'Linnea Saunders/Sandbox 1 CLOCK:BMAL1 Transcriptional Activator Complex'
Function
The circadian locomotor output cycles protein kaput and brain-muscle-arnt-like (CLOCK:BMAL1) transcriptional activator complex is an important protein involved in the regulation of our circadian rhythm. This protein is a heterodimer of CLOCK and BMAL1. Its main function is to interact with DNA at regulatory elements to upregulate the production of proteins period (PER) and cryptochrome (CRY) during the day. These proteins (PER and CRY) heterodimerize at night and interact with CLOCK:BMAL1 to repress the transcription of PER and CRY.1 They are then degraded, allowing their transcription to occur again. This process takes approximately 24 hours and is the main mechanism of the circadian rhythm, and CLOCK:BMAL1 lies at the heart of this process. In addition to regulating PER and CRY, CLOCK:BMAL1 regulates the transcription of Rev-erbα, which is a nuclear hormone receptor).2 Rev-erbα once transcribed, inhibits the transcription of BMAL1.
CLOCK:BMAL1 contains two necessary domain structures to facilitate its function in the cell, as well as sites for phosphorylation, acetylation, O-glycosylation and sumoylation, which serve a variety of purposes for the protein.
Disease
Relevance
Structural highlights
The main domains of interest with the CLOCK:BMAL1 complex are the PAS domains which are necessary for the two proteins to dimerize, and the , which allows the complex to interact with DNA. Each subunit contains two PAS domains
Mechanism of Interactions
