BMAL1 binds CLOCK,NPAS2 forming BMAL1:CLOCK,NPAS2 heterodimer

Stable Identifier
R-HSA-400228
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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BMAL1 binds CLOCK,NPAS2 forming BMAL1:CLOCK,NPAS2 heterodimer
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BMAL1 (ARNTL), CLOCK, and NPAS2 are basic helix-loop-helix transcription factors. In humans BMAL1 has been demonstrated to form a heterodimer with CLOCK. In mouse, BMAL1 can form a heterodimer with either CLOCK or NPAS2. By analogy with other basic helix-loop-helix proteins the basic domain binds DNA, in this case the E-box motif, and the helix-loop-helix domains interact to form the heterodimer. BMAL1 and CLOCK/NPAS2 are codependently phosphorylated by unknown kinases after dimerization. The phosphorylation enhances transactivation activity and is inhibited by PER:CRY complexes. Both CLOCK and NPAS2 are expressed in the suprachiasmatic nucleus of the hypothalamus and act redundantly there. The tissue distributions of CLOCK and NPAS2 do not entirely overlap, however. For example, NPAS2 but not CLOCK is found in forebrain.
Literature References
PubMed ID Title Journal Year
11441147 NPAS2: an analog of clock operative in the mammalian forebrain

Dudley, C, Garcia, JA, Reick, M, McKnight, SL

Science 2001
11441146 Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors

Rutter, J, Reick, M, Wu, LC, McKnight, SL

Science 2001
9576906 The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors

Jain, S, Hogenesch, JB, Gu, YZ, Bradfield, CA

Proc Natl Acad Sci U S A 1998
9616112 Role of the CLOCK protein in the mammalian circadian mechanism

King, DP, Nguyen, HB, Weitz, CJ, Takahashi, JS, Staknis, D, Gekakis, N, Davis, FC, Wilsbacher, LD

Science 1998
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Bmal1 binds Clock,Npas2 forming Bmal1:Clock,Npas2 heterodimer (Mus musculus)
Authored
May, B  (2009-05-18)
Reviewed
Delaunay, F  (2010-06-23)
Hirota, T  (2010-06-23)
Kay, SA  (2010-06-23)
Albrecht, U  (2010-06-23)
D'Eustachio, P  (2009-05-27)
Created
May, B  (2009-03-24)
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