Aryl Hydrocarbon Receptor Nuclear Translocator Like Protein (ARNTL)

ARNTL 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 those encoding the Period (Per1, Per2, Per3) and Cryptochrome (Cry1 and Cry2) proteins. These repressor proteins are translated, and bind in a complex with casein kinase 1ε (Csnk1e)^[5] and 1δ (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.