The basic helix-loop-helix-PAS protein MOP9 is a brain-specific heterodimeric partner of circadian and hypoxia factors

PAS (PER, ARNT, SIM) proteins play important roles in adaptation to low atm ospheric and cellular oxygen levels, exposure to certain environmental poll utants, and diurnal oscillations in light and temperature. In an attempt to better understand how organisms sense environmental changes, we have chara cterized a novel member of the PAS superfamily, MOP9 (member of PAS superfa mily), that maps to human chromosome 12p11.22-11.23. This protein displays significant homology to the Drosophila circadian factor CYCLE and its putat ive mammalian ortholog MOP3/bMAL1. Like its homologs, MOP9 forms a transcri ptionally active heterodimer with the circadian CLOCK protein, the structur ally related MOP4, and hypoxia-inducible factors, such as HIF1 alpha. In a manner consistent with its role as a biologically relevant partner of these proteins, MOP9 is coexpressed in regions of the brain such as the thalamus , hypothalamus, and amygdala. Importantly, MOP9 is coexpressed with CLOCK i n the suprachiasmatic nucleus, the site of the master circadian oscillator in mammals.