A Census of Human Soluble Protein Complexes

被引:706
作者
Havugimana, Pierre C. [2 ,3 ]
Hart, G. Traver [2 ,3 ]
Nepusz, Tamas [1 ]
Yang, Haixuan [1 ]
Turinsky, Andrei L. [5 ]
Li, Zhihua [6 ]
Wang, Peggy I. [6 ]
Boutz, Daniel R. [6 ]
Fong, Vincent [2 ]
Phanse, Sadhna [2 ]
Babu, Mohan [2 ]
Craig, Stephanie A. [6 ]
Hu, Pingzhao [2 ]
Wan, Cuihong [2 ]
Vlasblom, James [3 ,5 ]
Dar, Vaqaar-un-Nisa [7 ]
Bezginov, Alexandr [7 ]
Clark, Gregory W. [7 ]
Wu, Gabriel C. [6 ]
Wodak, Shoshana J. [3 ,4 ,5 ]
Tillier, Elisabeth R. M. [7 ]
Paccanaro, Alberto [1 ]
Marcotte, Edward M. [6 ]
Emili, Andrew [2 ,3 ]
机构
[1] Univ London, Dept Comp Sci, Egham TW20 0EX, Surrey, England
[2] Univ Toronto, Banting & Best Dept Med Res, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada
[3] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada
[4] Univ Toronto, Dept Biochem, Toronto, ON M5S 3E1, Canada
[5] Hosp Sick Children, Toronto, ON M5G 1X8, Canada
[6] Univ Texas Austin, Dept Chem & Biochem, Ctr Syst & Synthet Biol, Inst Cellular & Mol Biol, Austin, TX 78712 USA
[7] Univ Toronto, Campbell Family Inst Canc Res, Ontario Canc Inst, Univ Hlth Network, Toronto, ON M5G 1L7, Canada
基金
美国国家科学基金会; 美国国家卫生研究院; 英国生物技术与生命科学研究理事会;
关键词
SYSTEMATIC ANALYSIS; INTERACTION NETWORK; CELL; ORGANIZATION; GENES; SCALE; MUTATIONS; DISCOVERY; 8Q24; MAP;
D O I
10.1016/j.cell.2012.08.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Cellular processes often depend on stable physical associations between proteins. Despite recent progress, knowledge of the composition of human protein complexes remains limited. To close this gap, we applied an integrative global proteomic profiling approach, based on chromatographic separation of cultured human cell extracts into more than one thousand biochemical fractions that were subsequently analyzed by quantitative tandem mass spectrometry, to systematically identify a network of 13,993 high-confidence physical interactions among 3,006 stably associated soluble human proteins. Most of the 622 putative protein complexes we report are linked to core biological processes and encompass both candidate disease genes and unannotated proteins to inform on mechanism. Strikingly, whereas larger multiprotein assemblies tend to be more extensively annotated and evolutionarily conserved, human protein complexes with five or fewer subunits are far more likely to be functionally unannotated or restricted to vertebrates, suggesting more recent functional innovations.
引用
收藏
页码:1068 / 1081
页数:14
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