Evidence map›Paper›PMID 25419960›Full record

ArticleNature methods2015

Directed evolution of APEX2 for electron microscopy and proximity labeling.

Stephanie S Lam, Jeffrey D Martell, Kimberli J Kamer, Thomas J Deerinck, Mark H Ellisman, Vamsi K Mootha, Alice Y Ting

Open access · bronzeAbstract read
In one paragraph

Article in Nature methods, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 870 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
870citing papers in PubMed, 1 pooled it
25.7field-weighted citation impact, top 1% 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

870 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,401 citations in OpenAlex.

  1. Pooled it
  2. Review
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  15. Article
  16. Evolving faster proximity chemistry.Nature chemical biology · 2026
    Article
  17. Article
  18. Review
  19. Article
  20. A Spatiotemporal Atlas of the Androgen Receptor Proximal Interactome.bioRxiv : the preprint server for biology · 2026
    Article

810 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 3 institutions in 1 country.

Stephanie S LamDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Jeffrey D MartellDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Kimberli J KamerDepartment of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID 0000000187287793
Thomas J DeerinckNational Center for Microscopy and Imaging Research, University of California at San Diego, La Jolla, California, USA.
Mark H Ellisman1] National Center for Microscopy and Imaging Research, University of California at San Diego, La Jolla, California, USA. [2] Department of Neurosciences, University of California at San Diego, La Jolla, California, USA.
Vamsi K MoothaDepartment of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Alice Y TingDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Massachusetts Institute of Technology · USMassachusetts General Hospital · USUniversity of California San Diego · US

Funding

IVEM and Image Analysis ResourceP41GM103412 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELLISMAN, MARK H · 2012 to 2019
$17.9M
New Probe and Methods for Correlated LM & EMR01GM086197 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ADAMS, STEPHEN ROY, BOASSA, DANIELA · 2008 to 2020
$8.3M
Characterization of the Mitochondrial ProteomeR01GM077465 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MOOTHA, VAMSI KRISHNA · 2007 to 2016
$4.3M
Enabling the study of endogenous proteins in live cellsDP1OD003961 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TING, ALICE Y · 2008 to 2011
$3.4M
Howard Hughes Medical InstituteNIGMS NIH HHS 5R01GM077465-08NIGMS NIH HHS P41 GM103412NIGMS NIH HHS R01 GM077465NIGMS NIH HHS R01 GM086197NIGMS NIH HHS R01GM086197NIH HHS DP1 OD003961
6 · The paper itself

Abstract

APEX is an engineered peroxidase that functions as an electron microscopy tag and a promiscuous labeling enzyme for live-cell proteomics. Because limited sensitivity precludes applications requiring low APEX expression, we used yeast-display evolution to improve its catalytic efficiency. APEX2 is far more active in cells, enabling the use of electron microscopy to resolve the submitochondrial localization of calcium uptake regulatory protein MICU1. APEX2 also permits superior enrichment of endogenous mitochondrial and endoplasmic reticulum membrane proteins.

Indexed as

AnimalsAscorbate PeroxidasesCalcium-Binding ProteinsCation Transport ProteinsChlorocebus aethiopsCOS CellsDirected Molecular EvolutionHEK293 CellsHeLa CellsHumansMicroscopy, Electron, TransmissionMitochondriaMitochondrial Membrane Transport ProteinsProteomicsSaccharomyces cerevisiaeAscorbate PeroxidasesCalcium-Binding ProteinsCation Transport ProteinsMICU1 protein, humanMitochondrial Membrane Transport Proteins

Identifiers

PMID25419960
PMCPMC4296904
OpenAlexW2023949937

What OpenQuestion holds

Textmetadata
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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.