Evidence map›Paper›PMID 30374462›Full record

ArticleCommunications biology2018

Mannosidase activity of EDEM1 and EDEM2 depends on an unfolded state of their glycoprotein substrates.

Marina Shenkman, Efrat Ron, Rivka Yehuda, Ron Benyair, Isam Khalaila, Gerardo Z Lederkremer

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

32 citing papers in PubMed, 58 citations in OpenAlex.

  1. Studying Glycan-Dependent ERAD of Misfolded Glycoproteins in Plants.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  2. N-glycan-dependent protein maturation and quality control in the ER.Nature reviews. Molecular cell biology · 2025
    Review
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  6. StaufenC facilitates utilization of the ERAD pathway to transport dsRNA through the endoplasmic reticulum to the cytosol.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Turnover of EDEM1, an ERAD-enhancing factor, is mediated by multiple degradation routes.Genes to cells : devoted to molecular & cellular mechanisms · 2024
    Article
  8. Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?Current issues in molecular biology · 2024
    Review
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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

6 authors at 2 institutions in 1 country.

Marina ShenkmanSchool of Molecular Cell Biology and Biotechnology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.
Efrat RonSchool of Molecular Cell Biology and Biotechnology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.
Rivka YehudaAvram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.
Ron BenyairSchool of Molecular Cell Biology and Biotechnology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.
Isam KhalailaAvram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.
Gerardo Z LederkremerSchool of Molecular Cell Biology and Biotechnology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel. gerardo@post.tau.ac.il.
Tel Aviv University · ILBen-Gurion University of the Negev · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Extensive mannose trimming of nascent glycoprotein N-glycans signals their targeting to endoplasmic reticulum-associated degradation (ERAD). ER mannosidase I (ERManI) and the EDEM protein family participate in this process. However, whether the EDEMs are truly mannosidases can be addressed only by measuring mannosidase activity in vitro. Here, we reveal EDEM1 and EDEM2 mannosidase activities in vitro. Whereas ERManI significantly trims free N-glycans, activity of the EDEMs is modest on free oligosaccharides and on glycoproteins. However, mannosidase activity of ERManI and the EDEMs is significantly higher on a denatured glycoprotein. The EDEMs associate with oxidoreductases, protein disulfide isomerase, and especially TXNDC11, enhancing mannosidase activity on glycoproteins but not on free N-glycans. The finding that substrate unfolded status increases mannosidase activity solves an important conundrum, as current models suggest general slow mannose trimming. As we show, misfolded or unfolded glycoproteins are subject to differentially faster trimming (and targeting to ERAD) than well-folded ones.

Identifiers

PMID30374462
PMCPMC6194124
OpenAlexW2897545365

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.