F2
Prothrombin
Also known as: THRB_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P00734
- Gene
- F2
- Ensembl
- ENSG00000180210
- Chromosome
- 11
- Canonical length
- 622 aa
- Protein class
- Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins
- Secretome location
- Secreted to blood
OverviewNCBI Gene
This gene encodes the prothrombin protein (also known as coagulation factor II). This protein is proteolytically cleaved in multiple steps to form the activated serine protease thrombin. The activated thrombin enzyme plays an important role in thrombosis and hemostasis by converting fibrinogen to fibrin during blood clot formation, by stimulating platelet aggregation, and by activating additional coagulation factors. Thrombin also plays a role in cell proliferation, tissue repair, and angiogenesis as well as maintaining vascular integrity during development and postnatal life. Peptides derived from the C-terminus of this protein have antimicrobial activity against E. coli and P. aeruginosa. Mutations in this gene lead to various forms of thrombosis and dysprothrombinemia. Rapid increases in cytokine levels following coronavirus infections can dysregulate the coagulation cascade and produce thrombosis, compromised blood supply, and organ failure. [provided by RefSeq, May 2020]
Canonical amino-acid sequenceUniProt
622 residues, UniProt reviewed canonical sequence.
>P00734|F2
1 MAHVRGLQLP GCLALAALCS LVHSQHVFLA PQQARSLLQR VRRANTFLEE VRKGNLEREC
61 VEETCSYEEA FEALESSTAT DVFWAKYTAC ETARTPRDKL AACLEGNCAE GLGTNYRGHV
121 NITRSGIECQ LWRSRYPHKP EINSTTHPGA DLQENFCRNP DSSTTGPWCY TTDPTVRRQE
181 CSIPVCGQDQ VTVAMTPRSE GSSVNLSPPL EQCVPDRGQQ YQGRLAVTTH GLPCLAWASA
241 QAKALSKHQD FNSAVQLVEN FCRNPDGDEE GVWCYVAGKP GDFGYCDLNY CEEAVEEETG
301 DGLDEDSDRA IEGRTATSEY QTFFNPRTFG SGEADCGLRP LFEKKSLEDK TERELLESYI
361 DGRIVEGSDA EIGMSPWQVM LFRKSPQELL CGASLISDRW VLTAAHCLLY PPWDKNFTEN
421 DLLVRIGKHS RTRYERNIEK ISMLEKIYIH PRYNWRENLD RDIALMKLKK PVAFSDYIHP
481 VCLPDRETAA SLLQAGYKGR VTGWGNLKET WTANVGKGQP SVLQVVNLPI VERPVCKDST
541 RIRITDNMFC AGYKPDEGKR GDACEGDSGG PFVMKSPFNN RWYQMGIVSW GEGCDRDGKY
601 GFYTHVFRLK KWIQKVIDQF GELocalizationUniProt · AlphaFold · HPA
Whether an antibody against F2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.29
- Highest tissue expression
- 1,138 nTPM
Expression across tissuesHPA
Tissue
- liver: 1,138 nTPM
- cerebellum: 0.9 nTPM
- ovary: 0.5 nTPM
- spleen: 0.5 nTPM
- testis: 0.5 nTPM
- blood vessel: 0.3 nTPM
Single-cell type
- hepatocytes: 1,119 nCPM
- oocytes: 147 nCPM
- hepatic stellate cells: 19 nCPM
- kupffer cells: 18 nCPM
- cholangiocytes: 18 nCPM
- endometrial glandular cells: 6.1 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- cerebellum: 1.4 nTPM
- cerebral cortex: 0.4 nTPM
- hypothalamus: 0.4 nTPM
- white matter: 0.4 nTPM
- basal ganglia: 0.3 nTPM
- medulla oblongata: 0.3 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about F2.
Disease | AllUniProt
Conditions F2 is implicated in, by any mechanism.
- Factor II deficiency (FA2D) MIM:613679
- Ischemic stroke (ISCHSTR) MIM:601367
- Thrombophilia due to thrombin defect (THPH1) MIM:188050
- Pregnancy loss, recurrent, 2 (RPRGL2) MIM:614390
Disease | GeneticClinVar
40 pathogenic / likely-pathogenic of 470 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Congenital prothrombin deficiency
- Thrombophilia due to thrombin defect
- Ischemic stroke
- Pregnancy loss, recurrent, susceptibility to, 2
- Prolonged prothrombin time
Disease | ImmuneIEDB
Conditions an epitope on F2 was assayed in.
- rheumatoid arthritis B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against F2 are reported. Each links to that disease's full target list.
- Antiphospholipid Syndrome 142
- Lupus Erythematosus, Systemic 71
- Thrombosis 65
- Abortion, Habitual 17
- Venous Thrombosis 16
- Abortion, Spontaneous 11
- Stroke 9
- Vasculitis 5
- Thrombocytopenia 4
- Atherosclerosis 3
- Celiac Disease 3
- COVID-19 3
- Multiple Sclerosis 3
- Pre-Eclampsia 3
Showing 14 of 22 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for F2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
293 publications
- Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study.
2009 · Lancet Neurol · RCR 9.8 · 317 citations - Anti-prothrombin antibodies and the lupus anticoagulant.
1988 · Blood · RCR 9.8 · 237 citations - Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus. Comparison between different assays for the detection of antiphospholipid antibodies.
1996 · Thromb Haemost · RCR 9 · 241 citations - Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review.
2014 · Thromb Haemost · RCR 8 · 198 citations - Association of autoantibodies against the phosphatidylserine-prothrombin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant.
2000 · Arthritis Rheum · RCR 7.4 · 238 citations
Show 20 more of 293 total
- Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events.
2012 · Arthritis Rheum · RCR 7.3 · 201 citations - Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulants.
1995 · Thromb Haemost · RCR 7.3 · 191 citations - Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies.
1996 · Thromb Haemost · RCR 5.1 · 131 citations - Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies.
1997 · Thromb Haemost · RCR 5 · 137 citations - Relationship of anti beta2-glycoprotein I and anti prothrombin antibodies to thrombosis and pregnancy loss in patients with antiphospholipid antibodies.
1997 · Thromb Haemost · RCR 4.6 · 122 citations - Lupus anticoagulants and the risk of a first episode of deep venous thrombosis.
2005 · J Thromb Haemost · RCR 4.5 · 154 citations - Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome.
1999 · Blood · RCR 4.3 · 136 citations - Abnormal prothrombin crossed-immunoelectrophoresis in patients with lupus inhibitors.
1984 · Blood · RCR 3.9 · 88 citations - COVID-19 and Antiphospholipid Antibodies: Time for a Reality Check?
2022 · Semin Thromb Hemost · RCR 3.7 · 42 citations - Lupus anticoagulant and antiprothrombin antibodies: embracing the future.
2025 · J Thromb Haemost · RCR 3.6 · 9 citations - A nomogram and risk stratification to predict subsequent pregnancy loss in patients with recurrent pregnancy loss.
2024 · Hum Reprod · RCR 3.4 · 13 citations - Antibodies to high-density lipoprotein and beta2-glycoprotein I are inversely correlated with paraoxonase activity in systemic lupus erythematosus and primary antiphospholipid syndrome.
2002 · Arthritis Rheum · RCR 3.4 · 149 citations - Differential effects of anti-beta2-glycoprotein I and antiprothrombin antibodies on the anticoagulant activity of activated protein C.
1998 · Blood · RCR 3.3 · 103 citations - Antiprothrombin antibodies detected in two different assay systems. Prevalence and clinical significance in systemic lupus erythematosus.
2005 · Thromb Haemost · RCR 3.2 · 101 citations - Association between the prevalence of antibodies to beta(2)-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications.
2001 · Clin Chem · RCR 3.1 · 107 citations - Lupus anticoagulant testing in Europe: an analysis of results from the first European Concerted Action on Thrombophilia (ECAT) survey using plasmas spiked with monoclonal antibodies against human beta2-glycoprotein I.
1999 · Thromb Haemost · RCR 3.1 · 82 citations - Lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature.
2015 · Lupus · RCR 3.1 · 60 citations - Mechanism and effects of the binding of lupus anticoagulant IgG and prothrombin to surface phospholipid.
1996 · Blood · RCR 3 · 81 citations - Antibodies to phospholipid-binding plasma proteins and occurrence of thrombosis in patients with systemic lupus erythematosus.
1996 · Clin Immunol Immunopathol · RCR 2.9 · 79 citations - Prevalence of hepatitis C virus infection in patients with antiphospholipid syndrome.
1999 · J Hepatol · RCR 2.7 · 80 citations
Reference: B cellIEDB
1 publication
- Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis.
2020 · Arthritis Rheumatol · RCR 1.7 · 30 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.54
- gnomAD pLI
- 0
- gnomAD missense Z
- 2.11
- DepMap mean gene effect
- -0.17
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- acute-phase response
- antimicrobial humoral immune response mediated by antimicrobial peptide
- blood coagulation
- blood coagulation, fibrin clot formation
- cell surface receptor signaling pathway
- cytolysis by host of symbiont cells
- fibrinolysis
- ligand-gated ion channel signaling pathway
- negative regulation of astrocyte differentiation
- negative regulation of blood coagulation
- 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
- 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 insulin secretion
- positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway
- positive regulation of protein localization to nucleus
- 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
- proteolysis
- regulation of blood coagulation
- regulation of cell shape
- regulation of cytosolic calcium ion concentration
- response to wounding
- thrombin-activated receptor signaling pathway
Molecular functions
- calcium ion binding
- growth factor activity
- heparin binding
- lipopolysaccharide binding
- receptor ligand activity
- serine-type endopeptidase activity
- signaling receptor binding
- thrombospondin receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Kringle
- Gamma-carboxyglutamic acid-rich (GLA) domain
- Serine proteases, trypsin domain
- Peptidase S1A, chymotrypsin family
- Peptidase S1, PA clan
- Kringle-like fold
- Kringle, conserved site
- Serine proteases, trypsin family, histidine active site
- Serine proteases, trypsin family, serine active site
- Gamma-carboxyglutamic acid-rich (GLA) domain superfamily
- Kringle superfamily
- Serine Protease S1 Domain-Containing Protein
- Kringle domain
- Trypsin
- Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain
- Prothrombin/thrombin
- Thrombin light chain
- Thrombin light chain domain superfamily
- Thrombin light chain
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads F2 as an antibody target. Whether an autoantibody or antibody against F2 could matter depends on whether native F2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
F2 is annotated as secreted, so native F2 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label F2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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