NP_035301

Location (UCSC)Chr 20: 35.17 – 35.22 MbChr 2: 155.59 – 155.6 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

EPCR is a transmembrane glycoprotein receptor that plays a crucial role in regulation of blood coagulation, inflammation, and vascular integrity. Its ability to enhance the anticoagulant activity of protein C, modulate inflammatory responses, and maintain endothelial barrier function highlights its importance in homeostasis maintanance.[8]

Structure

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EPCR protein is an N-glycosylated type I membrane protein that enhances the activation of protein C.[7] It belongs to the MHC class I/CD1 family of proteins, The structure of CD201 consists of an extracellular domain, a transmembrane domain, and a cytoplasmic tail. The extracellular domain of CD201 contains a high-affinity binding site for activated protein C (APC), a serine protease with anticoagulant properties.[8] The binding site for APC resembles a deep groove with a lipid inside. The bound lipid in EPCR is usually phosphatidylcholine or phosphatidylethanolamine, and it contributes to APC binding[9]

CD201 is expressed on the surface of endothelial cells, which form the inner lining of blood vessels. CD201 has also been identified as hematopoietic stem cell (HSC) marker.[10][11]

Function

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The main function of CD201 is to enhance the activation of protein C. The binding of APC to EPCR on the endothelial cell surface facilitates its anticoagulant activity by inhibiting factors Va and VIIIa. Apart from its anticoagulant role, CD201 also participates in an anti-inflammatory signaling. CD201 has been shown to affect the production of inflammatory cytokines upon binding a coagulation factor VIIa.[12]

Clinical significance

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CD201 is gaining recognition as a marker in patients with acute infections as well as in patients with vascular diseases. Recently, CD201 has been studied in relationship with rheumatoid arthritis.

In a recent study on emergency granulopoiesis, it has been observed that CD201 is highly expressed on lymphoid-biased HSCs under steady-state conditions. However, during emergency granulopoiesis, the loss of CD201 marked a transcriptional switch from a lymphoid to a myeloid identity in HSCs. These findings suggest that CD201 is involved in the regulation of the response to acute infection.[13] As with many signaling molecules, the context of their effect matters. It has been mentioned above that CD201 has anti-inflammatory properties during coagulation. However, in a rheumatoid arthritis (RA) murine model it has been shown that CD201 knock-out (KO) mice had 40% lower arthritis incidence and 50% less disease severity compared to wild-type (WT) mice. CD201 KO mice also had significantly fewer Th1/Th17 cells in synovial tissues, which implies that CD201 may play a role in the regulation of immune cell populations involved in the pathogenesis of RA.[14]

The importance of CD201 as a clinical marker has been demonstrated in another study where decreased patient serum levels of CD201 have been associated with vascular dysfunctions.[15]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000101000 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027611 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Fukudome K, Esmon CT (Nov 1994). "Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor". J Biol Chem. 269 (42): 26486–91. doi:10.1016/S0021-9258(18)47220-1. PMID 7929370.
  6. ^ Rothbarth K, Dabaghian AR, Stammer H, Werner D (Oct 1999). "One single mRNA encodes the centrosomal protein CCD41 and the endothelial cell protein C receptor (EPCR)". FEBS Lett. 458 (1): 77–80. doi:10.1016/S0014-5793(99)01074-1. PMID 10518938. S2CID 25425851.
  7. ^ a b "Entrez Gene: PROCR protein C receptor, endothelial (EPCR)".
  8. ^ a b Esmon CT (May 2004). "Structure and functions of the endothelial cell protein C receptor". Critical Care Medicine. 32 (Supplement): S298–S301. doi:10.1097/01.CCM.0000126128.64614.81. ISSN 0090-3493. PMID 15118534.
  9. ^ Esmon CT (May 2004). "Structure and functions of the endothelial cell protein C receptor". Critical Care Medicine. 32 (5 Suppl): S298-301. doi:10.1097/01.CCM.0000126128.64614.81. PMID 15118534.
  10. ^ Vazquez SE, Inlay MA, Serwold T (Jul 2015). "CD201 and CD27 identify hematopoietic stem and progenitor cells across multiple murine strains independently of Kit and Sca-1". Experimental Hematology. 43 (7): 578–585. doi:10.1016/j.exphem.2015.04.001. PMC 4480781. PMID 25892186.
  11. ^ Balazs AB, Fabian AJ, Esmon CT, Mulligan RC (2006-03-15). "Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow". Blood. 107 (6): 2317–2321. doi:10.1182/blood-2005-06-2249. ISSN 0006-4971. PMC 1895725. PMID 16304059.
  12. ^ Kondreddy V, Wang J, Keshava S, Esmon CT, Rao LV, Pendurthi UR (2018-05-24). "Factor VIIa induces anti-inflammatory signaling via EPCR and PAR1". Blood. 131 (21): 2379–2392. doi:10.1182/blood-2017-10-813527. ISSN 1528-0020. PMC 5969379. PMID 29669778.
  13. ^ Vanickova K, Milosevic M, Ribeiro Bas I, Burocziova M, Yokota A, Danek P, Grusanovic S, Chiliński M, Plewczynski D, Rohlena J, Hirai H, Rohlenova K, Alberich-Jorda M (2023-12-01). "Hematopoietic stem cells undergo a lymphoid to myeloid switch in early stages of emergency granulopoiesis". The EMBO Journal. 42 (23): e113527. doi:10.15252/embj.2023113527. ISSN 1460-2075. PMC 10690458. PMID 37846891.
  14. ^ Xue M, Lin H, Liang HP, Bereza-Malcolm L, Lynch T, Sinnathurai P, Weiler H, Jackson C, March L (2024-02-01). "EPCR deficiency ameliorates inflammatory arthritis in mice by suppressing the activation and migration of T cells and dendritic cells". Rheumatology. 63 (2): 571–580. doi:10.1093/rheumatology/kead230. ISSN 1462-0332. PMC 10834933. PMID 37228024.
  15. ^ Krug J, Bochenek ML, Gogiraju R, Laubert-Reh D, Lackner KJ, Münzel T, Wild PS, Espinola-Klein C, Schäfer K (2023-09-04). "Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function". Biomedicines. 11 (9): 2459. doi:10.3390/biomedicines11092459. ISSN 2227-9059. PMC 10526050. PMID 37760900.

Further reading

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  • Overview of all the structural information available in the PDB for UniProt: Q9UNN8 (Endothelial protein C receptor) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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