BMAL1 Recombinant Rabbit Monoclonal Antibody [JM17-34]

Function

Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) or Brain and Muscle ARNT-Like 1 (BMAL1) is a protein that in humans is encoded by the Bmal1 gene, also known as ARNTL, MOP3, and, less commonly, BHLHE5, BMAL, BMAL1C, JAP3, PASD3, and TIC. BMAL1 encodes a transcription factor with a basic helix-loop-helix (bHLH) and two PAS domains. The human Arntl gene has a predicted 24 exons and is located on the p15 band of the 11th chromosome. The BMAL1 protein is 626 amino acids long and plays a key role as one of the positive elements in the mammalian auto-regulatory transcription-translation negative feedback loop (TTFL), which is responsible for generating molecular circadian rhythms. Research has revealed that Bmal1 is the only clock gene without which the circadian clock fails to function in humans. Bmal1 has also been identified as a candidate gene for susceptibility to hypertension, diabetes, and obesity, and mutations in Bmal1 have been linked to infertility, gluconeogenesis and lipogenesis problems, and altered sleep patterns. BMAL1, according to genome-wide profiling, is estimated to target more than 150 sites in the human genome, including all of the clock genes and genes encoding for proteins that regulate metabolism.

Background References

1. Fernandez-Castaneda, A. et al. Identification of the low density lipoprotein (LDL) receptor-related protein-1 interactome in central nervous system myelin suggests a role in the clearance of necrotic cell debris. J. Biol. Chem 288: 4538-4548 (2013).

2. Yahiro, K. et al. Low-density lipoprotein receptor-related protein-1 (LRP1) mediates autophagy and apoptosis caused by Helicobacter pylori VacA. J. Biol. Chem. 287: 31104-31115 (2012).

Tissue Specificity

Hair follicles (at protein level). Highly expressed in the adult brain, skeletal muscle and heart.

Post-translational Modification

Ubiquitinated, leading to its proteasomal degradation. Deubiquitinated by USP9X.; O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-ARNTL/BMAL1 heterodimer thereby increasing CLOCK-ARNTL/BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2/3 and CRY1/2.; Acetylated on Lys-538 upon dimerization with CLOCK. Acetylation facilitates CRY1-mediated repression. Deacetylated by SIRT1, which may result in decreased protein stability.; Phosphorylated upon dimerization with CLOCK. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the CLOCK-ARNTL/BMAL1 heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver with a peak between CT10 to CT14. Phosphorylation at Ser-90 by CK2 is essential for its nuclear localization, its interaction with CLOCK and controls CLOCK nuclear entry (By similarity). Dephosphorylation at Ser-78 is important for dimerization with CLOCK and transcriptional activity.; Sumoylated on Lys-259 upon dimerization with CLOCK. Predominantly conjugated to poly-SUMO2/3 rather than SUMO1 and the level of these conjugates undergo rhythmic variation, peaking at CT9-CT12. Sumoylation localizes it exclusively to the PML body and promotes its ubiquitination in the PML body, ubiquitin-dependent proteasomal degradation and the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer.; Undergoes lysosome-mediated degradation in a time-dependent manner in the liver.

Subcellular Location

Nucleus, PML body, Cytoplasm.

UNIPROT

SwissProt: O00327 Human

SwissProt: Q9WTL8 Mouse

SwissProt: Q9EPW1 Rat

Synonyms