Prothrombin (F2)
The protein contains 622 amino acids for an estimated molecular weight of 70037 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.
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Biological Process
Acute-phase response
Antimicrobial humoral immune response mediated by antimicrobial peptide
Blood coagulation
Blood coagulation, intrinsic pathway
Cell surface receptor signaling pathway
Cellular protein metabolic process
Cytolysis by host of symbiont cells
Endoplasmic reticulum to Golgi vesicle-mediated transport
Fibrinolysis
G protein-coupled receptor signaling pathway
Leukocyte migration
Multicellular organism development
Negative regulation of astrocyte differentiation
Negative regulation of cytokine production involved in inflammatory response
Negative regulation of fibrinolysis
Negative regulation of platelet activation
Negative regulation of proteolysis
Neutrophil-mediated killing of gram-negative bacterium
Peptidyl-glutamic acid carboxylation
Platelet activation
Positive regulation of blood coagulation
Positive regulation of cell growth
Positive regulation of cell population proliferation
Positive regulation of collagen biosynthetic process
Positive regulation of lipid kinase activity
Positive regulation of phosphatidylinositol 3-kinase signaling
Positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway
Positive regulation of protein localization to nucleus
Positive regulation of protein phosphorylation
Positive regulation of reactive oxygen species metabolic process
Positive regulation of receptor signaling pathway via JAK-STAT
Positive regulation of release of sequestered calcium ion into cytosol
Positive regulation of STAT protein import into nucleus
Post-translational protein modification
Proteolysis
Regulation of blood coagulation
Regulation of cell shape
Regulation of complement activation
Regulation of cytosolic calcium ion concentration
Regulation of gene expression
Response to wounding
Signal peptide processing
The reference OMIM entry for this protein is 176930
Coagulation factor ii; f2
Thrombin
Prothrombin
Factor ii
DESCRIPTION
The F2 gene encodes coagulation factor II (EC 3.4.21.5), or prothrombin, a vitamin K-dependent glycoprotein synthesized in the liver as an inactive zymogen. Prothrombin is activated to the serine protease thrombin by factor Xa (F10; 613872) in the presence of phospholipids, calcium, and factor Va (F5; 612309). The activated thrombin enzyme plays an important role in hemostasis and thrombosis: it converts fibrinogen (134820) to fibrin for blood clot formation, stimulates platelet aggregation, and activates coagulation factors V, VIII (F8; 300841), and XIII (F13A1; 134570). Thrombin also inhibits coagulation by activating protein C (PROC; 612283) (summary by Lancellotti and De Cristofaro, 2009).CLONING
Degen and Davie (1987) determined the nucleotide sequence of the human prothrombin gene, which encodes a 622-residue pre-propeptide with a molecular mass of about 70 kD. The mature circulating protein has 579 residues. The prothrombin protein contains 5 domains: the propeptide (residues -43 to -1), the Gla domain (residues 1 to 40), a kringle domain (residues 41 to 155), a kringle-2 domain (residues 156 to 271), and a serine protease domain (residues 272 to 579). The prothrombin protein undergoes several cleavage events to generate the active enzyme alpha-thrombin, which is composed of a light (alpha) and heavy (beta) chain covalently linked by a disulfide bond (summary by Lancellotti and De Cristofaro, 2009). Degen et al. (1990) cloned cDNAs for mouse coagulation factor II and compared the gene and predicted protein structure with that of human prothrombin.GENE STRUCTURE
Degen and Davie (1987) determined that the prothrombin gene contains 14 exons and spans about 21 kb. The gene contains 30 Alu repeats and 2 Kpn repeats, which constitute about 40% of the gene.MAPPING
Royle et al. (1987) assigned the gene for human prothrombin (F2) to chromosome 11p11-q12 by analysis of a panel of somatic cell hybrid DNAs and by in situ hybridization, using both cDNA and genomic probes. Degen et al. (1990) mapped the mouse F2 gene to chromosome 2, about 1.8 map units proximal to the catalase locus.BIOCHEMICAL FEATURES
- Crystal Structure Celikel et al. (2003) determined that the structure of platelet GP1BA (606672) bound to thrombin at 2.3 angstrom resolution and defined 2 sites that bind to exosite II and exosite I of 2 distinct alpha-thrombin molecules, respectively. GP1BA occupancy may be sequential, as the site binding to alpha-thrombin exosite I appears to be cryptic in the unoccupied receptor but exposed when a first thrombin molecule is bound through exosite II. Celikel et al. (2003) suggested that these interactions may modulate alpha-thrombin function by mediating GP1BA clustering and cleavage of protease-activator receptors, which promote platelet activation, while limiting fibrinogen clotting through blockade of exosite I. Dumas et al. (2003) independently determined the crystal structure of the GP1BA-thrombin complex at 2.6 angstrom resolution. They found that in the crystal lattice, the periodic arrangement of GP1BA-thrombin complexes mirrors a scaffold that could serve as a driving force for tight platelet adhesion. Kroh et al. (2009) found that von Willebrand factor-binding protein (VWFBP), which is secreted by Staphyloccocus aureus, is a potent nonenzymatic conformational activator of prothrombin. VWFBP was found to share homology with staphylocoagulase, another protein s ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 176930 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed