Potential experimental approaches for functional characterization of uPE1 proteins. This can be divided into two workflows, PPI-based function prediction, and Multi-Omics Knowledge-based function prediction. The prediction results can further be tested by using Phenotypic Cell-based Screens that can utilize biochemical or immunologic assays for verification of the prediction results. These experiments can be used in a flexible manner as appropriate to verify and validate the function(s) of target dark proteins. Functionally validated dark uPE1 proteins will be promoted to PE1 and curated by neXtProt. (from Paik et al., J. Proteome Res. 2018, 17, 4042−4050)

• neXt-CP50 Reports (a Dark Protein Initiative)

By analogy to the term “dark proteins” coined to represent structurally uncharacterized regions, C-HPP investigators have recently adopted the term “dark proteome” to collectively refer to those proteins for which we have insufficient information on either protein expression, structure, function, or all of these: They include, for example, MPs (PE2−4), PE5, uPE1 proteins, and any potential proteins translated from smORF or lncRNAs. When focused on uPE1 proteins, there are nearly 2,000 proteins which have no functional information (Paik et al., 2018, JPR, DOI:10.1021/acs.jproteome.8b00383).

On March 1, 2018, HUPO C-HPP announced launching the neXt-CP50 where CP stands for “characterization of proteins”. This pilot project aims to characterize function of 50 uPE1 proteins during ~3 years (2018-2021). This challenge is to test the feasibility of the functional characterization of large numbers of dark proteins, 2000 at present the 15 teams are focusing on specific tractable targets that can be investigated Of the C-HPP consortium international teams, 15 from 12 countries joined this project: Chr 2 (Switzerland), Chr 3 (Japan), Chr 4 (Taiwan), Chr 9, 11, 13 (Korea), Chr 10, Chr 14 (France), Chr 15 (Brazil), Chr 16 (Spain), Chr 17 (USA), Chr 18 (Russia), Chr 19 (Mexico), Chr 20 (China), and Chr Y (Iran).