{"doi":"10.3390/ijms232314568","title":"Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β","abstract":"<jats:p>Orai1, the first identified member of the Orai protein family, is ubiquitously expressed in the animal kingdom. Orai1 was initially characterized as the channel responsible for the store-operated calcium entry (SOCE), a major mechanism that allows cytosolic calcium concentration increments upon receptor-mediated IP3 generation, which results in intracellular Ca2+ store depletion. Furthermore, current evidence supports that abnormal Orai1 expression or function underlies several disorders. Orai1 is, together with STIM1, the key element of SOCE, conducting the Ca2+ release-activated Ca2+ (CRAC) current and, in association with TRPC1, the store-operated Ca2+ (SOC) current. Additionally, Orai1 is involved in non-capacitative pathways, as the arachidonate-regulated or LTC4-regulated Ca2+ channel (ARC/LRC), store-independent Ca2+ influx activated by the secretory pathway Ca2+-ATPase (SPCA2) and the small conductance Ca2+-activated K+ channel 3 (SK3). Furthermore, Orai1 possesses two variants, Orai1α and Orai1β, the latter lacking 63 amino acids in the N-terminus as compared to the full-length Orai1α form, which confers distinct features to each variant. Here, we review the current knowledge about the differences between Orai1α and Orai1β, the implications of the Ca2+ signals triggered by each variant, and their downstream modulatory effect within the cell.</jats:p>","journal":"International Journal of Molecular Sciences","year":2022,"id":643089,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":151736,"name":"Alejandro Berna-Erro","orcid":null,"position":1,"is_corresponding":false},{"id":1673115,"name":"Joel Nieto-Felipe","orcid":"0000-0001-6342-3893","position":2,"is_corresponding":false},{"id":1673116,"name":"Alvaro Macias","orcid":null,"position":3,"is_corresponding":false},{"id":1510663,"name":"Jose Sanchez-Collado","orcid":null,"position":4,"is_corresponding":false},{"id":1510662,"name":"Jose J. Lopez","orcid":"0000-0002-5234-1478","position":5,"is_corresponding":false},{"id":151739,"name":"Ginés M. Salido","orcid":"0000-0002-8687-2445","position":6,"is_corresponding":false},{"id":151740,"name":"Juan A. Rosado","orcid":"0000-0002-9749-2325","position":7,"is_corresponding":false},{"id":151734,"name":"Isaac Jardin","orcid":"0000-0003-4575-8264","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β","abstract":"<jats:p>Orai1, the first identified member of the Orai protein family, is ubiquitously expressed in the animal kingdom. Orai1 was initially characterized as the channel responsible for the store-operated calcium entry (SOCE), a major mechanism that allows cytosolic calcium concentration increments upon receptor-mediated IP3 generation, which results in intracellular Ca2+ store depletion. Furthermore, current evidence supports that abnormal Orai1 expression or function underlies several disorders. Orai1 is, together with STIM1, the key element of SOCE, conducting the Ca2+ release-activated Ca2+ (CRAC) current and, in association with TRPC1, the store-operated Ca2+ (SOC) current. Additionally, Orai1 is involved in non-capacitative pathways, as the arachidonate-regulated or LTC4-regulated Ca2+ channel (ARC/LRC), store-independent Ca2+ influx activated by the secretory pathway Ca2+-ATPase (SPCA2) and the small conductance Ca2+-activated K+ channel 3 (SK3). Furthermore, Orai1 possesses two variants, Orai1α and Orai1β, the latter lacking 63 amino acids in the N-terminus as compared to the full-length Orai1α form, which confers distinct features to each variant. Here, we review the current knowledge about the differences between Orai1α and Orai1β, the implications of the Ca2+ signals triggered by each variant, and their downstream modulatory effect within the cell.</jats:p>","is_dataset_classified":null,"base_score":2.70805020110221,"endowment":2.70805020110221,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36498894","pmcid":"PMC9735889","openalex_id":"https://openalex.org/W4309712946","authors":[],"funders":[{"funder_name":"Agencia Estatal de Investigación","grant_id":"PID2019-104084GB-C21/AEI/10.13039/501100011033","title":null},{"funder_name":"Agencia Estatal de Investigación","grant_id":"IB20007","title":null},{"funder_name":"Agencia Estatal de Investigación","grant_id":"GR21008","title":null},{"funder_name":"Agencia Estatal de Investigación","grant_id":"TA18011","title":null},{"funder_name":"Agencia Estatal de Investigación/AEI/10.13039/501100011033","grant_id":"PID2019-104084GB-C21","title":null}],"total_grants":5,"fwci":1.4105,"citation_percentile":0.79516129,"influential_citations":0,"citation_trend":[{"year":2023,"count":2},{"year":2024,"count":4},{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/23/23/14568/pdf?version=1669183032","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/23/23/14568/pdf?version=1669183032","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/23/23/14568/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms232314568","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36498894","host_type":"repository"},{"url":"http://hdl.handle.net/10662/18850","host_type":"repository"},{"url":"https://doaj.org/article/0531e30ecf4b449ab52b29d8f83e26e4","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms232314568","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9735889","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9735889","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9735889?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Ion Channels and Receptors","Phytochemicals and Antioxidant Activities","Neurobiology and Insect Physiology Research","Animals","ORAI1 Protein","Calcium","Calcium Channels","TRPC Cation Channels","Stromal Interaction Molecule 1","Ion Transport","Calcium Signaling"],"mesh_terms":["Stromal Interaction Molecule 1","ORAI1 Protein","Animals","Calcium","Calcium Channels","Ion Transport","Calcium Signaling","TRPC Cation Channels"],"keywords":["ORAI1","STIM1","Cell biology","Calcium signaling","Chemistry","Intracellular","Voltage-dependent calcium channel","TRPC1","Biology","Calcium","Receptor","Biophysics","Ion channel","Endoplasmic reticulum","Biochemistry","NFAT","Crac","Ac8","Orai1α","Orai1β"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-08T12:37:37.237048Z","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":[]}