BHLHE40

This gene encodes a basic helix-loop-helix protein expressed in various tissues. The encoded protein can interact with ARNTL or compete for E-box binding sites in the promoter of PER1 and repress CLOCK/ARNTL's transactivation of PER1. This gene is believed to be involved in the control of circadian rhythm and cell differentiation.

Full Name

basic helix-loop-helix family, member e40

Function

Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes (PubMed:12397359, PubMed:18411297).
Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop) (PubMed:14672706).
Both these loops are interlocked as it represses the expression of PER1/2 and in turn is repressed by PER1/2 and CRY1/2 (PubMed:15193144).
Represses the activity of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes (PubMed:15560782).
Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2 (PubMed:14672706).
Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA and NR1H3/LXRA transactivation activity (PubMed:19786558).
May be involved in the regulation of chondrocyte differentiation via the cAMP pathway (PubMed:19786558).
Represses the transcription of NR0B2 and attentuates the transactivation of NR0B2 by the CLOCK-ARNTL/BMAL1 complex (PubMed:28797635).
Drives the circadian rhythm of blood pressure through transcriptional repression of ATP1B1 in the cardiovascular system (PubMed:30012868).

Biological Process

Anterior/posterior pattern specification Source: GO_Central
Circadian regulation of gene expression Source: BHF-UCL
Circadian rhythm Source: UniProtKB
Entrainment of circadian clock by photoperiod Source: BHF-UCL
Negative regulation of DNA-binding transcription factor activity Source: BHF-UCL
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Regulation of circadian rhythm Source: UniProtKB
Regulation of neurogenesis Source: GO_Central
Regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central

Cellular Location

Nucleus; Cytoplasm. Predominantly localized in the nucleus (PubMed:11278694).

PTM

Ubiquitinated; which may lead to proteasomal degradation.
Sumoylation inhibits its ubiquitination and promotes its negative regulation of the CLOCK-ARNTL/BMAL1 heterodimer transcriptional activator activity.