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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: 1) 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 2) it is not known whether 1 or 2 smaller activation peptides, with additional cleavage after Arg-314, are released in natural blood clotting 3) thrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its activation by factor Xa 4) the cleavage after Arg-198, observed in vitro, does not occur in plasma

Interactions

molecular events

Related

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

Specific

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

General

coagulation factor enzyme precursor (zymogen)

Properties

SIZE: entity length = 622 aa MW = 70 kD COMPARTMENT: plasma MOTIF: signal sequence {1-24} Gla {44-89} MOTIF: cysteine residue {C60} MODIFICATION: cysteine residue {C65} cysteine residue {C65} MODIFICATION: cysteine residue {C60} cysteine residue {C90} MODIFICATION: cysteine residue {C103} cysteine residue {C103} MODIFICATION: cysteine residue {C90} Kringle 1 {108-186} MOTIF: cysteine residue {C108} MODIFICATION: cysteine residue {C186} N-glycosylation site {N121} cysteine residue {C129} MODIFICATION: cysteine residue {C169} N-glycosylation site {N143} cysteine residue {C157} MODIFICATION: cysteine residue {C181} cysteine residue {C169} MODIFICATION: cysteine residue {C129} cysteine residue {C181} MODIFICATION: cysteine residue {C157} cysteine residue {C186} MODIFICATION: cysteine residue {C108} proteolytic site {198-199} Kringle 2 {213-291} MOTIF: cysteine residue {C213} MODIFICATION: cysteine residue {C291} cysteine residue {C234} MODIFICATION: cysteine residue {C274} cysteine residue {C262} MODIFICATION: cysteine residue {C286} cysteine residue {C274} MODIFICATION: cysteine residue {C234} cysteine residue {C286} MODIFICATION: cysteine residue {C262} cysteine residue {C291} MODIFICATION: cysteine residue {C213} proteolytic site {327-328} cysteine residue {C336} MODIFICATION: cysteine residue {C-INTERCHAIN} proteolytic site {363-364} S1 domain {364-618} MOTIF: cysteine residue {C391} MODIFICATION: cysteine residue {C407} histidine residue {H406} cysteine residue {C407} MODIFICATION: cysteine residue {C391} N-glycosylation site {N416} aspartate residue {D462} cysteine residue {C536} MODIFICATION: cysteine residue {C550} cysteine residue {C550} MODIFICATION: cysteine residue {C536} binding site SITE: 551-573 FOR-BINDING-OF: HIGH motif cysteine residue {C564} MODIFICATION: cysteine residue {C594} serine residue {S568} cysteine residue {C594} MODIFICATION: cysteine residue {C564} PRECURSOR-FOR: thrombin COMPARTMENT: plasma STATE: active state MISC-INFO: 1/2life 50 HOURS

Database Correlations

OMIM correlations MORBIDMAP 176930 UniProt P00734 PFAM correlations Entrez Gene 2147 Kegg hsa:2147 ENZYME 3.4.21.5

References

  1. UniProt :accession P00734
  2. Wikipedia; Note: Thrombin entry http://en.wikipedia.org/wiki/Thrombin
  3. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/F2
  4. SeattleSNPs http://pga.gs.washington.edu/data/f2/
  5. Clinical Diagnosis and Management by Laboratory Methods, 18th ed, J.B. Henry (ed), W.B. Saunders, Philadelphia, PA, 1991 pg 735
  6. Suttie JW. Synthesis of vitamin K-dependent proteins. FASEB J. 1993 Mar;7(5):445-52. Review. PMID: 8462786

Component-of

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