SOAT (SLC10A6)

Molecular structure and Tissue distribution
Recently, we have cloned human sodium-dependent organic anion transporter (SOAT) cDNA, which consists of 1502 bp and encodes a 377-amino acid protein. SOAT shows 42% sequence identity to the ileal apical sodium-dependent bile acid transporter ASBT and 33% sequence identity to the hepatic Na+/taurocholate-cotransporting polypeptide NTCP. The human SOAT gene is located on chromosome 4q21. SOAT protein exhibits a seven-transmembrane domain topology with an outside-to-inside orientation of the N-terminal and C-terminal ends. SOAT mRNA is most highly expressed in testis. Relatively high SOAT expression was also detected in placenta and pancreas.

Interaction of SOAT with endogenous compounds and drugs
SOAT-HEK293 cell line showed sodium-dependent transport of dehydroepiandrosterone sulfate, estrone-3-sulfate, and pregnenolone sulfate with apparent Km values of 28.7, 12.0, and 11.3 μm, respectively. Although bile acids, such as taurocholic acid, cholic acid, and chenodeoxycholic acid, were not substrates of SOAT, the sulfoconjugated bile acid taurolithocholic acid-3-sulfate was transported by SOAT-HEK293 cells in a sodium-dependent manner and showed competitive inhibition of SOAT transport with an apparent Ki value of 0.24 μm. Several nonsteroidal organosulfates also strongly inhibited SOAT, including 1-(ω-sulfooxyethyl)pyrene, bromosulfophthalein, 2- and 4-sulfooxymethylpyrene, and α-naphthylsulfate. Among these inhibitors, 2- and 4-sulfooxymethylpyrene were competitive inhibitors of SOAT, with apparent Ki values of 4.3 and 5.5 μm, respectively, and they were also transported by SOAT-HEK293 cells.

Scientific Background

Organic anion Transporters

Organic cation Transporters

SLC 10-family Transporters
    NTCP  - ASBT  - SOAT

SLCO OATPs

Summary

Literatur