Evidence map›Paper›PMID 34033676›Full record

ArticleThe Journal of experimental medicine2021

Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity is required for V(D)J recombination.

Chun-Chin Chen, Bo-Ruei Chen, Yinan Wang, Philip Curman, Helen A Beilinson, Ryan M Brecht, Catherine C Liu, Ryan J Farrell, Jaime de Juan-Sanz, Louis-Marie Charbonnier and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

20 citing papers in PubMed, 24 citations in OpenAlex.

  1. Darier disease-A review highlighting new insights from the Darier Disease International Task Force.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Darier disease: Current insights and challenges in pathogenesis and management.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. CaBiophysics reports · 2024
    Article
  15. Article
  16. Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024
    Review
  17. Article
  18. Article
  19. Article
  20. CaInternational journal of molecular sciences · 2023
    Article
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

17 authors at 6 institutions in 2 countries.

Chun-Chin Chen *Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.ORCID 0000-0001-8247-8734
Bo-Ruei Chen *Department of Medicine, Division of Hematology and Oncology, University of Alabama at Birmingham School of Medicine, Birmingham, AL.ORCID 0000-0001-6404-2099
Yinan WangDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.ORCID 0000-0001-8030-9494
Philip CurmanDermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.ORCID 0000-0003-2051-8491
Helen A BeilinsonDepartment of Immunobiology, Yale School of Medicine, New Haven, CT.ORCID 0000-0002-2888-5256
Ryan M BrechtDepartment of Immunobiology, Yale School of Medicine, New Haven, CT.ORCID 0000-0003-4989-6111
Catherine C LiuDepartment of Immunobiology, Yale School of Medicine, New Haven, CT.ORCID 0000-0002-2093-7170
Ryan J FarrellDepartment of Biochemistry, Weill Cornell Medicine, New York, NY.ORCID 0000-0003-4022-8707
Jaime de Juan-SanzDepartment of Biochemistry, Weill Cornell Medicine, New York, NY.ORCID 0000-0002-1212-5623
Louis-Marie CharbonnierDivision of Immunology, Department of Pediatrics, Boston Children's Hospital, Boston, MA.ORCID 0000-0002-4594-7893
Shingo KajimuraBeth Israel Deaconess Medical Center, Division of Endocrinology, Diabetes and Metabolism, Harvard Medical School, Boston, MA.ORCID 0000-0003-0672-5910
Timothy A RyanDepartment of Biochemistry, Weill Cornell Medicine, New York, NY.ORCID 0000-0003-2533-9548
David G SchatzDepartment of Immunobiology, Yale School of Medicine, New Haven, CT.ORCID 0000-0002-5669-1176
Talal A ChatilaDivision of Immunology, Department of Pediatrics, Boston Children's Hospital, Boston, MA.ORCID 0000-0001-7439-2762
Jakob D WikstromDermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.ORCID 0000-0002-9241-6817
Jessica K TylerDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.ORCID 0000-0001-9765-1659
Barry P SleckmanDepartment of Medicine, Division of Hematology and Oncology, University of Alabama at Birmingham School of Medicine, Birmingham, AL.ORCID 0000-0001-8295-4462
Cornell University · USYale University · USBoston Children's Hospital · USKarolinska University Hospital · SEUniversity of Alabama at Birmingham · USBeth Israel Deaconess Medical Center · US

Funding

THE V(D)J RECOMBINATION REACTION AND ITS IMPACT ON LYMPHOCYTE DEVELOPMENTR01AI047829 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI SLECKMAN, BARRY P · 2000 to 2021
$7.0M
Mechanism and Targeting of V(D)J RecombinationR01AI032524 · NIAID · YALE UNIVERSITY · PI David G. Schatz · 1992 to 2026
$6.7M
ATM FUNCTION DURING V(D)J RECOMBINATIONR01AI074953 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI SLECKMAN, BARRY P · 2009 to 2023
$5.9M
Molecular mechanisms of UCP1-independent pathways in metabolic healthR01DK097441 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Shingo Kajimura · 2012 to 2026
$5.9M
Chromatin's Role in Repair of Radiation-induced Damage.R01CA095641 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI TYLER, JESSICA K · 2002 to 2023
$5.2M
Chromatin Assembly, Structure and FunctionR01GM064475 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI TYLER, JESSICA K · 2002 to 2019
$4.4M
Physiology of Single Synaptic CNS TerminalsR37NS036942 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI RYAN, TIMOTHY AIDAN · 2016 to 2022
$3.5M
Immunoglobulin and T Cell Receptor Gene AssemblyR37AI032524 · NIAID · YALE UNIVERSITY · PI SCHATZ, DAVID G. · 2007 to 2016
$3.5M
Novel pathways that regulate DNA double-strand break repair events in mammalian cellsR35GM139816 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI TYLER, JESSICA K · 2021 to 2025
$2.1M
NCI NIH HHS R01 CA095641NIAID NIH HHS R01 AI032524NIAID NIH HHS R01 AI047829NIAID NIH HHS R01 AI074953NIAID NIH HHS R37 AI032524NIDDK NIH HHS R01 DK097441NIGMS NIH HHS R01 GM064475NIGMS NIH HHS R35 GM139816NINDS NIH HHS R37 NS036942
6 · The paper itself

Abstract

A whole-genome CRISPR/Cas9 screen identified ATP2A2, the gene encoding the Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2 protein, as being important for V(D)J recombination. SERCAs are ER transmembrane proteins that pump Ca2+ from the cytosol into the ER lumen to maintain the ER Ca2+ reservoir and regulate cytosolic Ca2+-dependent processes. In preB cells, loss of SERCA2 leads to reduced V(D)J recombination kinetics due to diminished RAG-mediated DNA cleavage. SERCA2 deficiency in B cells leads to increased expression of SERCA3, and combined loss of SERCA2 and SERCA3 results in decreased ER Ca2+ levels, increased cytosolic Ca2+ levels, reduction in RAG1 and RAG2 gene expression, and a profound block in V(D)J recombination. Mice with B cells deficient in SERCA2 and humans with Darier disease, caused by heterozygous ATP2A2 mutations, have reduced numbers of mature B cells. We conclude that SERCA proteins modulate intracellular Ca2+ levels to regulate RAG1 and RAG2 gene expression and V(D)J recombination and that defects in SERCA functions cause lymphopenia.

Indexed as

AnimalsB-LymphocytesCalciumDNA-Binding ProteinsGene Expression RegulationHomeodomain ProteinsHomeostasisHumansLymphopeniaMiceSarcoplasmic Reticulum Calcium-Transporting ATPasesV(D)J RecombinationCalciumDNA-Binding ProteinsHomeodomain ProteinsRAG-1 proteinRag2 protein, mouseSarcoplasmic Reticulum Calcium-Transporting ATPases

Identifiers

PMID34033676
PMCPMC8155808
OpenAlexW3163964422

What OpenQuestion holds

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Read underepoch 390

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.