Evidence map›Paper›PMID 34326324›Full record

ArticleNature communications2021

Antibody toolkit reveals N-terminally ubiquitinated substrates of UBE2W.

Christopher W Davies, Simon E Vidal, Lilian Phu, Jawahar Sudhamsu, Trent B Hinkle, Scott Chan Rosenberg, Frances-Rose Schumacher, Yi Jimmy Zeng, Carsten Schwerdtfeger, Andrew S Peterson and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Substrate biasing in UCHL5 proteoforms.bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Proteomic approaches to study ubiquitinomics.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023
    Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Non-lysine ubiquitylation: Doing things differently.Frontiers in molecular biosciences · 2022
    Review
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

16 authors at 5 institutions in 2 countries.

Christopher W Davies *Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9559-438X
Simon E Vidal *Departments of Molecular Oncology and Early Discovery Biochemistry, Genentech, Inc., South San Francisco, CA, USA.
Lilian Phu *Department of Microchemistry, Proteomics, and Lipidomics, Genentech, Inc., South San Francisco, CA, USA.
Jawahar SudhamsuDepartment of Structural Biology, Genentech, Inc., South San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0737-2299
Trent B HinkleDepartment of Microchemistry, Proteomics, and Lipidomics, Genentech, Inc., South San Francisco, CA, USA.
Scott Chan RosenbergDepartments of Molecular Oncology and Early Discovery Biochemistry, Genentech, Inc., South San Francisco, CA, USA.
Frances-Rose SchumacherDepartment of Microchemistry, Proteomics, and Lipidomics, Genentech, Inc., South San Francisco, CA, USA.
Yi Jimmy ZengDepartment of Microchemistry, Proteomics, and Lipidomics, Genentech, Inc., South San Francisco, CA, USA.
Carsten SchwerdtfegerBoston Biochem, a Bio-Techne Brand 840 Memorial Drive, Cambridge, MA, USA.
Andrew S PetersonDepartment of Molecular Biology, Genentech, Inc., South San Francisco, CA, USA.
Jennie R LillDepartment of Microchemistry, Proteomics, and Lipidomics, Genentech, Inc., South San Francisco, CA, USA.
Christopher M RoseDepartment of Microchemistry, Proteomics, and Lipidomics, Genentech, Inc., South San Francisco, CA, USA.
Andrey S ShawResearch Biology, Genentech, Inc., South San Francisco, CA, USA.
Ingrid E WertzDepartments of Molecular Oncology and Early Discovery Biochemistry, Genentech, Inc., South San Francisco, CA, USA. ingrid.wertz@bms.com.ORCID http://orcid.org/0000-0002-7979-9374
Donald S KirkpatrickDepartment of Microchemistry, Proteomics, and Lipidomics, Genentech, Inc., South San Francisco, CA, USA. dkirkpatrick@interlinetx.com.
James T KoerberDepartment of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA. koerberj@gene.com.ORCID http://orcid.org/0000-0001-7756-972X
Molecular Oncology (United States) · USBioChem Technology (United States) · USBristol-Myers Squibb (United States) · USGene Therapy Laboratory · FRInterScience (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ubiquitin conjugating enzyme UBE2W catalyzes non-canonical ubiquitination on the N-termini of proteins, although its substrate repertoire remains unclear. To identify endogenous N-terminally-ubiquitinated substrates, we discover four monoclonal antibodies that selectively recognize tryptic peptides with an N-terminal diglycine remnant, corresponding to sites of N-terminal ubiquitination. Importantly, these antibodies do not recognize isopeptide-linked diglycine (ubiquitin) modifications on lysine. We solve the structure of one such antibody bound to a Gly-Gly-Met peptide to reveal the molecular basis for its selective recognition. We use these antibodies in conjunction with mass spectrometry proteomics to map N-terminal ubiquitination sites on endogenous substrates of UBE2W. These substrates include UCHL1 and UCHL5, where N-terminal ubiquitination distinctly alters deubiquitinase (DUB) activity. This work describes an antibody toolkit for enrichment and global profiling of endogenous N-terminal ubiquitination sites, while revealing functionally relevant substrates of UBE2W.

Indexed as

Amino Acid SequenceAnimalsAntibodiesCells, CulturedCrystallography, X-RayHumansMass SpectrometryPeptidesProtein BindingProteomicsRabbitsUbiquitinated ProteinsUbiquitinationUbiquitin-Conjugating EnzymesAntibodiesPeptidesUBE2W protein, humanUbiquitinated ProteinsUbiquitin-Conjugating Enzymes

Identifiers

PMID34326324
PMCPMC8322077
OpenAlexW3186208044

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.