UniProt: the Universal Protein Knowledgebase in 2025
Open accessAbstract
The aim of the UniProt Knowledgebase (UniProtKB; https://www.uniprot.org/) is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this publication, we describe ongoing changes to our production pipeline to limit the sequences available in UniProtKB to high-quality, non-redundant reference proteomes. We continue to manually curate the scientific literature to add the latest functional data and use machine learning techniques. We also encourage community curation to ensure key publications are not missed. We provide an update on the automatic annotation methods used by UniProtKB to predict information for unreviewed entries describing unstudied proteins. Finally, updates to the UniProt website are described, including a new tab linking protein to genomic information. In recognition of its value to the scientific community, the UniProt database has been awarded Global Core Biodata Resource status.
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All EXOSC3 G191 variants promote increased skipping of exon 3 in EXOSC3 transcripts.
“All EXOSC3 G191 variants promoted increased skipping of exon 3 in EXOSC3 transcripts, generating a short isoform predicted to encode an unstable proteoform.”
From EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery (2026) · cites this paper as [73]
The Expert curation and Managing the sequence space sections discuss UniProt annotations and sequence records, not EXOSC3 splicing. Searches for EXOSC3 G191, exon 3 skipping, and the proposed short isoform found no relevant passage in our copy, so it cannot verify the claim. (LLM, conf=0.75)
Experimental — accuracy not yet measuredThe EXOSC3 transcript itself was significantly affected, with G191 variants promoting a switch to an EXOSC3 isoform with exon 3 being spliced out.
“Among these splicing phenomenon, the EXOSC3 transcript itself was significantly affected, with G191 variants promoting a switch to an EXOSC3 isoform with exon 3 being spliced out73.”
From EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery (2026) · cites this paper as [73]
The paper’s Expert curation and Managing the sequence space sections discuss UniProt annotations and protein sequences, not EXOSC3 splicing. Searches for EXOSC3, G191 variants, and an exon 3–skipping isoform found no passage addressing the claim; the cited paper’s copy therefore cannot verify it. (LLM, conf=0.75)
Experimental — accuracy not yet measured
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Basic local alignment search tool
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UniProt: the Universal Protein Knowledgebase in 2023
The UniProt Consortium, Bateman, A., Martin, M.-J., Orchard, S., Magrane, M., Ahmad, S., Alpi, E., Bowler-Barnett, E. H., Britto, R., Bye-A-Jee, H., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkac1052 · Cited by 7,210 · see citing works
Self-citationLitSuggest: a web-based system for literature recommendation and curation using machine learning
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“Existing ML frameworks such as LitSuggest ( 17 ) are used by UniProt curators to identify papers on subjects such as amino acid variants linked to human disease, enzymatic reactions and protein complexes.”
Flagged first, then by citations
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“Then, we used the Gene Ontology database [ 31], to search for the key GOs in core/soft-core and shell/cloud genes of the differ - ent species using UNIPROT 2023_04 [ 32], including in the analysis only genomes from vaginal source.”
EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery
Wijeratne, H. R. S., Runnebohm, A. M., Barron, M. P., Hampton, A. J., Li, R., Peck Justice, S. A., Lenceski, S. H., Rooney, J. D., Smith-Kinnaman, W. R., Chang, G. S., et al. (2026) · doi:10.64898/2026.01.26.701775 · Cited by 1 · see citing works
“Among these splicing phenomenon, the EXOSC3 transcript itself was significantly affected, with G191 variants promoting a switch to an EXOSC3 isoform with exon 3 being spliced out 73 .”
Wu, Q., Yang, F., An, Q., Liu, Y., Tian, H., Du, Y., Cai, W., Lei, M., Xu, J., Deng, L., et al. (2026) · Journal of the American Heart Association · doi:10.1161/jaha.126.049987
Structural and mechanistic insights into the constitutive Themis–Grb2 complex in T cell signalling
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He, J., Zhou, T., Hu, L.-F., Jiao, Y., Wang, J., Yan, S., Jia, S., Chen, Q., Zhu, W., Zhang, J., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-72351-6
Self-citationYang, M., Li, R., Dong, Y., Zhou, M., Zhao, J., Liu, M., & Tan, R. (2026) · doi:10.64898/2026.01.28.702456
“If unavailable, predicted structures from the AlphaFold Protein Structure Database[47, 48], linked to UniProt[49] entries, can be used (Table S1).”
- Authors
- The UniProt Consortium, Bateman, A., Martin, M.-J., Orchard, S., Magrane, M., Adesina, A., Ahmad, S., Bowler-Barnett, E. H., Bye-A-Jee, H., Carpentier, D., Denny, P., Fan, J., Garmiri, P., Gonzales, L. J. D. C., Hussein, A., Ignatchenko, A., Insana, G., Ishtiaq, R., Joshi, V., Jyothi, D., Kandasaamy, S., Lock, A., Luciani, A., Luo, J., Lussi, Y., Marin, J. S. M., Raposo, P., Rice, D. L., Santos, R., Speretta, E., Stephenson, J., Totoo, P., Tyagi, N., Urakova, N., Vasudev, P., Warner, K., Wijerathne, S., Yu, C. W.-H., Zaru, R., Bridge, A. J., Aimo, L., Argoud-Puy, G., Auchincloss, A. H., Axelsen, K. B., Bansal, P., Baratin, D., Batista Neto, T. M., Blatter, M.-C., Bolleman, J. T., Boutet, E., Breuza, L., Gil, B. C., Casals-Casas, C., Echioukh, K. C., Coudert, E., Cuche, B., de Castro, E., Estreicher, A., Famiglietti, M. L., Feuermann, M., Gasteiger, E., Gaudet, P., Gehant, S., Gerritsen, V., Gos, A., Gruaz, N., Hulo, C., Hyka-Nouspikel, N., Jungo, F., Kerhornou, A., Mercier, P. L., Lieberherr, D., Masson, P., Morgat, A., Paesano, S., Pedruzzi, I., Pilbout, S., Pourcel, L., Poux, S., Pozzato, M., Pruess, M., Redaschi, N., Rivoire, C., Sigrist, C. J. A., Sonesson, K., Sundaram, S., Sveshnikova, A., Wu, C. H., Arighi, C. N., Chen, C., Chen, Y., Huang, H., Laiho, K., Lehvaslaiho, M., McGarvey, P., Natale, D. A., Ross, K., Vinayaka, C. R., Wang, Y., & Zhang, J.
- ORCID
- Bateman, Alex
- Martin, Maria-Jesus
- Orchard, Sandra
- Magrane, Michele
- Adesina, Aduragbemi
- Ahmad, Shadab
- Bowler-Barnett, Emily H
- Carpentier, David
- Denny, Paul
- Fan, Jun
- Garmiri, Penelope
- Gonzales, Leonardo Jose da Costa
- Hussein, Abdulrahman
- Ignatchenko, Alexandr
- Insana, Giuseppe
- Ishtiaq, Rizwan
- Joshi, Vishal
- Jyothi, Dushyanth
- Kandasaamy, Swaathi
- Lock, Antonia
- Luo, Jie
- Lussi, Yvonne
- Raposo, Pedro
- Rice, Daniel L
- Santos, Rafael
- Speretta, Elena
- Stephenson, James
- Totoo, Prabhat
- Tyagi, Nidhi
- Urakova, Nadya
- Warner, Kate
- Yu, Conny Wing-Heng
- Zaru, Rossana
- Bridge, Alan J
- Aimo, Lucila
- Auchincloss, Andrea H
- Axelsen, Kristian B
- Bansal, Parit
- Baratin, Delphine
- Blatter, Marie-Claude
- Bolleman, Jerven T
- Boutet, Emmanuel
- Breuza, Lionel
- Gil, Blanca Cabrera
- Coudert, Elisabeth
- Cuche, Beatrice
- Estreicher, Anne
- Famiglietti, Maria L
- Feuermann, Marc
- Gasteiger, Elisabeth
- Gaudet, Pascale
- Gos, Arnaud
- Hulo, Chantal
- Jungo, Florence
- Kerhornou, Arnaud
- Mercier, Philippe Le
- Lieberherr, Damien
- Masson, Patrick
- Morgat, Anne
- Pedruzzi, Ivo
- Pourcel, Lucille
- Poux, Sylvain
- Pozzato, Monica
- Redaschi, Nicole
- Rivoire, Catherine
- Sigrist, Christian J A
- Sundaram, Shyamala
- Sveshnikova, Anastasia
- Wu, Cathy H
- Arighi, Cecilia N
- Chen, Chuming
- Huang, Hongzhan
- McGarvey, Peter
- Natale, Darren A
- Ross, Karen
- Wang, Yuqi
- Zhang, Jian
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2024-11-18
- Volume
- 53
- Issue
- D1
- Pages
- D609-D617
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC11701636
- OpenAlex
- W4404458588
- Cited by
- 2,537
- References
- 3
- Citations by year
- 2026: 1579 · 2025: 882 · 2024: 31 · 2023: 32 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 1 · 2013: 1
- FWCI
- 339.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Human Genome Research Institute (HG002273)
- Office of the Director (U24HG007822)
- National Institute of Allergy and Infectious Diseases
- National Institute on Aging
- National Institute of General Medical Sciences (R35GM141873)
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Eye Institute
- National Cancer Institute
- National Heart, Lung, and Blood Institute
- Biotechnology and Biological Sciences Research Council (BB/T015608/1)
- National Science Foundation’s Directorate for Biological Sciences (BB/X002179/1)
- Horizon 2020 - Research and Innovation Framework Programme (825575)
- State Secretariat for Education, Research and Innovation
- European Molecular Biology Laboratory (EMBL) Australia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biomedical Text Mining and Ontologies
- Keywords
- protein sequence annotation, reference proteomes, functional annotation, literature curation, machine learning annotation, community curation
- MeSH terms
- Machine Learning, Animals, Humans, Proteins, Software, Internet, Proteome, Databases, Protein, Proteomics, Knowledge Bases, Molecular Sequence Annotation
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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.
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