9dxp

Structural highlights

Function

SO1C1_HUMAN Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones L-thyroxine (T4), L-thyroxine sulfate (T4S), and 3,3',5'-triiodo-L-thyronine (reverse T3, rT3) at the plasma membrane (PubMed:12351693, PubMed:18566113, PubMed:19129463). Regulates T4 levels in different brain regions by transporting T4, and also by serving as an export pump for T4S, which is a source of T4 after hydrolysis by local sulfatases (PubMed:18566113). Increases the access of these substrates to the intracellular sites where they are metabolized by the deiodinases (PubMed:18566113). Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol (17beta-estradiol 17-O-(beta-D-glucuronate)), estrone-3-sulfate (E1S) and sulfobromophthalein (BSP) are transported with much lower efficiency (PubMed:12351693, PubMed:19129463). Transports T4 and E1S in a pH-insensitive manner (PubMed:19129463). Facilitates the transport of thyroid hormones across the blood-brain barrier and into glia and neuronal cells in the brain (PubMed:30296914).^{[1] [2] [3] [4]}

References

1. ↑ Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ. Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. PMID:12351693 doi:10.1210/me.2001-0309
2. ↑ van der Deure WM, Hansen PS, Peeters RP, Kyvik KO, Friesema EC, Hegedüs L, Visser TJ. Thyroid hormone transport and metabolism by organic anion transporter 1C1 and consequences of genetic variation. Endocrinology. 2008 Oct;149(10):5307-14. PMID:18566113 doi:10.1210/en.2008-0430
3. ↑ Leuthold S, Hagenbuch B, Mohebbi N, Wagner CA, Meier PJ, Stieger B. Mechanisms of pH-gradient driven transport mediated by organic anion polypeptide transporters. Am J Physiol Cell Physiol. 2009 Mar;296(3):C570-82. PMID:19129463 doi:10.1152/ajpcell.00436.2008
4. ↑ Strømme P, Groeneweg S, Lima de Souza EC, Zevenbergen C, Torgersbråten A, Holmgren A, Gurcan E, Meima ME, Peeters RP, Visser WE, Høneren Johansson L, Babovic A, Zetterberg H, Heuer H, Frengen E, Misceo D, Visser TJ. Mutated Thyroid Hormone Transporter OATP1C1 Associates with Severe Brain Hypometabolism and Juvenile Neurodegeneration. Thyroid. 2018 Nov;28(11):1406-1415. PMID:30296914 doi:10.1089/thy.2018.0595