Protein: Class E basic helix-loop-helix protein 40 (bHLHe40) (Class B basic helix-loop-helix protein 2) (bHLHb2) (Differentially expressed in chondrocytes protein 1) (DEC1) (Enhancer-of-split and hairy-related protein 2) (SHARP-2) (Stimulated by retinoic acid gene 13 protein) (O14503)
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 PER1/2 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-BMAL1|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. Represses the transcription of NR0B2 and attentuates the transactivation of NR0B2 by the CLOCK-BMAL1 complex. Drives the circadian rhythm of blood pressure through transcriptional repression of ATP1B1 in the cardiovascular system.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:21829689}. Nucleus {ECO:0000269|PubMed:11278694, ECO:0000269|PubMed:21829689, ECO:0000269|PubMed:28797635}. Note=Predominantly localized in the nucleus (PubMed:11278694). {ECO:0000269|PubMed:11278694}.
InterPro domains:
- IPR011598: Myc-type, basic helix-loop-helix (bHLH) domain (domain) [52-113]
- IPR003650: Orange domain (domain) [140-184]
- IPR036638: Helix-loop-helix DNA-binding domain superfamily (homologous_superfamily) [44-124]
- IPR050370: Hairy and Enhancer of Split/HEY-related (family) [51-368]
Sequence:
MERIPSAQPPPACLPKAPGLEHGDLPGMYPAHMYQVYKSRRGIKRSEDSKETYKLPHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHLEKAVVLELTLKHVKALTNLIDQQQQKIIALQSGLQAGELSGRNVETGQEMFCSGFQTCAREVLQYLAKHENTRDLKSSQLVTHLHRVVSELLQGGTSRKPSDPAPKVMDFKEKPSSPAKGSEGPGKNCVPVIQRTFAHSSGEQSGSDTDTDSGYGGESEKGDLRSEQPCFKSDHGRRFTMGERIGAIKQESEEPPTKKNRMQLSDDEGHFTSSDLISSPFLGPHPHQPPFCLPFYLIPPSATAYLPMLEKCWYPTSVPVLYPGLNASAAALSSFMNPDKISAPLLMPQRLPSPLPAHPSVDSSVLLQALKPIPPLNLETKD
Predicted GO terms:
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)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048511 (rhythmic process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0009628 (response to abiotic stimulus), GO:0042752 (regulation of circadian rhythm), GO:0019222 (regulation of metabolic process), GO:0007623 (circadian rhythm), GO:0050794 (regulation of cellular process), GO:0048523 (negative regulation of cellular process), GO:0009892 (negative regulation of metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0009314 (response to radiation), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0009649 (entrainment of circadian clock), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0032922 (circadian regulation of gene expression), GO:0009416 (response to light stimulus), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010468 (regulation of gene expression), GO:0043153 (entrainment of circadian clock by photoperiod), GO:0009648 (photoperiodism), GO:2001141 (regulation of RNA biosynthetic process), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0045892 (negative regulation of DNA-templated transcription)
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)