ARNTL

Aryl hydrocarbon receptor nuclear translocator-like protein 1 is protein that in humans is encoded by the ARNTL gene also known as Bmal, Mop3, TIC, JAP3, PASD3, Bmal1c, bHLHe5.

ARNTL encodes for a transcription factor with a basic helix-loop-helix (bHLH) and a PAS domain. 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 autoregulatory transcription translation negative feedback loop (TTFL), which is responsible for generating molecular circadian rhythms. 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.

ARNTL2

Aryl hydrocarbon receptor nuclear translocator-like 2, also known as Mop9, Bmal2, Clif, or Arntl2, is a gene.

Arntl2 is a paralog to Arntl, which are both homologs of the Drosophila Cycle. Homologs were also isolated in fish, birds and mammals such as mice and humans. Based on phylogenetic analyses, it was proposed that Arntl2 arose from duplication of the Arntl gene early in the vertebrate lineage, followed by rapid divergence of the Arntl gene copy. The protein product of the gene interacts with both CLOCK and NPAS2 to bind to E-box sequences in regulated promoters and activate their transcription. Although Arntl2 is not required for normal function of the mammalian circadian oscillator, it may play an important role in mediating the output of the circadian clock. Perhaps because of this, there is relatively little published literature on the role of Arntl2 in regulation of physiology.

Arntl2 is a candidate gene for human type 1 diabetes.

In over expression studies, ARNTL2 protein forms a heterodimer with CLOCK to regulate E-box sequences in the Pai-1 promoter. Recent work suggest that this interaction may be in concert with ARNTL/CLOCK heterodimeric complexes.