Protein C

Protein C

Identifiers Symbols PROC; PROC1 External IDs OMIM: 176860 MGI: 97771 HomoloGene: 37288 GeneCards: PROC Gene EC number 3.4.21.69

Gene Ontology
Molecular function	• protein C (activated) activity • calcium ion binding • peptidase activity
Cellular component	• extracellular region
Biological process	• proteolysis • blood coagulation • negative regulation of blood coagulation • negative regulation of apoptosis
Sources: Amigo / QuickGO

RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez 5624 19123 Ensembl ENSG00000115718 ENSMUSG00000024386 UniProt P04070 P33587 RefSeq (mRNA) NM_000312 NM_008934 RefSeq (protein) NP_000303 NP_032960 Location (UCSC) Chr 2:
127.89 – 127.9 Mb Chr 18:
32.27 – 32.28 Mb PubMed search

Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic (inactive) protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death, and maintaining the permeability of blood vessel walls in humans and other animals. Activated protein C (APC) performs these operations primarily by proteolytically inactivating proteins Factor V_a and Factor VIII_a. APC is classified as a serine protease as it contains a residue of serine in its active site. In humans, protein C is encoded by the PROC gene, which is found on chromosome 2.

The zymogenic form of protein C is a vitamin K-dependent glycoprotein that circulates in blood plasma. Its structure is that of a two-chain polypeptide consisting of a light chain and a heavy chain connected by a disulfide bond. The protein C zymogen is activated when it binds to thrombin, another protein heavily involved in coagulation, and protein C's activation is greatly promoted by the presence of thrombomodulin and endothelial protein C receptors (EPCRs). Because of EPCR's role, activated protein C is found primarily near endothelial cells (i.e., those that make up the walls of blood vessels), and it is these cells and leukocytes (white blood cells) that APC affects. Because of the crucial role that protein C plays as an anticoagulant, those with deficiencies in protein C, or some kind of resistance to APC, suffer from a significantly increased risk of forming dangerous blood clots (thrombosis).

Research into the clinical use of activated protein C also known as drotrecogin alfa-activated (branded Xigris) has been surrounded by controversy. The manufacturer Eli Lilly and Company ran an aggressive marketing campaign to promote its use in people with severe sepsis and septic shock including the sponsoring of the 2004 Surviving Sepsis Campaign Guidelines. A 2011 Cochrane review however found that its use cannot be recommended as it does not improve survival (and increases bleeding risk).