Characterization of the human sulfate anion transporter (hsat-1) protein and gene (SAT1; SLC26A1)
Characterization of the human sulfate anion transporter (hsat-1) protein and gene (SAT1; SLC26A1)
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DOI：
10.1089/104454903321515913
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发表时间：
2003-02-01
影响因子：
3.1
通讯作者：
Markovich, D
中科院分区：
文献类型：
--
作者：
Regeer, RR;Lee, A;Markovich, D
硫酸盐在生长、发育、骨/软骨形成和细胞代谢过程中起着至关重要的作用。在本研究中，我们分离了人硫酸根转运蛋白基因(hsat-1；SCL26A1)和基因(SAT1)，并测定了其在非洲爪哇卵母细胞中的蛋白功能，以及在哺乳动物肾细胞系中SAT1启动子的活性。HSAT-1编码一个75 kDa的蛋白，含有12个可能的跨膜区，可诱导非洲爪哇卵母细胞中硫酸盐、氯化物和草酸的转运。HSAT-1mRNA在肾脏和肝脏中表达最丰富，在胰腺、睾丸、脑、小肠、结肠和肺中表达较低。SAT1基因由4个外显子组成，全长6kb，可选的外显子有一个选择性的剪接位点。SAT1 5‘侧翼区在肾OK和LLC-PK1细胞中具有启动子活性。使用SAT1 5‘侧翼区截短，前135个碱基对基本启动子活性是足够的。激活蛋白-1(AP-1)在SAT1启动子第252位的突变导致转录活性丧失，提示其需要SAT1基础表达。本研究首次对阴离子转运蛋白hsat-1编码的人类SAT1基因和蛋白进行了功能鉴定。
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 252 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.