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XB-ART-53806
Mol Syst Biol June 8, 2017; 13 (6): 932.
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Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes.

Drew K , Lee C , Huizar RL , Tu F , Borgeson B , McWhite CD , Ma Y , Wallingford JB , Marcotte EM .


Abstract
Macromolecular protein complexes carry out many of the essential functions of cells, and many genetic diseases arise from disrupting the functions of such complexes. Currently, there is great interest in defining the complete set of human protein complexes, but recent published maps lack comprehensive coverage. Here, through the synthesis of over 9,000 published mass spectrometry experiments, we present hu.MAP, the most comprehensive and accurate human protein complex map to date, containing > 4,600 total complexes, > 7,700 proteins, and > 56,000 unique interactions, including thousands of confident protein interactions not identified by the original publications. hu.MAP accurately recapitulates known complexes withheld from the learning procedure, which was optimized with the aid of a new quantitative metric (k-cliques) for comparing sets of sets. The vast majority of complexes in our map are significantly enriched with literature annotations, and the map overall shows improved coverage of many disease-associated proteins, as we describe in detail for ciliopathies. Using hu.MAP, we predicted and experimentally validated candidate ciliopathy disease genes in vivo in a model vertebrate, discovering CCDC138, WDR90, and KIAA1328 to be new cilia basal body/centriolar satellite proteins, and identifying ANKRD55 as a novel member of the intraflagellar transport machinery. By offering significant improvements to the accuracy and coverage of human protein complexes, hu.MAP (http://proteincomplexes.org) serves as a valuable resource for better understanding the core cellular functions of human proteins and helping to determine mechanistic foundations of human disease.

PubMed ID: 28596423
PMC ID: PMC5488662
Article link:
Grant support: [+]

Species referenced: Xenopus
Genes referenced: ankrd55 ccdc138 cplane1 eif3a fh ift52 ift80 kiaa1328 lztfl1 ofd1 pigy wdr19 wdr90
Morpholinos: ankrd55 MO1 cplane1 MO1 ift52 MO1


Article Images: [+] show captions
References [+] :
Airik, SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling. 2016, Pubmed