Gene Symbol: PROC
Description: protein C, inactivator of coagulation factors Va and VIIIa
Alias: APC, PROC1, THPH3, THPH4, vitamin K-dependent protein C, Protein C-Nagoya, anticoagulant protein C, autoprothrombin IIA, blood coagulation factor XIV, prepro-protein C, type I protein C
Species: human
Products:     PROC

Top Publications

  1. Grundy C, Schulman S, Tengborn L, Kakkar V, Cooper D. Two different missense mutations at Arg 178 of the protein C (PROC) gene causing recurrent venous thrombosis. Hum Genet. 1992;89:685-6 pubmed
    ..Non-identical missense mutations were identified at Arg 178 in the protein C genes of two patients with heterozygous type 1 protein C deficiency and recurrent venous thrombosis. ..
  2. Sugahara Y, Miura O, Yuen P, Aoki N. Protein C deficiency Hong Kong 1 and 2: hereditary protein C deficiency caused by two mutant alleles, a 5-nucleotide deletion and a missense mutation. Blood. 1992;80:126-33 pubmed
  3. Mosnier L, Zampolli A, Kerschen E, Schuepbach R, Banerjee Y, Fernandez J, et al. Hyperantithrombotic, noncytoprotective Glu149Ala-activated protein C mutant. Blood. 2009;113:5970-8 pubmed publisher
    Activated protein C (APC) reduces mortality in severe sepsis patients...
  4. Cheng T, Liu D, Griffin J, Fernandez J, Castellino F, Rosen E, et al. Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat Med. 2003;9:338-42 pubmed
    Activated protein C (APC) is a systemic anti-coagulant and anti-inflammatory factor. It reduces organ damage in animal models of sepsis, ischemic injury and stroke and substantially reduces mortality in patients with severe sepsis...
  5. Perera L, Foley C, Darden T, Stafford D, Mather T, Esmon C, et al. Modeling zymogen protein C. Biophys J. 2000;79:2925-43 pubmed
    ..Calculated electrostatic potential surfaces support the involvement of the serine protease calcium ion binding loop in providing a suitable electrostatic environment around the scissile bond for II(a)/thrombomodulin interaction. ..
  6. Xue M, Minhas N, Chow S, Dervish S, Sambrook P, March L, et al. Endogenous protein C is essential for the functional integrity of human endothelial cells. Cell Mol Life Sci. 2010;67:1537-46 pubmed publisher
    ..These newly described actions of endogenous PC act to stabilize endothelial cells and enhance barrier function, to potentially promote the functional integrity of blood vessels. ..
  7. Riewald M, Petrovan R, Donner A, Mueller B, Ruf W. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science. 2002;296:1880-2 pubmed
    ..Activated PC (APC) was shown to use the endothelial cell PC receptor (EPCR) as a coreceptor for cleavage of protease activated ..
  8. Reiner A, Carty C, Jenny N, Nievergelt C, Cushman M, Stearns Kurosawa D, et al. PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study. J Thromb Haemost. 2008;6:1625-32 pubmed publisher
    ..approach, and data from the Cardiovascular Health Study (CHS), we assessed associations of common polymorphisms of PROC, PROS1 and PROCR with: (i) plasma protein C, soluble protein C endothelial receptor (sEPCR) and protein S levels ..
  9. Riewald M, Ruf W. Protease-activated receptor-1 signaling by activated protein C in cytokine-perturbed endothelial cells is distinct from thrombin signaling. J Biol Chem. 2005;280:19808-14 pubmed
    Activated protein C (APC) has anti-inflammatory and vascular protective effects independent of anticoagulation...

More Information


  1. Franscini N, Bachli E, Blau N, Leikauf M, Schaffner A, Schoedon G. Gene expression profiling of inflamed human endothelial cells and influence of activated protein C. Circulation. 2004;110:2903-9 pubmed
    ..Recent data suggest a link between coagulation and inflammation through the activated protein C (APC) pathway...
  2. Yuksel M, Okajima K, Uchiba M, Horiuchi S, Okabe H. Activated protein C inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production by inhibiting activation of both nuclear factor-kappa B and activator protein-1 in human monocytes. Thromb Haemost. 2002;88:267-73 pubmed
    Activated protein C (APC), an important natural anticoagulant, inhibits tumor necrosis factor-alpha (TNF-alpha) production and attenuates various deleterious events induced by lipopolysaccharide (LPS), contributing thereby to a ..
  3. Schmidt A, Padmanabhan K, Underwood M, Bode W, Mather T, Bajaj S. Thermodynamic linkage between the S1 site, the Na+ site, and the Ca2+ site in the protease domain of human activated protein C (APC). Sodium ion in the APC crystal structure is coordinated to four carbonyl groups from two separate loops. J Biol Chem. 2002;277:28987-95 pubmed
    The serine protease domain of activated protein C (APC) contains a Na+ and a Ca2+ site. However, the number and identity of the APC residues that coordinate to Na+ is not precisely known...
  4. Tjeldhorn L, Sandset P, Haugbro K, Skretting G. Hereditary protein C deficiency caused by the Ala267Thr mutation in the protein C gene is associated with symptomatic and asymptomatic venous thrombosis. Thromb Res. 2010;125:230-4 pubmed publisher
    ..The factor V Leiden mutation causing activated PC (APC) resistance is an additional risk factor for VT...
  5. Poort S, Pabinger Fasching I, Mannhalter C, Reitsma P, Bertina R. Twelve novel and two recurrent mutations in 14 Austrian families with hereditary protein C deficiency. Blood Coagul Fibrinolysis. 1993;4:273-80 pubmed
    ..Only two of the genetic defects (157Arg-->Stop and 178Arg-->Gln) have been found previously in other geographic locations. These data confirm the large genetic heterogeneity of protein C deficiency. ..
  6. Fisher C, Greengard J, Griffin J. Models of the serine protease domain of the human antithrombotic plasma factor activated protein C and its zymogen. Protein Sci. 1994;3:588-99 pubmed
    ..The human serine protease anticoagulant protein C is currently the object of many genetic site-directed mutagenesis studies...
  7. Plutzky J, Hoskins J, Long G, Crabtree G. Evolution and organization of the human protein C gene. Proc Natl Acad Sci U S A. 1986;83:546-50 pubmed
    ..The similarity of the genes for factor IX and protein C suggests that they may be the most closely related members of the serine protease gene family involved in coagulation and fibrinolysis. ..
  8. Grinnell B, Walls J, Gerlitz B. Glycosylation of human protein C affects its secretion, processing, functional activities, and activation by thrombin. J Biol Chem. 1991;266:9778-85 pubmed
    ..Furthermore, we demonstrate the ability to improve the catalytic efficiency of this enzyme through carbohydrate modifications. ..
  9. Liaw P, Esmon C, Kahnamoui K, Schmidt S, Kahnamoui S, Ferrell G, et al. Patients with severe sepsis vary markedly in their ability to generate activated protein C. Blood. 2004;104:3958-64 pubmed
    Activated protein C (APC) supplementation significantly reduces mortality in patients with severe sepsis, presumably by down-regulating coagulation, inflammation, and apoptosis...
  10. Chen Q, Wu S, Wang H, Lv C, Cheng B, Xie G, et al. Protein C -1641A/-1654C haplotype is associated with organ dysfunction and the fatal outcome of severe sepsis in Chinese Han population. Hum Genet. 2008;123:281-7 pubmed publisher
    ..004, OR 2.270, 95% CI 1.312-3.930). These findings suggest that protein C haplotype -1641A/-1654C is associated with organ dysfunction and is an independent risk factor for the fatal outcome of severe sepsis in Chinese Han population. ..
  11. Auro K, Alanne M, Kristiansson K, Silander K, Kuulasmaa K, Salomaa V, et al. Combined effects of thrombosis pathway gene variants predict cardiovascular events. PLoS Genet. 2007;3:e120 pubmed
    ..the role of four thrombosis genes: coagulation factor V (F5), intercellular adhesion molecule 1 (ICAM1), protein C (PROC), and thrombomodulin (THBD) in cardiovascular diseases...
  12. Turunen A, Fernandez J, Lindgren L, Salmela K, Kyllönen L, Makisalo H, et al. Activated protein C reduces graft neutrophil activation in clinical renal transplantation. Am J Transplant. 2005;5:2204-12 pubmed
    We studied the role of endogenous activated protein C (APC), the major physiological anti-coagulant with concomitant anti-inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing ..
  13. Pomp E, Doggen C, Vos H, Reitsma P, Rosendaal F. Polymorphisms in the protein C gene as risk factor for venous thrombosis. Thromb Haemost. 2009;101:62-7 pubmed
    ..There is no clear synergistic effect of the CC/GG genotype with factor V Leiden or oral contraceptive use on thrombotic risk. ..
  14. Urano T, Castellino F, Ihara H, Suzuki Y, Ohta M, Suzuki K, et al. Activated protein C attenuates coagulation-associated over-expression of fibrinolytic activity by suppressing the thrombin-dependent inactivation of PAI-1. J Thromb Haemost. 2003;1:2615-20 pubmed
    ..The presence of activated protein C (aPC) suppressed thrombin generation, and attenuated the shortening of ECLT in a dose-dependent manner, an effect ..
  15. Beckmann R, Schmidt R, Santerre R, Plutzky J, Crabtree G, Long G. The structure and evolution of a 461 amino acid human protein C precursor and its messenger RNA, based upon the DNA sequence of cloned human liver cDNAs. Nucleic Acids Res. 1985;13:5233-47 pubmed
    ..Human protein C also has similar homology with prothrombin in the "leader", gamma-carboxyglutamate and serine protease domains, but lacks the two "kringle" domains found in prothrombin. ..
  16. Foster D, Yoshitake S, Davie E. The nucleotide sequence of the gene for human protein C. Proc Natl Acad Sci U S A. 1985;82:4673-7 pubmed
  17. Lind B, Koefoed P, Thorsen S. Symptomatic type 1 protein C deficiency caused by a de novo Ser270Leu mutation in the catalytic domain. Br J Haematol. 2001;113:642-8 pubmed
    ..Non-paternity was excluded after the analysis of three intragenic protein C polymorphisms and six dinucleotide repeat allele sets located in five different chromosomes. ..
  18. Komissarov A, Andreasen P, Declerck P, Kamikubo Y, Zhou A, Gruber A. Redirection of the reaction between activated protein C and a serpin to the substrate pathway. Thromb Res. 2008;122:397-404 pubmed
    Activated protein C (APC) reduces mortality in severe sepsis. Protecting APC in the circulatory system from inactivation by serine protease inhibitors (serpins) could improve its therapeutic efficiency...
  19. Tjeldhorn L, Iversen N, Sandvig K, Bergan J, Sandset P, Skretting G. Functional characterization of the protein C A267T mutation: evidence for impaired secretion due to defective intracellular transport. BMC Cell Biol. 2010;11:67 pubmed publisher
    ..Our results indicate that the A267T mutation most likely caused misfolding of PC, which might lead to increased retention of the mutated PC in ER. ..
  20. Finigan J, Dudek S, Singleton P, Chiang E, Jacobson J, Camp S, et al. Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation. J Biol Chem. 2005;280:17286-93 pubmed
    ..Activated protein C (APC), a serine protease critically involved in the regulation of coagulation and inflammatory processes, improves ..
  21. Scaldaferri F, Sans M, Vetrano S, Graziani C, De Cristofaro R, Gerlitz B, et al. Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease. J Clin Invest. 2007;117:1951-60 pubmed
    ..Restoring the PC pathway may represent a new therapeutic approach to suppress intestinal inflammation in IBD. ..
  22. Foster D, Rudinski M, Schach B, Berkner K, Kumar A, Hagen F, et al. Propeptide of human protein C is necessary for gamma-carboxylation. Biochemistry. 1987;26:7003-11 pubmed
  23. Liaw P, Neuenschwander P, Smirnov M, Esmon C. Mechanisms by which soluble endothelial cell protein C receptor modulates protein C and activated protein C function. J Biol Chem. 2000;275:5447-52 pubmed
    ..EPCR binds to both protein C and activated protein C (APC) with high affinity. A soluble form of EPCR (sEPCR) circulates in plasma and inhibits APC anticoagulant activity...
  24. Yamamoto K, Matsushita T, Sugiura I, Takamatsu J, Iwasaki E, Wada H, et al. Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C. J Lab Clin Med. 1992;119:682-9 pubmed
  25. Cramer T, Griffin J, Gale A. Factor V is an anticoagulant cofactor for activated protein C during inactivation of factor Va. Pathophysiol Haemost Thromb. 2010;37:17-23 pubmed publisher
    Coagulation factor V (FV) promotes inactivation of activated factor VIII (FVIIIa) by activated protein C (APC) and protein S...
  26. Schuepbach R, Feistritzer C, Brass L, Riewald M. Activated protein C-cleaved protease activated receptor-1 is retained on the endothelial cell surface even in the presence of thrombin. Blood. 2008;111:2667-73 pubmed
    Activated protein C (APC) signals in endothelial cells ex vivo through protease activated receptor-1 (PAR1)...
  27. Isermann B, Vinnikov I, Madhusudhan T, Herzog S, Kashif M, Blautzik J, et al. Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis. Nat Med. 2007;13:1349-58 pubmed
    ..Here we show that activated protein C (APC) formation, which is regulated by endothelial thrombomodulin, is reduced in diabetic mice and causally linked to ..
  28. Xue M, Chow S, Dervish S, Chan Y, Julovi S, Jackson C. Activated protein C enhances human keratinocyte barrier integrity via sequential activation of epidermal growth factor receptor and Tie2. J Biol Chem. 2011;286:6742-50 pubmed publisher
    Keratinocytes play a critical role in maintaining epidermal barrier function. Activated protein C (APC), a natural anticoagulant with anti-inflammatory and endothelial barrier protective properties, significantly increased the barrier ..
  29. Smith N, Hindorff L, Heckbert S, Lemaitre R, Marciante K, Rice K, et al. Association of genetic variations with nonfatal venous thrombosis in postmenopausal women. JAMA. 2007;297:489-98 pubmed
    ..Replication of these novel associations in other populations is necessary to corroborate these findings and identify which genetic factors may influence VT risk in postmenopausal women. ..
  30. Dahlback B, Villoutreix B. Regulation of blood coagulation by the protein C anticoagulant pathway: novel insights into structure-function relationships and molecular recognition. Arterioscler Thromb Vasc Biol. 2005;25:1311-20 pubmed
    ..The endothelial protein C receptor (EPCR) further stimulates the protein C activation. Activated protein C (APC) together with its cofactor protein S inhibits coagulation by degrading FVIIIa and FVa on the surface of negatively ..
  31. Reitsma P, Poort S, Allaart C, Briet E, Bertina R. The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I: heterogeneity and founder effects. Blood. 1991;78:890-4 pubmed
  32. Pérez Casal M, Downey C, Fukudome K, Marx G, Toh C. Activated protein C induces the release of microparticle-associated endothelial protein C receptor. Blood. 2005;105:1515-22 pubmed
    Activated protein C (APC) treatment is now used for patients with severe sepsis...
  33. Zhu T, Ding Q, Bai X, Wang X, Kaguelidou F, Alberti C, et al. Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group. Haematologica. 2011;96:1033-40 pubmed publisher
    ..This is the largest survey ever conducted in the healthy general Chinese population. These normal ranges provide the essential basis for the diagnosis and treatment of thrombosis in Chinese. ..
  34. Tian L, Xu P, Chukhutsina V, Holzwarth A, Croce R. Zeaxanthin-dependent nonphotochemical quenching does not occur in photosystem I in the higher plant Arabidopsis thaliana. Proc Natl Acad Sci U S A. 2017;114:4828-4832 pubmed publisher
    ..Recently, Ballottari et al. [Ballottari M, et al. (2014) Proc Natl Acad Sci USA 111:E2431-E2438], analyzing PSI particles isolated from an Arabidopsis thaliana mutant ..
  35. Ji Z, LeBaron M, Schisler M, Zhang F, Bartels M, Gollapudi B, et al. Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU. Mutagenesis. 2016;31:297-308 pubmed publisher
    ..Two separate dose-response models, the Lutz and Lutz model and the stepwise approach using PROC REG both supported a bilinear/threshold dose-response for MN induction...
  36. Cabello Gutiérrez C, Manjarrez Zavala M, Huerta Zepeda A, Cime Castillo J, Monroy Martínez V, Correa B, et al. Modification of the cytoprotective protein C pathway during Dengue virus infection of human endothelial vascular cells. Thromb Haemost. 2009;101:916-28 pubmed
    ..C complex formation at the endothelial surface, with a reduction in activated protein C (APC)...
  37. Sheehy M, Fahey A, Aungier S, Carter F, Crowe M, Mulligan F. A comparison of serum metabolic and production profiles of dairy cows that maintained or lost body condition 15 days before calving. J Dairy Sci. 2017;100:536-547 pubmed publisher when analyzing milk production records), their interactions, and a random effect of cow were analyzed using PROC MIXED of SAS (SAS Institute Inc., Cary, NC)...
  38. Gao T, Yapuncich G, DAUBECHIES I, Mukherjee S, Boyer D. Development and Assessment of Fully Automated and Globally Transitive Geometric Morphometric Methods, With Application to a Biological Comparative Dataset With High Interspecific Variation. Anat Rec (Hoboken). 2017;: pubmed publisher
    ..Here, we reassess the accuracy of published automated methods-cPDist (Boyer et al. Proc Nat Acad Sci 108 (2011) 18221-18226) and auto3Dgm (Boyer et al...
  39. Chapel N, Byrd C, Lugar D, Morello G, Baumgard L, Ross J, et al. Determining the effects of early gestation in utero heat stress on postnatal fasting heat production and circulating biomarkers associated with metabolism in growing pigs. J Anim Sci. 2017;95:3914-3921 pubmed publisher
    ..77; 37.0 ± 0.5 kg BW). Data were analyzed using PROC MIXED in SAS 9.4. No boar vs. barrow differences were observed with any analysis...
  40. Becker J, Brackbill D, Centola D. Network dynamics of social influence in the wisdom of crowds. Proc Natl Acad Sci U S A. 2017;114:E5070-E5076 pubmed publisher
    ..diversity without a corresponding increase in group accuracy [Lorenz J, Rauhut H, Schweitzer F, Helbing D (2011) Proc Natl Acad Sci USA 108:9020-9025]...
  41. Koltes D, Lester H, Frost M, Aldridge D, Christensen K, Scanes C. Effects of bacitracin methylene disalicylate and diet change on gastrointestinal integrity and endotoxin permeability in the duodenum of broiler chicken. BMC Res Notes. 2017;10:470 pubmed publisher
    ..Data were analyzed using Proc Glimmix of SAS with the model fitting BMD treatment, time, and the interaction of BMD treatment and time as fixed ..
  42. Lind B, van Solinge W, Schwartz M, Thorsen S. Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis. Blood. 1993;82:2423-32 pubmed
    ..In conclusion, evidence is provided showing that the mutation abolishes formation of correctly spliced mRNA. This agrees with the observation that the mutation results in a type 1 protein C deficiency. ..
  43. Ding Q, Shen W, Ye X, Wu Y, Wang X, Wang H. Clinical and genetic features of protein C deficiency in 23 unrelated Chinese patients. Blood Cells Mol Dis. 2013;50:53-8 pubmed publisher
    ..Mutational analysis was then performed by direct sequencing of the protein C gene (PROC) in the patients and their family members. Of the 23 patients, 30.4% (7/23) had additional risk factors, 51...
  44. Undas A, Potaczek D, Nishiyama C, Okumura K. Non-severe allergic asthma is associated with elevated plasma protein C and protein S. Thromb Haemost. 2012;107:1000-2 pubmed publisher
  45. Muller J, Friedrich M, Becher T, Braunstein J, Kupper T, Berdel P, et al. Monitoring of plasma levels of activated protein C using a clinically applicable oligonucleotide-based enzyme capture assay. J Thromb Haemost. 2012;10:390-8 pubmed publisher
    Human-activated protein C (APC) is a serine protease with anticoagulant, anti-inflammatory and cytoprotective functions. This feature renders APC to be a promising vascular-inflammatory biomarker...
  46. Glock C, Nagpal J, Gottschalk A. Microbial Rhodopsin Optogenetic Tools: Application for Analyses of Synaptic Transmission and of Neuronal Network Activity in Behavior. Methods Mol Biol. 2015;1327:87-103 pubmed publisher
    ..Nat Neurosci 8:1263-1268, 2005; Nagel et al., Curr Biol 15:2279-2284, 2005; Zemelman et al., Proc Natl Acad Sci USA 100:1352-1357, 2003)...
  47. Shorr A, Janes J, Artigas A, Tenhunen J, Wyncoll D, Mercier E, et al. Randomized trial evaluating serial protein C levels in severe sepsis patients treated with variable doses of drotrecogin alfa (activated). Crit Care. 2010;14:R229 pubmed publisher identifier: NCT00386425. ..
  48. Regan L, Mollica J, Rezaie A, Esmon C. The interaction between the endothelial cell protein C receptor and protein C is dictated by the gamma-carboxyglutamic acid domain of protein C. J Biol Chem. 1997;272:26279-84 pubmed
    The endothelial cell protein C receptor (EPCR) binds to both protein C and activated protein C (APC) with similar affinity. Removal of the Gla domain of protein C results in the loss of most of the binding affinity...
  49. Witt I. [Molecular biological basis and diagnosis of hereditary defect of antithrombin III, protein c and protein S]. Hamostaseologie. 2002;22:14-24 pubmed
    ..biology enabled the elucidation of the nucleotide sequences of the genes for antithrombin III (AT III), protein C (PROC) and protein S (PROS)...
  50. Medina P, Navarro S, Estelles A, Vaya A, Woodhams B, Mira Y, et al. Contribution of polymorphisms in the endothelial protein C receptor gene to soluble endothelial protein C receptor and circulating activated protein C levels, and thrombotic risk. Thromb Haemost. 2004;91:905-11 pubmed
    Endothelial cell protein C receptor (EPCR) enhances the generation of activated protein C (APC) by the thrombin-thrombomodulin complex. A soluble form of EPCR (sEPCR), which is generated by metalloprotease activity, is present in plasma...
  51. Kinoshita S, Iida H, Inoue S, Watanabe K, Kurihara M, Wada Y, et al. Protein S and protein C gene mutations in Japanese deep vein thrombosis patients. Clin Biochem. 2005;38:908-15 pubmed
    ..Our study reinforces that the genetic anomaly in the protein S/protein C anticoagulation system is an important risk factor for thrombophilia in the Japanese population. ..
  52. Gómez Puerta J, Sanin Blair J, Galarza Maldonado C. Pregnancy and catastrophic antiphospholipid syndrome. Clin Rev Allergy Immunol. 2009;36:85-90 pubmed publisher
  53. Uszyński M, Uszyński W, Zekanowska E, Kuczyński J, Szymanski M. A comparative study of the protein C system in mother's blood, cord blood and amniotic fluid. Folia Histochem Cytobiol. 2010;48:262-6 pubmed publisher
    Activated protein C (APC) is an important anticoagulant which plays a role in pathophysiology of pregnancy, e.g. in maintenance of the uteroplacental circulation and development of the fetus as well as in pathogenesis of preeclampsia...
  54. Bouchama A, Kunzelmann C, Dehbi M, Kwaasi A, Eldali A, Zobairi F, et al. Recombinant activated protein C attenuates endothelial injury and inhibits procoagulant microparticles release in baboon heatstroke. Arterioscler Thromb Vasc Biol. 2008;28:1318-25 pubmed publisher
    ..We tested the hypothesis that the antithrombotic and cytoprotective effects of recombinant human activated protein C (rhAPC) protect baboons against the lethal effects of heatstroke...
  55. Ireland H, Boisclair M, Taylor J, Thompson E, Thein S, Girolami A, et al. Two novel (R(-11)C; T394D) and two repeat missense mutations in the protein C gene associated with venous thrombosis in six kindreds. Hum Mutat. 1996;7:176-9 pubmed
  56. DeRossi R, Pagliosa R, de Carvalho A, Macedo G, Hermeto L. Fentanyl and methadone used as adjuncts to bupivacaine for lumbosacral epidural analgesia in sheep. Vet Rec. 2017;180:96 pubmed publisher
    ..Parametrical data were analysed by proc glimmix (SAS) for repeated measures on time and means tested by ls-means...
  57. Qobadi M, Collier C, Zhang L. The Effect of Stressful Life Events on Postpartum Depression: Findings from the 2009-2011 Mississippi Pregnancy Risk Assessment Monitoring System. Matern Child Health J. 2016;20:164-172 pubmed
    ..Descriptive statistics, Chi square tests, t tests, and logistic regression analyses were conducted using SAS 9.3 Proc Survey procedure (SAS Institute, Cary, NC, USA). Results The overall prevalence of self-reported PPD was 14.8 %...
  58. Zhang L, Jhingan A, Castellino F. Role of individual gamma-carboxyglutamic acid residues of activated human protein C in defining its in vitro anticoagulant activity. Blood. 1992;80:942-52 pubmed
    ..acid (gla) residues to the overall Ca(2+)-dependent anticoagulant activity of activated human protein C (APC), we used recombinant (r) DNA technology to generate protein C (PC) variants in which each of the gla precursor ..
  59. Vossen C, Koeleman B, Hasstedt S, Nijman I, Renkens I, Callas P, et al. Genetic variants associated with protein C levels. J Thromb Haemost. 2013;11:715-23 pubmed publisher
    ..Failure to replicate our findings in LETS might be due to differences between the studies in genetic background and linkage disequilibrium patterns. ..
  60. Luo L, Lv T, Wang Q, Zhang T, Gu X, Xu F, et al. Activated protein C induces endoplasmic reticulum stress and attenuates lipopolysaccharide-induced apoptosis mediated by glycogen synthase kinase-3?. Mediators Inflamm. 2012;2012:485279 pubmed publisher
    ..In summary, activated protein C induced endoplasmic reticulum stress and attenuated lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis mediated by glycogen synthase kinase-3?. ..
  61. Lopez Sagaseta J, Puy C, Tamayo I, Allende M, Cerveró J, Velasco S, et al. sPLA2-V inhibits EPCR anticoagulant and antiapoptotic properties by accommodating lysophosphatidylcholine or PAF in the hydrophobic groove. Blood. 2012;119:2914-21 pubmed publisher
    ..C receptor (EPCR) plays an important role in cardiovascular disease by binding protein C/activated protein C (APC). EPCR structure contains a hydrophobic groove filled with an unknown phospholipid needed to perform its function...
  62. Mukherjee S, Swystun L, Mackman N, Wang J, Pond G, Levine M, et al. Impact of chemotherapy on thrombin generation and on the protein C pathway in breast cancer patients. Pathophysiol Haemost Thromb. 2010;37:88-97 pubmed publisher
    ..MP TF activity, and components of the protein C anticoagulant pathway, including protein C, activated protein C (APC), soluble thrombomodulin (sTM), and soluble endothelial protein C receptor (sEPCR), were measured...
  63. Marchetti M, Castoldi E, Spronk H, van Oerle R, Balducci D, Barbui T, et al. Thrombin generation and activated protein C resistance in patients with essential thrombocythemia and polycythemia vera. Blood. 2008;112:4061-8 pubmed publisher
    ..Thrombin generation was determined in the presence and absence of activated protein C (APC), and APC resistance was expressed as normalized APC sensitivity ratio (nAPCsr)...
  64. Berg L, Scopes D, Alhaq A, Kakkar V, Cooper D. Disruption of a binding site for hepatocyte nuclear factor 1 in the protein C gene promoter is associated with hereditary thrombophilia. Hum Mol Genet. 1994;3:2147-52 pubmed
    ..transition was detected in the putative promoter region of the protein C (PROC) gene in a patient with type I protein C deficiency and a history of recurrent venous thrombosis...
  65. Fay P, Smudzin T, Walker F. Activated protein C-catalyzed inactivation of human factor VIII and factor VIIIa. Identification of cleavage sites and correlation of proteolysis with cofactor activity. J Biol Chem. 1991;266:20139-45 pubmed
    ..These results suggest a mechanism for activated protein C-catalyzed inactivation of factor VIII(alpha) involving both covalent alteration and fragment dissociation. ..
  66. Esmon C, Stenflo J, Suttie J. A new vitamin K-dependent protein. A phospholipid-binding zymogen of a serine esterase. J Biol Chem. 1976;251:3052-6 pubmed
    ..Although the lipid-binding properties of Protein C may suggest that it is associated with membrane structures, its biological function remains unknown. ..
  67. Wu C, Dwivedi D, Pepler L, Lysov Z, Waye J, Julian J, et al. Targeted gene sequencing identifies variants in the protein C and endothelial protein C receptor genes in patients with unprovoked venous thromboembolism. Arterioscler Thromb Vasc Biol. 2013;33:2674-81 pubmed publisher
    ..We performed targeted gene sequencing of the PC gene (PROC) and EPCR genes (PROCR) in patients with unprovoked venous thromboembolism (VTE) to determine whether mutations ..
  68. Ocak G, Drechsler C, Vossen C, Vos H, Rosendaal F, Reitsma P, et al. Single nucleotide variants in the protein C pathway and mortality in dialysis patients. PLoS ONE. 2014;9:e97251 pubmed publisher the factor V gene (F5 rs6025; factor V Leiden), the thrombomodulin gene (THBD rs1042580), the protein C gene (PROC rs1799808 and 1799809) and the endothelial protein C receptor gene (PROCR rs867186, rs2069951, and rs2069952) were ..
  69. Tsay W, Shen M. R147W mutation of PROC gene is common in venous thrombotic patients in Taiwanese Chinese. Am J Hematol. 2004;76:8-13 pubmed
    ..Among these mutations, a common genetic mutation of protein C (PROC) gene recurred in 43% (nine propositi from these 21 families)...
  70. Couture P, Demers C, Morissette J, Delage R, Jomphe M, Couture L, et al. Type I protein C deficiency in French Canadians: evidence of a founder effect and association of specific protein C gene mutations with plasma protein C levels. Thromb Haemost. 1998;80:551-6 pubmed
    Protein C (PROC) deficiency is one of the most common autosomal codominant diseases...
  71. Patrick Higgins N. Muprints and Whole Genome Insertion Scans: Methods for Investigating Chromosome Accessibility and DNA Dynamics using Bacteriophage Mu. Methods Mol Biol. 2018;1681:303-314 pubmed publisher
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