Evidence map›Paper›PMID 29305423›Full record

ArticleThe Journal of biological chemistry2018

Endoplasmic reticulum-resident protein 57 (ERp57) oxidatively inactivates human transglutaminase 2.

Michael C Yi, Arek V Melkonian, James A Ousey, Chaitan Khosla

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
4.2field-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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Pooled it
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  8. Structural and mechanistic analysis of CaProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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  13. Article
  14. ERp57/PDIA3: new insight.Cellular & molecular biology letters · 2022
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Michael C YiDepartment of Chemical Engineering, Stanford University, Stanford, California 94305.
Arek V MelkonianDepartment of Chemical Engineering, Stanford University, Stanford, California 94305; School of Medicine, Stanford University, Stanford, California 94305.
James A OuseyDepartment of Chemical Engineering, Stanford University, Stanford, California 94305.
Chaitan KhoslaDepartment of Chemical Engineering, Stanford University, Stanford, California 94305; Department of Chemistry, Stanford University, Stanford, California 94305; Stanford ChEM-H, Stanford University, Stanford, California 94305. Electronic address: khosla@stanford.edu.
Stanford University · US

Funding

Role of Transglutaminase 2 in Celiac SprueR01DK063158 · NIDDK · STANFORD UNIVERSITY · PI CHAITAN KHOSLA · 2003 to 2026
$11.2M
NIDDK NIH HHS R01 DK063158
6 · The paper itself

Abstract

Transglutaminase 2 (TG2) is a ubiquitously expressed, intracellular as well as extracellular protein with multiple modes of post-translational regulation, including an allosteric disulfide bond between Cys-370-Cys-371 that renders the enzyme inactive in the extracellular matrix. Although recent studies have established that extracellular TG2 is switched "on" by the redox cofactor protein thioredoxin-1 (TRX), it is unclear how TG2 is switched "off." Here, we demonstrate that TG2 oxidation by small-molecule biological oxidants, including glutathione, cystine, and hydrogen peroxide, is unlikely to be the inactivation mechanism. Instead, endoplasmic reticulum (ER)-resident protein 57 (ERp57), a protein in the ER that promotes folding of nascent proteins and is also present in the extracellular environment, has the cellular and biochemical characteristics for inactivating TG2. We found that ERp57 colocalizes with extracellular TG2 in cultured human umbilical vein endothelial cells (HUVECs). ERp57 oxidized TG2 with a rate constant that was 400-2000-fold higher than those of the aforementioned small molecule oxidants. Moreover, its specificity for TG2 was also markedly higher than those of other secreted redox proteins, including protein disulfide isomerase (PDI), ERp72, TRX, and quiescin sulfhydryl oxidase 1 (QSOX1). Lastly, siRNA-mediated ERp57 knockdown in HUVECs increased TG2-catalyzed transamidation in the extracellular environment. We conclude that, to the best of our knowledge, the disulfide bond switch in human TG2 represents the first example of a post-translational redox regulatory mechanism that is reversibly and allosterically modulated by two distinct proteins (ERp57 and TRX).

Indexed as

Protein Processing, Post-TranslationalAllosteric RegulationBiocatalysisCells, CulturedCystineEnzymes, ImmobilizedExtracellular MatrixGlutathioneGTP-Binding ProteinsHumansHuman Umbilical Vein Endothelial CellsHydrogen PeroxideMembrane GlycoproteinsOxidantsOxidation-ReductionOxidoreductases Acting on Sulfur Group DonorsCystineendoplasmic reticulum glycoprotein p72Enzymes, ImmobilizedGlutathioneGTP-Binding ProteinsHydrogen PeroxideMembrane GlycoproteinsOxidantsOxidoreductases Acting on Sulfur Group DonorsPDIA3 protein, humanPeptide FragmentsProtein Disulfide-IsomerasesProtein Glutamine gamma Glutamyltransferase 2QSOX1 protein, humanRecombinant ProteinsThioredoxinsTransglutaminasesceliac diseasedisulfideERp57oxidation-reduction (redox)PDIA3post-translational modification (PTM)protein disulfide isomerase family A member 3redox switchthioredoxintransglutaminasetransglutaminase 2

Identifiers

PMID29305423
PMCPMC5827427
OpenAlexW2782190004

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.