Affinage

F2

Prothrombin · UniProt P00734

Round 2 corrected
Length
622 aa
Mass
70.0 kDa
Annotated
2026-04-28
130 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Prothrombin (F2) is a serine protease zymogen that, upon cleavage to thrombin, serves as the central effector of the coagulation cascade and a multifunctional signaling protease whose substrate specificity is modulated by cofactors and whose concentration at gelation governs fibrin clot architecture. Thrombin's crystal structure reveals a trypsin-like fold with unique insertions—including the 60-loop that restricts the active-site cleft—and an anion-binding fibrinogen-recognition exosite critical for substrate and inhibitor engagement (PMID:2583108, PMID:2374926, PMID:8102368). Thrombin activates platelets and other cells through proteolytic unmasking of tethered-ligand receptors PAR1, PAR3, and PAR4, and amplifies its own generation via a Factor XI feedback loop (PMID:1672265, PMID:9087410, PMID:9618465, PMID:1652157). The thrombin–thrombomodulin complex redirects substrate specificity from procoagulant targets to protein C activation (anticoagulant) and TAFI activation (antifibrinolytic), while thrombin concentration at the point of gelation directly determines fibrin fiber thickness and fibrinolytic susceptibility (PMID:2538457, PMID:8663147, PMID:17208341).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1989 High

    Determination of the 1.9 Å crystal structure of alpha-thrombin established the structural basis for its restricted substrate specificity and identified the fibrinogen-recognition exosite, answering how thrombin achieves selectivity despite its trypsin-like fold.

    Evidence X-ray crystallography of human alpha-thrombin complexed with D-Phe-Pro-Arg chloromethylketone at 1.92 Å resolution

    PMID:2583108

    Open questions at the time
    • Structural basis for cofactor-induced substrate switching (e.g., by thrombomodulin) not resolved
    • No structure of prothrombin zymogen to understand activation conformational changes
  2. 1989 High

    Demonstration that thrombomodulin redirects thrombin from procoagulant substrates to protein C activation established the cofactor-dependent switch between procoagulant and anticoagulant functions of thrombin.

    Evidence In vitro enzyme kinetics and endothelial cell surface binding assays measuring protein C activation ± thrombomodulin

    PMID:2538457

    Open questions at the time
    • Structural mechanism by which thrombomodulin alters thrombin's active-site specificity was unknown
    • Relative contribution of the thrombomodulin pathway in vivo not quantified
  3. 1990 High

    The hirudin–thrombin co-crystal structure mapped the molecular determinants of ultra-high-affinity inhibition, revealing that the fibrinogen-recognition exosite serves as a general substrate/inhibitor docking platform distinct from the catalytic cleft.

    Evidence X-ray crystallography of recombinant hirudin–thrombin complex at 2.3 Å resolution

    PMID:2374926

    Open questions at the time
    • Whether endogenous serpins exploit the same exosite for initial docking was unresolved
    • Dynamics of exosite engagement in solution not captured
  4. 1991 High

    Cloning of PAR1 and the discovery of the tethered-ligand mechanism revealed how thrombin converts a proteolytic event into transmembrane signaling, establishing the paradigm for protease-activated receptor biology.

    Evidence Expression cloning in Xenopus oocytes, cleavage-site mutagenesis, and synthetic tethered-ligand peptide agonist assays

    PMID:1672265

    Open questions at the time
    • Existence of additional thrombin receptor subtypes not yet known
    • Downstream G-protein coupling specificity of PAR1 not fully characterized
  5. 1991 High

    Demonstration that thrombin directly activates Factor XI more efficiently than Factor XIIa established a positive feedback loop through which thrombin amplifies its own generation independently of the contact pathway.

    Evidence In vitro kinetic comparison of thrombin vs. Factor XIIa activation of Factor XI with purified components

    PMID:1652157

    Open questions at the time
    • Physiologic surface cofactors for thrombin-mediated Factor XI activation in vivo not identified
    • Relative contribution of this feedback loop versus the intrinsic pathway in different vascular beds unclear
  6. 1993 High

    The thrombin–DNA aptamer co-crystal structure confirmed the fibrinogen-recognition exosite as a druggable surface and revealed an unexpected G-quartet binding mode, providing a structural template for exosite-targeted inhibitor design.

    Evidence X-ray crystallography at 2.9 Å with Arg75→Glu mutagenesis confirming functional exosite engagement

    PMID:8102368

    Open questions at the time
    • Whether aptamer binding fully occludes all exosite-dependent substrates was not tested
    • In vivo pharmacology of aptamer-mediated thrombin inhibition not assessed
  7. 1996 High

    Kinetic characterization of TAFI activation revealed that the thrombin–thrombomodulin complex is the physiologic activator (1250-fold efficiency increase), establishing a direct mechanistic link between thrombin generation and downregulation of fibrinolysis.

    Evidence Quantitative enzyme kinetics with purified thrombin, thrombomodulin, and TAFI; fibrinolysis inhibition assays

    PMID:8663147

    Open questions at the time
    • Crystal structure of the ternary thrombin–thrombomodulin–TAFI complex not determined
    • Regulation of TAFI activation under flow conditions in vivo not addressed
  8. 1997 High

    Cloning of PAR3 as a second thrombin receptor extended the tethered-ligand paradigm to multiple receptor subtypes, indicating tissue-specific thrombin signaling.

    Evidence Molecular cloning, heterologous expression, phosphoinositide hydrolysis assays, and PAR1 knockout mouse studies

    PMID:9087410

    Open questions at the time
    • Whether PAR3 functions as a signaling receptor or a cofactor for PAR4 in human platelets not resolved
    • PAR3 downstream signaling pathways incompletely characterized
  9. 1998 High

    Cloning and functional validation of PAR4 completed the inventory of thrombin-activated PARs, demonstrating a third receptor through which thrombin triggers G-protein-coupled signaling via tethered-ligand unmasking.

    Evidence cDNA cloning, COS cell expression, R47A mutagenesis abolishing thrombin response, synthetic GYPGQV peptide agonist

    PMID:9618465

    Open questions at the time
    • Relative contributions of PAR1 vs. PAR4 to human platelet activation kinetics not quantified
    • Structural basis for differential thrombin affinity across PAR subtypes unknown
  10. 2007 Medium

    Establishing that thrombin concentration at the gelation point determines fibrin fiber diameter and fibrinolytic susceptibility linked thrombin generation dynamics directly to clot mechanical and lytic properties.

    Evidence In vitro fibrin clot formation with defined thrombin concentrations, turbidimetry, and fibrinolysis assays (review synthesizing multiple studies)

    PMID:17208341

    Open questions at the time
    • Molecular mechanism by which thrombin concentration controls lateral fibrin protofibril association not defined
    • In vivo validation of concentration-dependent clot architecture under physiologic flow not performed
    • Role of other coagulation factors in modulating this relationship not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the thrombomodulin-induced substrate specificity switch at atomic resolution, the contribution of prothrombin's kringle domains to its zymogen activation mechanism, and the relative signaling outputs of PAR1/PAR3/PAR4 in specific human vascular beds.
  • No high-resolution structure of full-length prothrombin zymogen on a membrane surface
  • Integrated quantitative model of thrombin's substrate hierarchy in vivo lacking
  • PAR subtype-specific signaling in human vascular endothelium not systematically compared

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016787 hydrolase activity 5 GO:0048018 receptor ligand activity 3
Localization
GO:0005576 extracellular region 5
Pathway
R-HSA-109582 Hemostasis 6 R-HSA-162582 Signal Transduction 3
Partners
CPB2F11F2RF2RL2F2RL3FGAPROCTHBD
Complex memberships
Prothrombinase complex (Factor Xa/Va)Thrombin–thrombomodulin complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 X-ray crystal structure of human alpha-thrombin (at 1.9 Å resolution) complexed with D-Phe-Pro-Arg chloromethylketone revealed the characteristic trypsin-like fold with unique insertions: the Tyr60A-Pro60B-Pro60C-Trp60D loop restricts the active site cleft and explains poor binding of most natural proteinase inhibitors; a narrow active site cleft with hydrophobic cage (Ile174, Trp215, Leu99, His57, Tyr60A, Trp60D) accounts for specificity toward Arg-containing substrates; the Lys70-Glu80 loop forms part of the anionic fibrinogen-recognition exosite. X-ray crystallography at 1.92 Å resolution with Patterson search refinement (R = 0.171) The EMBO journal High 2583108
1989 Thrombin activates Protein C in a reaction dramatically enhanced by thrombomodulin on endothelial cell surfaces; the thrombin-thrombomodulin complex shifts thrombin's substrate specificity from procoagulant substrates (fibrinogen, platelets) to the anticoagulant protein C, establishing thrombomodulin as a cofactor that redirects thrombin activity. In vitro enzyme kinetics, endothelial cell surface binding assays, functional coagulation assays The Journal of biological chemistry High 2538457
1990 Crystal structure of the recombinant hirudin-thrombin complex at 2.3 Å resolution showed that hirudin's NH2-terminal globular domain forms a parallel β-strand with thrombin residues Ser214–Glu217 near the active site (without occupying the specificity pocket), while the COOH-terminal extended domain makes extensive electrostatic interactions with thrombin's fibrinogen-recognition exosite (anion-binding exosite); 27 of 65 hirudin residues contact thrombin (10 ion pairs, 23 hydrogen bonds), explaining the extremely high affinity and specificity of this inhibitor. X-ray crystallography at 2.3 Å resolution Science High 2374926
1991 Molecular cloning of a functional human thrombin receptor (PAR1) by expression cloning in Xenopus oocytes revealed a novel proteolytic activation mechanism: thrombin cleaves the receptor's extracellular amino-terminal extension at LDPR/S (position R41), generating a new receptor amino terminus that functions as a tethered ligand to activate the receptor intramolecularly. A peptide mimicking this new amino terminus was a potent agonist for receptor and platelet activation, while uncleavable mutant receptors failed to respond to thrombin but remained responsive to the tethered-ligand peptide. cDNA expression cloning in Xenopus oocytes, site-directed mutagenesis of cleavage site, synthetic peptide agonist assays, platelet activation assays Cell High 1672265
1991 In a revised model of blood coagulation, thrombin (F2 product) activates Factor XI directly without requiring Factor XIIa; in the absence of cofactors, thrombin is more effective than Factor XIIa (kcat/Km = 1.6×10⁵ vs. 1.7×10⁴). Dextran sulfate enhances Factor XI activation by thrombin ~2000-fold, partly through autoactivation by Factor XIa. This establishes a feedback loop in which thrombin amplifies its own generation by activating Factor XI. In vitro enzyme kinetics with purified factors, comparison of Factor XIIa and thrombin activation efficiencies, cofactor enhancement assays Science High 1652157
1993 Crystal structure of human alpha-thrombin complexed with a 15-mer single-stranded DNA aptamer (GGTTGGTGTGGTTGG) at 2.9 Å resolution showed the DNA folds into a G-quartet structure and binds to the fibrinogen-recognition exosite of thrombin through ionic and hydrophobic interactions; the heparin-binding site of a symmetry-related molecule also contacts the DNA. Mutational analysis (Arg75→Glu) confirmed the fibrinogen exosite as the functionally relevant binding site, consistent with inhibition of fibrinogen clotting and platelet activation. X-ray crystallography at 2.9 Å resolution, site-directed mutagenesis (Arg75→Glu), functional platelet activation and fibrinogen clotting assays The Journal of biological chemistry High 8102368
1996 TAFI (thrombin-activatable fibrinolysis inhibitor/plasma procarboxypeptidase B) is activated by thrombin-catalyzed proteolysis, but the thrombin-thrombomodulin complex is the physiologic activator. Thrombomodulin increases catalytic efficiency 1250-fold, primarily through increased kcat. Kinetic modeling defined a ternary thrombin-thrombomodulin-TAFI complex (Km for TAFI = 1.0 µM; Kd for thrombomodulin = 8.6 nM; kcat = 1.2 s⁻¹). Activated TAFI inhibits tPA-induced fibrinolysis at ~1 nM, establishing that thrombin (via thrombomodulin) directly down-regulates fibrinolysis through TAFI activation. In vitro enzyme kinetics with purified components, Km/Kd/kcat determination, fibrinolysis inhibition assays The Journal of biological chemistry High 8663147
1997 Cloning and characterization of protease-activated receptor 3 (PAR3) as a second human thrombin receptor. PAR3 mediates thrombin-triggered phosphoinositide hydrolysis and is expressed in human bone marrow and mouse megakaryocytes. The receptor uses the same proteolytic tethered-ligand activation mechanism as PAR1, demonstrating that thrombin can signal through multiple receptor subtypes in a tissue-specific manner. Molecular cloning, expression in heterologous cells, phosphoinositide hydrolysis assay, Northern blot, PAR1 knockout mouse studies Nature High 9087410
1998 Cloning of protease-activated receptor 4 (PAR4), a fourth member of the PAR family activated by thrombin and trypsin. Thrombin cleaves PAR4 at Arg-47/Gly-48 to generate a tethered ligand; the R47A mutant abolished thrombin/trypsin responses but retained responsiveness to the tethered-ligand hexapeptide GYPGQV. COS cells transfected with PAR4 produced inositol triphosphate upon thrombin stimulation, confirming G-protein coupling. cDNA cloning from lymphoma library, heterologous expression in COS cells, inositol triphosphate assay, site-directed mutagenesis (R47A), synthetic peptide agonist assays, Northern blot Proceedings of the National Academy of Sciences of the United States of America High 9618465
2007 The rate and extent of thrombin generation profoundly determines fibrin clot structure: low thrombin concentrations produce thick fibrin fibers that are highly susceptible to fibrinolysis, while high thrombin concentrations produce thin fibers that are resistant to fibrinolysis. Abnormal patterns of thrombin generation produce clots with altered fibrin structure associated with increased bleeding or thrombosis risk, demonstrating that F2/thrombin concentration at gelation is a key determinant of clot mechanical properties and fibrinolytic susceptibility. In vitro fibrin clot formation assays with defined purified thrombin concentrations, turbidimetric fiber thickness measurement, fibrinolysis susceptibility assays Blood reviews Medium 17208341

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2873 20686565
1991 Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 2832 1672265
1996 A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 2518 8916933
2013 Discovery and refinement of loci associated with lipid levels. Nature genetics 2409 24097068
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2002 Cellular actions of the insulin-like growth factor binding proteins. Endocrine reviews 1450 12466191
1999 Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nature genetics 1381 10391209
1989 The roles of protein C and thrombomodulin in the regulation of blood coagulation. The Journal of biological chemistry 927 2538457
1989 The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. The EMBO journal 876 2583108
1997 Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 761 9087410
1998 Cloning and characterization of human protease-activated receptor 4. Proceedings of the National Academy of Sciences of the United States of America 712 9618465
1990 The structure of a complex of recombinant hirudin and human alpha-thrombin. Science (New York, N.Y.) 710 2374926
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2005 PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell 664 15707890
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1991 Factor XI activation in a revised model of blood coagulation. Science (New York, N.Y.) 656 1652157
2008 Genome-scale RNAi screen for host factors required for HIV replication. Cell host & microbe 627 18976975
2009 Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 606 19362088
1995 Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 572 7566121
2007 Thrombin generation and fibrin clot structure. Blood reviews 555 17208341
1996 TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex. The Journal of biological chemistry 537 8663147
1987 Isolation of the thrombospondin membrane receptor. The Journal of clinical investigation 515 2435757
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2010 Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation 389 20351233
2003 The dynamics of thrombin formation. Arteriosclerosis, thrombosis, and vascular biology 387 12524220
1993 The structure of alpha-thrombin inhibited by a 15-mer single-stranded DNA aptamer. The Journal of biological chemistry 377 8102368
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
1994 The mechanism of inactivation of human factor V and human factor Va by activated protein C. The Journal of biological chemistry 347 7989361
2007 What is an epigenetic transgenerational phenotype? F3 or F2. Reproductive toxicology (Elmsford, N.Y.) 345 17949945
2006 Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice. Journal of virology 249 16873254
2014 Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity. Nature communications 197 25140902
2001 Elevated plasma F2-isoprostanes in patients on long-term hemodialysis. Kidney international 187 11318969
2020 Influenza A virus protein PB1-F2 impairs innate immunity by inducing mitophagy. Autophagy 158 32013669
2006 The sorry state of F2 hybrids: consequences of rapid mitochondrial DNA evolution in allopatric populations. The American naturalist 156 17109325
2010 PB1-F2 proteins from H5N1 and 20 century pandemic influenza viruses cause immunopathology. PLoS pathogens 136 20661425
1984 Regional distribution of prostaglandins D2, E2, and F2 alpha and related enzymes in postmortem human brain. Journal of neurochemistry 136 6427411
2007 Prevalence of PB1-F2 of influenza A viruses. The Journal of general virology 124 17251572
1977 Levels of prostaglandins F2 alpha and E2 and thromboxane B2 in joint fluid in rheumatoid arthritis. Scandinavian journal of rheumatology 120 929121
2003 Prostaglandin F2(alpha) stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway. The Journal of cell biology 119 12695501
2002 Identification of Drosophila melanogaster yellow-f and yellow-f2 proteins as dopachrome-conversion enzymes. The Biochemical journal 114 12164780
2004 Plasma F2-isoprostanes and coronary artery calcification: the CARDIA Study. Clinical chemistry 108 15514100
1996 Protein F2, a novel fibronectin-binding protein from Streptococcus pyogenes, possesses two binding domains. Molecular microbiology 98 8858591
1966 Replication of the RNA of Bacteriophage f2. Science (New York, N.Y.) 91 17775172
2012 Investigations on transgenerational epigenetic response down the male line in F2 pigs. PloS one 86 22359544
2004 Plasma F2-isoprostanes are elevated in newborns and inversely correlated to gestational age. Free radical biology & medicine 86 15288129
1999 AL-8810: a novel prostaglandin F2 alpha analog with selective antagonist effects at the prostaglandin F2 alpha (FP) receptor. The Journal of pharmacology and experimental therapeutics 82 10454504
2010 Differential localization and function of PB1-F2 derived from different strains of influenza A virus. Journal of virology 75 20660199
2010 Current knowledge on PB1-F2 of influenza A viruses. Medical microbiology and immunology 75 20953627
1993 Effects and interactions of prostaglandin F2 alpha, oxytocin, and cytokines on steroidogenesis of porcine luteal cells. Endocrinology 75 8425493
1999 Elevated plasma levels of F2 alpha isoprostane in cystic fibrosis. Lipids 73 10405967
1997 Evidence for the distinct nature of F2-isoprostane receptors from those of thromboxane A2. The American journal of physiology 71 9140048
2001 The hairpin structure of the (6)F1(1)F2(2)F2 fragment from human fibronectin enhances gelatin binding. The EMBO journal 69 11285216
1995 Control of endometrial oxytocin receptors and prostaglandin F2 alpha production in cows by progesterone and oestradiol. Journal of reproduction and fertility 66 7707303
2011 The influenza virus PB1-F2 protein has interferon antagonistic activity. Biological chemistry 65 22050228
2007 The PB1-F2 protein of Influenza A virus: increasing pathogenicity by disrupting alveolar macrophages. Virology journal 62 17224071
2011 Effect of 1918 PB1-F2 expression on influenza A virus infection kinetics. PLoS computational biology 61 21379324
2018 Forkhead Box F2 Suppresses Gastric Cancer through a Novel FOXF2-IRF2BPL-β-Catenin Signaling Axis. Cancer research 59 29374064
2019 Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice. The Journal of physiology 57 31617219
2006 Structural characterization and oligomerization of PB1-F2, a proapoptotic influenza A virus protein. The Journal of biological chemistry 57 17052982
2017 Adapting Genotyping-by-Sequencing for Rice F2 Populations. G3 (Bethesda, Md.) 56 28082325
2007 Influenza A virus PB1-F2: a small protein with a big punch. Cell host & microbe 55 18005736
2017 Evolution and Virulence of Influenza A Virus Protein PB1-F2. International journal of molecular sciences 53 29286299
2008 Endothelin-1 and F2-isoprostane relate to and predict renal dysfunction in hypertensive patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 53 18772174
1983 Topography of human uterine prostaglandin E and F2 alpha receptors and their profiles during pathological states. The Journal of clinical endocrinology and metabolism 52 6134747
2018 Antibacterial efficacy of a fucoidan fraction (Fu-F2) extracted from Sargassum polycystum. International journal of biological macromolecules 50 30529554
2012 Enzymatic Biotransformation of Ginsenoside Rb1 and Gypenoside XVII into Ginsenosides Rd and F2 by Recombinant β-glucosidase from Flavobacterium johnsoniae. Journal of ginseng research 49 23717145
1971 Structure of the poly(G) polymerase component of the bacteriophage f2 replicase. Proceedings of the National Academy of Sciences of the United States of America 49 5288771
2010 Effect of prostaglandin F2 alpha on local luteotropic and angiogenic factors during induced functional luteolysis in the bovine corpus luteum. Biology of reproduction 45 20056670
1993 Prostaglandin F2 alpha receptor concentrations in corpora lutea of cycling, pregnant, and pseudopregnant pigs. Biology of reproduction 44 8399855
1993 Prostaglandin F2 alpha activates protein kinase C in human ovarian cells. Molecular and cellular endocrinology 43 8472854
2010 Prostaglandin F2α stimulates PI3K/ERK/mTOR signaling and skeletal myotube hypertrophy. American journal of physiology. Cell physiology 42 21191105
2008 Two pathways for prostaglandin F2 alpha synthesis by the primate periovulatory follicle. Reproduction (Cambridge, England) 42 18390687
2016 Ectoine and 5-hydroxyectoine accumulation in the halophile Virgibacillus halodenitrificans PDB-F2 in response to salt stress. Applied microbiology and biotechnology 40 27106915
2015 Hypoglycemic effects of Grifola frondosa (Maitake) polysaccharides F2 and F3 through improvement of insulin resistance in diabetic rats. Food & function 40 26311233
1985 Prostaglandin F2 alpha in benign and malignant breast tumours. British journal of cancer 39 3859318
1990 Control of bovine uterine prostaglandin F2 alpha release in vitro. Biology of reproduction 38 2159809
2010 Identification of genes and networks driving cardiovascular and metabolic phenotypes in a mouse F2 intercross. PloS one 37 21179467
2010 Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice. BMC genomics 35 21167066
2021 Ginsenoside F2 Suppresses Adipogenesis in 3T3-L1 Cells and Obesity in Mice via the AMPK Pathway. Journal of agricultural and food chemistry 33 34342980
2015 Transgenerational effects of obesity and malnourishment on diabetes risk in F2 generation. Molecular and cellular biochemistry 33 26708218
2005 Mapping and exclusion mapping of genomic imprinting effects in mouse F2 families. The Journal of heredity 33 15761081
1969 The metabolism of 2-furoic acid by Pseudomanas F2. The Biochemical journal 33 4318274
2011 The influenza A virus protein PB1-F2: killing two birds with one stone? Virulence 32 21971186
1993 Intermodulation distortion (F2-F1) in inner hair cell and basilar membrane responses. The Journal of the Acoustical Society of America 32 8473618
2017 Influenza virus protein PB1-F2 interacts with CALCOCO2 (NDP52) to modulate innate immune response. The Journal of general virology 31 28613140
2014 Pregestational maternal obesity impairs endocrine pancreas in male F1 and F2 progeny. Nutrition (Burbank, Los Angeles County, Calif.) 31 25441581
2013 The influenza virus protein PB1-F2 interacts with IKKβ and modulates NF-κB signalling. PloS one 30 23704945
1987 Prostaglandin F2 alpha and oxytocin interactions in ovarian and uterine function. Journal of steroid biochemistry 30 2826898
2008 Electron cryomicroscopy reveals different F1+F2 protein States in intact parainfluenza virions. Journal of virology 29 18216117
1989 Prostaglandins E2 and F2 alpha affect glycogen synthase and phosphorylase in isolated hepatocytes. The Biochemical journal 29 2505758
1980 Hormone receptor control of prostaglandin F2 alpha secretion by the ovine uterus. Advances in prostaglandin and thromboxane research 29 6246781
2002 Ca2+-mediated activation of ERK in hepatocytes by norepinephrine and prostaglandin F2 alpha: role of calmodulin and Src kinases. BMC cell biology 28 11914123
1996 Negative regulatory activity of a prostaglandin F2 alpha receptor associated protein (FPRP). Prostaglandins, leukotrienes, and essential fatty acids 27 8804121
2014 Electrochemical detection of the oligomerization of PB1-F2 influenza A virus protein in infected cells. Analytical chemistry 26 25051456
1990 Comparison of oxytocin/prostaglandin F-2 alpha interrelationships in cyclic and pregnant cows. Journal of reproduction and fertility 26 2172533
2023 A large-scale transcriptional analysis reveals herb-derived ginsenoside F2 suppressing hepatocellular carcinoma via inhibiting STAT3. Phytomedicine : international journal of phytotherapy and phytopharmacology 25 37666060
2006 Brassica vegetable consumption reduces urinary F2-isoprostane levels independent of micronutrient intake. Carcinogenesis 25 16704986
1968 The effects of prostaglandins E1, F1-alpha and F2-alpha on monosynaptic reflexes. The Journal of physiology 25 5659846
2020 Influenza A virus PB1-F2 protein: An ambivalent innate immune modulator and virulence factor. Journal of leukocyte biology 24 32323899
2015 Production of Ginsenoside F2 by Using Lactococcus lactis with Enhanced Expression of β-Glucosidase Gene from Paenibacillus mucilaginosus. Journal of agricultural and food chemistry 24 26494255
2014 Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro. International journal of oncology 24 25385044
2005 Classifying genotype F of hepatitis B virus into F1 and F2 subtypes. World journal of gastroenterology 24 16419158
1971 Inhibition of replication of ribonucleic acid bacteriophage f2 by superinfection with bacteriophage T4. Journal of virology 24 4943076
2020 Maternal Bisphenol S exposure affects the reproductive capacity of F1 and F2 offspring in mice. Environmental pollution (Barking, Essex : 1987) 23 32866863
2017 Glutathione Peroxidase Activity, Plasma Total Antioxidant Capacity, and Urinary F2- Isoprostanes as Markers of Oxidative Stress in Anemic Dogs. Journal of veterinary internal medicine 23 29031029
2015 Schizophrenia-Like Phenotype Inherited by the F2 Generation of a Gestational Disruption Model of Schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 23 26068729
2008 Prostaglandin F2-alpha receptor regulation in human uterine myocytes. Molecular human reproduction 23 18337234
2009 Antibodies to PB1-F2 protein are induced in response to influenza A virus infection. Archives of virology 22 19672555
2004 Influenza A virus PB1-F2 gene in recent Taiwanese isolates. Emerging infectious diseases 22 15200852
2002 The effect of estrogen receptor genotype on litter size and placental traits at term in F2 crossbred gilts. Theriogenology 22 12035975
1990 Inner hair cell responses to the 2f1-f2 intermodulation distortion product. The Journal of the Acoustical Society of America 22 2307775
1989 Conception rates and calving intervals after prostaglandin F2 alpha or prebreeding progesterone in dairy cows. Journal of dairy science 22 2925947
2021 The heme-binding protein PhuS transcriptionally regulates the Pseudomonas aeruginosa tandem sRNA prrF1,F2 locus. The Journal of biological chemistry 21 33428928
1986 Associations between quantitative traits and enzyme loci in the F2 population of a maize hybrid. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 21 24247765
1995 Prostaglandin F2 alpha mediates ovarian sterol carrier protein-2 expression during luteolysis. Endocrinology 20 7588230
2011 BID-F1 and BID-F2 domains of Bartonella henselae effector protein BepF trigger together with BepC the formation of invasome structures. PloS one 19 22043280
1997 Localization of the prostaglandin F2 alpha receptor in rat tissues. Prostaglandins, leukotrienes, and essential fatty acids 19 9431817
1968 Cell Lysis: Another Function of the Coat Protein of the Bacteriophage f2. Science (New York, N.Y.) 19 17737475
2013 PB1-F2 expedition from the whole protein through the domain to aa residue function. Acta virologica 18 23600872
1995 Prostaglandin F2 alpha stimulates transforming growth factor-alpha expression in adipocyte precursors. Endocrinology 18 7628355
1993 Divergent actions of prostaglandins-E2 and -F2 alpha on the regulation of insulin-like growth factor-binding protein-3 in luteinized granulosa cells. Endocrinology 18 7679982
2022 Ammonium and hydroxylamine can be preferentially removed during simultaneous nitrification and denitrification by Pseudomonas taiwanensis EN-F2. Bioresource technology 17 35231598
2018 Loading of doxorubicin and thymoquinone with F2 gel nanofibers improves the antitumor activity and ameliorates doxorubicin-associated nephrotoxicity. Life sciences 17 29885348
2021 Evidence for the metal resistance of earthworm Eisenia fetida across generations (F1 and F2) under laboratory metal exposure. Journal of hazardous materials 16 34896725
2020 Influenza PB1-F2 Inhibits Avian MAVS Signaling. Viruses 16 32272772
2017 Characterization of VdASP F2 Secretory Factor from Verticillium dahliae by a Fast and Easy Gene Knockout System. Molecular plant-microbe interactions : MPMI 16 28291379
2011 Functional polymorphisms of the coagulation factor II gene (F2) and susceptibility to systemic lupus erythematosus. The Journal of rheumatology 16 21239755
2003 Inheritance of Oryza sativa endornavirus in F1 and F2 hybrids between japonica and indica rice. Genes & genetic systems 16 12893964