Elisabeth Coudert - Annotation of biologically relevant ligands in UniProtKB using ChEBI
Channel: Biocuration Conference 2023
Date: 2023-06-21

*Session:* April 25 - Applications 1 - 03

*Abstract:* The UniProt Knowledgebase (UniProtKB, at www.uniprot.org) is a reference resource of protein sequences and functional annotation that covers over 200 million protein sequences from all branches of the tree of life. UniProtKB provides a wealth of information on protein sequences and their functions, including descriptions of the nature of biologically relevant ligands (also known as cognate ligands) such as substrates/products of enzymes, cofactors, activators and inhibitors, as well as their binding sites. UniProtKB captures this information through expert literature curation and from experimentally resolved protein structures in the Protein Data Bank (PDB/PDBe). Here we describe improvements to the representation of cognate ligands in binding site annotations in UniProtKB using the chemical ontology ChEBI (www.ebi.ac.uk/chebi/). In 2022, we performed a complete reannotation of all cognate ligand binding sites in UniProtKB, replacing textual descriptions of defined ligands with stable unique identifiers from the ChEBI ontology, which we now use as the reference vocabulary for all new ligand annotations. The last UniProt release includes about 800 unique cognate ligands from ChEBI, which feature in over 65 million binding site annotations and over 15 million protein sequence records. This work continues the standardization of small molecule annotation in UniProtKB, which also covers the use of Rhea (www.rhea-db.org) and ChEBI for the annotation of enzymes, transporters, and cofactors. This enhanced dataset will provide improved support for efforts to study and predict functionally relevant interactions between proteins and their cognate ligands using computational approaches. Users can access the dataset via the UniProt website, REST API, and SPARQL endpoint, which have been modified to support ligand searches using the chemical ontology and chemical structure data of ChEBI.