title: Accounting for Protein Subcellular Localization: A Compartmental Map of the Rat Liver Proteome.
abstract: Accurate knowledge of the intracellular location of proteins is important for numerous areas of biomedical research including assessing fidelity of putative protein-protein interactions, modeling cellular processes at a system-wide level and investigating metabolic and disease pathways. Many proteins have not been localized, or have been incompletely localized, partly because most studies do not account for entire subcellular distribution. Thus, proteins are frequently assigned to one organelle whereas a significant fraction may reside elsewhere. As a step toward a comprehensive cellular map, we used subcellular fractionation with classic balance sheet analysis and isobaric labeling/quantitative mass spectrometry to assign locations to >6000 rat liver proteins. We provide quantitative data and error estimates describing the distribution of each protein among the eight major cellular compartments: nucleus, mitochondria, lysosomes, peroxisomes, endoplasmic reticulum, Golgi, plasma membrane and cytosol. Accounting for total intracellular distribution improves quality of organelle assignments and assigns proteins with multiple locations. Protein assignments and supporting data are available online through the Prolocate website (http://prolocate.cabm.rutgers.edu). As an example of the utility of this data set, we have used organelle assignments to help analyze whole exome sequencing data from an infant dying at 6 months of age from a suspected neurodegenerative lysosomal storage disorder of unknown etiology. Sequencing data was prioritized using lists of lysosomal proteins comprising well-established residents of this organelle as well as novel candidates identified in this study. The latter included copper transporter 1, encoded by SLC31A1, which we localized to both the plasma membrane and lysosome. The patient harbors two predicted loss of function mutations in SLC31A1, suggesting that this may represent a heretofore undescribed recessive lysosomal storage disease gene.
authors.affiliation: From the ‡URPhyM-Laboratoire de Chimie Physiologique, Université de Namur, 61 rue de Bruxelles, Namur 5000, Belgium; michel.jadot@unamur.be sleat@cabm.rutgers.edu lobel@cabm.rutgers.edu.
authors.forename: Michel
authors.initials: M
authors.lastname: Jadot
authors.affiliation: From the ‡URPhyM-Laboratoire de Chimie Physiologique, Université de Namur, 61 rue de Bruxelles, Namur 5000, Belgium.
authors.forename: Marielle
authors.initials: M
authors.lastname: Boonen
authors.affiliation: From the ‡URPhyM-Laboratoire de Chimie Physiologique, Université de Namur, 61 rue de Bruxelles, Namur 5000, Belgium.
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Thirion
authors.affiliation: §Department of Genetics, Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ 08854.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: §Department of Genetics, Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ 08854.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Xing
authors.affiliation: ¶Center for Advanced Biotechnology and Medicine, Rutgers Biomedical and Health Sciences, 679 Hoes Lane West, Piscataway, New Jersey 08854.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Zhao
authors.affiliation: ¶Center for Advanced Biotechnology and Medicine, Rutgers Biomedical and Health Sciences, 679 Hoes Lane West, Piscataway, New Jersey 08854.
authors.forename: Abla
authors.initials: A
authors.lastname: Tannous
authors.affiliation: ¶Center for Advanced Biotechnology and Medicine, Rutgers Biomedical and Health Sciences, 679 Hoes Lane West, Piscataway, New Jersey 08854.
authors.forename: Meiqian
authors.initials: M
authors.lastname: Qian
authors.affiliation: ¶Center for Advanced Biotechnology and Medicine, Rutgers Biomedical and Health Sciences, 679 Hoes Lane West, Piscataway, New Jersey 08854.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zheng
authors.affiliation: ¶Center for Advanced Biotechnology and Medicine, Rutgers Biomedical and Health Sciences, 679 Hoes Lane West, Piscataway, New Jersey 08854.
authors.forename: John K
authors.initials: JK
authors.lastname: Everett
authors.affiliation: ‖Department of Biostatistics, School of Public Health, Rutgers Biomedical and Health Sciences, 683 Hoes Lane West, Piscataway, New Jersey 08854.
authors.forename: Dirk F
authors.initials: DF
authors.lastname: Moore
authors.affiliation: ¶Center for Advanced Biotechnology and Medicine, Rutgers Biomedical and Health Sciences, 679 Hoes Lane West, Piscataway, New Jersey 08854; michel.jadot@unamur.be sleat@cabm.rutgers.edu lobel@cabm.rutgers.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Sleat
authors.affiliation: ¶Center for Advanced Biotechnology and Medicine, Rutgers Biomedical and Health Sciences, 679 Hoes Lane West, Piscataway, New Jersey 08854; michel.jadot@unamur.be sleat@cabm.rutgers.edu lobel@cabm.rutgers.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Lobel
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics / Q000378:metabolism; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030562:Databases, Protein; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism*; D016464:Lysosomal Storage Diseases / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D013058:Mass Spectrometry; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017422:Sequence Analysis, DNA; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; D020543:Proteome; C489857:SLC3A1 protein, human