Specific Binding of Tetratricopeptide Repeat Proteins to Heat Shock Protein 70 (Hsp70) and Heat Shock Protein 90 (Hsp90) Is Regulated by Affinity and Phosphorylation
Open accessAbstract
Heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90) require the help of tetratricopeptide repeat (TPR) domain-containing cochaperones for many of their functions. Each monomer of Hsp70 or Hsp90 can interact with only a single TPR cochaperone at a time, and each member of the TPR cochaperone family brings distinct functions to the complex. Thus, competition for TPR binding sites on Hsp70 and Hsp90 appears to shape chaperone activity. Recent structural and biophysical efforts have improved our understanding of chaperone-TPR contacts, focusing on the C-terminal EEVD motif that is present in both chaperones. To better understand these important protein-protein interactions on a wider scale, we measured the affinity of five TPR cochaperones, CHIP, Hop, DnaJC7, FKBP51, and FKBP52, for the C-termini of four members of the chaperone family, Hsc70, Hsp72, Hsp90α, and Hsp90β, in vitro. These studies identified some surprising selectivity among the chaperone-TPR pairs, including the selective binding of FKBP51/52 to Hsp90α/β. These results also revealed that other TPR cochaperones are only able to weakly discriminate between the chaperones or between their paralogs. We also explored whether mimicking phosphorylation of serine and threonine residues near the EEVD motif might impact affinity and found that pseudophosphorylation had selective effects on binding to CHIP but not other cochaperones. Together, these findings suggest that both intrinsic affinity and post-translational modifications tune the interactions between the Hsp70 and Hsp90 proteins and the TPR cochaperones.
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?
The TPR:EEVD interaction supplies most of the binding energy for Hsp70/Hsp90:cochaperone complexes, allowing cochaperones such as PP5, Hop and CHIP to work in both the Hsp70 and Hsp90 pathways.
“The TPR:EEVD interaction is known to provide the majority of binding energy for Hsp70/Hsp90:cochaperone complexes, enabling cochaperones such as PP5, Hop and CHIP to function in both Hsp70 and Hsp90 pathways”
From The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state (2021) · cites this paper as Assimon et al., 2015
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
Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein
Hartl, F. U., & Hayer-Hartl, M. K. (2002) · Science · doi:10.1126/science.1068408 · Cited by 3,335 · see citing works
Molecular Chaperones and Protein Quality Control
Bukau, B., Weissman, J. S., & Horwich, A. L. (2006) · Cell · doi:10.1016/j.cell.2006.04.014 · Cited by 1,556 · see citing works
Structure of TPR Domain–Peptide Complexes
Scheufler, C., Brinker, A., Bourenkov, G., Pegoraro, S., Moroder, L., Bartunik, H., Hartl, F. U., & Moarefi, I. (2000) · Cell · doi:10.1016/s0092-8674(00)80830-2 · Cited by 1,188 · see citing works
TPR proteins: the versatile helix
D’Andrea, L. D. (2003) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.10.007 · Cited by 1,154 · see citing works
Pathways of chaperone-mediated protein folding in the cytosol
Young, J. C., Agashe, V. R., Siegers, K., & Hartl, F. U. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1492 · Cited by 1,101 · see citing works
The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins
Connell, P. M., Ballinger, C. A., Jiang, J., Wu, Y., Thompson, L. J., Höhfeld, J., & Patterson, C. (2000) · Nature Cell Biology · doi:10.1038/35050618 · Cited by 1,002 · see citing works
A Role for a 70-Kilodalton Heat Shock Protein in Lysosomal Degradation of Intracellular Proteins
Chiang, H.-L., Terlecky, S. R., Plant, C. P., & Dice, J. F. (1989) · Science · doi:10.1126/science.2799391 · Cited by 982 · see citing works
Ballinger, C. A., Connell, P. M., Wu, Y., Hu, Z., Thompson, L. J., Yin, L.-Y., & Patterson, C. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.4535 · Cited by 943 · see citing works
Warrick, J. M., Chan, H. Y. E., Gladys L. Gray-Board, Chai, Y., Paulson, H. L., & Bonini, N. M. (1999) · Nature Genetics · doi:10.1038/70532 · Cited by 830 · see citing works
Heemers, H. V., & Tindall, D. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0019 · Cited by 753 · see citing works
Cummings, C. J. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.14.1511 · Cited by 485 · see citing works
A New First Step in Activation of Steroid Receptors
Davies, T. H., Ning, Y.-M., & Sánchez, E. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c100531200 · Cited by 427 · see citing works
Zhang, M., Windheim, M., Roe, S. M., Peggie, M. W., Cohen, P., Prodromou, C., & Pearl, L. H. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.09.023 · Cited by 420 · see citing works
Kirschke, E., Goswami, D., Southworth, D., Griffin, P. R., & Agard, D. A. (2014) · Cell · doi:10.1016/j.cell.2014.04.038 · Cited by 399 · see citing works
Self-citationCHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70
Qian, S., McDonough, H., Boellmann, F., Cyr, D., & Patterson, C. (2006) · Nature · doi:10.1038/nature04600 · Cited by 369 · see citing works
A novel Hsp90 inhibitor to disrupt Hsp90/Cdc37 complex against pancreatic cancer cells
Zhang, T., Hamza, A., Cao, X., Wang, B., Yu, S., Zhan, C., & Sun, D. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0484 · Cited by 365 · see citing works
Hop Modulates hsp70/hsp90 Interactions in Protein Folding
Johnson, B. D., Schumacher, R. J., Ross, E. D., & Toft, D. O. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.6.3679 · Cited by 358 · see citing works
From the cradle to the grave: molecular chaperones that may choose between folding and degradation
Höhfeld, J., Cyr, D., & Patterson, C. (2001) · EMBO Reports · doi:10.1093/embo-reports/kve206 · Cited by 338 · see citing works
Hop as an Adaptor in the Heat Shock Protein 70 (Hsp70) and Hsp90 Chaperone Machinery
Chen, S., & Smith, D. F. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.52.35194 · Cited by 334 · see citing works
Smith, D. F. (1993) · Molecular Endocrinology · doi:10.1210/me.7.11.1418 · Cited by 300 · see citing works
Bercovich, B., Stancovski, I., Mayer, A., Blumenfeld, N., Laszlo, A., Schwartz, A. L., & Ciechanover, A. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.14.9002 · Cited by 298 · see citing works
Identification of a 60-Kilodalton Stress-Related Protein, p60, which Interacts with hsp90 and hsp70
Smith, D. F., Sullivan, W. P., Marion, T. N., Zaitsu, K., Madden, B. J., McCormick, D., & Toft, D. O. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.2.869 · Cited by 269 · see citing works
Sinars, C. R., Cheung-Flynn, J., Rimerman, R. A., Scammell, J. G., Smith, D. F., & Clardy, J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0231020100 · Cited by 254 · see citing works
Isolation and characterization of STI1, a stress-inducible gene from Saccharomyces cerevisiae.
Nicolet, C. M., & Craig, E. A. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.9.3638 · Cited by 247 · see citing works
Ligand Discrimination by TPR Domains
Brinker, A., Scheufler, C., von der Muelbe, F., Fleckenstein, B. T., Herrmann, C., Jung, G., Moarefi, I., & Hartl, F. U. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109002200 · Cited by 227 · see citing works
Müller, P., Růčková, E., Halada, P., Coates, P. J., Hrstka, R., Lane, D. P., & Vojtěšek, B. (2012) · Oncogene · doi:10.1038/onc.2012.314 · Cited by 226 · see citing works
Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2
Patel, P. D., Yan, P., Seidler, P. M., Patel, H. J., Sun, W., Yang, C., Que, N. S., Taldone, T., Finotti, P., Stephani, R. A., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1335 · Cited by 218 · see citing works
The Assembly and Intermolecular Properties of the hsp70-Hop-hsp90 Molecular Chaperone Complex
Hernández, M. P., Sullivan, W. P., & Toft, D. O. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206566200 · Cited by 181 · see citing works
Steroid up-regulation of FKBP51 and its role in hormone signaling
Jääskeläinen, T., Makkonen, H., & Palvimo, J. J. (2011) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2011.04.006 · Cited by 167 · see citing works
Morishima, Y., Murphy, P. J. M., Li, D.-P., Sanchez, E. R., & Pratt, W. B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000434200 · Cited by 166 · see citing works
Hutchison, K. A., Dittmar, K. D., Czar, M. J., & Pratt, W. B. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37651-2 · Cited by 165 · see citing works
Russell, L. C., Whitt, S. R., Chen, M.-S., & Chinkers, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.29.20060 · Cited by 165 · see citing works
Wu, B., Li, P., Liu, Y., Lou, Z., Ding, Y., Shu, C., Ye, S., Bartlam, M., Shen, B., & Rao, Z. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305969101 · Cited by 165 · see citing works
Adachi, H., Waza, M., Tokui, K., Katsuno, M., Minamiyama, M., Tanaka, F., Doyu, M., & Sobue, G. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1242-07.2007 · Cited by 156 · see citing works
Riggs, D. L., Cox, M. B., Tardif, H. L., Hessling, M., Buchner, J., & Smith, D. F. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00985-07 · Cited by 150 · see citing works
Southworth, D. R., & Agard, D. A. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.04.023 · Cited by 143 · see citing works
Self-citationCofactor Tpr2 combines two TPR domains and a J domain to regulate the Hsp70/Hsp90 chaperone system
Brychzy, A., Rein, T., Winklhofer, K. F., Hartl, F. U., Young, J. C., & Obermann, W. M. J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg362 · Cited by 135 · see citing works
A Novel Class of Small Molecule Inhibitors of Hsp90
Yi, F., & Regan, L. (2008) · ACS Chemical Biology · doi:10.1021/cb800162x · Cited by 117 · see citing works
Imbalance of Hsp70 family variants fosters tau accumulation
Jinwal, U. K., Akoury, E., Abisambra, J. F., O’Leary, J. C., Thompson, A. D., Blair, L. J., Jin, Y., Bacon, J. A., Nordhues, B. A., Cockman, M. E., et al. (2012) · The FASEB Journal · doi:10.1096/fj.12-220889 · Cited by 117 · see citing works
Self-citationBalance between Folding and Degradation for Hsp90-Dependent Client Proteins: A Key Role for CHIP
Kundrat, L., & Regan, L. (2010) · Biochemistry · doi:10.1021/bi100386w · Cited by 114 · see citing works
Carrello, A., Ingley, E., Minchin, R. F., Tsai, S., & Ratajczak, T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.5.2682 · Cited by 113 · see citing works
High Levels of Heat Shock Protein Hsp72 in Cancer Cells Suppress Default Senescence Pathways
Yaglom, J. A., Gabai, V. L., & Sherman, M. Y. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3796 · Cited by 110 · see citing works
Designed TPR Modules as Novel Anticancer Agents
Cortajarena, A. L., Fang, Y., & Regan, L. (2008) · ACS Chemical Biology · doi:10.1021/cb700260z · Cited by 108 · see citing works
Identification of Residues on Hsp70 and Hsp90 Ubiquitinated by the Cochaperone CHIP
Kundrat, L., & Regan, L. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.11.017 · Cited by 106 · see citing works
Mechanistic studies of Sansalvamide A-amide: An allosteric modulator of Hsp90
Vasko, R. C., Rodriguez, R. A., Cunningham, C. N., Ardi, V. C., Agard, D. A., & McAlpine, S. R. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml900003t · Cited by 105 · see citing works
Sarkar, S., Brautigan, D. L., Parsons, S. J., & Larner, J. M. (2012) · Oncogene · doi:10.1038/onc.2012.561 · Cited by 99 · see citing works
Zhang, H., Amick, J., Chakravarti, R., Santarriaga, S., Schlanger, S., McGlone, C., Dare, M., Nix, J. C., Scaglione, K. M., Stuehr, D. J., et al. (2015) · Structure · doi:10.1016/j.str.2015.01.003 · Cited by 98 · see citing works
Waza, M., Adachi, H., Katsuno, M., Minamiyama, M., Tanaka, F., Doyu, M., & Sobue, G. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-006-0066-0 · Cited by 98 · see citing works
Cheung-Flynn, J., Roberts, P. J., Riggs, D. L., & Smith, D. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300955200 · Cited by 96 · see citing works
Fine-Tuning Multiprotein Complexes Using Small Molecules
Thompson, A. D., Dugan, A. E., Gestwicki, J. E., & Mapp, A. K. (2012) · ACS Chemical Biology · doi:10.1021/cb300255p · Cited by 93 · see citing works
Self-citationStructure and function of Hip, an attenuator of the Hsp70 chaperone cycle
Li, Z., Hartl, F. U., & Bracher, A. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2608 · Cited by 87 · see citing works
Multiple Domains of the Co-chaperone Hop Are Important for Hsp70 Binding
Carrigan, P. E., Nelson, G. M., Roberts, P. J., Stoffer, J. B., Riggs, D. L., & Smith, D. F. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314130200 · Cited by 80 · see citing works
Conformational Diversity in the TPR Domain-Mediated Interaction of Protein Phosphatase 5 with Hsp90
Cliff, M. J., Harris, R., Barford, D., Ladbury, J. E., & Williams, M. A. (2006) · Structure · doi:10.1016/j.str.2005.12.009 · Cited by 76 · see citing works
Hsp90 as an anti-cancer target
Neckers, L., Mimnaugh, E. G., & Schulte, T. W. (1999) · Drug Resistance Updates · doi:10.1054/drup.1999.0082 · Cited by 75 · see citing works
Identification of small molecules that modify the protein folding activity of heat shock protein 70
Wisén, S., & Gestwicki, J. E. (2008) · Analytical Biochemistry · doi:10.1016/j.ab.2007.12.009 · Cited by 75 · see citing works
Self-citationMacrocycles That Inhibit the Binding between Heat Shock Protein 90 and TPR-Containing Proteins
Ardi, V. C., Alexander, L. D., Johnson, V. A., & McAlpine, S. R. (2011) · ACS Chemical Biology · doi:10.1021/cb200203m · Cited by 69 · see citing works
Isolation and Characterization of STI1 , a Stress-Inducible Gene from Saccharomyces cerevisiae
Nicolet, C. M., & Craig, E. A. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.9.3638-3646.1989 · Cited by 66 · see citing works
Wang, L., Liu, Y., Hao, R., Chen, L., Chang, Z., Wang, H., Wang, Z., & Wu, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.201814 · Cited by 64 · see citing works
Pimienta, G., Herbert, K. M., & Regan, L. (2011) · Molecular Pharmaceutics · doi:10.1021/mp200346y · Cited by 63 · see citing works
Molecular genetics of human hypertension
Gong, M., & Hübner, N. (2006) · Clinical Science · doi:10.1042/cs20050208 · Cited by 59 · see citing works
The E3 Ubiquitin Ligase CHIP and the Molecular Chaperone Hsc70 Form a Dynamic, Tethered Complex
Smith, M. C. P., Scaglione, K. M., Assimon, V. A., Patury, S., Thompson, A. D., Dickey, C. A., Southworth, D. R., Paulson, H. L., Gestwicki, J. E., & Zuiderweg, E. R. P. (2013) · Biochemistry · doi:10.1021/bi4009209 · Cited by 59 · see citing works
Self-citationFontaine, S. N., Rauch, J. N., Nordhues, B. A., Assimon, V. A., Stothert, A. R., Jinwal, U. K., Sabbagh, J. J., Chang, L., Stevens, S. M., Zuiderweg, E. R. P., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.637595 · Cited by 50 · see citing works
Self-citationRole of the Cochaperone Tpr2 in Hsp90 Chaperoning
Moffatt, N., Bruinsma, E. S., Uhl, C. B., Obermann, W. M. J., & Toft, D. O. (2008) · Biochemistry · doi:10.1021/bi800770g · Cited by 50 · see citing works
Connarn, J. N., Assimon, V. A., Reed, R. A., Tse, E., Southworth, D. R., Zuiderweg, E. R. P., Gestwicki, J. E., & Sun, D. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.519421 · Cited by 48 · see citing works
Self-citationIdentification of a 60-Kilodalton Stress-Related Protein, p60, which Interacts with hsp90 and hsp70
Smith, D. F., Sullivan, W. P., Marion, T. N., et al. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.2.869-876.1993 · Cited by 48 · see citing works
Designed Proteins To Modulate Cellular Networks
Cortajarena, A. L., Liu, T. Y., Hochstrasser, M., & Regan, L. (2009) · ACS Chemical Biology · doi:10.1021/cb9002464 · Cited by 46 · see citing works
Bacterial Lipopolysaccharide Induces Expression of the Stress Response Genes hop and H411
Heine, H., Delude, R. L., Monks, B. G., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.21049 · Cited by 40 · see citing works
Redesign of a protein–peptide interaction: Characterization and applications
Jackrel, M. E., Valverde, R., & Regan, L. (2009) · Protein Science · doi:10.1002/pro.75 · Cited by 39 · see citing works
Morishima, Y., Lau, M., Peng, H., Miyata, Y., Gestwicki, J. E., Pratt, W. B., & Osawa, Y. (2011) · Biochemistry · doi:10.1021/bi200751t · Cited by 15 · see citing works
Self-citationHsp90-containing multiprotein complexes in the eukaryotic microbe Achlya
Brunt, S. A., Perdew, G. H., Toft, D. O., & Silver, J. C. (1998) · Cell Stress and Chaperones · doi:10.1379/1466-1268(1998)003 · Cited by 14 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [18]Ballinger CA Hu ZY Connell P Patterson C 1999 Identification of CHIP, a novel striated muscle-restricted TPR-containing protein that negatively regulates chaperone functions Faseb J 13 A442 A442 PMC104411 10330192
Cited by
Sorted by citations
FKBP Ligands—Where We Are and Where to Go?
Kolos, J. M., Voll, A. M., Bauder, M., & Hausch, F. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01425 · Cited by 158 · see citing works
Hähle, A., Merz, S., Meyners, C., & Hausch, F. (2019) · Biomolecules · doi:10.3390/biom9010035 · Cited by 119 · see citing works
Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients
Miller-Vedam, L. E., Bräuning, B., Popova, K. D., Schirle Oakdale, N. T., Bonnar, J. L., Prabu, J. R., Boydston, E. A., Sevillano, N., Shurtleff, M. J., Stroud, R. M., et al. (2020) · eLife · doi:10.7554/elife.62611 · Cited by 87 · see citing works
Lee, K., Thwin, A. C., Nadel, C. M., Tse, E., Gates, S. N., Gestwicki, J. E., & Southworth, D. R. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.07.023 · Cited by 76 · see citing works
Self-citation
- Authors
- Assimon, V. A., Southworth, D. R., & Gestwicki, J. E.
- Affiliations
- University of Michigan (US)
- University of California, San Francisco (US)
- Corresponding author
- Gestwicki, Jason E.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-11-25
- Volume
- 54
- Issue
- 48
- Pages
- 7120-7131
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- PMC
- PMC4714923
- OpenAlex
- W2238888716
- Cited by
- 112
- References
- 70
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 9 · 2023: 9 · 2022: 11 · 2021: 13 · 2020: 8 · 2019: 15 · 2018: 13 · 2017: 12 · 2016: 8
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS059690)
- National Institute of General Medical Sciences (GM109896)
- National Institute on Aging (F31 AG043266-02)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- tetratricopeptide repeat proteins, HSP70, HSP90, co-chaperones, protein-protein interaction, EEVD motif, binding affinity, phosphorylation, CHIP, Humulus lupulus, FKBP51, FKBP52, Hsc70, HSP72, HSP90α, HSP90β
- MeSH terms
- Tacrolimus Binding Protein 5, Amino Acid Sequence, Humans, Models, Molecular, Phosphorylation, Protein Binding, Protein Conformation, Homeodomain Proteins, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Amino Acid Motifs, Tacrolimus Binding Proteins, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Protein Interaction Domains and Motifs, Protein Interaction Maps
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
