SubCellBarCode: Proteome-wide Mapping of Protein Localization and Relocalization

Mol Cell. 2019 Jan 3;73(1):166-182.e7. doi: 10.1016/j.molcel.2018.11.035.

Abstract

Subcellular localization is a main determinant of protein function; however, a global view of cellular proteome organization remains relatively unexplored. We have developed a robust mass spectrometry-based analysis pipeline to generate a proteome-wide view of subcellular localization for proteins mapping to 12,418 individual genes across five cell lines. Based on more than 83,000 unique classifications and correlation profiling, we investigate the effect of alternative splicing and protein domains on localization, complex member co-localization, cell-type-specific localization, as well as protein relocalization after growth factor inhibition. Our analysis provides information about the cellular architecture and complexity of the spatial organization of the proteome; we show that the majority of proteins have a single main subcellular location, that alternative splicing rarely affects subcellular location, and that cell types are best distinguished by expression of proteins exposed to the surrounding environment. The resource is freely accessible via www.subcellbarcode.org.

Keywords: mass spectrometry; organelle proteome; protein domains; protein localization; proteogenomics; proteomics; splice variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Cell Fractionation
  • Chromatography, Liquid*
  • Computational Biology
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Gefitinib / pharmacology
  • Humans
  • Isoelectric Focusing
  • MCF-7 Cells
  • Mass Spectrometry*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Transport
  • Proteins / antagonists & inhibitors
  • Proteins / classification
  • Proteins / genetics
  • Proteins / metabolism*
  • Proteome*
  • Proteomics / methods*
  • Reproducibility of Results
  • Subcellular Fractions / classification
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism*

Substances

  • Biomarkers
  • Protein Kinase Inhibitors
  • Proteins
  • Proteome
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib