{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:01:03Z","timestamp":1791234063522,"version":"4.1.0"},"reference-count":14,"publisher":"Zoological Society of Japan","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Zoological Science"],"published-print":{"date-parts":[[2026,7,9]]},"abstract":"<jats:p>Mammalian ovarian cancer G protein-coupled receptor 1 (OGR1; also known as GPR68) functions as both a proton- and metal-ion-sensing receptor, activating multiple intracellular signaling pathways. Although OGR1 homologs across vertebrates are commonly activated under low pH conditions, their responsiveness to metal ions varies by species, possibly reflecting differences in physiological metal requirements. To identify the residues responsible for metal ion sensing, we analyzed human OGR1 and its homologs in zebrafish and African clawed frog. Nickel ions activated human OGR1 and one African clawed frog homolog (xLOGR1#3) but not zebrafish OGR1 and another African clawed frog homolog (xLOGR1#1), which lack a specific histidine residue in the first extracellular loop. Substituting histidine with alanine in human OGR1 reduced metal-ion-induced activation, without significantly affecting proton responsiveness. Conversely, introducing histidine at the corresponding position restored the metal ion sensitivity. This histidine-dependent activation has also been observed for cobalt and manganese ions. These findings suggest that, beyond its role as a proton sensor, OGR1 has evolved metal-ion-sensing capabilities, potentially reflecting species-specific adaptation.<\/jats:p>","DOI":"10.2108\/zs250115","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:52:52Z","timestamp":1783489972000},"page":"446-454","source":"Crossref","is-referenced-by-count":0,"title":["A Specific Histidine Residue Determines Species-Specific Sensitivity to Metal Ions in Ovarian Cancer G Protein-Coupled Receptor 1"],"prefix":"10.2108","volume":"43","author":[{"given":"Ryo","family":"Tachihara","sequence":"first","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manami","family":"Tachino","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rio","family":"Koike","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Arase","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Miyake","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Uchida","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Ichimura","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurumi","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Futae","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Tomura","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"848","reference":[{"key":"2","doi-asserted-by":"crossref","unstructured":"MD Glitsch,  \"Pflugers Arch.\"  476, \"Recent advances in acid sensing by G protein coupled receptors.\" 445 (2024)","DOI":"10.1007\/s00424-024-02919-y"},{"key":"3","doi-asserted-by":"crossref","unstructured":"L Guo, K Zhu, YN Zhong, et al.  \"Mol Cell.\"  85, \"Structural basis and biased signaling of proton sensation by GPCRs mediated by extracellular histidine rearrangement.\" 1658 (2025)","DOI":"10.1016\/j.molcel.2025.03.018"},{"key":"4","doi-asserted-by":"crossref","unstructured":"XP Huang, TP Kenakin, S Gu, et al.  \"Biochemistry.\"  59, \"Differential roles of extracellular histidine residues of GPR68 for proton-sensing and allosteric modulation by divalent metal ions.\" 3594 (2020)","DOI":"10.1021\/acs.biochem.0c00576"},{"key":"6","doi-asserted-by":"crossref","unstructured":"JA Jenkins, M Musgrove, SJO White,  \"Toxics.\"  11, 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