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How many human proteoforms are there?
Aebersold, Ruedi; Agar, Jeffrey N; Amster, I Jonathan; Baker, Mark S; Bertozzi, Carolyn R; Boja, Emily S; Costello, Catherine E; Cravatt, Benjamin F; Fenselau, Catherine; Garcia, Benjamin A; Ge, Ying; Gunawardena, Jeremy; Hendrickson, Ronald C; Hergenrother, Paul J; Huber, Christian G; Ivanov, Alexander R; Jensen, Ole N; Jewett, Michael C; Kelleher, Neil L; Kiessling, Laura L; Krogan, Nevan J; Larsen, Martin R; Loo, Joseph A; Ogorzalek Loo, Rachel R; Lundberg, Emma; MacCoss, Michael J; Mallick, Parag; Mootha, Vamsi K; Mrksich, Milan; Muir, Tom W; Patrie, Steven M; Pesavento, James J; Pitteri, Sharon J; Rodriguez, Henry; Saghatelian, Alan; Sandoval, Wendy; Schlüter, Hartmut; Sechi, Salvatore; Slavoff, Sarah A; Smith, Lloyd M; Snyder, Michael P; Thomas, Paul M; Uhlén, Mathias; Van Eyk, Jennifer E; Vidal, Marc; Walt, David R; White, Forest M; Williams, Evan R; Wohlschlager, Therese; Wysocki, Vicki H.
Afiliação
  • Aebersold R; Department of Biology, ETH Zurich, Zürich, Switzerland.
  • Agar JN; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA.
  • Amster IJ; Department of Chemistry, University of Georgia, Athens, Georgia, USA.
  • Baker MS; Department of Biomedical Sciences, Macquarie University, Sydney, New South Wales, Australia.
  • Bertozzi CR; Department of Chemistry, Stanford University, Stanford, California, USA.
  • Boja ES; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, Maryland, USA.
  • Costello CE; Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, USA.
  • Cravatt BF; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.
  • Fenselau C; Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, USA.
  • Garcia BA; Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, and Epigenetics Institute, Philadelphia, Pennsylvania, USA.
  • Ge Y; Department of Cell and Regenerative Biology, Human Proteomics Program, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • Gunawardena J; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • Hendrickson RC; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
  • Hergenrother PJ; Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Huber CG; Department of Chemistry, University of Illinois, Urbana, Illinois, USA.
  • Ivanov AR; Department of Biosciences and Christian Doppler Laboratory for Biosimilar Characterization, University of Salzburg, Salzburg, Austria.
  • Jensen ON; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA.
  • Jewett MC; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
  • Kelleher NL; The Center for Synthetic Biology, Northwestern University, Evanston, Illinois, USA.
  • Kiessling LL; Department of Chemistry, Molecular Biosciences and the Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA.
  • Krogan NJ; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Larsen MR; Department of Cellular Molecular Pharmacology, University of California, San Francisco, California, USA.
  • Loo JA; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
  • Ogorzalek Loo RR; Department of Biological Chemistry, University of California, Los Angeles, California, USA.
  • Lundberg E; Department of Biological Chemistry, University of California, Los Angeles, California, USA.
  • MacCoss MJ; Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Mallick P; Department of Genetics, Stanford University, Stanford, California, USA.
  • Mootha VK; Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
  • Mrksich M; Department of Chemistry, Stanford University, Stanford, California, USA.
  • Muir TW; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
  • Patrie SM; The Center for Synthetic Biology, Northwestern University, Evanston, Illinois, USA.
  • Pesavento JJ; Department of Chemistry, Princeton University, Princeton, New Jersey, USA.
  • Pitteri SJ; Department of Chemistry, Molecular Biosciences and the Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA.
  • Rodriguez H; Department of Biology, Saint Mary's College of California, Moraga, California, USA.
  • Saghatelian A; Department of Chemistry, Stanford University, Stanford, California, USA.
  • Sandoval W; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, Maryland, USA.
  • Schlüter H; Salk Institute for Biological Studies, Torrey Pines, California, USA.
  • Sechi S; Applied Proteomics, Genentech, Inc., San Francisco, California, USA.
  • Slavoff SA; Department of Clinical Chemistry/Central Laboratories, University Medical Center Hamburg - Eppendorf, Hamburg, Germany.
  • Smith LM; National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA.
  • Snyder MP; Department of Chemistry, Yale University, New Haven, Connecticut, USA.
  • Thomas PM; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • Uhlén M; Genome Center of Wisconsin, Madison, Wisconsin, USA.
  • Van Eyk JE; Department of Genetics, Stanford University, Stanford, California, USA.
  • Vidal M; Department of Chemistry, Molecular Biosciences and the Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA.
  • Walt DR; Department of Microbiology, KTH Royal Institute of Technology, Stockholm, Sweden.
  • White FM; Cedars Sinai Medical Center, Los Angeles, California, USA.
  • Williams ER; Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
  • Wohlschlager T; Department of Pathology, Harvard Medical School and Wyss Institute at Harvard University, Boston, Massachusetts, USA.
  • Wysocki VH; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Nat Chem Biol ; 14(3): 206-214, 2018 02 14.
Article em En | MEDLINE | ID: mdl-29443976
Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas / Genoma Humano / Processamento de Proteína Pós-Traducional / Proteoma / Proteômica Limite: Humans Idioma: En Revista: Nat Chem Biol Assunto da revista: BIOLOGIA / QUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas / Genoma Humano / Processamento de Proteína Pós-Traducional / Proteoma / Proteômica Limite: Humans Idioma: En Revista: Nat Chem Biol Assunto da revista: BIOLOGIA / QUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Suíça