Evidence map›Paper›PMID 26091039›Full record

ArticleCell2015

A Single Kinase Generates the Majority of the Secreted Phosphoproteome.

Vincent S Tagliabracci, Sandra E Wiley, Xiao Guo, Lisa N Kinch, Eric Durrant, Jianzhong Wen, Junyu Xiao, Jixin Cui, Kim B Nguyen, James L Engel and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers.

0numbers the graph read from it
0cells of the map it votes in
206citing papers in PubMed
12.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

206 citing papers in PubMed, 350 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Article
  7. Reduced Dietary Protein Induces Changes in the Dental Proteome.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2026
    Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

146 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Vincent S TagliabracciDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Sandra E WileyDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Xiao GuoDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Lisa N KinchDepartment of Biophysics, University of Texas, Southwestern Medical Center, Dallas, TX 75390-9050, USA.
Eric DurrantDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Jianzhong WenDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Junyu XiaoDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Jixin CuiDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Kim B NguyenDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
James L EngelDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Joshua J CoonDepartment of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Nick GrishinDepartment of Biophysics, University of Texas, Southwestern Medical Center, Dallas, TX 75390-9050, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Lorenzo A PinnaDepartment of Biomedical Sciences, University of Padova, 35121 Padova, Italy; Venetian Institute of Molecular Medicine, 35129 Padova, Italy.
David J PagliariniDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Jack E DixonDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: jedixon@mail.ucsd.edu.
University of California, San Diego · USUniversity of Wisconsin–Madison · USHoward Hughes Medical Institute · USThe University of Texas Southwestern Medical Center · USUniversity of Padua · IT

Funding

GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
REGULATION OF NEUROPEPTIDE BIOSYNTHESISR01DK018849 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DIXON, JACK E, WORBY, CAROLYN ANN · 1986 to 2020
$7.0M
STUDIES ON PANCREATIC HORMONESR37DK018024 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DIXON, JACK E · 1988 to 2013
$5.6M
Regulation of Mitochondrial Metabolism by Post-Translational ModificationsR01DK098672 · NIDDK · WASHINGTON UNIVERSITY · PI David J Pagliarini · 2013 to 2026
$4.8M
Computational methods for structural-functional studies of proteinsR01GM094575 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI GRISHIN, NICK V. · 2010 to 2017
$2.4M
STUDIES ON PANCREATIC HORMONESR01DK018024 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIXON, JACK E, WORBY, CAROLYN ANN · 1986 to 2018
$2.1M
Phosphorylation of FGF23 coordinates crosstalk between the skeleton and kidneyK99DK099254 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAGLIABRACCI, VINCENT SCOTT · 2013 to 2014
$180k
NIDDK NIH HHS DK018024-37NIDDK NIH HHS DK018849-36NIDDK NIH HHS K99 DK099254NIDDK NIH HHS K99DK099254NIDDK NIH HHS R01 DK018024NIDDK NIH HHS R01 DK018849NIDDK NIH HHS R01 DK098672NIDDK NIH HHS R01DK098672NIDDK NIH HHS R37 DK018024NIGMS NIH HHS GM094575NIGMS NIH HHS R01 GM094575NIGMS NIH HHS T32 GM007752
6 · The paper itself

Abstract

The existence of extracellular phosphoproteins has been acknowledged for over a century. However, research in this area has been undeveloped largely because the kinases that phosphorylate secreted proteins have escaped identification. Fam20C is a kinase that phosphorylates S-x-E/pS motifs on proteins in milk and in the extracellular matrix of bones and teeth. Here, we show that Fam20C generates the majority of the extracellular phosphoproteome. Using CRISPR/Cas9 genome editing, mass spectrometry, and biochemistry, we identify more than 100 secreted phosphoproteins as genuine Fam20C substrates. Further, we show that Fam20C exhibits broader substrate specificity than previously appreciated. Functional annotations of Fam20C substrates suggest roles for the kinase beyond biomineralization, including lipid homeostasis, wound healing, and cell migration and adhesion. Our results establish Fam20C as the major secretory pathway protein kinase and serve as a foundation for new areas of investigation into the role of secreted protein phosphorylation in human biology and disease.

Indexed as

Amino Acid SequenceBlood ProteinsCasein Kinase ICell AdhesionCell MovementCerebrospinal Fluid ProteinsExtracellular Matrix ProteinsGene Knockout TechniquesGene OntologyHumansMolecular Sequence DataPhosphoproteinsSecretory PathwaySubstrate SpecificityBlood ProteinsCasein Kinase ICerebrospinal Fluid ProteinsExtracellular Matrix ProteinsFAM20C protein, humanPhosphoproteins

Identifiers

PMID26091039
PMCPMC4963185
OpenAlexW1866421377

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.