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. [provided by RefSeq, Feb 2014]
Function:
Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. 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). Both these loops are interlocked as it represses the expression of PER1/2 and in turn is repressed by PER1/2 and CRY1/2. 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. Negatively regulates its own expression and the expression of DBP and SHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA and NR1H3/LXRA transactivation activity. May be involved in the regulation of chondrocyte differentiation via the cAMP pathway
Subunit:
Homodimer. Heterodimer with SHLHE41/DEC2. Interacts with TCF3/E47. Interacts with ubiquitin-conjugating enzyme UBE2I/UBC9. Interacts with HDAC1, SUMO1, RXRA and ARNTL/BMAL1.
Subcellular Location:
Nuclear
Tissue Specificity:
Expressed in cartilage, spleen, intestine, lung, and to a lesser extent in heart, brain, liver, muscle and stomach.
Post-translational modifications:
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.
Similarity:
Contains 1 bHLH (basic helix-loop-helix) domain;
Contains 1 Orange domain.
SWISS:
O14503
Gene ID:
8553
Database links:
Entrez Gene: 8553 Human
Entrez Gene: 20893 Mouse
Entrez Gene: 79431 Rat
Entrez Gene: 324413 Zebrafish
Omim: 604256 Human
SwissProt: Q5EA15 Cow
SwissProt: O14503 Human
SwissProt: O35185 Mouse
SwissProt: O35780 Rat
Unigene: 171825 Human
Unigene: 2436 Mouse
Unigene: 81055 Rat
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