prothrombin; coagulation factor II; contains: activation peptide fragment 1; activation peptide fragment 2; thrombin light chain; thrombin heavy chain (F2)

Function

• vitamin K-dependent zymogen of serine proteinase thrombin
• functions in blood homeostasis, inflammation & wound healing
• the gamma-carboxyglutamyl residues, which bind Ca+2, result from carboxylation of Glu by a microsomal enzyme, the vitamin K-dependent carboxylase
• the modified Glu are necessary for the Ca+2-dependent interaction with a negatively charged phospholipid surface, essential for conversion of prothrombin to thrombin

Structure

• belongs to the peptidase S1 family
• contains 1 Gla (gamma-carboxy-glutamate) domain
• contains 2 kringle domains
• contains 1 peptidase S1 domain

Compartment

• secreted, extracellular space

Expression

• expressed by the liver & secreted in plasma

Pathology

• defects in prothrombin are the cause of factor II deficiency
• genetic variations in factor II may be a cause of susceptibility to ischemic stroke
• defects in factor II are a cause of susceptibility to thrombosis
  • common genetic variation in the 3' untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels & an increased risk of venous thrombosis
  • mutation in prothrombin gene: prothrombin G20210A

Pharmacology

• the peptide TP508 also known as chrysalin (Orthologic) could be used to accelerate repair of both soft & hard tissues

Notes

• prothrombin is activated on the surface of a phospholipid membrane that binds the amino end of prothrombin & factor Va & factor Xa in Ca-dependent interactions; factor Xa removes the activation peptide & cleaves the remaining part into light & heavy chains
  • the activation process starts slowly because factor V itself has to be activated by the initial, small amounts of thrombin
• it is not known whether 1 or 2 smaller activation peptides, with additional cleavage after Arg-314, are released in natural blood clotting
• thrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its activation by factor Xa
• the cleavage after Arg-198, observed in vitro, does not occur in plasma

More general terms

• coagulation factor
• enzyme precursor (zymogen)

More specific terms

• des-gamma-carboxy-prothrombin; protein induced by vitamin K absence or antagonist II
• prothrombin variant

Additional terms

• coagulation cascade
• prothrombin antibody in serum/plasma
• thrombin; coagulation factor IIa

Component of

• factor ix/factor vii/factor x/protein c/protein s/prothrombin
• prothrombin complex concentrate (Autoplex-T, Kcentra)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2147
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:2147
• OMIM: https://mirror.omim.org/entry/176930
• OMIM: https://mirror.omim.org/entry/188050
• OMIM: https://mirror.omim.org/entry/601367
• UniProt: http://www.uniprot.org/uniprot/P00734.html