Aryl hydrocarbon receptor nuclear translocator-like
|RNA expression pattern|
Aryl hydrocarbon receptor nuclear translocator-like, also known as ARNTL, Bmal1, or Mop3, is a gene.
The protein encoded by this gene is a basic-helix-loop-helix PAS (bHLH-PAS) domain containing protein that forms a heterodimer with a second bHLH-PAS protein, Clock, or its ortholog, Npas2. This complex binds to E-box response elements in promoter regions of many genes including two families of repressor proteins, the Per genes (Per1, Per2, Per3) and the Cryptochromes (Cry1 and Cry2). These repressor proteins are translated, and bind in a complex with casein kinase one epsilon (Csnk1e) and delta (Csnk1d). Next, the entire complex translocates to the nucleus, where it interacts with the Arntl/Clock heterodimer to inhibit its transactivation. This hypothesis is supported by the observation that point mutants in the Arntl or Clock render them resistant to interaction and repression by Cryptochromes. Transcription of Period and Cryptochrome genes, therefore, is inhibited, the protein levels of Period and Cryptochrome genes drop, and eventually repression is relieved to allow their transcription to build up again. This process occurs with a period length of approximately 24 hours.
Three transcript variants encoding two different isoforms have been found for this gene. The importance of these transcript variants is unknown.
Arntl (or Bmal1 or Mop3) is the only component of the mammalian circadian clock whose sole deletion in a mouse model generates arrhythmicity. In addition to defects in the clock, these Arntl null-mice also have reproductive problems, are small in stature, age quickly, and have progressive arthropathy that results in having less overall locomotor activity than wild type mice. Recent phenotyping data suggests that this gene and its partner Clock also play a role in regulation of glucose homeostasis and metabolism. Finally, Arntl, Npas2, and Per2 have been associated with seasonal affective disorder in humans.
- ↑ Hogenesch JB, Gu YZ, Jain S, Bradfield CA (1998). "The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors". Proc. Natl. Acad. Sci. U.S.A. 95 (10): 5474–9. PMID 9576906.
- ↑ Gekakis N, Staknis D, Nguyen HB, et al (1998). "Role of the CLOCK protein in the mammalian circadian mechanism". Science 280 (5369): 1564–9. PMID 9616112.
- ↑ Kume K, Zylka MJ, Sriram S, et al (1999). "mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop". Cell 98 (2): 193–205. PMID 10428031.
- ↑ Griffin EA, Staknis D, Weitz CJ (1999). "Light-independent role of CRY1 and CRY2 in the mammalian circadian clock". Science 286 (5440): 768–71. PMID 10531061.
- ↑ Lowrey PL, Shimomura K, Antoch MP, et al (2000). "Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau". Science 288 (5465): 483–92. PMID 10775102.
- ↑ Sato TK, Yamada RG, Ukai H, et al (2006). "Feedback repression is required for mammalian circadian clock function". Nat. Genet. 38 (3): 312–9. doi:10.1038/ng1745. PMID 16474406.
- ↑ Ikeda M, Nomura M (1997). "cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS protein (BMAL1) and identification of alternatively spliced variants with alternative translation initiation site usage". Biochem. Biophys. Res. Commun. 233 (1): 258–64. doi:10.1006/bbrc.1997.6371. PMID 9144434.
- ↑ Bunger MK, Wilsbacher LD, Moran SM, et al (2000). "Mop3 is an essential component of the master circadian pacemaker in mammals". Cell 103 (7): 1009–17. PMID 11163178.
- ↑ Boden MJ, Kennaway DJ (2006). "Circadian rhythms and reproduction". Reproduction 132 (3): 379–92. doi:10.1530/rep.1.00614. PMID 16940279.
- ↑ Kondratov RV (2007). "A role of the circadian system and circadian proteins in aging". Ageing Res. Rev. 6 (1): 12–27. doi:10.1016/j.arr.2007.02.003. PMID 17369106.
- ↑ Bunger MK, Walisser JA, Sullivan R, et al (2005). "Progressive arthropathy in mice with a targeted disruption of the Mop3/Bmal-1 locus". Genesis 41 (3): 122–32. doi:10.1002/gene.20102. PMID 15739187.
- ↑ Rudic RD, McNamara P, Curtis AM, et al (2004). "BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis". PLoS Biol. 2 (11): e377. doi:10.1371/journal.pbio.0020377. PMID 15523558.
- ↑ Turek FW, Joshu C, Kohsaka A, et al (2005). "Obesity and metabolic syndrome in circadian Clock mutant mice". Science 308 (5724): 1043–5. doi:10.1126/science.1108750. PMID 15845877.
- ↑ Partonen T, Treutlein J, Alpman A, et al (2007). "Three circadian clock genes Per2, Arntl, and Npas2 contribute to winter depression". Ann. Med. 39 (3): 229–38. doi:10.1080/07853890701278795. PMID 17457720.
- ↑ Preitner N, Damiola F, Lopez-Molina L, et al (2002). "The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator". Cell 110 (2): 251–60. PMID 12150932.
- ↑ Sato TK, Panda S, Miraglia LJ, et al (2004). "A functional genomics strategy reveals Rora as a component of the mammalian circadian clock". Neuron 43 (4): 527–37. doi:10.1016/j.neuron.2004.07.018. PMID 15312651.
- ↑ Shearman LP, Sriram S, Weaver DR, et al (2000). "Interacting molecular loops in the mammalian circadian clock". Science 288 (5468): 1013–9. PMID 10807566.
Transcription factors and intracellular receptors
|(1) Basic domains|
|(2) Zinc finger|
|(4) β-Scaffold factors with|
minor groove contacts
| (0) Other|
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