title: Characterization and prediction of lysine (K)-acetyl-transferase specific acetylation sites.
abstract: Lysine acetylation is a well-studied post-translational modification on both histone and nonhistone proteins. More than 2000 acetylated proteins and 4000 lysine acetylation sites have been identified by large scale mass spectrometry or traditional experimental methods. Although over 20 lysine (K)-acetyl-transferases (KATs) have been characterized, which KAT is responsible for a given protein or lysine site acetylation is mostly unknown. In this work, we collected KAT-specific acetylation sites manually and analyzed sequence features surrounding the acetylated lysine of substrates from three main KAT families (CBP/p300, GCN5/PCAF, and the MYST family). We found that each of the three KAT families acetylates lysines with different sequence features. Based on these differences, we developed a computer program, Acetylation Set Enrichment Based method to predict which KAT-families are responsible for acetylation of a given protein or lysine site. Finally, we evaluated the efficiency of our method, and experimentally detected four proteins that were predicted to be acetylated by two KAT families when one representative member of the KAT family is over expressed. We conclude that our approach, combined with more traditional experimental methods, may be useful for identifying KAT families responsible for acetylated substrates proteome-wide.
authors.affiliation: Department of Biomedical Informatics, Peking University Health Science Center, Beijing 100191, China; Institute of Systems Biomedicine, Peking University Health Science Center, Beijing 100191, China. Electronic address: litt@hsc.pku.edu.cn.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Du
authors.affiliation: MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing 100084, China; College of Computer Science and Technology, Jilin University, Changchun 130012, China.
authors.forename: Likun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Advanced Computing Research Laboratory, Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China; Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Biomedical Informatics, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.affiliation: MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Xuegong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China; The Center for Life Science, Peking University, Beijing 100871, China. Electronic address: zhuweiguo@bjmu.edu.cn.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Zhu
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D003198:Computer Simulation; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D051548:Histone Acetyltransferases