Changes to UniProt proteomes

UniProt, the data resource for protein sequence and function information, is making major changes to its proteomes resource and to the UniProt Knowledgebase. 

UniProt has developed a new workflow that selects at least one reference proteome for each species, which best represents the protein diversity for that organism. With the resulting increased coverage of the Tree of Life, UniProtKB will be reduced in size so that it will exclusively contain only proteins from reference proteomes, providing users with only the best quality protein data. 

The process started in October 2025 (release 2025_04) and is set to be finalised by the end of the second quarter of 2026 (release 2026_02), at its conclusion resulting in the removal of all protein entries that are not part of a reference proteome from UniProtKB.

Proteins removed from UniProtKB will continue to be available in UniParc.

Users should check this UniProt FTP folder to see if the proteomes they work on are among those set to be removed from UniProtKB. 

Why is UniProt changing its reference proteome set?

Large-scale genome-sequencing projects, such as the Earth BioGenome and the Darwin Tree of Life are producing high-quality reference genomes for thousands of species. Each genome provides a foundation for defining a reference proteome, which is the best set of proteins expressed by that species. 

Additionally, the number of genomic data submissions to archives such as the European Nucleotide Archive (ENA) has grown in recent years, due to large sequencing capabilities. This results in a large influx of proteomes into UniProt, often with significant protein redundancy and limited biological insight.

To ensure UniProt can deliver this expanding wealth of data in a meaningful, sustainable and accessible way, UniProt is enhancing the content and structures of its resources. 

When is this happening?

Starting with release 2025_04, dated 15 October 2025, UniProt introduced a new reference proteomes selection workflow. Additionally, the team started the process of removing proteins from UniProtKB that are not part of a reference proteome. The first step, which has already happened, was the removal of proteins from taxonomically unclassified species. 

In release 2026_02, currently expected before the end of the second quarter of 2026, the team will remove the remaining proteins that are not part of a reference proteome from UniProtKB.

What will UniProtKB include after the reference proteome changes are implemented?

UniProt contains data on proteins for all species, including bacteria, viruses, animals and plants. From release 2026_02 onwards, UniProt will restrict the data available in the UniProt KnowledgeBase (UniProtKB) to: 

• protein sequences that are part of a reference proteome
• expert-reviewed entries in UniProKB/Swiss-Prot
• protein entries that are considered to have high biological relevance

What will happen to the proteomes that are not selected as reference proteomes?

Proteins that are not part of a reference genome will continue to be available in UniParc. When users search for such proteomes in the Proteomes portal, they will be directed to UniParc to access and download the protein set. 

How will the new reference proteome workflow function?

Until recently, not all species had a reference proteome in UniProt, but going forward, the new workflow will enable selection of at least one reference proteome per species as part of the usual UniProt release cycle. 

Additional proteomes of well-studied model organisms and other proteomes of interest for biomedical research may be selected as reference proteomes by UniProt curators. 

UniProt’s new workflow will provide a much better representation of the biodiversity of life and coverage of the sequence space. It is set to improve user experience when searching and selecting the best proteome for their research work.

What do users need to do next?

The UniProt team encourages all its users to check this UniProt FTP folder to see if the proteomes they work on are among those set to be removed from UniProtKB. 

If the annotation provided by UniProtKB is particularly important to your work, or if your organism is actively worked on by the research community, but has not been selected as a reference proteome, please contact the UniProt team.

Read more about the workflow on the UniProt blog and the upcoming plans per release on the ‘A summary of proteomes changes’ UniProt help page.