Protein Ontology: a controlled structured network of protein entities

Abstract

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to UniProtKB in that PRO's organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO's representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments.

Figure 1.

Illustration of PRO categories and relation to external resources. Categories (aka metaclasses) are listed along the top, with example terms for IRF5 (interferon regulatory factor 5) shown directly below. Circles denote protein terms, whereas squares denote protein complex terms. For each, blue indicates terms that are defined in an organism-agnostic way; green indicates terms that are organism-specific. Solid lines show is_a relationships and broken lines show has_component relationships (though the complexes in this example have components in the modification category, this need not be the case). Filled circles and filled squares indicate how UniProtKB and GO, respectively, fit into the hierarchy. Not all terms and relationships are shown. IRF, interferon regulatory factor; Phos, phosphorylated; m, mouse; h, human; iso, isoform; BMv, bone marrow variant.

Figure 2.

Display for protein products of the mouse Irf8 gene. Top panel, defined PRO terms; Middle panel, GO-centric view of annotations; Bottom panel, PRO-centric view of the annotations.

Figure 3.

Cytoscape view of BUB1:BUB1B complexes. The is_a relationship between child and parent in the PRO hierarchy and the has_component relationship between complexes and their components are shown by black arrows and blue dotted arrows, respectively. Clicking on a node (e.g. frog-BUB1B/Phos:2) brings a pop-up box that provides details and allows additional actions. Only a subset of nodes is shown, which have been rearranged for clarity.