Endothelial protein C receptor

Last updated
PROCR
Protein PROCR PDB 1l8j.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PROCR , CCCA, CCD41, EPCR, protein C receptor
External IDs OMIM: 600646 MGI: 104596 HomoloGene: 4670 GeneCards: PROCR
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 Mb Chr 2: 155.59 – 155.6 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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).

Contents

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

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

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] .

Moreover, CD201 has been associated with vascular integrity and endothelial barrier function. It plays a role in protecting the endothelium from damage, maintaining the structural integrity of blood vessels, and preventing leakage of fluids and proteins into the surrounding tissues [13] .

Clinical significance

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 suggests that CD201 is involved in the regulation of the response to acute infection [14] . 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 [15] .

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 [16] .

Related Research Articles

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<span class="mw-page-title-main">Protein S</span>

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<span class="mw-page-title-main">Protein C</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">P-selectin</span> Type-1 transmembrane protein

P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene.

<span class="mw-page-title-main">Thrombomodulin</span>

Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. It reduces blood coagulation by converting thrombin to an anticoagulant enzyme from a procoagulant enzyme. Thrombomodulin is also expressed on human mesothelial cell, monocyte and a dendritic cell subset.

<span class="mw-page-title-main">VCAM-1</span> Protein-coding gene in the species Homo sapiens

Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 (VCAM-1) or cluster of differentiation 106 (CD106) is a protein that in humans is encoded by the VCAM1 gene. VCAM-1 functions as a cell adhesion molecule.

<span class="mw-page-title-main">Heparin cofactor II</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Apolipoprotein H</span> Protein-coding gene in humans

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<span class="mw-page-title-main">Integrin beta 3</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">Integrin alpha 2b</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">F2RL2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">F2RL3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Carboxypeptidase B2</span>

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<span class="mw-page-title-main">CD47</span> Protein-coding gene in humans

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<span class="mw-page-title-main">Multimerin 1</span> Protein-coding gene in the species Homo sapiens

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References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000101000 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 "Entrez Gene: PROCR protein C receptor, endothelial (EPCR)".
  8. 1 2 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. ↑ Niessen F, Furlan-Freguia C, Fernández JA, Mosnier LO, Castellino FJ, Weiler H, Rosen H, Griffin JH, Ruf W (2009-03-19). "Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality". Blood. 113 (12): 2859–2866. doi:10.1182/blood-2008-12-192385. ISSN   1528-0020. PMC   2661868 . PMID   19141861.
  14. ↑ 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.
  15. ↑ 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 (Oxford, England). 63 (2): 571–580. doi:10.1093/rheumatology/kead230. ISSN   1462-0332. PMC   10834933 . PMID   37228024.
  16. ↑ 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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