This Critical Guide in the Introduction to Bioinformatics series provides a brief outline of the UniProt protein sequence database, with a particular focus on the UniProt Knowledgebase – UniProtKB. The rationale for creating the resource, its contributing databases and the kinds of information they provide are discussed, and issues behind the quality of their annotations are explored.
Specifically, this Guide introduces the principal components of the UniProt Knowledgebase, and the differences between them. On reading this Guide, users will be able to: i) identify and explain the characteristic features of UniProtKB/Swiss-Prot and UniProtKB/TrEMBL entries; ii) distinguish annotations that are computed, and hence not experimentally validated; iii) search UniProtKB using keywords, full sequences and peptides, and interpret the results; iv) analyse and track the provenance of annotations; and v) infer which annotations are likely to be accurate and which erroneous.