Prothrombin
Also known as: F2
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. Activates coagulation factor XI (F11); activation is promoted by the contact with negatively charged surfaces. Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL8/CXCL8, in endothelial cells.
Classification
- Family (Pfam)
- PF00594 Gla, PF00051 Kringle, PF09396 Thrombin_light, PF00089 Trypsin
- InterPro
- GLA-like_dom_SF, GLA_domain, Kringle, Kringle-like, Kringle_CS, Kringle_sf, Peptidase_S1_PA, Peptidase_S1_PA_chymotrypsin, Peptidase_S1A, Prothrombin/thrombin, Serine_Protease_S1-Domain, Thrombin_light_chain, Thrombin_light_chain_sf, Trypsin_dom, TRYPSIN_HIS, TRYPSIN_SER
- Functional cluster
- Venom Serine Proteases & Phospholipase A2
Experimental structures · PDB · 472
- 1A2C X-ray 2.10A
- 1A3B X-ray 1.80A
- 1A3E X-ray 1.85A
- 1A46 X-ray 2.12A
- 1A4W X-ray 1.80A
- 1A5G X-ray 2.06A
- 1A61 X-ray 2.20A
- 1ABI X-ray 2.30A
- 1ABJ X-ray 2.40A
- 1AD8 X-ray 2.00A
- 1AE8 X-ray 2.00A
- 1AFE X-ray 2.00A
- … and 460 more
A predicted model is available from AlphaFold.
Gene Ontology · 42
- GO:0072562 blood microparticle
- GO:0005788 endoplasmic reticulum lumen
- GO:0070062 extracellular exosome
- GO:0031012 extracellular matrix
- GO:0005576 extracellular region
- GO:0005615 extracellular space
- GO:0005796 Golgi lumen
- GO:0005886 plasma membrane
- GO:0005509 calcium ion binding
- GO:0008083 growth factor activity
- GO:0008201 heparin binding
- GO:0001530 lipopolysaccharide binding
- GO:0048018 receptor ligand activity
- GO:0004252 serine-type endopeptidase activity
- GO:0005102 signaling receptor binding
- GO:0070053 thrombospondin receptor activity
- GO:0006953 acute-phase response
- GO:0061844 antimicrobial humoral immune response mediated by antimicrobial peptide
- GO:0007596 blood coagulation
- GO:0007166 cell surface receptor signaling pathway
- GO:0051838 cytolysis by host of symbiont cells
- GO:0042730 fibrinolysis
- GO:0048712 negative regulation of astrocyte differentiation
- GO:0030195 negative regulation of blood coagulation
- GO:1900016 negative regulation of cytokine production involved in inflammatory response
- GO:0051918 negative regulation of fibrinolysis
- GO:0010544 negative regulation of platelet activation
- GO:0045861 negative regulation of proteolysis
- GO:0070945 neutrophil-mediated killing of gram-negative bacterium
- GO:0030168 platelet activation
- GO:0030194 positive regulation of blood coagulation
- GO:0032967 positive regulation of collagen biosynthetic process
- GO:1900738 positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway
- GO:1900182 positive regulation of protein localization to nucleus
- GO:2000379 positive regulation of reactive oxygen species metabolic process
- GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT
- GO:0051281 positive regulation of release of sequestered calcium ion into cytosol
- GO:0006508 proteolysis
- GO:0030193 regulation of blood coagulation
- GO:0051480 regulation of cytosolic calcium ion concentration
- GO:0009611 response to wounding
- GO:0070493 thrombin-activated receptor signaling pathway
Disease associations
- thrombophilia due to thrombin defect MONDO:0008559
- obsolete susceptibility to ischemic stroke MONDO:0020671
- congenital prothrombin deficiency MONDO:0013361
- pregnancy loss, recurrent, susceptibility to, 2 MONDO:0013728
Drugs targeting this protein · 5
- ARGATROBAN inhibitor
- DABIGATRAN ETEXILATE MESYLATE inhibitor
- ATECEGATRAN METOXIL inhibitor
- DABIGATRAN inhibitor
- XIMELAGATRAN inhibitor
Related proteins · sequence + function similarity
- Prothrombin 0.99
- Prothrombin 0.98
- Prothrombin 0.98
- Prothrombin 0.98
- Prothrombin 0.98
- Salivary plasminogen activator gamma 0.86
- Coagulation factor X 0.86
- Salivary plasminogen activator alpha 2 0.85
- Salivary plasminogen activator alpha 1 0.85
- Salivary plasminogen activator beta 0.85
- Coagulation factor X 0.85
- Coagulation factor X 0.84
Co-cited proteins · studied together in the literature
- Hirudin variant-1 3 shared papers
- Hirudin variant-2 1 shared papers
- Variegin 1 shared papers
- Coagulation factor XI 2 shared papers
- Salivary thrombin inhibitor anophelin 2 shared papers
- Coagulation factor X 4 shared papers
- Salivary thrombin inhibitor XC-42 1 shared papers
- Salivary thrombin inhibitor XC-43 1 shared papers
- Plasma serine protease inhibitor 1 shared papers
- Salivary thrombin inhibitor anophelin 2 shared papers
- Iripin-3 1 shared papers
- Coagulation factor V 2 shared papers
Literature · 59 cited papers
- Identification of a substrate-like cleavage-resistant thrombin inhibitor from the saliva of the flea Xenopsylla cheopis. J. Biol. Chem. · 2021
- Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement. Int. J. Mol. Sci. · 2021
- Role of sequence and position of the cleavage sites in prothrombin activation. J. Biol. Chem. · 2021
- Iripin-3, a New Salivary Protein Isolated From Ixodes ricinus Ticks, Displays Immunomodulatory and Anti-Hemostatic Properties In Vitro. Front. Immunol. · 2021
- TAK-442, a Direct Factor Xa Inhibitor, Inhibits Monocyte Chemoattractant Protein 1 Production in Endothelial Cells via Involvement of Protease-Activated Receptor 1. Front. Pharmacol. · 2018
- Functional analyses yield detailed insight into the mechanism of thrombin inhibition by the antihemostatic salivary protein cE5 from Anopheles gambiae. J. Biol. Chem. · 2017
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Unique thrombin inhibition mechanism by anophelin, an anticoagulant from the malaria vector. Proc. Natl. Acad. Sci. U.S.A. · 2012
- Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. Mol. Cell. Proteomics · 2012
- Crystal structure of thrombin in complex with S-variegin: insights of a novel mechanism of inhibition and design of tunable thrombin inhibitors. PLoS ONE · 2011
- Quantitative detection of single amino acid polymorphisms by targeted proteomics. J. Mol. Cell Biol. · 2011
- Polyphosphate is a cofactor for the activation of factor XI by thrombin. Blood · 2011
- … and 47 more in the literature graph
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