Evidence map›Paper›PMID 25581026›Full record

ArticlePloS one2015

Members of the chloride intracellular ion channel protein family demonstrate glutaredoxin-like enzymatic activity.

Heba Al Khamici, Louise J Brown, Khondker R Hossain, Amanda L Hudson, Alxcia A Sinclair-Burton, Jane Phui Mun Ng, Elizabeth L Daniel, Joanna E Hare, Bruce A Cornell, Paul M G Curmi and 2 more

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

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

59 citing papers in PubMed, 109 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. CLIC1 Supports Mechanisms Related to Platelet Activation and Thrombosis.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Biomolecules · 2023
    Article
  15. CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA.Arteriosclerosis, thrombosis, and vascular biology · 2023
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

12 authors at 3 institutions in 1 country.

Heba Al KhamiciSchool of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, New South Wales 2007, Australia.
Louise J BrownDepartment of Chemistry and Bimolecular Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.
Khondker R HossainSchool of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, New South Wales 2007, Australia; Bragg Institute, Australian Nuclear Science and Technology Organisation, Sydney, New South Wales 2234, Australia.
Amanda L HudsonSchool of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, New South Wales 2007, Australia.
Alxcia A Sinclair-BurtonSchool of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, New South Wales 2007, Australia.
Jane Phui Mun NgSchool of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, New South Wales 2007, Australia.
Elizabeth L DanielDepartment of Chemistry and Bimolecular Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.
Joanna E HareDepartment of Chemistry and Bimolecular Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.
Bruce A CornellSurgical Diagnostics, Roseville, Sydney, New South Wales 2069, Australia.
Paul M G CurmiSchool of Physics, University of New South Wales, Sydney, New South Wales 2052, Australia; Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales 2010, Australia.
Mary W DaveySchool of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, New South Wales 2007, Australia.
Stella M ValenzuelaSchool of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, New South Wales 2007, Australia; Centre for Health Technologies, University of Technology Sydney, Sydney, New South Wales 2007, Australia.
University of Technology Sydney · AUMacquarie University · AUUNSW Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Chloride Intracellular Ion Channel (CLIC) family consists of six evolutionarily conserved proteins in humans. Members of this family are unusual, existing as both monomeric soluble proteins and as integral membrane proteins where they function as chloride selective ion channels, however no function has previously been assigned to their soluble form. Structural studies have shown that in the soluble form, CLIC proteins adopt a glutathione S-transferase (GST) fold, however, they have an active site with a conserved glutaredoxin monothiol motif, similar to the omega class GSTs. We demonstrate that CLIC proteins have glutaredoxin-like glutathione-dependent oxidoreductase enzymatic activity. CLICs 1, 2 and 4 demonstrate typical glutaredoxin-like activity using 2-hydroxyethyl disulfide as a substrate. Mutagenesis experiments identify cysteine 24 as the catalytic cysteine residue in CLIC1, which is consistent with its structure. CLIC1 was shown to reduce sodium selenite and dehydroascorbate in a glutathione-dependent manner. Previous electrophysiological studies have shown that the drugs IAA-94 and A9C specifically block CLIC channel activity. These same compounds inhibit CLIC1 oxidoreductase activity. This work for the first time assigns a functional activity to the soluble form of the CLIC proteins. Our results demonstrate that the soluble form of the CLIC proteins has an enzymatic activity that is distinct from the channel activity of their integral membrane form. This CLIC enzymatic activity may be important for protecting the intracellular environment against oxidation. It is also likely that this enzymatic activity regulates the CLIC ion channel function.

Indexed as

Protein ConformationAmino Acid SequenceChloride ChannelsGlutaredoxinsGlutathione TransferaseModels, MolecularProtein Structure, TertiaryChloride ChannelsGLRX protein, humanGlutaredoxinsGlutathione Transferase

Identifiers

PMID25581026
PMCPMC4291220
OpenAlexW2025436502

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.