{"doi":"10.1084/jem.20201708","title":"Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity is required for V(D)J recombination","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.","journal":"The Journal of Experimental Medicine","year":2021,"id":170867,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":415570,"name":"Bo-Ruei Chen","orcid":"0000-0001-6404-2099","position":1,"is_corresponding":false},{"id":704489,"name":"Yinan Wang","orcid":"0000-0001-8030-9494","position":2,"is_corresponding":false},{"id":704490,"name":"Philip Curman","orcid":"0000-0003-2051-8491","position":3,"is_corresponding":false},{"id":704491,"name":"Helen A. Beilinson","orcid":"0000-0002-2888-5256","position":4,"is_corresponding":false},{"id":704492,"name":"Ryan M. Brecht","orcid":"0000-0003-4989-6111","position":5,"is_corresponding":false},{"id":616360,"name":"Catherine C. Liu","orcid":"0000-0002-2093-7170","position":6,"is_corresponding":false},{"id":704493,"name":"Ryan Farrell","orcid":"0000-0003-4022-8707","position":7,"is_corresponding":false},{"id":704494,"name":"Jaime de Juan‐Sanz","orcid":"0000-0002-1212-5623","position":8,"is_corresponding":false},{"id":273572,"name":"Louis‐Marie Charbonnier","orcid":"0000-0002-4594-7893","position":9,"is_corresponding":false},{"id":34059,"name":"Shingo Kajimura","orcid":"0000-0003-0672-5910","position":10,"is_corresponding":false},{"id":568496,"name":"Timothy Aidan Ryan","orcid":"0000-0003-2533-9548","position":11,"is_corresponding":false},{"id":375810,"name":"David G. Schatz","orcid":"0000-0002-5669-1176","position":12,"is_corresponding":false},{"id":273573,"name":"Talal A. Chatila","orcid":"0000-0001-7439-2762","position":13,"is_corresponding":false},{"id":704495,"name":"Jakob D. Wikström","orcid":"0000-0002-9241-6817","position":14,"is_corresponding":false},{"id":675415,"name":"Jessica K. Tyler","orcid":"0000-0001-9765-1659","position":15,"is_corresponding":false},{"id":244456,"name":"Barry P. Sleckman","orcid":"0000-0001-8295-4462","position":16,"is_corresponding":false},{"id":704488,"name":"Chun-Chin Chen","orcid":"0000-0001-8247-8734","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:46:28.747384Z","pmid":"34033676","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}