Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter

Mol Endocrinol. 2002 Oct;16(10):2283-96. doi: 10.1210/me.2001-0309.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism*
  • CHO Cells / metabolism
  • Chromosomes, Human, Pair 12
  • Cloning, Molecular
  • Cricetinae
  • Diiodothyronines / pharmacology
  • Estradiol / analogs & derivatives*
  • Estradiol / metabolism
  • Estrone / analogs & derivatives*
  • Estrone / metabolism
  • Female
  • Humans
  • Leydig Cells / metabolism
  • Male
  • Membrane Proteins
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Organ Specificity
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism*
  • Sequence Homology, Amino Acid
  • Sulfobromophthalein / metabolism
  • Testis / metabolism*
  • Thyroxine / metabolism*
  • Triiodothyronine / metabolism
  • Xenopus


  • Diiodothyronines
  • Membrane Proteins
  • Organic Anion Transporters
  • SLCO1C1 protein, human
  • Triiodothyronine
  • Sulfobromophthalein
  • estradiol-17 beta-glucuronide
  • Estrone
  • Estradiol
  • 3,5-diiodothyronine
  • Thyroxine
  • estrone sulfate

Associated data

  • GENBANK/AF260704