Protein C
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[[Image:Blood_Coagulation_and_Protein_C_Pathways.jpg|right|thumb|310px|Blood coagulation and protein C pathway]]
'''Protein C''' is a major physiological [[anticoagulant]]. It is a [[vitamin K]]-dependent [[serine protease]] [[enzyme]] ({{EC number|3.4.21.69}}) that is activated by [[thrombin]] into '''activated protein C''' (APC). The activated form (with [[protein S]] and phospholipid as a [[cofactor]]) degrades [[Factor V]]a and [[Factor VIII]]a. It should not be confused with [[C peptide]] or [[c-reactive protein]] or [[protein kinase C]].
The protein C pathway’s key enzyme, activated protein C, provides physiologic antithrombotic activity and exhibits both [[anti-inflammatory]] and anti-[[apoptotic]] activities. Its actions are related to development of [[thrombosis]] and [[ischemic stroke]]. The protein C pathway of the coagulation of the blood involves the influences of [[lipid]]s and [[lipoprotein]]s and the study of the strong epidemiologic association between [[hyperlipidemia]] and [[hypercoagulability]].<ref>[https://www.scripps.edu/research/faculty.php?rec_id=1981 Thrombosis, Blood Coagulation and the Antithrombotic Protein C Pathway] - John H. Griffin, [[TSRI]]</ref>
:''See: detailed diagram of [[:Image:Blood Coagulation and Protein C Pathways.jpg|Blood Coagulation (Thrombin) and Protein C Pathways]]''
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==Role in disease==
[[Image:Protein_C_anticoagulant.jpg|right|thumb|310px|'''The Protein C Anticoagulant Pathway:''' Thrombin escaping from a site of vascular injury binds to its receptor thrombomodulin (TM) on the intact cell surface. As a result, thrombin loses its procoagulant properties and instead becomes a potent activator of protein C. Activated protein C (APC) functions as a circulating anticoagulant, which specifically degrades and inactivates the phospholipid-bound factors Va and VIIIa. This effectively down-regulates the coagulation cascade and limits clot formation to sites of vascular injury. T = Thrombin, PC= Protein C, Activated Protein C= APC, PS= Protein S<ref>[[Activated protein C resistance]]</ref>]]
[[Protein C deficiency]] is a rare [[genetic disorder]] that predisposes to [[venous]] [[thrombosis]] and [[habitual abortion]]. If [[homozygous]], this presents with a form of [[disseminated intravascular coagulation]] in newborns termed [[purpura fulminans]]; it is treated by replacing the defective protein C.
[[Activated protein C resistance]] is the inability of protein C to cleave factors V and/or VIII. This may be hereditary or acquired. The best known and most common hereditary form is [[Factor V Leiden]]. Acquired forms occur in the presence of elevated Factor VIII concentrations.
[[Warfarin necrosis]] is acquired protein C deficiency due to treatment with the vitamin K inhibitor anticoagulant [[warfarin]]. In initial stages of action, inhibition of protein C may be stronger than inhibition of the vitamin K-dependent coagulation factors (II, VII, IX and X), leading to paradoxical activation of coagulation and [[necrosis]] of skin areas.
[[High density lipoprotein|HDL]] and the effects of activated protein C (APC) on cells is very important.<ref>Blood review by Mosnier, Zlokovic and Griffin 2006 ePub</ref>
==Pharmacology==
[[Drotrecogin alpha]](activated) is [[recombinant]] activated protein C from Ely Lilly Co, USA. It is used in the treatment of [[sepsis|severe sepsis]], [[septic shock]] and [[disseminated intravascular coagulation]].
==Genetics==
The ''PROC'' gene is located on the second [[chromosome]] (2q13-q14).
{{PBB|geneid=5624}}
==See also==
{{col-begin}}
* [[Activated protein C resistance]]
* [[Protein C inhibitor]]
* [[Hemostasis]]
* [[Thrombosis]]
* [[Coagulation]]
* [[Anticoagulant]]s
{{col-end}}
==Notes==
<references/>
==External links==
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=GRIFFIN+JH Relative antithrombotic and antihemostatic effects of protein C activator versus low molecular weight heparin in primates], Gruber A, Marzec UM, Bush L, Di Cera E, Fernandez JA, Berny MA, Tucker EI, McCarty OJ, Griffin JH, Hanson SR., Blood (2007) '''- 310 articles by Griffin, et al. are represented at this link'''
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Link&db=PubMed&dbFrom=PubMed&from_uid=17110453 The cytoprotective protein C pathway], Mosnier LO, Zlokovic BV, Griffin JH., Blood (2006)
* [http://www.scripps.edu/mem/eht/griffin/research.html The Protein C Pathway]- John H. Griffin, retired, [[TSRI]], La Jolla, California
* Diagram of [http://www.scripps.edu/mem/eht/griffin/index.html The Blood Coagulation Pathway and Protein C Pathway]
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{{Coagulation}}
{{Glycoproteins}}
[[Category:Coagulation system]]
[[Category:Peripheral membrane proteins]]
[[Category:Angiology]]
[[Category:Hematology]]
[[Category:EC 3.4.21]]
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