Molecular cloning of ADIR, a novel interferon responsive gene encoding a protein related to the torsins.
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.
Dron
Michel
M
Laboratory of Viral Oncology CNRS UPR 9045, Institute André Lwoff, Villejuif Cedex, 94801, France.
Meritet
Jean François
JF
Dandoy-Dron
Françoise
F
Meyniel
Jean-Philippe
JP
Maury
Chantal
C
Tovey
Michael G
MG
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D006801:Humans; D007372:Interferons / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens; D018832:Molecular Chaperones / Q000235:genetics*; D008969:Molecular Sequence Data; D017385:Sequence Homology
D002352:Carrier Proteins; C491548:Dyt1 protein, mouse; D015778:Minor Histocompatibility Antigens; D018832:Molecular Chaperones; C108175:TOR1A protein, human; C491547:TOR1B protein, human; C400325:Tor1b protein, mouse; D000255:Adenosine Triphosphate; D007372:Interferons; D000251:Adenosine Triphosphatases; C486741:TOR3A protein, human; C455506:Tor3a protein, mouse