Evidence map›Paper›PMID 23994600›Full record

ArticleBiochimica et biophysica acta2014

Non-canonical translation start sites in the TMEM16A chloride channel.

Elvira Sondo, Paolo Scudieri, Valeria Tomati, Emanuela Caci, Amelia Mazzone, Gianrico Farrugia, Roberto Ravazzolo, Luis J V Galietta

Open access · hybridAbstract read
In one paragraph

Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Polymodal Control of TMEM16x Channels and Scramblases.International journal of molecular sciences · 2022
    Review
  2. Review
  3. Recent progress in structural studies on TMEM16A channel.Computational and structural biotechnology journal · 2020
    Review
  4. Direct repression of anoctamin 1 (FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  5. CaThe Journal of biological chemistry · 2018
    Article
  6. Article
  7. Article
  8. EAVK segment "c" sequence confers CaAmerican journal of physiology. Gastrointestinal and liver physiology · 2017
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. A novel exon in the human Ca2+-activated Cl- channel Ano1 imparts greater sensitivity to intracellular Ca2.American journal of physiology. Gastrointestinal and liver physiology · 2015
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. 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

8 authors at 3 institutions in 2 countries.

Elvira SondoU.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
Paolo Scudieri
Valeria Tomati
Emanuela Caci
Amelia Mazzone
Gianrico Farrugia
Roberto Ravazzolo
Luis J V Galietta
Istituto Giannina Gaslini · ITMayo Clinic · USUniversity of Genoa · IT

Funding

CALCIUM DYNAMICS IN INTERSTITIAL CELLS OF CAJALR01DK057061 · NIDDK · MAYO CLINIC ROCHESTER · PI GIANRICO FARRUGIA, Tamas Ordog · 2000 to 2026
$8.2M
NIDDK NIH HHS DK57061NIDDK NIH HHS R01 DK057061Telethon GGP10026
6 · The paper itself

Abstract

TMEM16A is a plasma membrane protein with voltage- and calcium-dependent chloride channel activity. The role of the various TMEM16A domains in expression and function is poorly known. In a previous study, we found that replacing the first ATG of the TMEM16A coding sequence with a nonsense codon (M1X mutation), to force translation from the second ATG localized at position 117, only had minor functional consequences. Therefore, we concluded that this region is dispensable for TMEM16A processing and channel activity. We have now removed the first 116 codons from the TMEM16A coding sequence. Surprisingly, the expression of the resulting mutant, Δ(1-116), resulted in complete loss of activity. We hypothesized that, in the mutant M1X, translation may start at a position before the second ATG, using a non-canonical start codon. Therefore, we placed an HA-epitope at position 89 in the M1X mutant. We found, by western blot analysis, that the HA-epitope can be detected, thus demonstrating that translation starts from an upstream non-ATG codon. We truncated the N-terminus of TMEM16A at different sites while keeping the HA-epitope. We found that stepwise shortening of TMEM16A caused an in parallel stepwise decrease in TMEM16A expression and function. Our results indicate that indeed the N-terminus of TMEM16A is important for its activity. The use of an alternative start codon appears to occur in a naturally-occurring TMEM16A isoform that is particularly expressed in human testis. Future experiments will need to address the role of normal and alternative amino-terminus in TMEM16A structure and function.

Indexed as

Anoctamin-1Bacterial ProteinsBase SequenceCalciumChloride ChannelsChloridesGenes, ReporterHEK293 CellsHumansIon TransportLuminescent ProteinsMaleMolecular Sequence DataMutationNeoplasm ProteinsOpen Reading FramesANO1 protein, humanAnoctamin-1Bacterial ProteinsCalciumChloride ChannelsChloridesLuminescent ProteinsNeoplasm Proteinsyellow fluorescent protein, BacteriaCa(2+)-activated Cl(−) channelCaCCChloride channelhalide-sensitive yellow fluorescent proteinHS-YFPNon-canonical start codonProtein translationStructure–function relationship

Identifiers

PMID23994600
PMCPMC3898931
OpenAlexW2225840870

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.