title: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter.
abstract: 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.
mesh_terms: 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
chemical_list: 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