Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates
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Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates. / Yee, Sook Wah; Ferrández-Peral, Luis; Alentorn-Moron, Pol; Fontsere, Claudia; Ceylan, Merve; Koleske, Megan L.; Handin, Niklas; Artegoitia, Virginia M.; Lara, Giovanni; Chien, Huan-Chieh; Zhou, Xujia; Dainat, Jacques; Zalevsky, Arthur; Sali, Andrej; Brand, Colin M.; Wolfreys, Finn D.; Yang, Jia; Gestwicki, Jason E.; Capra, John A.; Artursson, Per; Newman, John W.; Marquès-Bonet, Tomàs; Giacomini, Kathleen M.
I: Nature Communications, Bind 15, Nr. 1, 4380, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates
AU - Yee, Sook Wah
AU - Ferrández-Peral, Luis
AU - Alentorn-Moron, Pol
AU - Fontsere, Claudia
AU - Ceylan, Merve
AU - Koleske, Megan L.
AU - Handin, Niklas
AU - Artegoitia, Virginia M.
AU - Lara, Giovanni
AU - Chien, Huan-Chieh
AU - Zhou, Xujia
AU - Dainat, Jacques
AU - Zalevsky, Arthur
AU - Sali, Andrej
AU - Brand, Colin M.
AU - Wolfreys, Finn D.
AU - Yang, Jia
AU - Gestwicki, Jason E.
AU - Capra, John A.
AU - Artursson, Per
AU - Newman, John W.
AU - Marquès-Bonet, Tomàs
AU - Giacomini, Kathleen M.
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-024-48569-7
DO - 10.1038/s41467-024-48569-7
M3 - Journal article
C2 - 38782905
AN - SCOPUS:85194126861
VL - 15
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4380
ER -
ID: 395142564