Solute carrier family 10 member 6 (SLC10A6), also known as sodium-dependent organic anion transporter (SOAT in man and Soat in mice) represents a plasma membrane uptake carrier for sulfated steroid hormones. It belongs to the solute carrier family 10. SLC10A6 shows transport activity for estrone sulfate (E1S), estradiol sulfate (E2S), pregnenolone sulfate (PregS), dehydroepiandrosterone sulfate (DHEAS), 16α-hydroxydehydroepiandrosterone sulfate (16-OH-DHEAS), and androstenediol sulfate (AnDiolS). However, SLC10A6 does not accept other steroid compounds as substrates including bile acids such as taurocholic acid and chenodeoxycholic acid, cardiac glycosides such as ouabain and digoxin, or steroid glucuronides such as estrone-3-D-glucuronide and estradiol-17-D-glucuronide.
|Basic Information of SLC10A6|
|Protein Name||Solute carrier family 10 member 6|
|Aliases||Sodium-dependent organic anion transporter|
|Organism||Homo sapiens (Human)|
SOAT is a plasma membrane transporter for sulfated steroids which is highly expressed in germ cells of the testis. SLC10A6 can transport biologically inactive sulfated steroids into specific target cells, where they can be reactivated by the steroid sulfatase (STS) to biologically active, unconjugated steroids known to regulate spermatogenesis. Significantly reduced SLC10A6 mRNA expression is previously found in different forms of impaired spermatogenesis in man. It is supposed that SLC10A6 plays a role for the local supply of steroids in the testis and consequently for spermatogenesis and fertility.
Fig.1 Identification of novel inhibitors of the steroid sulfate carrier SOAT by pharmacophore modeling. (Grosser, 2016)
This article shows that SOAT 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. In placenta and pancreas, SOAT shows extremely high expression. Several nonsteroidal organosulfates also strongly inhibit SOAT, including 1-(omega-sulfooxyethyl) pyrene, bromosulfophthalein, 2- and 4-sulfooxymethylpyrene, and alpha-naphthylsulfate.
This article indicates the characteristics of SOAT substrates from the group of sulfated steroids and identifies 17β-estradiol-3,17-disulfate is not transported by SOAT.
This article suggests that Soat is not essential for reproduction because the Slc10a6-/- knockout mice show normal fertile, produce normal litter sizes, and have normal spermatogenesis and sperm vitality.
The article shows polymorphism L204F of the SOAT significantly reduces transport function for DHEAS. Besides, it is also shown that SOAT-L204F polymorphism is not a cause of hypospermatogenesis.
In this article, the SLC10A6 gene is analyzed for rare genetic variants which might affect transport function or membrane expression of SOAT. Results show that L44P, Q75R, P107L, G109S, S112F, N113K, S133F, G241D, G263E, G294R, and Y308N have no transport activity for DHEAS at all among 31 analyzed SOAT variants.
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