Functional characterization of the mouse organic-anion-transporting polypeptide 2.
We have isolated and functionally characterized an additional murine member of the organic-anion-transporting polypeptide (Oatp) family of membrane transport proteins from mouse liver. The 3.6 kb cDNA insert contains an open reading frame of 2010 bp coding for a 670 amino acid protein. Based on its amino acid identity of 88% to the rat Oatp2, it is considered the mouse Oatp2 orthologue. Functional expression in Xenopus laevis oocytes demonstrated that mouse Oatp2 transports several general Oatp substrates such as estrone-3-sulfate, dehydroepiandrosterone sulfate (DHEAS), ouabain and BQ-123 but hardly any taurocholate nor rocuronium or deltorphin II. The high-affinity rat Oatp2 substrate digoxin is transported with a rather low affinity with an apparent K(m) value of 5.7 microM. Bromosulfophthalein (BSP), a substrate not transported by the rat Oatp2, is transported very well by mouse Oatp2. Northern blot analysis demonstrated a predominant expression in the liver with additional signals in kidney and brain. Using fluorescence in situ hybridization, the Oatp2 gene (gene symbol Slc21a5) was mapped to chromosome 6G1-G3.
van Montfoort
Jessica E
JE
Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, Rämistr. 100, CH-8091 Zürich, Switzerland.
Schmid
Thomas E
TE
Adler
Ilse-Dore
ID
Meier
Peter J
PJ
Hagenbuch
Bruno
B
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D007700:Kinetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D027701:Organic Cation Transport Proteins; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014982:Xenopus laevis
D018076:DNA, Complementary; D026901:Membrane Transport Proteins; C464433:Oatp2 protein, mouse; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D011994:Recombinant Proteins