Table 1

Circadian clock genes and their functions in Drosophila and mice

Organism
Gene
Protein function
Clock function

Drosophila
per
Binds to dClk-Cyc as a heterodimer with Tim
Inhibits dClk-Cyc-dependent transcription

tim
Stabilizes phosphorylated Per
Contributes to delayed Per accumulation


Promotes Per nuclear localization
Acts with Per to inhibit dClk-Cyc-dependent transcription


Binds to dClk-Cyc as a heterodimer with Per
Mediates phase-resetting in response to light


Degraded in response to light


dClk
Forms a heterodimeric complex with Cyc
Activates per and tim transcription and inhibits dClk transcription

Cyc (Bmal1)
Forms a heterodimeric complex with dClk
Activates per and tim transcription and inhibits dClk transcription

dbt (CK1ε)
Phosphorylates Per
Destabilizes Per

cry
Photoreceptor element that binds to Tim
Initiates light signaling required for phase resetting
Mouse
mPer1
Interacts with Clock-Bmal1?
Moderate inhibition of Clock-Bmal1-dependent transcription

mPer2
Interacts with Clock-Bmal1?
Activation of Bmal1 transcription



Moderate inhibition of Clock-Bmal1-dependent transcription

mPer3
Interacts with Clock-Bmal1?
Moderate inhibition of Clock-Bmal1-dependent transcription

mTim
Interacts with Clock-Bmal1?
Moderate inhibition of Clock-Bmal1-dependent transcription

Clock
Forms a heterodimeric complex with Bmal1
Activates mPer1-3 and mCry1

Bmal1
Forms a heterodimeric complex with Clock
Activates mPer1-3 and mCry1

CK1ε (tau)
Phosphorylates mPer1 and mPer2
Destabilizes mPers

mCry1
Dimerizes with mPer1-3
Strongly inhibits Clock-Bmal1-dependent transcription


Binds to Clock-Bmal1



Promotes mPer1-3 nuclear localization


mCry2
Dimerizes with mPer1-3
Strongly inhibits Clock-Bmal1-dependent transcription


Binds to Clock-Bmal1



Promotes mPer1-3 nuclear localization


Gene symbols are as described in the text. Protein functions are derived from in vivo and/or in vitro experiments. Clock function is derived from mutant phenotypes and/or in vivo experiments. The '?' for mPer1-3 and mTim protein function indicates that the indicated activity is presumed on the basis of the clock function of these proteins. Cyc is the Drosophila homolog of mouse Bmal1 and dbt is the homolog of mouse CK1ε and hamster tau.

Hardin Genome Biology 2000 1:reviews1023.1   doi:10.1186/gb-2000-1-4-reviews1023