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MGP003598

UniProt Annotations

Entry Information
Gene Namebasic helix-loop-helix family, member e40
Protein EntryBHE40_HUMAN
UniProt IDO14503
SpeciesHuman
Comments
Comment typeDescription
FunctionTranscriptional 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 BHLHE41/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. {ECO:0000269|PubMed:12397359, ECO:0000269|PubMed:14672706, ECO:0000269|PubMed:15193144, ECO:0000269|PubMed:15560782, ECO:0000269|PubMed:18411297, ECO:0000269|PubMed:19786558}.
InteractionP0C206:- (xeno); NbExp=3; IntAct=EBI-711810, EBI-9675596; P04637:TP53; NbExp=5; IntAct=EBI-711810, EBI-366083; P63279:UBE2I; NbExp=3; IntAct=EBI-711810, EBI-80168;
PtmSumoylation inhibits its ubiquitination and promotes its negative regulation of the CLOCK-ARNTL/BMAL1 heterodimer transcriptional activator activity. {ECO:0000269|PubMed:11278694, ECO:0000269|PubMed:21829689}.
PtmUbiquitinated; which may lead to proteasomal degradation. {ECO:0000269|PubMed:11278694}.
SimilarityContains 1 bHLH (basic helix-loop-helix) domain. {ECO:0000255|PROSITE-ProRule:PRU00981}.
SimilarityContains 1 Orange domain. {ECO:0000255|PROSITE- ProRule:PRU00380}.
Subcellular LocationCytoplasm. Nucleus. Nucleus, nucleolus. Note=Predominantly localized in the nucleus.
SubunitHomodimer. Heterodimer with BHLHE41/DEC2. Interacts with TCF3/E47. Interacts with ubiquitin-conjugating enzyme UBE2I/UBC9. Interacts with HDAC1, SUMO1, RXRA and ARNTL/BMAL1. {ECO:0000269|PubMed:11278694, ECO:0000269|PubMed:12397359, ECO:0000269|PubMed:15193144, ECO:0000269|PubMed:15560782, ECO:0000269|PubMed:19786558, ECO:0000269|PubMed:21829689}.
Tissue SpecificityExpressed in cartilage, spleen, intestine, lung, and to a lesser extent in heart, brain, liver, muscle and stomach.
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