title: Systems-wide Identification of cis-Regulatory Elements in Proteins.
abstract: Protein interactions in cis that can activate or autoinhibit protein function play an important role in the fine-tuning of regulatory and signaling processes in the cell, but thus far cis-regulatory elements (CREs) in proteins have not been systematically identified and studied. Here, we introduce a computational tool that identifies intrinsically disordered protein segments that contribute to protein function regulation via interactions in cis. We apply this tool to estimate the prevalence of CREs in the human proteome and reveal that cis regulation is enriched in several signaling pathways, including the MAP kinase pathway, for which we provide a detailed map of its "cis regulome." We also show that disease-causing mutations are highly enriched in CREs, but not in motifs that classically mediate protein-protein interactions of disordered protein segments. Our approach should facilitate the discovery and characterization of CREs in proteins and the identification of disease-causing mutations that disrupt protein regulation in cis.
authors.affiliation: Department of Integrative Bioscience, University of Brain Education, 284-31 Gyocheonjisan-gil, Mokcheon-eup, Dongnam-gu, Cheonan, Chungcheongnam-do 31228, Republic of Korea.
authors.forename: Ju Hun
authors.initials: JH
authors.lastname: Yeon
authors.affiliation: Department of Biochemistry and Molecular Biology, Michael Smith Laboratories, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Florian
authors.initials: F
authors.lastname: Heinkel
authors.affiliation: School of Integrative Engineering, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
authors.forename: Minhui
authors.initials: M
authors.lastname: Sung
authors.affiliation: School of Integrative Engineering, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea; Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada. Electronic address: blisszen@cau.ac.kr.
authors.forename: Dokyun
authors.initials: D
authors.lastname: Na
authors.affiliation: Department of Biochemistry and Molecular Biology, Michael Smith Laboratories, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada; Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada. Electronic address: gsponer@chibi.ubc.ca.
authors.forename: Jörg
authors.initials: J
authors.lastname: Gsponer
mesh_terms: D019295:Computational Biology; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D011506:Proteins; D050436:Regulatory Elements, Transcriptional; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D011506:Proteins