Protein C

PROC
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPROC, APC, PC, PROC1, THPH3, THPH4, protein C, inactivator of coagulation factors Va and VIIIa
External IDsOMIM: 612283; MGI: 97771; HomoloGene: 37288; GeneCards: PROC; OMA:PROC - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000312

NM_001042767
NM_001042768
NM_008934
NM_001313938

RefSeq (protein)

NP_001036232
NP_001036233
NP_001300867
NP_032960

Location (UCSC)Chr 2: 127.42 – 127.43 MbChr 18: 32.26 – 32.27 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV,[5]: 6822 [6] is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and 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 Va and Factor VIIIa. APC is classified as a serine protease since it contains a residue of serine in its active site.[7]: 35  In humans, protein C is encoded by the PROC gene, which is found on chromosome 2.[8]

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.[8]: 4673  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.[7]: 34 [9]: 3162  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 a recombinant form of human Activated Protein C (rhAPC) known as Drotrecogin alfa-activated, branded Xigris by Eli Lilly and Company, has been surrounded by controversy. Eli Lilly ran an aggressive marketing campaign to promote its use for people with severe sepsis and septic shock and sponsored the 2004 Surviving Sepsis Campaign Guidelines.[10] However, a 2012 Cochrane review found that its use cannot be recommended since it does not improve survival and increases bleeding risk.[11] In October 2011, Xigris was withdrawn from the market by Eli Lilly due to a higher mortality in a trial among adults.[12]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115718Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024386Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Hall JA, Morton I (1999). Concise dictionary of pharmacological agents: properties and synonyms. Kluwer Academic. ISBN 978-0-7514-0499-9.
  6. ^ Cite error: The named reference morton was invoked but never defined (see the help page).
  7. ^ a b Cite error: The named reference nicolaes was invoked but never defined (see the help page).
  8. ^ a b Cite error: The named reference foster was invoked but never defined (see the help page).
  9. ^ Cite error: The named reference mosnier was invoked but never defined (see the help page).
  10. ^ Cite error: The named reference pmid17050887 was invoked but never defined (see the help page).
  11. ^ Cite error: The named reference pmid23235609 was invoked but never defined (see the help page).
  12. ^ Cite error: The named reference Kylat was invoked but never defined (see the help page).

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