Protein C

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.

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.

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

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

• Activated protein C resistance
• Protein C inhibitor
• Hemostasis
• Thrombosis
• Coagulation
• Anticoagulants

External links

• 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)
• The cytoprotective protein C pathway, Mosnier LO, Zlokovic BV, Griffin JH., Blood (2006)
• The Protein C Pathway- John H. Griffin, TSRI, La Jolla, California
• Diagram of The Blood Coagulation Pathway and Protein C Pathway

Cost Effectiveness of Protein C

| group5 = Clinical Trials Involving Protein C | list5 = Ongoing Trials on Protein C at Clinical Trials.gov • Trial results on Protein C • Clinical Trials on Protein C at Google

| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Protein C | list6 = US National Guidelines Clearinghouse on Protein C • NICE Guidance on Protein C • NHS PRODIGY Guidance • FDA on Protein C • CDC 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 C • AND (drug interactions)}} Drug interactions with Protein C • AND (side effects)}} Side effects of Protein C • AND (Allergy)}} Allergic reactions to Protein C • AND (overdose)}} Overdose information on Protein C • AND (carcinogenicity)}} Carcinogenicity information on Protein C • AND (pregnancy)}} Protein C in pregnancy • AND (pharmacokinetics)}} Pharmacokinetics of Protein C •

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

| group10 = Newstories on Protein C | list10 = Protein C in the news • Be alerted to news on Protein C • News 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 C • Discussion groups on Protein C • Patient Handouts on Protein C • Directions to Hospitals Treating Protein C • Risk calculators and risk factors for Protein C

| group13 = Healthcare Provider Resources on Protein C | list13 = Symptoms of Protein C • Causes & Risk Factors for Protein C • Diagnostic studies for Protein C • Treatment 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 Espanol • Protein C en Francais

| group16 = Business Resources on Protein C | list16 = Protein C in the Marketplace • Patents on Protein C

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

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