Protein C

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Blood Coagulation and Protein C Pathways.jpg
Blood Coagulation (Thrombin) Pathway, and Protein C Pathway. John H. Griffin PhD., TSRI
protein C
Identifiers
Symbol PROC
Entrez 5624
HUGO 9451
OMIM 176860
RefSeq NM_000312
UniProt P04070
Other data
Locus Chr. 2 q13-q21

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Protein C is a major physiological anticoagulant. It is a vitamin K-dependent serine protease enzyme (EC 3.4.21.69) that is activated by thrombin into activated protein C (APC). The activated form (with protein S as a cofactor) degrades Factor Va and Factor VIIIa. 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 lipids and lipoproteins and the study of the strong epidemiologic association between hyperlipidemia and hypercoagulability.[1]

See: detailed diagram of Blood Coagulation (Thrombin) and Protein C Pathways

Role in disease

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.

HDL and the effects of activated protein C (APC) on cells is very important.[2]

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[3]

Pharmacology

Drotrecogin alpha (activated) is recombinant activated protein C from Ely Lilly Co, USA. It is used in the treatment of severe sepsis, septic shock and disseminated intravascular coagulation.

Genetics

The PROC gene is located on the second chromosome (2q13-q14).

See also

References

  1. Thrombosis, Blood Coagulation and the Antithrombotic Protein C Pathway - John H. Griffin, TSRI
  2. Blood review by Mosnier, Zlokovic and Griffin 2006 ePub
  3. Activated protein C resistance

External links


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| group5 = Clinical Trials Involving Protein C | list5 = Ongoing Trials on Protein C at Clinical Trials.govTrial results on Protein CClinical Trials on Protein C at Google


| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Protein C | list6 = US National Guidelines Clearinghouse on Protein CNICE Guidance on Protein CNHS PRODIGY GuidanceFDA on Protein CCDC on Protein C


| group7 = Textbook Information on Protein C | list7 = Books and Textbook Information on Protein C


| group8 = Pharmacology Resources on Protein C | list8 = AND (Dose)}} Dosing of Protein CAND (drug interactions)}} Drug interactions with Protein CAND (side effects)}} Side effects of Protein CAND (Allergy)}} Allergic reactions to Protein CAND (overdose)}} Overdose information on Protein CAND (carcinogenicity)}} Carcinogenicity information on Protein CAND (pregnancy)}} Protein C in pregnancyAND (pharmacokinetics)}} Pharmacokinetics of Protein C


| group9 = Genetics, Pharmacogenomics, and Proteinomics of Protein C | list9 = AND (pharmacogenomics)}} Genetics of Protein CAND (pharmacogenomics)}} Pharmacogenomics of Protein CAND (proteomics)}} Proteomics of Protein C


| group10 = Newstories on Protein C | list10 = Protein C in the newsBe alerted to news on Protein CNews trends on Protein C</small>


| group11 = Commentary on Protein C | list11 = Blogs on Protein C

| group12 = Patient Resources on Protein C | list12 = Patient resources on Protein CDiscussion groups on Protein CPatient Handouts on Protein CDirections to Hospitals Treating Protein CRisk calculators and risk factors for Protein C


| group13 = Healthcare Provider Resources on Protein C | list13 = Symptoms of Protein CCauses & Risk Factors for Protein CDiagnostic studies for Protein CTreatment of Protein C

| group14 = Continuing Medical Education (CME) Programs on Protein C | list14 = CME Programs on Protein C

| group15 = International Resources on Protein C | list15 = Protein C en EspanolProtein C en Francais

| group16 = Business Resources on Protein C | list16 = Protein C in the MarketplacePatents on Protein C

| group17 = Informatics Resources on Protein C | list17 = List of terms related to Protein C


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