Organo anion transporter family

Members of the Organo Anion Transporter (OAT) Family (TC# 2.A.60) catalyze electrogenic anion uniport or more frequently, anion exchange, and are part of the major facilitator superfamily. Mammalian homologues consist of 640-722 amino acyl residues and possess 12 putative α-helical transmembrane segments.

Function

Proteins of the OAT family catalyze the Na+-independent facilitated transport of fairly large amphipathic organic anions (and less frequently neutral or cationic drugs), such as bromosulfobromophthalein, prostaglandins, conjugated and unconjugated bile acids (taurocholate and cholate), steroid conjugates, thyroid hormones, anionic oligopeptides, drugs, toxins and other xenobiotics.[1] One family member, OATP2B1, has been shown to use cytoplasmic glutamate as the exchanging anion.[2] Among the well characterized substrates are numerous drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives and anticancer drugs.[3] Other substrates include luciferin, thyroid hormones and quinolones.[1][4][5]

Homology

The various paralogues in a mammal have differing but overlapping substrate specificities and tissue distributions as summarized by Hagenbuch and Meier.[3] These authors also provide a phylogenetic tree of the mammalian members of the family, showing that they fall into five recognizable subfamilies, four of which exhibit deep branching sub-subfamilies. However, all sequences within a subfamily are >60% identical while those between subfamilies are >40% identical.[3] As also shown by Hagenbuch and Meier, all but one (OatP4a1) of the mammalian homologues cluster together, separately from all other animal (insect and worm) homologues.[3]

OAT family homologues have been found in other animals but not outside of the animal kingdom. These transporters have been characterized in mammals, but homologues are present in Drosophila melanogaster, Anopheles gambiae, and Caenorhabditis elegans. The mammalian OAT family proteins exhibit a high degree of tissue specificity.

Transport Reaction

The generalized transport reactions catalyzed by members of the OAT family are:

Anion (in) → Anion (out)

Anion1 (in) + Anion2 (out) → Anion1 (out) + Anion2 (in)

References

  1. 1 2 Hong, Weifang; Wu, Zhixuan; Fang, Zihui; Huang, Jiujiu; Huang, Hong; Hong, Mei (2015-12-07). "Amino Acid Residues in the Putative Transmembrane Domain 11 of Human Organic Anion Transporting Polypeptide 1B1 Dictate Transporter Substrate Binding, Stability, and Trafficking". Molecular Pharmaceutics. 12 (12): 4270–4276. doi:10.1021/acs.molpharmaceut.5b00466. ISSN 1543-8392. PMID 26562723.
  2. ↑ Lofthouse, Emma M.; Brooks, Suzanne; Cleal, Jane K.; Hanson, Mark A.; Poore, Kirsten R.; O'Kelly, Ita M.; Lewis, Rohan M. (2015-10-15). "Glutamate cycling may drive organic anion transport on the basal membrane of human placental syncytiotrophoblast". The Journal of Physiology. 593 (20): 4549–4559. doi:10.1113/JP270743. ISSN 1469-7793. PMC 4606536Freely accessible. PMID 26277985.
  3. 1 2 3 4 Hagenbuch, Bruno; Stieger, Bruno (2013-06-01). "The SLCO (former SLC21) superfamily of transporters". Molecular Aspects of Medicine. 34 (2-3): 396–412. doi:10.1016/j.mam.2012.10.009. ISSN 1872-9452. PMC 3602805Freely accessible. PMID 23506880.
  4. ↑ Sugiyama, Daisuke; Kusuhara, Hiroyuki; Taniguchi, Hirokazu; Ishikawa, Shumpei; Nozaki, Yoshitane; Aburatani, Hiroyuki; Sugiyama, Yuichi (2003-10-31). "Functional characterization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier: high affinity transporter for thyroxine". The Journal of Biological Chemistry. 278 (44): 43489–43495. doi:10.1074/jbc.M306933200. ISSN 0021-9258. PMID 12923172.
  5. ↑ Patrick, P. Stephen; Lyons, Scott K.; Rodrigues, Tiago B.; Brindle, Kevin M. (2014-10-01). "Oatp1 enhances bioluminescence by acting as a plasma membrane transporter for D-luciferin". Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging. 16 (5): 626–634. doi:10.1007/s11307-014-0741-4. ISSN 1860-2002. PMC 4161938Freely accessible. PMID 24798747.

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