Evidence map›Paper›PMID 36806354›Full record

ArticleMolecular cell2023

Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames.

Clara-L Sandmann, Jana F Schulz, Jorge Ruiz-Orera, Marieluise Kirchner, Matthias Ziehm, Eleonora Adami, Maike Marczenke, Annabel Christ, Nina Liebe, Johannes Greiner and 13 more

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Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing 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

104 citing papers in PubMed.

  1. DetectNAR genomics and bioinformatics · 2026
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  13. Sketching microprotein portraits.Protein science : a publication of the Protein Society · 2026
    Review
  14. Article
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  18. Review
  19. Article
  20. Phenotypic CRISPR screens identify NLRX1 as an essential activator of the human mitochondrial permeability transition.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article

44 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

23 authors.

Clara-L SandmannMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 13347 Berlin, Germany.
Jana F SchulzMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 13347 Berlin, Germany.
Jorge Ruiz-OreraMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Marieluise KirchnerMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Facility Proteomics, 10117 Berlin, Germany.
Matthias ZiehmMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Facility Proteomics, 10117 Berlin, Germany.
Eleonora AdamiMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Maike MarczenkeMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Annabel ChristMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Nina LiebeMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Johannes GreinerMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Aaron SchoenenbergerMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Michael B MueckeMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 13347 Berlin, Germany; Charité-Universitätsmedizin, 10117 Berlin, Germany.
Ning LiangMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Robert L MoritzInstitute for Systems Biology, Seattle, WA 98109, USA.
Zhi SunInstitute for Systems Biology, Seattle, WA 98109, USA.
Eric W DeutschInstitute for Systems Biology, Seattle, WA 98109, USA.
Michael GotthardtMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 13347 Berlin, Germany; Charité-Universitätsmedizin, 10117 Berlin, Germany.
Jonathan M MudgeEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
John R PrensnerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Thomas E WillnowMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
Philipp MertinsMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Facility Proteomics, 10117 Berlin, Germany.
Sebastiaan van HeeschPrincess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, the Netherlands. Electronic address: s.vanheesch@prinsesmaximacentrum.nl.
Norbert HubnerMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 13347 Berlin, Germany; Charité-Universitätsmedizin, 10117 Berlin, Germany. Electronic address: nhuebner@mdc-berlin.de.

Funding

Systems BiologyU19AG023122 · NIA · TRANSLATIONAL GENOMICS RESEARCH INST · PI JODI A LAPIDUS · 2004 to 2026
$102.6M
GENCODE Resource ProjectU41HG007234 · NHGRI · SANGER INSTITUTE · PI FLICEK, PAUL · 2013 to 2020
$20.3M
GENCODE: comprehensive reference genome annotation for human and mouseU24HG007234 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI Fergal James Martin · 2021 to 2026
$16.1M
Shortening the development cycle time of Trans Proteomic Pipeline tools with high performance computingR01GM087221 · NIGMS · INSTITUTE FOR SYSTEMS BIOLOGY · PI DEUTSCH, ERIC, MORITZ, ROBERT L · 2010 to 2021
$6.0M
Deciphering non-canonical translation in high risk medulloblastomaK08CA263552 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Prensner · 2022 to 2026
$1.2M
British Heart FoundationNCI NIH HHS K08 CA263552NHGRI NIH HHS U24 HG007234NHGRI NIH HHS U41 HG007234NIA NIH HHS U19 AG023122NIGMS NIH HHS R01 GM087221
6 · The paper itself

Abstract

All species continuously evolve short open reading frames (sORFs) that can be templated for protein synthesis and may provide raw materials for evolutionary adaptation. We analyzed the evolutionary origins of 7,264 recently cataloged human sORFs and found that most were evolutionarily young and had emerged de novo. We additionally identified 221 previously missed sORFs potentially translated into peptides of up to 15 amino acids-all of which are smaller than the smallest human microprotein annotated to date. To investigate the bioactivity of sORF-encoded small peptides and young microproteins, we subjected 266 candidates to a mass-spectrometry-based interactome screen with motif resolution. Based on these interactomes and additional cellular assays, we can associate several candidates with mRNA splicing, translational regulation, and endocytosis. Our work provides insights into the evolutionary origins and interaction potential of young and small proteins, thereby helping to elucidate this underexplored territory of the human proteome.

Indexed as

PeptidesProtein BiosynthesisHumansMicropeptidesOpen Reading FramesProteomicsMicropeptidesPeptidesde novo genesmicroproteinsprimate-specific proteinsPRISMAprotein evolutionprotein interactomeribosome profilingshort linear motifs, SLiMsshort ORFsshort peptides

Identifiers

PMID36806354
PMCPMC10032668

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Textfull text, public
LicenceCC BY
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identifiers read3
Read underepoch 390

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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.