Human Gene BMAL1 (ENST00000389707.8) from GENCODE V44
Description: Homo sapiens aryl hydrocarbon receptor nuclear translocator like (ARNTL), transcript variant 11, mRNA. (from RefSeq NM_001351815) RefSeq Summary (NM_001297719): The protein encoded by this gene is a basic helix-loop-helix protein that forms a heterodimer with CLOCK. This heterodimer binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Defects in this gene have been linked to infertility, problems with gluconeogenesis and lipogenesis, and altered sleep patterns. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]. Gencode Transcript: ENST00000389707.8 Gencode Gene: ENSG00000133794.20 Transcript (Including UTRs) Position: hg38 chr11:13,277,798-13,387,266 Size: 109,469 Total Exon Count: 20 Strand: + Coding Region Position: hg38 chr11:13,354,309-13,386,756 Size: 32,448 Coding Exon Count: 16
ID:BMAL1_HUMAN DESCRIPTION: RecName: Full=Aryl hydrocarbon receptor nuclear translocator-like protein 1; AltName: Full=Basic-helix-loop-helix-PAS protein MOP3; AltName: Full=Brain and muscle ARNT-like 1; AltName: Full=Class E basic helix-loop-helix protein 5; Short=bHLHe5; AltName: Full=Member of PAS protein 3; AltName: Full=PAS domain-containing protein 3; AltName: Full=bHLH-PAS protein JAP3; FUNCTION: ARNTL-CLOCK heterodimers activate E-box element (5'- CACGTG-3') transcription of a number of proteins of the circadian clock. This transcription is inhibited in a feedback loop by PER, and also by CRY proteins (By similarity). SUBUNIT: Interacts with CRY2 (By similarity). Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, ARNTL or ARNTL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerization with CLOCK is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and, for phosphorylation of both CLOCK and ARNTL. Interaction with PER and CRY proteins requires translocation to the nucleus. Interaction of the CLOCK-ARNTL heterodimer with PER or CRY inhibits transcription activation. Interacts with HSP90; with AHR in vitro, but not in vivo. Part of a nuclear complex which also includes GNB2L1/RACK1 and PRKCA; GNB2L1 and PRKCA are recruited to the complex in a circadian manner. SUBCELLULAR LOCATION: Nucleus (By similarity). TISSUE SPECIFICITY: Highly expressed in the adult brain, skeletal muscle and heart. PTM: Acetylated on Lys-538 upon dimerization with CLOCK. Acetylation facilitates CRY1-mediated repression (By similarity). PTM: Phosphorylated upon dimerization with CLOCK (By similarity). PTM: Sumoylated on Lys-259 upon dimerization with CLOCK (By similarity). MISCELLANEOUS: CLOCK-ARNTL double mutations within the PAS domains result in syngernistic desensitization to high levels of CRY on repression of CLOCK-ARNTL transcriptional activity of PER1 and, disrupt circadian rhythmicity. SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. SIMILARITY: Contains 1 PAC (PAS-associated C-terminal) domain. SIMILARITY: Contains 2 PAS (PER-ARNT-SIM) domains.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00010 - Helix-loop-helix DNA-binding domain PF00989 - PAS fold PF08447 - PAS fold
ModBase Predicted Comparative 3D Structure on O00327
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000976 transcription regulatory region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001046 core promoter sequence-specific DNA binding GO:0001047 core promoter binding GO:0001190 transcriptional activator activity, RNA polymerase II transcription factor binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0017162 aryl hydrocarbon receptor binding GO:0043425 bHLH transcription factor binding GO:0043565 sequence-specific DNA binding GO:0046982 protein heterodimerization activity GO:0046983 protein dimerization activity GO:0051879 Hsp90 protein binding GO:0070491 repressing transcription factor binding GO:0070888 E-box binding
Biological Process: GO:0000060 protein import into nucleus, translocation GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0007283 spermatogenesis GO:0007623 circadian rhythm GO:0032007 negative regulation of TOR signaling GO:0032922 circadian regulation of gene expression GO:0042176 regulation of protein catabolic process GO:0042634 regulation of hair cycle GO:0042753 positive regulation of circadian rhythm GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0045599 negative regulation of fat cell differentiation GO:0045892 negative regulation of transcription, DNA-templated GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048511 rhythmic process GO:0050767 regulation of neurogenesis GO:0050796 regulation of insulin secretion GO:0051726 regulation of cell cycle GO:0051775 response to redox state GO:0060137 maternal process involved in parturition GO:0090263 positive regulation of canonical Wnt signaling pathway GO:0090403 oxidative stress-induced premature senescence GO:1901985 positive regulation of protein acetylation GO:2000074 regulation of type B pancreatic cell development GO:2000323 negative regulation of glucocorticoid receptor signaling pathway GO:2000772 regulation of cellular senescence GO:2001016 positive regulation of skeletal muscle cell differentiation