UNIPROT #

O00327

PROTEIN NAME

BMAL1

SYNONYMS

ARNT like protein 1 brain and muscle antibody; Arntl antibody; Aryl hydrocarbon receptor nuclear translocator like antibody; Aryl hydrocarbon receptor nuclear translocator like protein 1 antibody; Aryl hydrocarbon receptor nuclear translocator-like protein 1 antibody; Basic helix loop helix PAS orphan MOP3 antibody; Basic helix loop helix PAS protein MOP3 antibody; Basic-helix-loop-helix-PAS protein MOP3 antibody; bHLH PAS protein JAP3 antibody; bHLH-PAS protein JAP3 antibody; bHLHe5 antibody; BMAL 1 antibody; BMAL1_HUMAN antibody; BMAL1c antibody; Brain and muscle ARNT like 1 antibody; Brain and muscle ARNT-like 1 antibody; CG8727 PA antibody; Class E basic helix-loop-helix protein 5 antibody; cycle antibody; JAP 3 antibody; JAP3 antibody; Member of PAS protein 3 antibody; Member of PAS superfamily 3 antibody; MGC47515 antibody; MOP 3 antibody; MOP3 antibody; PAS domain-containing protein 3 antibody; PASD 3 antibody; PASD3 antibody; TIC antibody

TISSUE SPECIFICITY

Hair follicles (at protein level). Highly expressed in the adult brain, skeletal muscle and heart.

POST-TRANSLATIONAL MODIFICATION

Ubiquitinated, leading to its proteasomal degradation. Deubiquitinated by USP9X.; O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-ARNTL/BMAL1 heterodimer thereby increasing CLOCK-ARNTL/BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2/3 and CRY1/2.; Acetylated on Lys-538 upon dimerization with CLOCK. Acetylation facilitates CRY1-mediated repression. Deacetylated by SIRT1, which may result in decreased protein stability.; Phosphorylated upon dimerization with CLOCK. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the CLOCK-ARNTL/BMAL1 heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver with a peak between CT10 to CT14. Phosphorylation at Ser-90 by CK2 is essential for its nuclear localization, its interaction with CLOCK and controls CLOCK nuclear entry (By similarity). Dephosphorylation at Ser-78 is important for dimerization with CLOCK and transcriptional activity.; Sumoylated on Lys-259 upon dimerization with CLOCK. Predominantly conjugated to poly-SUMO2/3 rather than SUMO1 and the level of these conjugates undergo rhythmic variation, peaking at CT9-CT12. Sumoylation localizes it exclusively to the PML body and promotes its ubiquitination in the PML body, ubiquitin-dependent proteasomal degradation and the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer.; Undergoes lysosome-mediated degradation in a time-dependent manner in the liver.

SUBCELLULAR LOCATION

Nucleus, PML body, Cytoplasm.

FUNCTION

Transcriptional activator which forms a core component of the circadian clock. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. ARNTL/BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway.