Alternative products:Additional isoforms seem to exist ,Function:ARNTL-CLOCK heterodimers activate E-box element (3'-CACGTG-5') transcription of a number of proteins of the circadian clock. This transcription is inhibited in a feedback loop by PER , and also by CRY proteins. ,miscellaneous:CLOCK-ARNTL double mutations within the PAS domains result in syngernistic desensitization to high levels of CRY on repression of CLOCK-ARNTL transcriptional activity of PER1 and , disrupt circadian rhythmicity. ,PTM:Acetylated on Lys-538 upon dimerization with CLOCK. Acetylation facilitates CRY1-mediated repression. ,PTM:Phosphorylated upon dimerization with CLOCK. ,PTM:Sumoylated on Lys-259 upon dimerization with CLOCK. ,similarity:Contains 1 basic helix-loop-helix (bHLH) domain. ,similarity:Contains 1 PAC (PAS-associated C-terminal) domain. ,similarity:Contains 2 PAS (PER-ARNT-SIM) domains. ,subunit:Component of the circadian clock oscillator which includes the CRY proteins , CLOCK or NPAS2 , ARNTL or ARNTL2 , CSNK1D and/or CSNK1E , TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerization with CLOCK is required for E-box-dependent transactivation , for CLOCK nuclear translocation and degradation , and , for phosphorylation of both CLOCK and ARNTL. Interaction with PER and CRY proteins requires translocation to the nucleus. Interaction of the CLOCK-ARNTL heterodimer with PER or CRY inhibits transcription activation. Interacts with HSP90; with AHR in vitro , but not in vivo. ,tissue specificity:Highly expressed in the adult brain , skeletal muscle and heart. ,
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