aryl hydrocarbon receptor nuclear translocator-like protein 1; basic-helix-loop-helix-PAS protein MOP3; brain & muscle ARNT-like 1; class E basic helix-loop-helix protein 5; bHLHe5; member of PAS protein 3; PAS domain-containing protein 3; bHLH-PAS protein JAP3 (ARNTL, BHLHE5, BMAL1, MOP3, PASD3)
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Function
- ARNTL-hCLOCK 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, & also by CRY proteins (putative)
- acetylated on Lys-538 upon dimerization with hCLOCK
- acetylation facilitates CRY1-mediated repression (putative)
- phosphorylated upon dimerization with hCLOCK (putative)
- sumoylated on Lys-259 upon dimerization with hCLOCK
- interacts with CRY2 (putative)
- component of the circadian clock oscillator
- heterodimerization with hCLOCK is required for
- E-box-dependent transactivation
- hCLOCK nuclear translocation & degradation
- phosphorylation of both hCLOCK & ARNTL
- interaction with PER & CRY proteins requires translocation to the nucleus
- interaction of the hCLOCK-ARNTL heterodimer with PER or CRY inhibits transcription activation
- interacts with HSP90; with AHR in vitro, but not in vivo
- part of a nuclear complex which also includes GNB2L1/RACK1 & PRKCA
Structure
- contains 1 basic helix-loop-helix (bHLH) domain
- contains 1 PAC (PAS-associated C-terminal) domain
- contains 2 PAS (PER-ARNT-SIM) domains
Compartment
Alternative splicing
Expression
- highly expressed in the adult brain, skeletal muscle & heart
Pathology
- 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 &, disrupt circadian rhythmicity