Novel human cDNAs homologous to Drosophila Orct and mammalian carnitine transporters.
The molecular basis of the transport of organic ions (which include such medically important compounds as drugs, toxins, and metabolites) has been intensively studied ever since the identification of the prototypical anion and cation transporters, OAT1 (originally cloned by us as NKT) and OCT1. Here we report the cloning of two novel putative organic ion transporters with 12 predicted membrane spanning segments that are most homologous to mammalian OCTNs (carnitine transporters) and to the Drosophila putative transporter, Orct, an intriguing correspondence that led us to name our sequences Fly-like putative transporters (Flipts). Another transporter we cloned has recently been identified as OAT5. Inclusion of Flipts reveals that the organic ion transporter family tree has trifurcated into three branches, one bearing Flipts, OCTNs, and fly transporters, and the other two bearing OATs and OCTs. Flipts are widely expressed in adult kidney, brain, muscle, and other tissues; in contrast, OAT1 is largely in kidney, and OAT5, in liver. In the embryo as well, Flipts are broadly distributed, whereas OAT5 was found only in fetal liver. Flipt expression patterns resemble those of the phylogenetically related OCTNs, suggesting that Flipts might also participate in carnitine transport, particularly in brain, which has relatively high Flipt expression, including EST matches from amygdala, hippocampus, and hypothalamus.
Eraly
Satish A
SA
Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093- 0693, USA.
Nigam
Sanjay K
SK
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D015152:Blotting, Northern; D002331:Carnitine / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins; D005091:Exons; D020224:Expressed Sequence Tags; D006801:Humans; D007438:Introns; D007477:Ions; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics*; D008969:Molecular Sequence Data; D027361:Organic Anion Transporters / Q000235:genetics; D027701:Organic Cation Transport Proteins; D010802:Phylogeny; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D002352:Carrier Proteins; D018076:DNA, Complementary; D029721:Drosophila Proteins; D007477:Ions; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C109679:Orct protein, Drosophila; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D020033:Protein Isoforms; C427208:SLC22A10 protein, human; C468776:SLC22A15 protein, human; C467737:SLC22A16 protein, human; D002331:Carnitine