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J Proteome Res. 2018 Nov 29. doi: 10.1021/acs.jproteome.8b00383. [Epub ahead of print]

Launching the C-HPP neXt-CP50 Pilot Project for Functional Characterization of Identified Proteins with No Known Function.

Author information

1
Yonsei Proteome Research Center and Department of Integrative Omics , Yonsei University , Sudaemoon-ku, 120-749 Seoul , Korea.
2
CALIPHO Group, Swiss Institute of Bioinformatics & Department of Microbiology and Molecular Medicine, Faculty of Medicine , University of Geneva , CH-1211 Geneva , Switzerland.
3
Proteomics Laboratory, Isotope Science Center , The University of Tokyo , Bunkyo-Ku, Tokyo 113-0032 , Japan.
4
Institute of Chemistry , Academia Sinica , 128 Academia Road Sec. 2 , Nankang, Taipei 115 , Taiwan.
5
Research Institute for Veterinary Science, College of Veterinary Medicine , Seoul University , 1 Kwanak-ro , Kwanak-gu, 151-742 Seoul , South Korea.
6
Biodesign Institute , Arizona State University , 1001 South McAllister Avenue , Tempe , Arizona 85287-5001 , United States.
7
Division of Mass Spectrometry Research , Korea Basic Science Institute , 28119 Ochang , Korea.
8
Federal University of Rio de Janeiro , Institute of Chemistry , Rio de Janeiro , Rio de Janeiro 21941-909 , Brazil.
9
Functional Proteomics Laboratory , National Center of Biotechnology, CSIC , 28049 Madrid , Spain.
10
Center for Computational Medicine and Bioinformatics , University of Michigan , Ann Arbor , Michigan 48109-2218 , United States.
11
Institute of Biomedical Chemistry RAS , Moscow 119121 , Russia.
12
Center for Genomic Sciences , National Autonomous University of Mexico , Cuernavaca , Morelos 62210 , Mexico.
13
BGI-Shenzhen , Beishan Industrial Zone, Yantian District, Shenzhen 518083 , China.
14
Department of Molecular Systems Biology , Royan Institute for Stem Cell Biology and Technology , 1665659911 Tehran , Iran.
15
Department of Molecular Sciences , Macquarie University , Sydney , New South Wales 2109 , Australia.
16
Centre for Blood Research, Departments of Oral Biological & Medical Sciences and Biochemistry & Molecular Biology, Faculty of Dentistry , University of British Columbia , Vancouver , British Columbia V6T 1Z3 , Canada.

Abstract

An important goal of the Human Proteome Organization (HUPO) Chromosome-centric Human Proteome Project (C-HPP) is to correctly define the number of canonical proteins encoded by their cognate open reading frames on each chromosome in the human genome. When identified with high confidence of protein evidence (PE), such proteins are termed PE1 proteins in the online database resource, neXtProt. However, proteins that have not been identified unequivocally at the protein level but that have other evidence suggestive of their existence (PE2-4) are termed missing proteins (MPs). The number of MPs has been reduced from 5511 in 2012 to 2186 in 2018 (neXtProt 2018-01-17 release). Although the annotation of the human proteome has made significant progress, the "parts list" alone does not inform function. Indeed, 1937 proteins representing ∼10% of the human proteome have no function either annotated from experimental characterization or predicted by homology to other proteins. Specifically, these 1937 "dark proteins" of the so-called dark proteome are composed of 1260 functionally uncharacterized but identified PE1 proteins, designated as uPE1, plus 677 MPs from categories PE2-PE4, which also have no known or predicted function and are termed uMPs. At the HUPO-2017 Annual Meeting, the C-HPP officially adopted the uPE1 pilot initiative, with 14 participating international teams later committing to demonstrate the feasibility of the functional characterization of large numbers of dark proteins (CP), starting first with 50 uPE1 proteins, in a stepwise chromosome-centric organizational manner. The second aim of the feasibility phase to characterize protein (CP) functions of 50 uPE1 proteins, termed the neXt-CP50 initiative, is to utilize a variety of approaches and workflows according to individual team expertise, interest, and resources so as to enable the C-HPP to recommend experimentally proven workflows to the proteome community within 3 years. The results from this pilot will not only be the cornerstone of a larger characterization initiative but also enhance understanding of the human proteome and integrated cellular networks for the discovery of new mechanisms of pathology, mechanistically informative biomarkers, and rational drug targets.

KEYWORDS:

C-HPP; Human Proteome Project; dark protein; missing protein; neXt-CP50; protein evidence; proteoform; uncharacterized missing protein (uMP); uncharacterized protein evidence 1 (uPE1)

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