prothrombin; coagulation factor II; contains: activation peptide fragment 1; activation peptide fragment 2; thrombin light chain; thrombin heavy chain (F2)
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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
Expression
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
- 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
More specific terms
- des-gamma-carboxy-prothrombin; protein induced by vitamin K absence or antagonist II
- prothrombin variant
Additional terms
Component of
- factor ix/factor vii/factor x/protein c/protein s/prothrombin/prothrombin complex concentrate
- prothrombin complex concentrate (Autoplex-T, Kcentra)
References
- ↑ UniProt http://www.uniprot.org/uniprot/P00734.html
- ↑ Wikipedia; Note: Thrombin entry http://en.wikipedia.org/wiki/Thrombin
- ↑ GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/F2
- ↑ SeattleSNPs http://pga.gs.washington.edu/data/f2/
- ↑ Clinical Diagnosis and Management by Laboratory Methods, 18th ed, J.B. Henry (ed), W.B. Saunders, Philadelphia, PA, 1991 pg 735
- ↑ Suttie JW. Synthesis of vitamin K-dependent proteins. FASEB J. 1993 Mar;7(5):445-52. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8462786
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