ID:THRB_HUMAN DESCRIPTION: RecName: Full=Prothrombin; EC=3.4.21.5; AltName: Full=Coagulation factor II; Contains: RecName: Full=Activation peptide fragment 1; Contains: RecName: Full=Activation peptide fragment 2; Contains: RecName: Full=Thrombin light chain; Contains: RecName: Full=Thrombin heavy chain; Flags: Precursor; FUNCTION: Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing. CATALYTIC ACTIVITY: Selective cleavage of Arg-|-Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A and B. ENZYME REGULATION: Inhibited by SERPINA5. SUBUNIT: Heterodimer (named alpha-thrombin) of a light and a heavy chain; disulfide-linked. Forms a heterodimer with SERPINA5. INTERACTION: Q846V4:- (xeno); NbExp=5; IntAct=EBI-297094, EBI-989571; P07204:THBD; NbExp=4; IntAct=EBI-297094, EBI-941422; SUBCELLULAR LOCATION: Secreted, extracellular space. TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma. PTM: The gamma-carboxyglutamyl residues, which bind calcium ions, result from the carboxylation of glutamyl residues by a microsomal enzyme, the vitamin K-dependent carboxylase. The modified residues are necessary for the calcium-dependent interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to thrombin. PTM: N-glycosylated. N-glycan heterogeneity at Asn-121: Hex3HexNAc3 (minor), Hex4HexNAc3 (minor) and Hex5HexNAc4 (major). At Asn-143: Hex4HexNAc3 (minor) and Hex5HexNAc4 (major). DISEASE: Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:613679]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels. DISEASE: Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [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. DISEASE: Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:188050]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. DISEASE: Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:614390]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. PHARMACEUTICAL: The peptide TP508 also known as Chrysalin (Orthologic) could be used to accelerate repair of both soft and hard tissues. MISCELLANEOUS: Prothrombin is activated on the surface of a phospholipid membrane that binds the amino end of prothrombin and factors Va and Xa in Ca-dependent interactions; factor Xa removes the activation peptide and cleaves the remaining part into light and heavy chains. The activation process starts slowly because factor V itself has to be activated by the initial, small amounts of thrombin. MISCELLANEOUS: It is not known whether 1 or 2 smaller activation peptides, with additional cleavage after Arg-314, are released in natural blood clotting. MISCELLANEOUS: Thrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its activation by factor Xa. MISCELLANEOUS: The cleavage after Arg-198, observed in vitro, does not occur in plasma. SIMILARITY: Belongs to the peptidase S1 family. SIMILARITY: Contains 1 Gla (gamma-carboxy-glutamate) domain. SIMILARITY: Contains 2 kringle domains. SIMILARITY: Contains 1 peptidase S1 domain. WEB RESOURCE: Name=Wikipedia; Note=Thrombin entry; URL="http://en.wikipedia.org/wiki/Thrombin"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/F2"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/f2/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P00734
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001934 positive regulation of protein phosphorylation GO:0006508 proteolysis GO:0006888 ER to Golgi vesicle-mediated transport GO:0006953 acute-phase response GO:0007166 cell surface receptor signaling pathway GO:0007186 G-protein coupled receptor signaling pathway GO:0007275 multicellular organism development GO:0007596 blood coagulation GO:0007597 blood coagulation, intrinsic pathway GO:0007599 hemostasis GO:0008284 positive regulation of cell proliferation GO:0008360 regulation of cell shape GO:0009611 response to wounding GO:0010468 regulation of gene expression GO:0010469 regulation of receptor activity GO:0010544 negative regulation of platelet activation GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling GO:0030168 platelet activation GO:0030193 regulation of blood coagulation GO:0030194 positive regulation of blood coagulation GO:0030307 positive regulation of cell growth GO:0030449 regulation of complement activation GO:0032967 positive regulation of collagen biosynthetic process GO:0042730 fibrinolysis GO:0044267 cellular protein metabolic process GO:0045861 negative regulation of proteolysis GO:0046427 positive regulation of JAK-STAT cascade GO:0048712 negative regulation of astrocyte differentiation GO:0051281 positive regulation of release of sequestered calcium ion into cytosol GO:0051480 regulation of cytosolic calcium ion concentration GO:0051838 cytolysis by host of symbiont cells GO:0051918 negative regulation of fibrinolysis GO:0070945 neutrophil mediated killing of gram-negative bacterium GO:0090218 positive regulation of lipid kinase activity GO:1900016 negative regulation of cytokine production involved in inflammatory response GO:1900182 positive regulation of protein localization to nucleus GO:1900738 positive regulation of phospholipase C-activating G-protein coupled receptor signaling pathway GO:2000379 positive regulation of reactive oxygen species metabolic process
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
