title: The basic helix-loop-helix-PAS protein MOP9 is a brain-specific heterodimeric partner of circadian and hypoxia factors.
abstract: PAS (PER, ARNT, SIM) proteins play important roles in adaptation to low atmospheric and cellular oxygen levels, exposure to certain environmental pollutants, and diurnal oscillations in light and temperature. In an attempt to better understand how organisms sense environmental changes, we have characterized a novel member of the PAS superfamily, MOP9 (member of PAS superfamily), that maps to human chromosome 12p11.22-11.23. This protein displays significant homology to the Drosophila circadian factor CYCLE and its putative mammalian ortholog MOP3/bMAL1. Like its homologs, MOP9 forms a transcriptionally active heterodimer with the circadian CLOCK protein, the structurally related MOP4, and hypoxia-inducible factors, such as HIF1alpha. 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 in the suprachiasmatic nucleus, the site of the master circadian oscillator in mammals.
authors.affiliation: The McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Hogenesch
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Gu
authors.forename: S M
authors.initials: SM
authors.lastname: Moran
authors.forename: K
authors.initials: K
authors.lastname: Shimomura
authors.forename: L A
authors.initials: LA
authors.lastname: Radcliffe
authors.forename: J S
authors.initials: JS
authors.lastname: Takahashi
authors.forename: C A
authors.initials: CA
authors.lastname: Bradfield
mesh_terms: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D056926:CLOCK Proteins; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D002874:Chromosome Mapping; D002940:Circadian Rhythm / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D017386:Sequence Homology, Amino Acid; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C538960:BMAL1 protein, human; C486615:BMAL2 protein, human; C497442:HIF1A protein, human; C112805:cyc protein, Drosophila; C538943:CLOCK protein, human