Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1.
We have isolated a novel liver-specific organic anion transporter, LST-1, that is expressed exclusively in the human, rat, and mouse liver. LST-1 is a new gene family located between the organic anion transporter family and prostaglandin transporter. LST-1 transports taurocholate (Km = 13.6 microM) in a sodium-independent manner. LST-1 also shows broad substrate specificity. It transports conjugated steroids (dehydroepiandrosterone sulfate, estradiol-17beta-glucuronide, and estrone-3-sulfate), eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, leukotriene E4), and thyroid hormones (thyroxine, Km = 3.0 microM and triiodothyronine, Km = 2.7 microM), reflecting hepatic multispecificity. LST-1 is probably the most important transporter in human liver for clearance of bile acids and organic anions because hepatic levels of another organic anion transporter, OATP, is very low. This is also the first report of the human molecule that transports thyroid hormones.
Abe
T
T
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, 980-8575, Tokyo, 140-8710, Japan. takaabe@mail.cc.tohoku.ac.jp
Kakyo
M
M
Tokui
T
T
Nakagomi
R
R
Nishio
T
T
Nakai
D
D
Nomura
H
H
Unno
M
M
Suzuki
M
M
Naitoh
T
T
Matsuno
S
S
Yawo
H
H
D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins; D001095:Arachidonic Acids / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013256:Steroids / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism
D027321:Anion Transport Proteins; D001095:Arachidonic Acids; D002352:Carrier Proteins; D002412:Cations; D018076:DNA, Complementary; D011994:Recombinant Proteins; D013256:Steroids; D013963:Thyroid Hormones; D013656:Taurocholic Acid