Prothrombin

From Anvita Health Wiki

Contents 1 More Specific Terms 2 Function 3 Structure 4 Compartment 5 Expression 6 Pathology 7 Pharmacology 8 Notes 9 More General Terms 10 Additional Terms 11 Internet Database 12 References

More Specific Terms

• des-gamma-carboxy-prothrombin; protein induced by vitamin K absence or antagonist II
• prothrombin 20210

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)

Additional Terms

• coagulation cascade
• coagulation factor II autoantibody; prothrombin antibody
• thrombin; coagulation factor IIa

Internet Database

Entrez gene: 2147
Kegg: [1]
OMIM: 176930
OMIM: 188050
OMIM: 601367
Prosite: [2]
Prosite: [3]
Prosite: [4]
Prosite: [5]
Prosite: [6]
Prosite: [7]
Prosite: [8]
UniProt: [9]

References

1. UniProt [10]
2. Wikipedia; Note: Thrombin entry [11]
3. GeneReviews [12]
4. SeattleSNPs [13]
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: [14]

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