Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

3.4.21.5

Official Name

thrombin

Name from literature

thrombin

Pathway from literature

formation of fibrin

Pathway from KEGG

Environmental Information Processing; Signaling Molecules and Interaction; Neuroactive ligand-receptor interaction; map04080

Cellular Processes; Cell Motility; Regulation of actin cytoskeleton; map04810

Cellular Processes; Immune System; Complement and coagulation cascades; map04610

Organisms

Human (9606)

Genome localization

11p11[2147 ],

Comments

Formed from prothrombin. More selective than trypsin and plasmin. In peptidase family S1 (trypsin family).

Rate-limiting Description

"It is suggested that at 37 degrees C the processes of thrombin binding to the receptor, of receptor modification and of cellular response are immediately coupled with one another and that the rate-limiting step is the binding of thrombin to the receptor.." (6743305)

"Finally, kinetic modeling demonstrated that acylation is the rate-limiting step in thrombin inhibition by PAI-1 (k approximately 10(-3) s(-1)) and this kinetic block is alleviated by the introduction of the tPA-VR1 into thrombin (k>1 s(-1))." (10543954)

"The objective of this study was to determine whether there was evidence of in vivo generation of thrombin, the rate-limiting enzyme responsible for the formation of fibrin." (12389649)

Regulatory Information

Upstream transcription factor

6667;3172;3170;6670

Regulatory type

Detail

key enzyme;

"Dabigatran has been shown to specifically and reversibly inhibit thrombin, the key enzyme in the coagulation cascade." (18399711)

transcriptional factor;"HNF4-alpha(3172),HNF3-beta(3170),Sp1(6667),Sp3(6670)"

"prothrombin expression is regulated by HNF4-alpha, HNF3-beta and Sp1/Sp3" (12911579)

Gene ontology

Gene ontology

GO:0007260 (P) tyrosine phosphorylation of STAT protein [P00734 ];
GO:0006919 (P) caspase activation [P00734 ];
GO:0005615 (C) extracellular space [P00734 ];
GO:0007275 (P) multicellular organismal development [P00734 ];
GO:0007166 (P) cell surface receptor linked signal transdu... [P00734 ];
GO:0005509 (F) calcium ion binding [P00734 ];
GO:0032967 (P) positive regulation of collagen biosyntheti... [P00734 ];
GO:0005625 (C) soluble fraction [P00734 ];
GO:0070053 (F) thrombospondin receptor activity [P00734 ];
GO:0030194 (P) positive regulation of blood coagulation [P00734 ];
GO:0042730 (P) fibrinolysis [P00734 ];
GO:0006508 (P) proteolysis [P00734 ];
GO:0007262 (P) STAT protein nuclear translocation [P00734 ];
GO:0003809 (F) thrombin activity [P00734 ];
GO:0005886 (C) plasma membrane [P00734 ];
GO:0004252 (F) serine-type endopeptidase activity [P00734 ];
GO:0005102 (F) receptor binding [P00734 ];
GO:0051209 (P) release of sequestered calcium ion into cyt... [P00734 ];
GO:0030168 (P) platelet activation [P00734 ];
GO:0006953 (P) acute-phase response [P00734 ];

Tissue expression

Tissue From HPRD

Serum [01488 ];
Plasma [01488 ];
Ovary [01488 ];
Liver [01488 ];

Tissue specificity

Expressed by the liver and secreted in plasma [P00734 ];

Subcellular localization

Localization

extracellular [P00734 ];

Disease relevance

Disease

Defects in F2 are the cause of various forms of dysprothrombinemia [MIM:176930] [P00734 ];

Genetic variations in F2 may be a cause of susceptibility to ischemic stroke [MIM:601367];
also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors [P00734 ];

Links

SwissProt

P00734

Entrez Gene

2147

HPRD

01488



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  Last Modified: 2009-03-24  
  Design by Zhao Min