Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter.
Transport of various amphipathic organic compounds is mediated by organic anion transporting polypeptides (OATPs in humans, Oatps in rodents), which belong to the solute carrier family 21A (SLC21A/Slc21a). Several of these transporters exhibit a broad and overlapping substrate specificity and are expressed in a variety of different tissues. We have isolated and functionally characterized OATP-F (SLC21A14), a novel member of the OATP family. The cDNA (3059 bp) contains an open reading frame of 2136 bp encoding a protein of 712 amino acids. Its gene containing 15 exons is located on chromosome 12p12. OATP-F exhibits 47-48% amino acid identity with OATP-A, OATP-C, and OATP8, the genes of which are clustered on chromosome 12p12. OATP-F is predominantly expressed in multiple brain regions and Leydig cells of the testis. OATP-F mediates high affinity transport of T(4) and reverse T(3) with apparent K(m) values of approximately 90 nM and 128 nM, respectively. Substrates less well transported by OATP-F include T(3), bromosulfophthalein, estrone-3-sulfate, and estradiol-17beta-glucuronide. Furthermore, OATP-F-mediated T(4) uptake could be cis-inhibited by L-T(4) and D-T(4), but not by 3,5-diiodothyronine, indicating that T(4) transport is not stereospecific, but that 3',5'-iodination is important for efficient transport by OATP-F. Thus, in contrast to most other family members, OATP-F has a more selective substrate preference and may play an important role in the disposition of thyroid hormones in brain and testis.
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D016466:CHO Cells / Q000378:metabolism; D002881:Chromosomes, Human, Pair 12; D003001:Cloning, Molecular; D006224:Cricetinae; D004104:Diiodothyronines / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D009928:Organ Specificity; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013448:Sulfobromophthalein / Q000378:metabolism; D013737:Testis / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism; D014981:Xenopus
D004104:Diiodothyronines; D008565:Membrane Proteins; D027361:Organic Anion Transporters; C473187:SLCO1C1 protein, human; D014284:Triiodothyronine; D013448:Sulfobromophthalein; C025483:estradiol-17 beta-glucuronide; D004970:Estrone; D004958:Estradiol; C030103:3,5-diiodothyronine; D013974:Thyroxine; C017296:estrone sulfate