Protein: Class E basic helix-loop-helix protein 41 (bHLHe41) (Class B basic helix-loop-helix protein 3) (bHLHb3) (Differentially expressed in chondrocytes protein 2) (hDEC2) (Enhancer-of-split and hairy-related protein 1) (SHARP-1) (Q9C0J9)
Organism: Homo sapiens (Human)
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 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-BMAL1 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/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 AND CYP3A11 (By similarity).
Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380, ECO:0000255|PROSITE-ProRule:PRU00981}.
Sequence: MDEGIPHLQERQLLEHRDFIGLDYSSLYMCKPKRSMKRDDTKDTYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHLKALTALTEQQHQKIIALQNGERSLKSPIQSDLDAFHSGFQTCAKEVLQYLSRFESWTPREPRCVQLINHLHAVATQFLPTPQLLTQQVPLSKGTGAPSAAGSAAAPCLERAGQKLEPLAYCVPVIQRTQPSAELAAENDTDTDSGYGGEAEARPDREKGKGAGASRVTIKQEPPGEDSPAPKRMKLDSRGGGSGGGPGGGAAAAAAALLGPDPAAAAALLRPDAALLSSLVAFGGGGGAPFPQPAAAAAPFCLPFCFLSPSAAAAYVQPFLDKSGLEKYLYPAAAAAPFPLLYPGIPAPAAAAAAAAAAAAAAAAFPCLSSVLSPPPEKAGAAAATLLPHEVAPLGAPHPQHPHGRTHLPFAGPREPGNPESSAQEDPSQPGKEAP
InterPro domains: - IPR011598: Myc-type, basic helix-loop-helix (bHLH) domain (domain) [44-105]
- IPR003650: Orange domain (domain) [129-175]
- IPR036638: Helix-loop-helix DNA-binding domain superfamily (homologous_superfamily) [36-114]
- IPR050370: Hairy and Enhancer of Split/HEY-related (family) [43-418]
Interaction partners: - Period circadian protein homolog 2
- Basic helix-loop-helix ARNT-like protein 1
- Nuclear factor interleukin-3-regulated protein
- Cryptochrome-1
- Class E basic helix-loop-helix protein 40
- Circadian locomoter output cycles protein kaput
- Neuronal PAS domain-containing protein 2
- Period circadian protein homolog 3
- Cryptochrome-2
- Nuclear receptor subfamily 1 group D member 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0140110 (transcription regulator activity), GO:0003700 (DNA-binding transcription factor activity), GO:0005515 (protein binding), GO:0008134 (transcription factor binding), GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific), GO:0140297 (DNA-binding transcription factor binding), GO:0061629 (RNA polymerase II-specific DNA-binding transcription factor binding), GO:0043425 (bHLH transcription factor binding)
Biological Process (BP): GO:0008150 (biological process), GO:0050789 (regulation of biological process), GO:0048519 (negative regulation of biological process), GO:0065007 (biological regulation), GO:0048523 (negative regulation of cellular process), GO:0050794 (regulation of cellular process), GO:0060548 (negative regulation of cell death), GO:0010941 (regulation of cell death), GO:0043069 (negative regulation of programmed cell death), GO:0043067 (regulation of programmed cell death), GO:0043066 (negative regulation of apoptotic process), GO:0042981 (regulation of apoptotic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005654 (nucleoplasm), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0016604 (nuclear body), GO:0043229 (intracellular organelle), GO:0043233 (organelle lumen), GO:0043227 (membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043231 (intracellular membrane-bounded organelle), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)