Evidence map›Paper›PMID 40739340›Full record

ArticleNature cell biology2025

PEX39 facilitates the peroxisomal import of PTS2-containing proteins.

Walter W Chen, Tony A Rodrigues, Daniel Wendscheck, Ana G Pedrosa, Chendong Yang, Tânia Francisco, Till Möcklinghoff, Alexandros Zografakis, Bernardo Nunes-Silva, Reut E Avraham and 16 more

Abstract read
In one paragraph

Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
  2. Building peroxisomes: perspectives on plant peroxins.Biochemical Society transactions · 2026
    Review
  3. Article
  4. Evolutionary remodeling of a remnant GET pathway factor into PEX38, an essential peroxin.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. 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

26 authors.

Walter W Chen *Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA. walter.chen@utsouthwestern.edu.ORCID http://orcid.org/0000-0002-7752-9581
Tony A Rodrigues *Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.ORCID http://orcid.org/0000-0003-2311-8258
Daniel Wendscheck *Biochemistry II, Theodor-Boveri-Institute, Biocenter and Faculty of Chemistry and Pharmacy, University of Würzburg, Würzburg, Germany.ORCID http://orcid.org/0000-0001-7445-4978
Ana G PedrosaInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.ORCID http://orcid.org/0000-0001-8887-2046
Chendong YangChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Tânia FranciscoInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.ORCID http://orcid.org/0000-0003-3571-5164
Till MöcklinghoffBiochemistry and Functional Proteomics, Institute of Biology II, Faculty of Biology, University of Freiburg, Freiburg, Germany.
Alexandros ZografakisBiochemistry II, Theodor-Boveri-Institute, Biocenter and Faculty of Chemistry and Pharmacy, University of Würzburg, Würzburg, Germany.
Bernardo Nunes-SilvaInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
Reut E AvrahamDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Ana R SilvaInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
Maria J FerreiraInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
Hirak DasBiochemistry II, Theodor-Boveri-Institute, Biocenter and Faculty of Chemistry and Pharmacy, University of Würzburg, Würzburg, Germany.ORCID http://orcid.org/0009-0009-6060-1557
Janet KosterLaboratory Genetic Metabolic Diseases, Amsterdam UMC-location AMC, University of Amsterdam, Amsterdam, the Netherlands.
Simone NeuwirthInstitute of Medical Physics and Biophysics, University of Münster, Münster, Germany.
Julian BenderBiochemistry II, Theodor-Boveri-Institute, Biocenter and Faculty of Chemistry and Pharmacy, University of Würzburg, Würzburg, Germany.ORCID http://orcid.org/0000-0003-3316-9999
Silke OeljeklausBiochemistry II, Theodor-Boveri-Institute, Biocenter and Faculty of Chemistry and Pharmacy, University of Würzburg, Würzburg, Germany.ORCID http://orcid.org/0000-0001-8908-4295
Varun SondhiChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-0253-7624
Christos GatsogiannisInstitute of Medical Physics and Biophysics, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0002-4922-4545
Maya SchuldinerDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.ORCID http://orcid.org/0000-0001-9947-115X
Einat ZalckvarDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Kay HofmannInstitute for Genetics, University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0002-2289-9083
Hans R WaterhamLaboratory Genetic Metabolic Diseases, Amsterdam UMC-location AMC, University of Amsterdam, Amsterdam, the Netherlands.
Ralph J DeBerardinisChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. ralph.deberardinis@utsouthwestern.edu.ORCID http://orcid.org/0000-0002-2705-7432
Jorge E AzevedoInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal. jazevedo@ibmc.up.pt.ORCID http://orcid.org/0000-0001-7714-5302
Bettina WarscheidBiochemistry II, Theodor-Boveri-Institute, Biocenter and Faculty of Chemistry and Pharmacy, University of Würzburg, Würzburg, Germany. bettina.warscheid@uni-wuerzburg.de.ORCID http://orcid.org/0000-0001-5096-1975

Funding

UT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Jeffrey M Zigman · 2022 to 2026
$7.4M
American Academy of Pediatrics (AAP) Marshall Klaus Neonatal-Perinatal Research AwardHoward Hughes Medical Institute (HHMI) Howard Hughes Medical Institute Investigator ProgramNIDDK NIH HHS P30 DK127984Thrasher Research Fund Early Career Award
6 · The paper itself

Abstract

Peroxisomes are metabolic organelles essential for human health. Defects in peroxisomal biogenesis proteins (also known as peroxins (PEXs)) cause devastating disease. PEX7 binds proteins containing a type 2 peroxisomal targeting signal (PTS2) to enable their import from the cytosol into peroxisomes, although many aspects of this process remain enigmatic. Utilizing in vitro assays, yeast and human cells, we show that PEX39, a previously uncharacterized protein, is a cytosolic peroxin that facilitates the import of PTS2-containing proteins by binding PEX7 and stabilizing its interaction with cargo proteins containing a PTS2. PEX39 and PEX13, a peroxisomal membrane translocon protein, both possess an (R/K)PWE motif necessary for PEX7 binding. Handover of PEX7 from PEX39 to PEX13 via these motifs provides a new paradigm for peroxisomal protein import and biogenesis. Collectively, this work reveals how PEX39 and (R/K)PWE motifs facilitate the import of PTS2-containing proteins and advances our understanding of peroxisomal disease.

Indexed as

Membrane ProteinsPeroxisomal Targeting SignalsPeroxisomesSaccharomyces cerevisiae ProteinsHumansPeroxinsPeroxisomal Targeting Signal 2 ReceptorProtein BindingProtein TransportSaccharomyces cerevisiaeMembrane ProteinsPeroxinsPeroxisomal Targeting Signal 2 ReceptorPeroxisomal Targeting SignalsPEX7 protein, humanSaccharomyces cerevisiae Proteins

Identifiers

PMID40739340
PMCPMC12339391

What OpenQuestion holds

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Registered trials

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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.