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Gene Review

Procr  -  protein C receptor, endothelial

Mus musculus

Synonyms: AI325044, APC receptor, Activated protein C receptor, Ccca, Ccd41, ...
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Disease relevance of Procr

  • Procr heterozygosity results in a mild increase of thrombosis tendency and little influence on the response to endotoxin [1].
  • Effects of membrane and soluble EPCR on the hemostatic balance and endotoxemia in mice [1].

High impact information on Procr

  • In these studies, thrombin infusion experiments revealed that EPCR heterozygosity (Procr(+/-)) impaired protein C activation by approximately 30% [1].
  • Challenge of the Procr(+/-) mice with lipopolysaccharide (LPS) did not significantly exaggerate their response compared with wild-type mice [1].
  • The endothelial cell protein C receptor (EPCR) is expressed by endothelial cells of large blood vessels and by hematopoietic stem cells [2].
  • Using conditional knock-out strategies, we demonstrate that Procr-deficient embryos with EPCR expression on placenta giant trophoblasts can be carried to term and then develop normally [3].
  • These findings show that extraembryonic EPCR expression is critical for embryo development [3].

Biological context of Procr

  • These data further show that minimal levels of EPCR are able to support male and female virility, as well as embryonic development, birth, and survival to adulthood [4].
  • The nucleotide sequence of the entire gene encoding the murine endothelial cell receptor for activated protein C (EPCR) has been determined [5].
  • From the locations of the introns in this gene and analysis of the exon structures, it is clear the EPCR gene is a member of the CD1 class of multiple histocompatibility proteins. and its cDNA sequence is nearly identical to that of CCD41, a centrosome-associated protein [5].
  • Replacing amino acids from residue 193 to residue 200 with the FLAG(TM) sequence (DYKDDDDK) completely blocks EPCR shedding, whereas a single amino acid substitution in this region has less effect on EPCR shedding [6].
  • SUMMARY: The emerging clinical evidence of endothelial cell protein C receptor involvement in thrombotic disease suggests that the understanding of endothelial cell protein C receptor genotype and the knowledge of auto-antibodies may aid in diagnosing the risk of thrombotic events in patients [7].

Anatomical context of Procr


Analytical, diagnostic and therapeutic context of Procr

  • Despite the retention of the entire endogenous EPCR coding sequence in the altered EPCR gene locus, only very low EPCR message contents were detected in mice by quantitative RT-PCR during embryogenesis and up to at least early adulthood [4].


  1. Effects of membrane and soluble EPCR on the hemostatic balance and endotoxemia in mice. Zheng, X., Li, W., Gu, J.M., Qu, D., Ferrell, G.L., Esmon, N.L., Esmon, C.T. Blood (2007) [Pubmed]
  2. Role of a 5'-enhancer in the transcriptional regulation of the human endothelial cell protein C receptor gene. Mollica, L.R., Crawley, J.T., Liu, K., Rance, J.B., Cockerill, P.N., Follows, G.A., Landry, J.R., Wells, D.J., Lane, D.A. Blood (2006) [Pubmed]
  3. Extraembryonic expression of EPCR is essential for embryonic viability. Li, W., Zheng, X., Gu, J.M., Ferrell, G.L., Brady, M., Esmon, N.L., Esmon, C.T. Blood (2005) [Pubmed]
  4. Mice with a severe deficiency of the endothelial protein C receptor gene develop, survive, and reproduce normally, and do not present with enhanced arterial thrombosis after challenge. Castellino, F.J., Liang, Z., Volkir, S.P., Haalboom, E., Martin, J.A., Sandoval-Cooper, M.J., Rosen, E.D. Thromb. Haemost. (2002) [Pubmed]
  5. Nucleotide structure and characterization of the murine gene encoding the endothelial cell protein C receptor. Liang, Z., Rosen, E.D., Castellino, F.J. Thromb. Haemost. (1999) [Pubmed]
  6. Regulated endothelial protein C receptor shedding is mediated by tumor necrosis factor-alpha converting enzyme/ADAM17. Qu, D., Wang, Y., Esmon, N.L., Esmon, C.T. J. Thromb. Haemost. (2007) [Pubmed]
  7. The endothelial protein C receptor. Esmon, C.T. Curr. Opin. Hematol. (2006) [Pubmed]
  8. Disruption of the endothelial cell protein C receptor gene in mice causes placental thrombosis and early embryonic lethality. Gu, J.M., Crawley, J.T., Ferrell, G., Zhang, F., Li, W., Esmon, N.L., Esmon, C.T. J. Biol. Chem. (2002) [Pubmed]
  9. Distribution of endothelial cell protein C/activated protein C receptor (EPCR) during mouse embryo development. Crawley, J.T., Gu, J.M., Ferrell, G., Esmon, C.T. Thromb. Haemost. (2002) [Pubmed]
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