3DSeqCheck: A Web-based Tool for Verifying Sequence Consistency Between a 3D Structure File and the Corresponding UniProt Entry

UniProt is a central repository of protein sequences and annotations, with entries being updated several times a year as new sequencing evidence is collected. By contrast, protein structure resources often evolve at a different pace. The AlphaFold database remained unchanged for four years, until September 2025, during which time nearly 3% of the associated sequences underwent revisions in UniProt. In a range of bioinformatics tasks, protein structure data is paired with sequence annotations from UniProt. Mapping annotations to outdated structure files can lead to errors in downstream analysis. While this concern has been addressed for experimental structures, efforts for the modeled structures are lacking. 3DSeqCheck is a lightweight web tool that enables quick comparison of the sequence of modeled and experimental structures to the latest UniProt entries. 3DSeqCheck provides an interactive visual panel of the alignment and the comparison of the residue numbering and can be accessed freely at: https://missense3d.bc.ic.ac.uk/3dseqcheck and https://github.ic.ac.uk/ImperialCollegeLondon/check3Dseq.