Evidence map›Paper›PMID 28665962›Full record

ArticlePloS one2017

Biochemical characterization of functional domains of the chaperone Cosmc.

Melinda S Hanes, Kelley W Moremen, Richard D Cummings

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. SLC10A7 regulates O-GalNAc glycosylation and CaCellular and molecular life sciences : CMLS · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Alzheimer's & dementia (New York, N. Y.) · 2020
    Article
  12. Article
  13. Cosmc overexpression enhances malignancies in human colon cancer.Journal of cellular and molecular medicine · 2020
    Article
  14. Article
  15. Accounting for sex in the genome.Nature medicine · 2017
    Article
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

3 authors at 2 institutions in 1 country.

Melinda S HanesDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
Kelley W MoremenComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia, United States of America.
Richard D CummingsDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.ORCID http://orcid.org/0000-0002-8918-5034
Beth Israel Deaconess Medical Center · USUniversity of Georgia · US

Funding

TR&D3. Approaches to Proteoglycan Function at Biochemical and Cellular LevelsP41GM103390 · NIGMS · UNIVERSITY OF GEORGIA · PI MOREMEN, KELLEY W. · 2012 to 2019
$14.5M
Recombinant Production of Glycosylation Enzymes for Biochem/Structural StudiesP01GM107012 · NIGMS · UNIVERSITY OF GEORGIA · PI PRESTEGARD, JAMES H. · 2013 to 2017
$7.5M
Cosmc - A Novel Molecular Chaperone Regulating O-GlycansR01GM068559 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CUMMINGS, RICHARD D · 2005 to 2009
$1.2M
Defining the Tn-glycoproteome of in situ colorectal tumors and mechanisms of Tn eF32CA183215 · NCI · EMORY UNIVERSITY · PI HANES, MELINDA S. · 2014 to 2016
$181k
NCI NIH HHS F32 CA183215NIGMS NIH HHS P01 GM107012NIGMS NIH HHS P41 GM103390NIGMS NIH HHS R01 GM068559
6 · The paper itself

Abstract

Cosmc is an endoplasmic reticulum chaperone necessary for normal protein O-GalNAc glycosylation through regulation of T-synthase, its single client. Loss-of-function of Cosmc results in expression of the Tn antigen, which is associated with multiple human diseases including cancer. Despite intense interest in dysregulated expression of the Tn antigen, little is known about the structure and function of Cosmc, including domain organization, secondary structure, oligomerization, and co-factors. Limited proteolysis experiments show that Cosmc contains a structured N-terminal domain (CosmcΔ256), and biochemical characterization of CosmcΔ256 reveals wild type chaperone activity. Interestingly, CosmcE152K, which shows loss of function in vivo, exhibits wild type-like activity in vitro. Cosmc and CosmcE152K heterogeneously oligomerize and form monomeric, dimeric, trimeric, and tetrameric species, while CosmcΔ256 is predominantly monomeric as characterized by chemical crosslinking and blue native page electrophoresis. Additionally, Cosmc selectively binds divalent cations in thermal shift assays and metal binding is abrogated by the CosmcΔ256 truncation, and perturbed by the E152K mutation. Therefore, the N-terminal domain of Cosmc mediates T-synthase binding and chaperone function, whereas the C-terminal domain is necessary for oligomerization and metal binding. Our results provide new structure-function insight to Cosmc, indicate that Cosmc behaves as a modular protein and suggests points of modulation or regulation of in vivo chaperone function.

Indexed as

Amino Acid SequenceCations, DivalentHEK293 CellsHumansMolecular ChaperonesProtein BindingRecombinant ProteinsSequence Homology, Amino AcidC1GALT1C1 protein, humanCations, DivalentMolecular ChaperonesRecombinant Proteins

Identifiers

PMID28665962
PMCPMC5493369
OpenAlexW2728153976

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.