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- The small protein floodgates are opening; now the functional analysis begins
December 8, 2014
Corresponding authors: Kumaran S Ramamurthi ramamurthiks@mail.nih.gov
Laboratory of Molecular Biology, National Cancer Institute, Bethesda 20892-5132, MD, USA
BMC Biology 2014, 12:96 doi:10.1186/s12915-014-0096-y
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Commentary
‘Small proteins’ is a description given to proteins that traditionally escaped detection and thus detailed study due to their extremely small size. We also define ‘small proteins’ to be polypeptides that, in contrast to ‘peptides’, are encoded by small open reading frames (ORFs), are synthesized by ribosomes, and are not produced by proteolytic cleavage of a much larger precursor protein. Small proteins are difficult to identify for a variety of reasons. From a bioinformatics perspective, due to the problem of a high background, only ORFs of greater than approximately 50 or 100 codons were typically annotated as encoding proteins in sequenced bacterial and eukaryotic genomes, respectively. The lack of annotation coupled with few known phenotypes associated with mutations in small protein genes has restricted the detection of these genes by genetic approaches. Detection of small proteins biochemically requires optimized approaches so that, for instance, small proteins are not simply run off gels during electrophoresis. However, several recent lines of evidence suggest that small proteins are far more prevalent than previously imagined, indicating that a significant portion of the proteome of all organisms remains to be identified and studied.
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7007/12/96
image source: Prion-Based Inheritance, Protein Folding/Misfolding, and Analysis of Cellular Systems