Protein C
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| Blood Coagulation (Thrombin) Pathway, and Protein C Pathway. John H. Griffin PhD., TSRI | |
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protein C
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| Identifiers | |
| Symbol | PROC |
| HUGO | 9451 |
| Entrez | 5624 |
| OMIM | 176860 |
| RefSeq | NM_000312 |
| UniProt | P04070 |
| Other data | |
| Locus | Chr. 2 q13-q21 |
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. It's 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
Figure: 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[2]
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[edit] 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.[3]
[edit] 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.
[edit] Genetics
The PROC gene is located on the second chromosome (2q13-q14).
[edit] See also
- Activated protein C resistance
- Protein C inhibitor
- Hemostasis
- Thrombosis
- Anticoagulants
- Mendelian Inheritance in Man (OMIM) 176860
[edit] Notes
- ^ Thrombosis, Blood Coagulation and the Antithrombotic Protein C Pathway - John H. Griffin, TSRI
- ^ Activated protein C resistance
- ^ Blood review by Mosnier, Zlokovic and Griffin 2006 ePub
[edit] 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) - 310 articles by Griffin, et. al. are represented at this link
- The cytoprotective protein C pathway, Mosnier LO, Zlokovic BV, Griffin JH., Blood (2006)
- The Protein C Pathway- John H. Griffin, retired, TSRI, La Jolla, California
- Diagram of The Blood Coagulation Pathway and Protein C Pathway
Hematological malignancy and White blood cells
Lymphoid: Lymphocytic leukemia (ALL, CLL, HCL) • Lymphoma (Hodgkin's disease, NHL) • LPD • Myeloma (Multiple myeloma, Extramedullary plasmacytoma)
Myeloid: Myelogenous leukemia (AML, CML) • MPD (Essential thrombocytosis, Polycythemia) • MDS • Myelofibrosis • Neutropenia
Red blood cells
Anemia • Hemochromatosis • Sickle-cell disease • Thalassemia • Hemolysis • Aplastic anemia • G6PD Deficiency • Hereditary spherocytosis • Hereditary elliptocytosis • Other hemoglobinopathies
Coagulation and Platelets
Thrombosis • Deep vein thrombosis • Pulmonary embolism • Hemophilia • ITP • TTP • DIC
