Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases
Open accessAbstract
The response to hypoxia in animals involves the expression of multiple genes regulated by the αβ-hypoxia-inducible transcription factors (HIFs). The hypoxia-sensing mechanism involves oxygen limited hydroxylation of prolyl residues in the N- and C-terminal oxygen-dependent degradation domains (NODD and CODD) of HIFα isoforms, as catalysed by prolyl hydroxylases (PHD 1–3). Prolyl hydroxylation promotes binding of HIFα to the von Hippel–Lindau protein (VHL)–elongin B/C complex, thus signalling for proteosomal degradation of HIFα. We reveal that certain PHD2 variants linked to familial erythrocytosis and cancer are highly selective for CODD or NODD. Crystalline and solution state studies coupled to kinetic and cellular analyses reveal how wild-type and variant PHDs achieve ODD selectivity via different dynamic interactions involving loop and C-terminal regions. The results inform on how HIF target gene selectivity is achieved and will be of use in developing selective PHD inhibitors.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Prolyl hydroxylation promotes HIF-α binding to the VHL complex, resulting in degradation of HIF proteins.
“Prolyl hydroxylation promotes HIF‐α binding to the VHL complex, resulting in chromosomal degradation of HIF proteins.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [167]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Comparison of simple potential functions for simulating liquid water
Jorgensen, W. L., Chandrasekhar, J., Madura, J., Impey, R., & Klein, M. (1983) · The Journal of Chemical Physics · doi:10.1063/1.445869 · Cited by 38,335 · see citing works
<i>Coot</i> : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
<i>PHENIX</i> : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716 · see citing works
A smooth particle mesh Ewald method
Essmann, U., Perera, L., Berkowitz, M., Darden, T., Lee, H.-C., & Pedersen, L. (1995) · The Journal of Chemical Physics · doi:10.1063/1.470117 · Cited by 21,329 · see citing works
<i>Phaser</i> crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612 · see citing works
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,720 · see citing works
All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins
MacKerell, A. D., Bashford, D., Bellott, M., Dunbrack, R. L., Evanseck, J. D., Field, M. J., Fischer, S., Gao, J., Guo, H., Ha, S., et al. (1998) · The Journal of Physical Chemistry B · doi:10.1021/jp973084f · Cited by 14,270 · see citing works
<i>MolProbity</i> : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115 · see citing works
Comparative Protein Modelling by Satisfaction of Spatial Restraints
Šali, A., & Blundell, T. L. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1626 · Cited by 12,977 · see citing works
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkòczi, G., Chen, V. B., Davis, I., Echols, N., Headd, J. J., Hung, L., Kapral, G. J., Grosse‐Kunstleve, R. W., et al. (2012) · International Tables for Crystallography · doi:10.1107/97809553602060000865 · Cited by 7,334 · see citing works
Constant pressure molecular dynamics algorithms
Martyna, G. J., Tobias, D. J., & Klein, M. L. (1994) · The Journal of Chemical Physics · doi:10.1063/1.467468 · Cited by 5,845 · see citing works
Constant pressure molecular dynamics simulation: The Langevin piston method
Feller, S., Zhang, Y., Pastor, R., & Brooks, B. (1995) · The Journal of Chemical Physics · doi:10.1063/1.470648 · Cited by 4,267 · see citing works
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333 · see citing works
Self-citationOxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Kaelin, W. G., & Ratcliffe, P. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.009 · Cited by 3,251 · see citing works
Self-citationA conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, R. K., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1066373 · Cited by 2,549 · see citing works
NAMD2: Greater Scalability for Parallel Molecular Dynamics
Kalé, L. V., Skeel, R. D., Bhandarkar, M. A., Brunner, R., Gürsoy, A., Krawetz, N., Phillips, J., Shinozaki, A., Varadarajan, K., & Schulten, K. J. (1999) · Journal of Computational Physics · doi:10.1006/jcph.1999.6201 · Cited by 2,428 · see citing works
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068 · see citing works
Self-citationBerra, E., Benizri, E., Ginouvès, A., Volmat, V., Roux, D., & Pouysségur, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg392 · Cited by 1,348 · see citing works
The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website
Bamford, S., Dawson, E., Forbes, S. A., Clements, J., Pettett, R., Doǧan, A., Flanagan, A. M., Teague, J. W., Futreal, P. A., Stratton, M. R., et al. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601894 · Cited by 1,248 · see citing works
Masson, N., Willam, C., Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.18.5197 · Cited by 1,014 · see citing works
Self-citationHydroxylation of HIF-1: Oxygen Sensing at the Molecular Level
Semenza, G. L. (2004) · Physiology · doi:10.1152/physiol.00001.2004 · Cited by 901 · see citing works
Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor
Hirsilä, M., Koivunen, P., Günzler, V., Kivirikko, K. I., & Myllyharju, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304982200 · Cited by 794 · see citing works
Structure of an HIF-1α-pVHL Complex: Hydroxyproline Recognition in Signaling
Min, J.-H., Yang, H., Ivan, M., Gertler, F., Kaelin, W. G., & Pavletich, N. P. (2002) · Science · doi:10.1126/science.1073440 · Cited by 765 · see citing works
Structural basis for the recognition of hydroxyproline in HIF-1α by pVHL
Hon, W.-C., Wilson, M. I., Harlos, K., Claridge, T. D. W., Schofield, C. J., Pugh, C. W., Maxwell, P. H., Ratcliffe, P. J., Stuart, D. I., & Jones, E. Y. (2002) · Nature · doi:10.1038/nature00767 · Cited by 751 · see citing works
Self-citationSmart, O. S., Womack, T. O., Flensburg, C., Keller, P., Paciorek, W., Sharff, A., Vonrhein, C., & Bricogne, G. (2012) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444911056058 · Cited by 612 · see citing works
Adam, J., Hatipoglu, E., O'Flaherty, L., Ternette, N., Sahgal, N., Lockstone, H., Baban, D., Nye, E., Stamp, G. W., Wolhuter, K., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.09.006 · Cited by 585 · see citing works
Self-citationBruick, R. K. (2003) · Genes & Development · doi:10.1101/gad.1145503 · Cited by 435 · see citing works
Takeda, K., Ho, V. C., Takeda, H., Duan, L.-J., Nagy, A., & Fong, G.-H. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00425-06 · Cited by 401 · see citing works
Percy, M. J., Zhao, Q., Flores, A., Harrison, C., Lappin, T. R. J., Maxwell, P. H., McMullin, M. F., & Lee, F. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508423103 · Cited by 330 · see citing works
Huang, J., Zhao, Q., Mooney, S. M., & Lee, F. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206955200 · Cited by 307 · see citing works
Provenzano, R., Besarab, A., Sun, C. H., Diamond, S. A., Durham, J. H., Cangiano, J. L., Aiello, J. R., Novak, J. E., Lee, T. T., Leong, R., et al. (2016) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.06890615 · Cited by 295 · see citing works
Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure
Minamishima, Y. A., Moslehi, J., Bardeesy, N., Cullen, D., Bronson, R. T., & Kaelin, W. G. (2008) · Blood · doi:10.1182/blood-2007-10-117812 · Cited by 294 · see citing works
HIF prolyl hydroxylase inhibitors for the treatment of renal anaemia and beyond
Maxwell, P. H., & Eckardt, K. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.193 · Cited by 286 · see citing works
Regulation of adult erythropoiesis by prolyl hydroxylase domain proteins
Takeda, K., Aguila, H. L., Parikh, N. S., Li, X., Lamothe, K., Duan, L.-J., Takeda, H., Lee, F. S., & Fong, G.-H. (2008) · Blood · doi:10.1182/blood-2007-09-114561 · Cited by 263 · see citing works
Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA
Yang, C., Yi, C., Duguid, E. M., Sullivan, C. T., Jian, X., Rice, P. A., & He, C. (2008) · Nature · doi:10.1038/nature06889 · Cited by 262 · see citing works
Structural Basis for Binding of Hypoxia-Inducible Factor to the Oxygen-Sensing Prolyl Hydroxylases
Chowdhury, R., McDonough, M. A., Mecinović, J., Loenarz, C., Flashman, E., Hewitson, K. S., Domene, C., & Schofield, C. J. (2009) · Structure · doi:10.1016/j.str.2009.06.002 · Cited by 241 · see citing works
Self-citationCoordinate Regulation of the Oxygen-Dependent Degradation Domains of Hypoxia-Inducible Factor 1α
Chan, D. A., Sutphin, P. D., Yen, S., & Giaccia, A. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.15.6415-6426.2005 · Cited by 240 · see citing works
Takeda, K., Cowan, A., & Fong, G.-H. (2007) · Circulation · doi:10.1161/circulationaha.107.701516 · Cited by 236 · see citing works
Loenarz, C., Coleman, M. L., Boleininger, A., Schierwater, B., Holland, P. W. H., Ratcliffe, P. J., & Schofield, C. J. (2010) · EMBO Reports · doi:10.1038/embor.2010.170 · Cited by 235 · see citing works
Self-citationTian, Y., Yeoh, K. K., Lee, M. K., Eriksson, T., Kessler, B. M., Kramer, H., Edelmann, M. J., Willam, C., Pugh, C. W., Schofield, C. J., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.211110 · Cited by 186 · see citing works
Self-citationThe HIF pathway and erythrocytosis
Lee, F. S., & Percy, M. J. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130321 · Cited by 177 · see citing works
Conserved Structure for Single-Stranded Telomeric DNA Recognition
Mitton-Fry, R. M., Anderson, E. M., Hughes, T., Lundblad, V., & Wuttke, D. S. (2002) · Science · doi:10.1126/science.1068799 · Cited by 174 · see citing works
HIF Hydroxylase Pathways in Cardiovascular Physiology and Medicine
Bishop, T., & Ratcliffe, P. J. (2015) · Circulation Research · doi:10.1161/circresaha.117.305109 · Cited by 169 · see citing works
Self-citationA novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove
Percy, M. J., Furlow, P. W., Beer, P. A., Lappin, T. R. J., McMullin, M. F., & Lee, F. S. (2007) · Blood · doi:10.1182/blood-2007-04-084434 · Cited by 155 · see citing works
Emerging novel functions of the oxygen-sensing prolyl hydroxylase domain enzymes
Wong, B. W., Kuchnio, A., Brüning, U., & Carmeliet, P. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.10.004 · Cited by 141 · see citing works
Pharmacological targeting of the HIF hydroxylases – A new field in medicine development
Chan, M. C., Holt‐Martyn, J. P., Schofield, C. J., & Ratcliffe, P. J. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.01.001 · Cited by 126 · see citing works
Self-citationSelective Small Molecule Probes for the Hypoxia Inducible Factor (HIF) Prolyl Hydroxylases
Chowdhury, R., Lena, J. I. C., Chan, M. C., Greenald, D., Yeoh, K. K., Tian, Y., McDonough, M. A., Tumber, A., Rose, N. R., Conejo‐García, A., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb400088q · Cited by 117 · see citing works
Self-citationRibosomal oxygenases are structurally conserved from prokaryotes to humans
Chowdhury, R., Sekirnik, R., Brissett, N. C., Krojer, T., Ho, C.-H., Ng, S. S., Clifton, I. J., Ge, W., Kershaw, N. J., Fox, G. C., et al. (2014) · Nature · doi:10.1038/nature13263 · Cited by 105 · see citing works
Self-citationEvidence for the slow reaction of hypoxia‐inducible factor prolyl hydroxylase 2 with oxygen
Flashman, E., Hoffart, L. M., Hamed, R. B., Bollinger, J. M., Jr., Krebs, C., & Schofield, C. J. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07804.x · Cited by 90 · see citing works
Self-citationKalverda, A. P., Thompson, G. S., Vogel, A., et al. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.09.048 · Cited by 90 · see citing works
Flashman, E., Bagg, E. A. L., Chowdhury, R., Mecinović, J., Loenarz, C., McDonough, M. A., Hewitson, K. S., & Schofield, C. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707411200 · Cited by 87 · see citing works
Self-citationYan, L. Y., Colandrea, V. J., & Hale, J. J. (2010) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2010.510836 · Cited by 86 · see citing works
Induction of human endometrial cancer cell senescence through modulation of HIF‐1α activity by EGLN1
Kato, H., Inoue, T., Asanoma, K., Nishimura, C., Matsuda, T., & Wake, N. (2005) · International Journal of Cancer · doi:10.1002/ijc.21488 · Cited by 74 · see citing works
Evidence for a Stereoelectronic Effect in Human Oxygen Sensing
Loenarz, C., Mecinović, J., Chowdhury, R., McNeill, L. A., Flashman, E., & Schofield, C. J. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200805427 · Cited by 68 · see citing works
Self-citationTarhonskaya, H., Chowdhury, R., Leung, I. K. H., Loik, N. D., McCullagh, J., Claridge, T. D. W., Schofield, C. J., & Flashman, E. (2014) · Biochemical Journal · doi:10.1042/bj20140779 · Cited by 54 · see citing works
Self-citationArsenault, P. R., Pei, F., Lee, R., Kerestes, H., Percy, M. J., Keith, B., Simon, M. C., Lappin, T. R. J., Khurana, T. S., & Lee, F. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.482364 · Cited by 54 · see citing works
Chen, R., Nagel, S., Papadakis, M., Bishop, T., Pollard, P. J., Ratcliffe, P. J., Pugh, C. W., & Buchan, A. M. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.232884 · Cited by 44 · see citing works
Self-citationOxygen sensing by protozoans: how they catch their breath
West, C. M., & Blader, I. J. (2015) · Current Opinion in Microbiology · doi:10.1016/j.mib.2015.04.006 · Cited by 40 · see citing works
Cavanagh, J., Fairbrother, W. J., Palmer, A. G. I., et al. (2007) · Elsevier eBooks · doi:10.1016/b978-012164491-8/50003-8 · Cited by 28 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Cavanagh, J., Fairbrother, W. J., Palmer, A. G., Rance, M. & Skelton, N. J. in Protein NMR Spectroscopy: Principles and Practice. 2nd edn (eds Cavanagh, J., Fairbrother, W. J., Palmer, A. G., III, Rance, M., & Skelton, N. J.) 1–888 (Elsevier Academic Press, Burlington, MA, 2007).
Cited by
Sorted by citations
2-Oxoglutarate-Dependent Oxygenases
Islam, M. S., Leissing, T. M., Chowdhury, R., Hopkinson, R. J., & Schofield, C. J. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044724 · Cited by 472 · see citing works
Self-citationMechanisms of hypoxia signalling: new implications for nephrology
Schödel, J., & Ratcliffe, P. J. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0182-z · Cited by 309 · see citing works
Self-citationThe EGLN-HIF O 2 -Sensing System: Multiple Inputs and Feedbacks
Ivan, M., & Kaelin, W. G. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.06.002 · Cited by 273 · see citing works
Hypoxia signaling in cancer: Implications for therapeutic interventions
Zhuang, Y., Liu, K., He, Q., Gu, X., Jiang, C., & Wu, J. (2023) · MedComm · doi:10.1002/mco2.203 · Cited by 119 · see citing works
Hypoxia inducible factor (HIF) as a model for studying inhibition of protein–protein interactions
Burslem, G. M., Kyle, H. F., Nelson, A., Edwards, T. A., & Wilson, A. J. (2017) · Chemical Science · doi:10.1039/c7sc00388a · Cited by 39 · see citing works
- Authors
- Chowdhury, R., Leung, I. K. H., Tian, Y.-M., Abboud, M. I., Ge, W., Domene, C., Cantrelle, F.-X., Landrieu, I., Hardy, A. P., Pugh, C. W., Ratcliffe, P. J., Claridge, T. D. W., & Schofield, C. J.
- Affiliations
- University of Oxford (GB)
- University of Auckland (NZ)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Schofield, Christopher J.
- ORCID
- Venue
- Nature Communications
- Published
- 2016-08-26
- Volume
- 7
- Issue
- 1
- Pages
- 12673-12673
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5007464
- OpenAlex
- W2516749516
- Cited by
- 145
- References
- 59
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 19 · 2023: 9 · 2022: 16 · 2021: 20 · 2020: 9 · 2019: 15 · 2018: 13 · 2017: 13 · 2016: 2
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion, cc-by)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion, cc-by)
- ResearchSpace (University of Auckland) (submittedVersion, cc-by)
- Funders
- Ludwig Institute for Cancer Research
- Wellcome Trust
- Diamond Light Source
- Cancer Research UK (16466)
- Royal Society
- University of Oxford
- Commonwealth Scholarship Commission
- Centre National de la Recherche Scientifique
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- HIF prolyl hydroxylase, oxygen-dependent degradation domain, nodD, hypoxia sensing, von Hippel-Lindau protein, Elongin B/C, proteasomal degradation, familial erythrocytosis, PHD inhibitors, protein structure-function relationship
- MeSH terms
- Protein Domains, Animals, Hypoxia, Cells, Cultured, Fibroblasts, Humans, Hydroxylation, Isoenzymes, Neoplasms, Oxygen, Polycythemia, Proline, Protein Binding, Recombinant Proteins, Structure-Activity Relationship, Crystallography, X-Ray, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular Dynamics Simulation, Hypoxia-Inducible Factor-Proline Dioxygenases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
