Evidence map›Paper›PMID 33310703›Full record

ArticleThe Journal of biological chemistry

ATP13A3 is a major component of the enigmatic mammalian polyamine transport system.

Norin Nabil Hamouda, Chris Van den Haute, Roeland Vanhoutte, Ragna Sannerud, Mujahid Azfar, Rupert Mayer, Álvaro Cortés Calabuig, Johannes V Swinnen, Patrizia Agostinis, Veerle Baekelandt and 6 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 5% 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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Pooled it
  2. Functional Characterization of the P-Type ATPases ATP13A3 and ATP13A4 as Plasma Membrane Polyamine Transporters.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  3. iScience · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Polyamine Metabolism in Brain Health and Disease.Neuropharmacology and therapy · 2026
    Article
  11. Review
  12. Article
  13. Polyamine homeostasisbioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Antitumor potential of polyamines in cancer.Acta biochimica et biophysica Sinica · 2025
    Review
  19. Article
  20. Article

1 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

16 authors at 5 institutions in 2 countries.

Norin Nabil HamoudaLaboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Chris Van den HauteLaboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium; Leuven Viral Vector Core, KU Leuven, Leuven, Belgium.
Roeland VanhoutteLaboratory of Chemical Biology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Ragna SannerudVIB-KU Leuven Laboratory of Membrane Trafficking, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Mujahid AzfarLaboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Rupert MayerDepartment for Biomolecular Medicine, VIB Center for Medical Biotechnology, VIB Proteomics Core, Ghent University, Ghent, Belgium.
Álvaro Cortés CalabuigGenomics Core Leuven, KU Leuven, Leuven, Belgium.
Johannes V SwinnenLaboratory of Lipid Metabolism and Cancer, Department of Oncology, LKI - Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
Patrizia AgostinisLaboratory of Cell Death Research & Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; Department of Oncology, VIB-KU Leuven Center for Cancer Biology, KU Leuven, Leuven, Belgium.
Veerle BaekelandtLaboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Wim AnnaertVIB-KU Leuven Laboratory of Membrane Trafficking, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Francis ImpensDepartment for Biomolecular Medicine, VIB Center for Medical Biotechnology, VIB Proteomics Core, Ghent University, Ghent, Belgium.
Steven H L VerhelstLaboratory of Chemical Biology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; Chemical Proteomics, Leibniz Institute for Analytical Sciences ISAS, Dortmund, Germany.
Jan EggermontLaboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Shaun MartinLaboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Peter VangheluweLaboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. Electronic address: peter.vangheluwe@kuleuven.be.
KU Leuven · BEGhent University · BEVIB-KU Leuven Center for Brain & Disease Research · BEVIB-KU Leuven Center for Cancer Biology · BELeibniz Institute for Analytical Sciences - ISAS · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Polyamines, such as putrescine, spermidine, and spermine, are physiologically important polycations, but the transporters responsible for their uptake in mammalian cells remain poorly characterized. Here, we reveal a new component of the mammalian polyamine transport system using CHO-MG cells, a widely used model to study alternative polyamine uptake routes and characterize polyamine transport inhibitors for therapy. CHO-MG cells present polyamine uptake deficiency and resistance to a toxic polyamine biosynthesis inhibitor methylglyoxal bis-(guanylhydrazone) (MGBG), but the molecular defects responsible for these cellular characteristics remain unknown. By genome sequencing of CHO-MG cells, we identified mutations in an unexplored gene, ATP13A3, and found disturbed mRNA and protein expression. ATP13A3 encodes for an orphan P5B-ATPase (ATP13A3), a P-type transport ATPase that represents a candidate polyamine transporter. Interestingly, ATP13A3 complemented the putrescine transport deficiency and MGBG resistance of CHO-MG cells, whereas its knockdown in WT cells induced a CHO-MG phenotype demonstrated as a decrease in putrescine uptake and MGBG sensitivity. Taken together, our findings identify ATP13A3, which has been previously genetically linked with pulmonary arterial hypertension, as a major component of the mammalian polyamine transport system that confers sensitivity to MGBG.

Indexed as

Adenosine TriphosphatasesAnimalsBiological TransportCHO CellsCricetinaeCricetulusEnzyme InhibitorsMembrane Transport ProteinsMitoguazoneMutationPolyaminesPutrescineWhole Genome SequencingAdenosine TriphosphatasesEnzyme InhibitorsMembrane Transport ProteinsMitoguazonePolyaminesPutrescineATP13A3P5B-ATPasepolyaminepolyamine transport systemP-type ATPaseputrescinetransporter

Identifiers

PMID33310703
PMCPMC7948421
OpenAlexW3110810222

What OpenQuestion holds

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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.