Evidence map›Paper›PMID 25527291›Full record

ArticleThe EMBO journal2015

Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis.

Tobias Wauer, Kirby N Swatek, Jane L Wagstaff, Christina Gladkova, Jonathan N Pruneda, Martin A Michel, Malte Gersch, Christopher M Johnson, Stefan M V Freund, David Komander

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
189citing papers in PubMed, 1 pooled it
13.4field-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

189 citing papers in PubMed, 1 synthesis or guideline pooled it, 307 citations in OpenAlex.

  1. Pooled it
  2. Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. Phospho-ubiquitin: rewriting the ubiquitin code.Molecular neurodegeneration · 2026
    Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Autophagy and Mitophagy in Diabetic Kidney Disease-A Literature Review.International journal of molecular sciences · 2025
    Review
  18. Review
  19. Article
  20. Review

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Tobias WauerMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Kirby N SwatekMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Jane L WagstaffMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Christina GladkovaMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Jonathan N PrunedaMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Martin A MichelMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Malte GerschMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Christopher M JohnsonMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Stefan M V FreundMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
David KomanderMedical Research Council Laboratory of Molecular Biology, Cambridge, UK dk@mrc-lmb.cam.ac.uk.
MRC Laboratory of Molecular Biology · GBMedical Research Council · GB

Funding

European Research Council 309756Medical Research Council MC_U105192732Medical Research Council U105192732
6 · The paper itself

Abstract

The protein kinase PINK1 was recently shown to phosphorylate ubiquitin (Ub) on Ser65, and phosphoUb activates the E3 ligase Parkin allosterically. Here, we show that PINK1 can phosphorylate every Ub in Ub chains. Moreover, Ser65 phosphorylation alters Ub structure, generating two conformations in solution. A crystal structure of the major conformation resembles Ub but has altered surface properties. NMR reveals a second phosphoUb conformation in which β5-strand slippage retracts the C-terminal tail by two residues into the Ub core. We further show that phosphoUb has no effect on E1-mediated E2 charging but can affect discharging of E2 enzymes to form polyUb chains. Notably, UBE2R1- (CDC34), UBE2N/UBE2V1- (UBC13/UEV1A), TRAF6- and HOIP-mediated chain assembly is inhibited by phosphoUb. While Lys63-linked poly-phosphoUb is recognized by the TAB2 NZF Ub binding domain (UBD), 10 out of 12 deubiquitinases (DUBs), including USP8, USP15 and USP30, are impaired in hydrolyzing phosphoUb chains. Hence, Ub phosphorylation has repercussions for ubiquitination and deubiquitination cascades beyond Parkin activation and may provide an independent layer of regulation in the Ub system.

Indexed as

Adaptor Proteins, Signal TransducingAllosteric RegulationEndopeptidasesEndosomal Sorting Complexes Required for TransportHumansHydrolysisMitochondrial ProteinsPhosphoproteinsPhosphorylationPolyubiquitinProtein MultimerizationProtein Structure, TertiarySerineThiolester HydrolasesTNF Receptor-Associated Factor 6Transcription FactorsAdaptor Proteins, Signal TransducingCDC34 protein, humanEndopeptidasesEndosomal Sorting Complexes Required for TransportMitochondrial Proteinsparkin proteinPhosphoproteinsPolyubiquitinRNF31 protein, humanSerineTAB2 protein, humanThiolester HydrolasesTNF Receptor-Associated Factor 6Transcription FactorsUBE2N protein, humanUBE2V1 protein, humanUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesUbiquitin-Specific ProteasesUbiquitin ThiolesteraseUSP15 protein, humanUsp30 protein, humanUSP8 protein, humandeubiquitinaseParkinphosphorylationPINK1ubiquitin

Identifiers

PMID25527291
PMCPMC4339119
OpenAlexW2106142195

What OpenQuestion holds

Textmetadata
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.