The Gene Ontology (GO) is a well-established, structured vocabulary used in the functional annotation of gene products. GO terms are used to replace the multiple nomenclatures used by scienti c databases that can hamper data integration. Currently, GO consists of more than 41,000 terms describing the molecular function, biological process and subcellular location of a gene product in a generic cell. The UniProt-Gene Ontology Annotation (UniProt-GOA) project [1] provides high-quality manual and electronic GO annotations, historically to proteins within the UniProt Knowledgebase. Recently, support for annotation of RNAs via RNAcentral IDs and to macromolecular complexes, identi ed by IntAct Complex Portal IDs, was added. For many species, no experimental data is available: electronic annotations are the only source of information for biological investigation, and it is therefore critical that solid pipelines for data integration across multiple resources be implemented. For example, we rely on Ensembl [2] to project GO annotations automatically according to orthology between species, or InterPro [3] to identify proteins with similar signatures to which GO terms describing the conserved function or location can be associated. In September 2015, an additional 1.5 million annotations from the UniProt Uni ed Rule (UniRule [4]) system were added electronically. In addition to increasing the number of annotations available, UniProtGOA also supports, as part of manual curation, the addition of information about the context of a GO term, such as the target gene or the location of a molecular function, via annotations extensions. For example, we can now describe that a gene product is located in a speci c compartment of a speci c cell type (e.g., gene product that localizes to the nucleus of a keratinocyte [5]). Annotation extensions are amenable to sophisticated queries and reasoning. A typical use case is for researchers studying a protein that is causative of a speci c rare cardiac phenotype: they will be more interested in speci c cardiomyocytes cell di erentiation proteins than all proteins involved in cell di erentiation. Annotation les for various reference proteomes are released monthly, including human, mouse, rat, zebra sh, cow, chicken, dog, pig, Arabidopsis and Dictyostelium, as well as a le for the multiple species within UniProtKB. The UniProt-GOA dataset can be queried through our user-friendly
QuickGO browser6 or downloaded in a parsable format via the
EMBLEBI [
UniProt-GOA is the largest and most comprehensive open-source contributor of annotations to the GO Consortium annotation e ort. The UniProt-GOA dataset has increasingly been integrated into tools that aid in the analysis of large datasets resulting from high-throughput experiments thus assisting researchers in biological interpretation of their results.