Characterization of the Human Sulfate Anion Transporter (hsat-1) Protein and Gene (SAT1; SLC26A1)

Abstract

Sulfate plays an essential role during growth, development, bone/cartilage formation, and cellular metabolism. In this study, we have isolated the human sulfate anion transporter cDNA (hsat-1; SCL26A1) and gene (SAT1), determined its protein function in Xenopus oocytes and characterized SAT1 promoter activity in mammalian renal cell lines. hsat-1 encodes a protein of 75 kDa, with 12 putative transmembrane domains, that induces sulfate, chloride, and oxalate transport in Xenopus oocytes. hsat-1 mRNA is expressed most abundantly in the kidney and liver, with lower levels in the pancreas, testis, brain, small intestine, colon, and lung. The SAT1 gene is comprised of four exons stretching 6 kb in length, with an alternative splice site formed from an optional exon. SAT1 5' flanking region led to promoter activity in renal OK and LLC-PK1 cells. Using SAT1 5' flanking region truncations, the first 135 bp was shown to be sufficient for basal promoter activity. Mutation of the activator protein-1 (AP-1) site at position -52 in the SAT1 promoter led to loss of transcriptional activity, suggesting its requirement for SAT1 basal expression. This study represents the first functional characterization of the human SAT1 gene and protein encoded by the anion transporter hsat-1.

The liver and kidney expression of sulfate anion transporter sat-1 in rats exhibits male-dominant gender differences

“…In this report, in isolated membranes from the rat liver and kidney cortex, the sat-1 protein was labeled as the 85-kDa band, which is comparable to the previously detected 80-kDa protein band in membrane fractions from the rabbit and rat renal cortex [18], probably reflecting the glycosylated form of the nascent, 704 amino acid protein (calculated Mr of ∼75 kDa) [18,24,39]. Our immunochemical studies further demonstrated clear male-dominant gender differences in sat-1 protein expression in the membranes from both rat organs, and these data were supported by the comparable transport (oxalate-sulfate exchange) in isolated membranes.…”

“…In rats, mice, and humans, sat-1 mRNA was detected strongly in liver and kidney and weakly in brain, skeletal muscle, and in few other organs [3,24,39]. The protein from the rat liver has been expression-cloned and characterized in Xenopus oocytes [3].…”

Molecular cloning and characterization of the mouse Na+ sulfate cotransporter gene (Slc13a4): structure and expression

“…These findings, together with a previous study showing its expression in the mouse choroid plexus (Matsumoto et al, 2003), suggests that mNaS2 may play a role in the transport of sulfate into cells of the central nervous system (CNS). Our previous studies which showed the expression of mouse, rat and human sat-1 mRNA in brain (Lee et al, 1999;Lee et al, 2003;Regeer et al, 2003), together with mNaS2, rNaS2 (Dawson et al, 2005a) and hNaS2 mRNA detected in brain, may suggest an important physiological role for sulfate transporters in the CNS. Sulfate plays an important role in the brain through the biosynthesis of sulfate proteoglycans, which are involved in modulating cell interactions in developing nervous tissues (Dow and Riopelle, 1994).…”

Oxalate: From the Environment to Kidney Stones

“…In addition to CFEX, other members of the Slc26 family are localized in the intestine. Sat-1 (Slc26a1) is usually associated with kidneys and liver, but recently its mRNA expression was also detected in mouse cecum (112) and human small intestine and colon (113). However, although it is presumed that Sat-1 is localized in the BLM of intestinal epithelial cells (114,115), in rats an anti-Sat-1 antibody clearly labeled the Sat-1 protein in specifi c membrane domains of hepatocytes and proximal tubules (116)(117)(118), whereas in the intestine, the same antibody stained intracellular organelles, possibly mitochondria, with (11,14).…”