Curation of the Mammalian Palmitoylome Indicates a Pivotal Role for Palmitoylation in Diseases and Disorders of the Nervous System and Cancers.
Palmitoylation involves the reversible posttranslational addition of palmitate to cysteines and promotes membrane binding and subcellular localization. Recent advancements in the detection and identification of palmitoylated proteins have led to multiple palmitoylation proteomics studies but these datasets are contained within large supplemental tables, making downstream analysis and data mining time-consuming and difficult. Consequently, we curated the data from 15 palmitoylation proteomics studies into one compendium containing 1,838 genes encoding palmitoylated proteins; representing approximately 10% of the genome. Enrichment analysis revealed highly significant enrichments for Gene Ontology biological processes, pathway maps, and process networks related to the nervous system. Strikingly, 41% of synaptic genes encode a palmitoylated protein in the compendium. The top disease associations included cancers and diseases and disorders of the nervous system, with Schizophrenia, HD, and pancreatic ductal carcinoma among the top five, suggesting that aberrant palmitoylation may play a pivotal role in the balance of cell death and survival. This compendium provides a much-needed resource for cell biologists and the palmitoylation field, providing new perspectives for cancer and neurodegeneration.
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Shaun S
SS
Sanders
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Dale D O
DD
Martin
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Stefanie L
SL
Butland
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, United States of America.
Mathieu
M
Lavallée-Adam
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, United States of America.
Diego
D
Calzolari
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Chris
C
Kay
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, United States of America.
John R
JR
Yates
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Michael R
MR
Hayden
D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D030562:Databases, Protein; D006801:Humans; D054878:Lipoylation; D009369:Neoplasms / Q000378:metabolism*; D009422:Nervous System Diseases / Q000378:metabolism*; D010168:Palmitates / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods*
D010168:Palmitates; D020543:Proteome; D003545:Cysteine