In the March 2013 issue of Nature Methods, Lloyd M. Smith, and Neil L. Kelleher, along with the Consortium for Top Down Proteomics, expressed concern with terminology used to describe the variations in the same protein.
To clarify the terminology, it has been proposed that “proteoform” be used to describe a “specific molecular form of a protein product arising from a specific gene.”1 This definition also includes proteins that arises from the same gene as a result of genetic variation, alternatively spliced RNA transcripts, and posttranslational modifications (PTMs). All PTMs included in the PSI-MOD ontology fall within this definition, with the exception of residues classified as reagent-derivatized or isotope-labeled residues.
“Current terminology is confusing,” Smith and Kelleher say. Terms like “variant” and “isoform” are widely used in the literature and in the comprehensive proteome database, UniProt. These terms were originally used to describe distinct proteins and are now used to describe modified proteins.
The International Union of Pure and Applied Chemistry (IUPAC), which clarifies these sorts of perplexities in naming, uses the term “isoform” to describe genetic differences and does not include variation at the protein level.2 “Isoform” is also used to describe proteins that contain posttranslational modifications. Another term used, “protein species,” was proposed in 2009;2 however, this term does not distinguish between proteins originating from different genes and those originating from a single gene.
Smith and Kelleher will use “proteoform” in future publications and encourage its acceptance by other researchers, including proteome databases such as UniProt, Protein Ontology, and others.
1. Smith, L.M., and Kelleher, N.L.; Consortium for Top Down Proteomics, (2013) ‘Proteoform: a single term describing protein complexity‘, Nature Methods, 10 (3), (pp. 186-187)
2. Schlüter, H., et al. (2009) ‘Finding one’s way in proteomics: a protein species nomenclature‘, Chemistry Central Journal, 3 (11), doi: /10.1186/1752-153X-3-11