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)

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 a) E-box-dependent transactivation b) hCLOCK nuclear translocation & degradation c) 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 - GNB2L1 & PRKCA are recruited to the complex in a circadian manner 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: nucleus (putative) Alternative splicing: - named isoforms=8 - additional isoforms seem to exist 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

Properties

SIZE: entity length = 626 aa MW = 69 kD COMPARTMENT: cell nucleus MOTIF: DNA-binding motif SITE: 73-85 helix-loop-helix NAME: helix-loop-helix SITE: 86-126 FOR-BINDING-VIA: helix-loop-helix PAS domain {143-215} PAS domain {326-396} PAC domain {401-444}

Database Correlations

OMIM 602550 UniProt O00327 PFAM correlations Entrez Gene 406 Kegg hsa:406

References

UniProt :accession O00327