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Molecular cloning of ADIR, a novel interferon responsive gene encoding a protein related to the torsins.

机译:ADIR的分子克隆,ADIR是一种新型的干扰素响应基因,编码与躯体相关的蛋白质。

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The expression of the previously uncharacterized gene Adir (for ATP dependent interferon responsive gene) was increased by 5- to 15-fold in tissue of the oral cavity or in spleen and liver of mice treated orally or intraperitoneally with IFN-alpha, and in mouse cells treated in vitro with IFN-alpha or IFN-gamma. The level of Adir mRNA was also increased 20- to 40-fold in the brains of animals infected with encephalomyocarditis virus. Adir is expressed ubiquitously in mouse tissues as 1.9-, 2.4-, and 3.5-kb mRNA transcripts encoding a 385-amino-acid protein with a conserved ATP binding domain containing typical nucleotide and Mg(2+) binding sites. We also characterized the human ortholog, ADIR, which is located on chromosome 1q25-q31 and contains six exons encoding a 397-amino-acid protein with 80% homology to the mouse protein. A single 2.3-kb mRNA was detected in all human tissues examined, except for placenta, which also contained a 1.25-kb tissue-specific transcript generated by alternative splicing and encoding a putative 336-amino-acid protein. Although ADIR exhibits low homology to DYT1 and TOR1B, the deduced ADIR protein sequences are highly homologous to torsin A and torsin B and more distantly related to members of the Clp/HSP100 family of proteins, suggesting that ADIR, like torsins, is related to the AAA chaperone-like family of ATPases. An ADIR-EGFP fusion protein expressed in HeLa cells was shown to be associated with the endoplasmic reticulum.
机译:口服或腹膜内用IFN-α处理的小鼠的口腔组织或脾脏和肝脏中,先前未鉴定的基因Adir(针对ATP依赖的干扰素应答基因)的表达提高了5至15倍体外用IFN-α或IFN-γ处理的细胞。在感染了脑心肌炎病毒的动物的大脑中,Adir mRNA的水平也增加了20至40倍。 Adir在小鼠组织中普遍表达为1.9-,2.4-和3.5-kb mRNA转录本,编码385个氨基酸的蛋白质,具有包含典型核苷酸和Mg(2+)结合位点的保守ATP结合域。我们还表征了人类直系同源基因ADIR,它位于1q25-q31染色体上,包含六个外显子,它们编码与小鼠蛋白质具有80%同源性的397个氨基酸的蛋白质。除胎盘外,在所有检查的人体组织中均检测到一个2.3kb的mRNA,胎盘中还含有1.25kb的组织特异性转录本,该转录本是通过选择性剪接和编码336个氨基酸的蛋白质生成的。尽管ADIR与DYT1和TOR1B的同源性较低,但推定的ADIR蛋白序列与Torsin A和Torsin B高度同源,并且与Clp / HSP100家族蛋白的成员关系更远,这表明ADIR与torsin一样与AAA分子伴侣状ATPase。已显示在HeLa细胞中表达的ADIR-EGFP融合蛋白与内质网有关。

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