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Illuminating the fu...
Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates
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Yee, Sook Wah (author)
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Ferrández-Peral, Luis (author)
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Alentorn-Moron, Pol (author)
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Fontsere, Claudia (author)
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- Ceylan, Merve (author)
- Uppsala universitet,Institutionen för farmaci
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Koleske, Megan L. (author)
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- Handin, Niklas (author)
- Uppsala universitet,Institutionen för farmaci
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Artegoitia, Virginia M. (author)
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Lara, Giovanni (author)
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Chien, Huan-Chieh (author)
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Zhou, Xujia (author)
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Dainat, Jacques (author)
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Zalevsky, Arthur (author)
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Sali, Andrej (author)
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Brand, Colin M. (author)
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Wolfreys, Finn D. (author)
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Yang, Jia (author)
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Gestwicki, Jason E. (author)
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Capra, John A. (author)
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- Artursson, Per (author)
- Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab
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Newman, John W. (author)
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Marquès-Bonet, Tomàs (author)
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Giacomini, Kathleen M. (author)
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(creator_code:org_t)
- Springer Nature, 2024
- 2024
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Yee, Sook Wah
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Ferrández-Peral, ...
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Alentorn-Moron, ...
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Fontsere, Claudi ...
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Ceylan, Merve
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Koleske, Megan L ...
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show more...
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Handin, Niklas
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Artegoitia, Virg ...
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Lara, Giovanni
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Chien, Huan-Chie ...
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Zhou, Xujia
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Dainat, Jacques
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Zalevsky, Arthur
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Sali, Andrej
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Brand, Colin M.
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Wolfreys, Finn D ...
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Yang, Jia
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Gestwicki, Jason ...
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Capra, John A.
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Artursson, Per
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Newman, John W.
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Marquès-Bonet, T ...
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Giacomini, Kathl ...
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Nature Communica ...
- By the university
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Uppsala University