Molecular cloning and identification of 3′- phosphoadenosine 5′-phosphosulfate transporter
Molecular cloning and identification of 3′- phosphoadenosine 5′-phosphosulfate transporter
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DOI：
10.1074/jbc.m302439200
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发表时间：
2003-07-11
影响因子：
4.8
通讯作者：
Nishihara, S
中科院分区：
文献类型：
--
作者：
Kamiyama, S;Suda, T;Nishihara, S
硫酸核苷酸，即3'-磷酸腺苷5'-磷酸硫酸酯（PAPS），是硫酸化的通用硫酰供体。虽然特异的PAPS转运体存在于高尔基膜中，但没有研究报道相应的基因。我们发现了一种新的人类基因编码PAPS转运体，我们将其命名为PAPST1，以及果蝇的同源基因slalom （sll）。PAPST1（432个氨基酸）与SLL（465个氨基酸）的氨基酸序列同源性为48.1%，亲水性分析预测两者为III型跨膜蛋白。PAPST1在SW480细胞中的瞬时表达表现为高尔基膜亚细胞定位。酵母中PAPST1和SLL的表达显著增加了PAPS向高尔基膜组分的转运。在人体组织中，PAPST1在胎盘和胰腺中高度表达，在结肠和心脏中表达水平较低。用GAL4-UAS系统产生的RNA干扰果蝇表明，PAPS转运体对生存能力至关重要。众所周知，一些与PAPS合成相关的基因突变是人类遗传性疾病的原因。我们的研究结果对PAPS转运和翻译后磺化的意义提供了见解。
Nucleotide sulfate, namely 3'-phosphoadenosine 5'-phosphosulfate (PAPS), is a universal sulfuryl donor for sulfation. Although a specific PAPS transporter is present in Golgi membrane, no study has reported the corresponding gene. We have identified a novel human gene encoding a PAPS transporter, which we have named PAPST1, and the Drosophila melanogaster ortholog, slalom (sll). The amino acid sequence of PAPST1 (432 amino acids) exhibited 48.1% identity with SLL (465 amino acids), and hydropathy analysis predicted the two to be type III transmembrane proteins. The transient expression of PAPST1 in SW480 cells showed a subcellular localization in Golgi membrane. The expression of PAPST1 and SLL in yeast Saccharomyces cerevisiae significantly increased the transport of PAPS into the Golgi membrane fraction. In human tissues, PAPST1 is highly expressed in the placenta and pancreas and present at lower levels in the colon and heart. An RNA interference fly of sll produced with a GAL4-UAS system revealed that the PAPS transporter is essential for viability. It is well known that mutations of some genes related to PAPS synthesis are responsible for human inherited disorders. Our findings provide insights into the significance of PAPS transport and post-translational sulfation.