Evidence map›Paper›PMID 25395623›Full record

ArticleThe Journal of biological chemistry2014

Unfolded protein response-regulated Drosophila Fic (dFic) protein reversibly AMPylates BiP chaperone during endoplasmic reticulum homeostasis.

Hyeilin Ham, Andrew R Woolery, Charles Tracy, Drew Stenesen, Helmut Krämer, Kim Orth

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

85 citing papers in PubMed, 143 citations in OpenAlex.

  1. bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Article
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  5. Inhibition of FicD-mediated AMPylation and deAMPylation by isoprenoid diphosphates.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. AMPylation: key roles in biological regulation across prokaryotes and eukaryotes.Frontiers in cellular and infection microbiology · 2026
    Review
  8. Review
  9. The functional dynamics of FicD's TPR domain are modulated by the interaction with ATP and BiP.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Article
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  17. FicD sensitizes cellular response to glucose fluctuations in mouse embryonic fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  18. Article
  19. Article
  20. Article

25 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

6 authors at 1 institution in 1 country.

Hyeilin HamFrom the Departments of Molecular Biology and.
Andrew R WooleryFrom the Departments of Molecular Biology and.
Charles TracyNeuroscience, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
Drew StenesenNeuroscience, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
Helmut KrämerNeuroscience, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
Kim OrthFrom the Departments of Molecular Biology and kim.orth@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · US

Funding

DIVISION OF CELL &MOLECULAR BIOLOGY TRAINING PROGRAMT32GM008203 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI COBB, MELANIE H. · 1987 to 2018
$7.0M
Biochemical Characterization of Yersinia Effector YopJ.R01AI056404 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI ORTH, KIM · 2003 to 2012
$2.8M
AMPylation, a novel mechanism regulating visual neurotransmissionR01EY021922 · NEI · UT SOUTHWESTERN MEDICAL CENTER · PI KRAMER, HELMUT J · 2011 to 2015
$1.7M
SEM for UT Southwestern EM Core FacilityS10OD020103 · OD · UT SOUTHWESTERN MEDICAL CENTER · PI LUBY-PHELPS, KATHERINE J · 2015 to 2015
$306k
NEI NIH HHS R01 EY021922NIAID NIH HHS R01 AI056404NIAID NIH HHS R01-AI056404NIGMS NIH HHS 5T32GM008203NIGMS NIH HHS T32 GM008203NIH HHS S10 OD020103
6 · The paper itself

Abstract

Drosophila Fic (dFic) mediates AMPylation, a covalent attachment of adenosine monophosphate (AMP) from ATP to hydroxyl side chains of protein substrates. Here, we identified the endoplasmic reticulum (ER) chaperone BiP as a substrate for dFic and mapped the modification site to Thr-366 within the ATPase domain. The level of AMPylated BiP in Drosophila S2 cells is high during homeostasis, whereas the level of AMPylated BiP decreases upon the accumulation of misfolded proteins in the ER. Both dFic and BiP are transcriptionally activated upon ER stress, supporting the role of dFic in the unfolded protein response pathway. The inactive conformation of BiP is the preferred substrate for dFic, thus endorsing a model whereby AMPylation regulates the function of BiP as a chaperone, allowing acute activation of BiP by deAMPylation during an ER stress response. These findings not only present the first substrate of eukaryotic AMPylator but also provide a target for regulating the unfolded protein response, an emerging avenue for cancer therapy.

Indexed as

Unfolded Protein ResponseAdenosine MonophosphateAmino Acid SequenceAnimalsCatalytic DomainCell LineDrosophila melanogasterDrosophila ProteinsEndoplasmic ReticulumEndoplasmic Reticulum StressHomeostasisHSC70 Heat-Shock ProteinsMolecular Sequence DataNucleotidyltransferasesProtein Processing, Post-TranslationalTranscription, GeneticAdenosine MonophosphateDrosophila ProteinsFic protein, DrosophilaHsc70-3 protein, DrosophilaHSC70 Heat-Shock ProteinsNucleotidyltransferasesAdenosineAMPAMPylationBiPChaperoneDrosophilaER Stressgrp78Unfolded Protein Response (UPR)

Identifiers

PMID25395623
PMCPMC4276871
OpenAlexW2088745167

What OpenQuestion holds

Textmetadata
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.