Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates

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• dc.contributor.author Yee, Sook Wah
• dc.contributor.author Ferrández Peral, Luis, 1991-
• dc.contributor.author Alentorn Moron, Pol
• dc.contributor.author Fontseré Alemany, Clàudia, 1992-
• dc.contributor.author Marquès i Bonet, Tomàs, 1975-
• dc.contributor.author Giacomini, Kathleen M.
• dc.date.accessioned 2024-06-13T06:21:54Z
• dc.date.available 2024-06-13T06:21:54Z
• dc.date.issued 2024
• dc.description.abstract SLC22A10 is an orphan transporter with unknown substrates and function. The goal of this study is to elucidate its substrate specificity and functional characteristics. In contrast to orthologs from great apes, human SLC22A10, tagged with green fluorescent protein, is not expressed on the plasma membrane. Cells expressing great ape SLC22A10 orthologs exhibit significant accumulation of estradiol-17β-glucuronide, unlike those expressing human SLC22A10. Sequence alignments reveal a proline at position 220 in humans, which is a leucine in great apes. Replacing proline with leucine in SLC22A10-P220L restores plasma membrane localization and uptake function. Neanderthal and Denisovan genomes show proline at position 220, akin to modern humans, indicating functional loss during hominin evolution. Human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220, while in great apes, its orthologs transport sex steroid conjugates. Characterizing SLC22A10 across species sheds light on its biological role, influencing organism development and steroid homeostasis.
• dc.description.sponsorship This research was supported by NIH GM117163 (SWY) and GM139875 (KMG, SWY) and EY032161 (JEG). Additional support was provided by the Swedish Research Council (0151) (M.C, N.H, P.A), USDA Intramural Projects 2032-51530-025-00D (JWN) and by Mary Anne Koda-Kimble Seed Award for Innovation (2020, 2021) (SWY). The USDA is an equal opportunity employer and provider. TMB is supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 864203), PID2021-126004NB-100 (MICIIN/FEDER, UE) and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2021 SGR 00177). We would like to acknowledge Esther Lizano, Alba Duch and Mina Azimi for their invaluable assistance and support in the successful execution of our research.
• dc.format.mimetype application/pdf
• dc.identifier.citation Yee SW, Ferrández-Peral L, Alentorn-Moron P, Fontsere C, Ceylan M, Koleske ML, et al. Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates. Nat Commun. 2024 May 23;15(1):4380. DOI: 10.1038/s41467-024-48569-7
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-024-48569-7
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/60451
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Commun. 2024 May 23;15(1):4380
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/864203
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-126004NB-100
• dc.rights © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Evolution
• dc.subject.keyword Gene expression profiling
• dc.subject.keyword Open reading frames
• dc.title Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion