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Description

Aryl hydrocarbon receptor nuclear translocator-like protein 1 (UniProt: Q9WTL8, also known as Arnt3, Brain and muscle ARNT-like 1, BMAL1) is encoded by the Arnt1 (also known as Bmal1) gene (Gene ID: 11865) in murine species. BMAL1 is a transcriptional activator that forms a core component of the circadian clock. These components include ARNTL/BMAL1, CLOCK, NPAS2, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1, and CRY2. CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2 form the positive limb of the feedback loop. They act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes that are involved in key metabolic processes. PER1/2/3 and CRY1/2, act as transcriptional repressors and form the negative limb of the feedback loop. They interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity. BMLA1 is highly expressed in the adult brain, skeletal muscle, and heart. It shuttles between the nucleus and the cytoplasm and this nucleocytoplasmic shuttling is essential for the nuclear accumulation of CLOCK, target gene transcription, and the degradation of the CLOCK-ARNTL/BMAL1 heterodimer. BMLA1 is reported to be phosphorylated upon dimerization with CLOCK and this phosphorylation enhances its transcriptional activity and reduces the stability of the CLOCK-ARNTL/BMAL1 heterodimer by promoting its degradation. BMAL1 null-mice are reported to have reproductive problems, reduced locomotor activity, and premature aging.