{"doi":"10.1073/pnas.1418852112","title":"Missense mutation in immunodeficient patients shows the multifunctional roles of coiled-coil domain 3 (CC3) in STIM1 activation","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>\n                    Stromal interaction molecule (STIM) 1 is an essential activator of the ORAI1 calcium (Ca\n                    <jats:sup>2+</jats:sup>\n                    ) channel that mediates Ca\n                    <jats:sup>2+</jats:sup>\n                    entry into many cell types. Patients with mutations in\n                    <jats:italic>STIM1</jats:italic>\n                    or\n                    <jats:italic>ORAI1</jats:italic>\n                    genes suffer from a severe immunodeficiency syndrome. Here, we studied a disease-causing mutant of STIM1 that is incapable of activating ORAI1 channels, thereby uncovering key molecular mechanisms of STIM1 function. The autosomal recessive R429C mutation interferes with the structural integrity of a protein–protein interaction domain in STIM1 and impairs the ability of STIM1 to multimerize and bind to ORAI1. Drugs targeting this domain may provide a means to selectively modulate STIM1–ORAI1 interaction and Ca\n                    <jats:sup>2+</jats:sup>\n                    entry as a novel approach to treat autoimmune diseases and other disorders associated with abnormal ORAI1-mediated Ca\n                    <jats:sup>2+</jats:sup>\n                    entry.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2015,"id":29195,"datarank":2.1392386008259736,"base_score":4.127134385045092,"endowment":4.127134385045092,"self_citation_contribution":0.6190701577567639,"citation_network_contribution":1.5201684430692095,"self_endowment_contribution":0.6190701577567639,"citer_contribution":1.5201684430692095,"corpus_percentile":null,"corpus_rank":null,"citation_count":61,"citer_count":44,"citers_with_citation_signal":39,"citers_with_endowment":39,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":161569,"name":"Amit Jairaman","orcid":null,"position":1,"is_corresponding":false},{"id":161570,"name":"Peter B. Stathopulos","orcid":null,"position":2,"is_corresponding":false},{"id":161172,"name":"Martin Muik","orcid":null,"position":3,"is_corresponding":false},{"id":161175,"name":"Marc Fahrner","orcid":null,"position":4,"is_corresponding":false},{"id":78755,"name":"Carl Weidinger","orcid":"0000-0002-9948-0088","position":5,"is_corresponding":false},{"id":161574,"name":"Melina Benson","orcid":null,"position":6,"is_corresponding":false},{"id":161576,"name":"Sebastian Fuchs","orcid":null,"position":7,"is_corresponding":false},{"id":161578,"name":"Stephan Ehl","orcid":null,"position":8,"is_corresponding":false},{"id":161177,"name":"Christoph Romanin","orcid":null,"position":9,"is_corresponding":false},{"id":161579,"name":"Mitsuhiko Ikura","orcid":null,"position":10,"is_corresponding":false},{"id":161580,"name":"Murali Prakriya","orcid":null,"position":11,"is_corresponding":false},{"id":156338,"name":"Stefan Feske","orcid":null,"position":12,"is_corresponding":false},{"id":161568,"name":"Mate Maus","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.127134385045092,"endowment":4.127134385045092,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25918394","pmcid":"PMC4434767","openalex_id":"https://openalex.org/W1976015442","authors":[],"funders":[{"funder_name":"Office of Extramural Research, National Institutes of Health","grant_id":"AI097302","title":null},{"funder_name":"Gouvernement du Canada | Canadian Institutes of Health Research","grant_id":"MOP 13552","title":null},{"funder_name":"Heart and Stroke Foundation of Canada","grant_id":"G130001814 and T7181","title":null},{"funder_name":"Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada","grant_id":"05239","title":null},{"funder_name":"Austrian Science Fund","grant_id":"P25172","title":null},{"funder_name":"Bundesministerium für Bildung und Forschung","grant_id":"01EO1303","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"We 5303/1-1","title":null},{"funder_name":"Office of Extramural Research, National Institutes of Health","grant_id":"NS057499","title":null},{"funder_name":"Austrian Science Fund FWF","grant_id":"P 27263","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI097302","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R56 NS057499","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM114210","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS057499","title":null},{"funder_name":"CIHR","grant_id":"","title":null},{"funder_name":" CIHR","grant_id":"","title":null}],"total_grants":15,"fwci":6.0154,"citation_percentile":0.97392665,"influential_citations":11,"citation_trend":[{"year":2015,"count":5},{"year":2016,"count":5},{"year":2017,"count":13},{"year":2018,"count":11},{"year":2019,"count":4},{"year":2020,"count":7},{"year":2021,"count":2},{"year":2022,"count":4},{"year":2023,"count":5},{"year":2024,"count":1},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"bronze","license":"http://www.pnas.org/site/misc/userlicense.xhtml","oa_locations":[{"url":"https://www.pnas.org/content/pnas/112/19/6206.full.pdf","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/112/19/6206.full.pdf","host_type":"GREEN"},{"url":"https://www.pnas.org/content/pnas/112/19/6206.full.pdf","host_type":"publisher"},{"url":"http://www.pnas.org/syndication/doi/10.1073/pnas.1418852112","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1418852112","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1418852112","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25918394","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4434767","host_type":"repository"},{"url":"https://freidok.uni-freiburg.de/data/126021","host_type":"repository"}],"fields_of_study":["Ion Channels and Receptors","Herbal Medicine Research Studies","Toxin Mechanisms and Immunotoxins","Medicine","Biology","Calcium","Calcium Channels","Cytoplasm","Dimerization","Endoplasmic Reticulum","Fluorescence Resonance Energy Transfer","Genes, Recessive","HEK293 Cells","Homozygote","Humans","Immunologic Deficiency Syndromes","Membrane Proteins","Microscopy, Confocal","Mutation, Missense","Neoplasm Proteins","ORAI1 Protein","Protein Structure, Tertiary","Stromal Interaction Molecule 1"],"mesh_terms":["Stromal Interaction Molecule 1","ORAI1 Protein","Calcium","Cytoplasm","Endoplasmic Reticulum","Genes, Recessive","Homozygote","Humans","Immunologic Deficiency Syndromes","Membrane Proteins","Neoplasm Proteins","Calcium Channels","Protein Structure, Tertiary","Microscopy, Confocal","Dimerization","Mutation, Missense","Fluorescence Resonance Energy Transfer","HEK293 Cells"],"keywords":["STIM1","ORAI1","Endoplasmic reticulum","Cell biology","Coiled coil","Mutant","Mutation","Cytoplasm","Biology","Chemistry","Biophysics","Biochemistry","Gene","Calcium","Immunodeficiency"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T22:51:12.734173Z","pmid":null,"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":[]}