Anti-CLOCK Antibody

HUABIO

Anti-CLOCK Antibody

7

Flow Cytometry, ImmunoFluorescence, Western Blot, ImmunoHistoChemistry, ImmunoHistoChemistry Paraffin

WB,IF-Cell,IHC-P,FC

Research Use Only

Polyclonal

1 mg/ml

Unconjugated

CLOCK

clock circadian regulator

KAT13D, bHLHe8, circadian locomoter output cycles protein kaput, circadian locomoter output cycles kaput protein, class E basic helix-loop-helix protein 8, clock homolog

Rabbit

IgG

Circadian locomoter output cycles protein kaput

CLOCK protein has been found to play a central role as a transcription factor in the circadian pacemaker. In Drosophila, newly synthesized CLOCK (CLK) is hypophosphorylated in the cytoplasm before entering the nucleus. Once in the nuclei, CLK is localized in nuclear foci and is later redistributed homogeneously. CYCLE (CYC) (also known as dBMAL for the BMAL1 ortholog in mammals) dimerizes with CLK via their respective PAS domains. This dimer then recruits co-activator CREB-binding protein (CBP) and is further phosphorylated. Once phosphorylated, this CLK-CYC complex binds to the E-box elements of the promoters of period (per) and timeless (tim) via its bHLH domain, causing the stimulation of gene expression of per and tim. A large molar excess of period (PER) and timeless (TIM) proteins causes formation of the PER-TIM heterodimer which prevents the CLK-CYC heterodimer from binding to the E-boxes of per and tim, essentially blocking per and tim transcription. CLK is hyperphosphorylated when doubletime (DBT) kinase interacts with the CLK-CYC complex in a PER reliant manner, destabilizing both CLK and PER, leading to the degradation of both proteins. Hypophosphorylated CLK then accumulates, binds to the E-boxes of per and tim and activates their transcription once again. This cycle of post-translational phosphorylation suggest that temporal phosphorylation of CLK helps in the timing mechanism of the circadian clock. CLOCK exhibits histone acetyl transferase (HAT) activity, which is enhanced by dimerization with BMAL1. Dr. Paolo Sassone-Corsi and colleagues demonstrated in vitro that CLOCK mediated HAT activity is necessary to rescue circadian rhythms in Clock mutants.

Human, Mouse, Rat

Human,Mouse,Rat

-20°C,2°C to 8°C

41116161