Evidence map›Paper›PMID 24980701›Full record

ArticleeLife2014

A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity.

Jason Tien, Christian J Peters, Xiu Ming Wong, Tong Cheng, Yuh Nung Jan, Lily Yeh Jan, Huanghe Yang

Open access · goldAbstract read
In one paragraph

Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
6.8field-weighted citation impact, top 2% 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

89 citing papers in PubMed, 133 citations in OpenAlex.

  1. Review
  2. Calcium-activated chloride channel TMEM16A opens via pi-helical transition in transmembrane segment 4.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Review
  5. Niclosamide potentiates TMEM16A and induces vasoconstriction.The Journal of general physiology · 2024
    Article
  6. Review
  7. The role of anoctamin 1 in liver disease.Journal of cellular and molecular medicine · 2024
    Review
  8. Article
  9. Review
  10. KCNE1 does not shift TMEM16A from a CaPflugers Archiv : European journal of physiology · 2023
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Polymodal Control of TMEM16x Channels and Scramblases.International journal of molecular sciences · 2022
    Review
  16. Review
  17. The diverse roles of TMEM16A CaJournal of advanced research · 2021
    Review
  18. Article
  19. An outer-pore gate modulates the pharmacology of the TMEM16A channel.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  20. The CaActa pharmaceutica Sinica. B · 2021
    Review

29 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

7 authors at 2 institutions in 1 country.

Jason TienDepartment of Physiology, University of California, San Francisco, San Francisco, United States.
Christian J PetersDepartment of Physiology, University of California, San Francisco, San Francisco, United States.
Xiu Ming WongGraduate Program in Chemistry and Chemical Biology, University of California, San Francisco, San Francisco, United States.
Tong ChengDepartment of Physiology, University of California, San Francisco, San Francisco, United States.
Yuh Nung JanDepartment of Physiology, University of California, San Francisco, San Francisco, United States.
Lily Yeh JanDepartment of Physiology, University of California, San Francisco, San Francisco, United States.
Huanghe YangDepartment of Physiology, University of California, San Francisco, San Francisco, United States.
University of California, San Francisco · USHoward Hughes Medical Institute · US

Funding

Molecular, Genetic & Physiological Studies of Calcium-activated Chloride ChannelsR01NS069229 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAN, LILY Y · 2011 to 2020
$3.5M
TMEM16A Channel Stoichiometry and Subunit InteractionF31NS076180 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TIEN, JASON · 2011 to 2013
$120k
Ca2+ activated TMEM16 channels and their physiological roles in the brainK99NS086916 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YANG, HUANGHE · 2014 to 2015
$117k
Howard Hughes Medical InstituteNINDS NIH HHS 5F31NS076180NINDS NIH HHS F31 NS076180NINDS NIH HHS K99 NS086916NINDS NIH HHS K99NS086916NINDS NIH HHS R01 NS069229NINDS NIH HHS R01NS069229
6 · The paper itself

Abstract

TMEM16A forms calcium-activated chloride channels (CaCCs) that regulate physiological processes such as the secretions of airway epithelia and exocrine glands, the contraction of smooth muscles, and the excitability of neurons. Notwithstanding intense interest in the mechanism behind TMEM16A-CaCC calcium-dependent gating, comprehensive surveys to identify and characterize potential calcium sensors of this channel are still lacking. By aligning distantly related calcium-activated ion channels in the TMEM16 family and conducting systematic mutagenesis of all conserved acidic residues thought to be exposed to the cytoplasm, we identify four acidic amino acids as putative calcium-binding residues. Alterations of the charge, polarity, and size of amino acid side chains at these sites alter the ability of different divalent cations to activate the channel. Furthermore, TMEM16A mutant channels containing double cysteine substitutions at these residues are sensitive to the redox potential of the internal solution, providing evidence for their physical proximity and solvent accessibility.

Indexed as

Gene Expression RegulationAlanineAmino Acid SequenceAnimalsAnoctamin-1Binding SitesCalciumCalmodulinChloride ChannelsCysteineDrosophilaElectrophysiologyGreen Fluorescent ProteinsHEK293 CellsHumansIonsAlanineANO1 protein, humanAnoctamin-1CalciumCalmodulinChloride ChannelsCysteineGreen Fluorescent ProteinsIonsNeoplasm ProteinsSolventsStrontiumANO1 channelsbiochemistrybiophysicscalcium activated chloride channelscalcium binding sitecalcium dependent activationfrogfruit flyhumanmousestructural biologyTMEM16A channelsTMEM16 channels

Identifiers

PMID24980701
PMCPMC4112547
OpenAlexW2124883248

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.