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Human Prestin: A Candidate PE1 Protein Lacking Stringent Mass Spectrometric Evidence?

Mohamedali, Abidali, Ahn, Seong Beom, Sreenivasan, Varun K. A., Ranganathan, Shoba, Baker, Mark S.
Journal of Proteome Research 2017 v.16 no.12 pp. 4531-4535
antibodies, chromosomes, clearcutting, humans, mass spectrometry, peptides, proteins, proteome, transcriptomics
The evidence that any protein exists in the Human Proteome Project (HPP; protein evidence 1 or PE1) has revolved primarily (although not exclusively) around mass spectrometry (MS) (93% of PE1 proteins have MS evidence in the latest neXtProt release), with robust and stringent, well-curated metrics that have served the community well. This has led to a significant number of proteins still considered “missing” (i.e., PE2–4). Many PE2–4 proteins have MS evidence of unacceptable quality (small or not enough unitypic peptides and unacceptably high protein/peptide FDRs), transcriptomic, or antibody evidence. Here we use a Chromosome 7 PE2 example called Prestin to demonstrate that clear and robust criteria/metrics need to be developed for proteins that may not or cannot produce clear-cut MS evidence while possessing significant non-MS evidence, including disease-association data. Many of the PE2–4 proteins are inaccessible, spatiotemporally expressed in a limited way, or expressed at such a very low copy number as to be unable to be detected by current MS methodologies. We propose that the HPP community consider and lead a communal initiative to accelerate the discovery and characterization of these types of “missing” proteins.