Looking for missing proteins

Proteins are important biological macromolecules critical for structure, function and regulation of cells and tissues. The human genome draft is available since 2003 but until now not all the coding genes have known protein products. Human Proteome Project (HPP) was launched in 2010 with the aim of mapping the entire human proteome. The HPP community has identified 88.62% of the coding genes as protein products. The remaining 11.38% of the proteins are missing. Since most of the missing proteins are membrane proteins, which might have clinical implications, therefore it is important to identify these proteins for utilizing their therapeutic potential. There are several technical challenges that make the missing protein (MP) identification through mass spectrometry (MS), a difficult task. In this article we discuss the challenges associated with MP identification and the possible solutions applied by the scientific community. In the absence of reliable MS evidence for the MPs, other important experimental methods must also be considered for which no guidelines have yet been devised by the HPP. The largest family among the missing proteins is the olfactory receptors (ORs), which comprises the superfamily of G-protein coupled receptors (GPCRs). There is, till date, no convincible MS evidence available, for a single human OR, although four ORs have been assigned protein-level evidence status, based entirely on orthogonal evidence. Hence, there are likely to be numerous other ORs, with non-MS evidence. Therefore, we have collated the available orthogonal evidence for 107 ORs from published literature. At the end of the article, we present a case study for tracking missing ORs from orthogonal evidence.