150 kDa oxygen-regulated protein (ORP 150) is one of the endoplasmic reticulum (ER)-resident stress proteins. We have cloned and sequenced the entire human ORP 150 gene covering over 15-kb. Analyses of transcription initiation sites and transcriptional regulatory sequences revealed that at least three distinct mRNA species were produced by alternative promoters: two of them starting from alternative exon 1 (1 A or 1 B), and the third one starting from exon 2, six nucleotides upstream of the first AUG initiation codon. Among them, the transcript that begins with exon 1 B was preferentially induced by hypoxia or tunicamycin treatment. A cis-acting segment involved in the stress-dependent induction was found at the 5'-end of exon 1 A, which could account for the selective induction of the transcription from exon 1 B. Furthermore, in vitro analyses of translation of the third mRNA suggested the constitutive expression of the cytosolic ORP 150 due to the lack of the signal peptide resulting from differential translation initiation.
The Japanese Biochemical Society