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 

Page IndexSequence and LinksUniProtKB CommentsPrimersRNA-Seq ExpressionMicroarray Expression
RNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathways
Other NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:13,277,798-13,387,266)mRNA (may differ from genome)Protein (625 aa)
Gene SorterGenome BrowserOther Species FASTATable SchemaAlphaFoldBioGPS
EnsemblEntrez GeneExonPrimerGencodeGeneCardsLynx
MalacardsMGIneXtProtOMIMPubMedReactome
UniProtKBBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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.

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 14.00 RPKM in Ovary
Total median expression: 386.63 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -143.90388-0.371 Picture PostScript Text
3' UTR -116.40510-0.228 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011598 - HLH_dom
IPR001067 - Nuc_translocat
IPR001610 - PAC
IPR000014 - PAS
IPR013767 - PAS_fold
IPR013655 - PAS_fold_3

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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD Ensembl  
Protein SequenceProtein Sequence Protein Sequence  
AlignmentAlignment Alignment  

-  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

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0016604 nuclear body
GO:0016605 PML body
GO:0033391 chromatoid body
GO:0043231 intracellular membrane-bounded organelle


-  Descriptions from all associated GenBank mRNAs
  AK315174 - Homo sapiens cDNA, FLJ96151, highly similar to Homo sapiens aryl hydrocarbon receptor nuclear translocator-like(ARNTL), mRNA.
BC041129 - Homo sapiens aryl hydrocarbon receptor nuclear translocator-like, mRNA (cDNA clone MGC:47515 IMAGE:5753529), complete cds.
AK291510 - Homo sapiens cDNA FLJ77694 complete cds, highly similar to Homo sapiens aryl hydrocarbon receptor nuclear translocator-like(ARNTL), mRNA.
U60415 - Human bHLH-PAS protein JAP3 mRNA, complete cds.
AF044288 - Homo sapiens basic-helix-loop-helix-PAS orphan MOP3 (MOP3) mRNA, complete cds.
AK095749 - Homo sapiens cDNA FLJ38430 fis, clone FEBRA2013699, highly similar to Aryl hydrocarbon receptor nucleartranslocator-like protein 1.
BC031214 - Homo sapiens aryl hydrocarbon receptor nuclear translocator-like, mRNA (cDNA clone MGC:39496 IMAGE:4793007), complete cds.
AB000816 - Homo sapiens mRNA for BMAL1d, partial cds.
HM005673 - Homo sapiens clone HTL-T-50e testis tissue sperm-binding protein Li 50e mRNA, complete cds.
AB000815 - Homo sapiens mRNA for BMAL1e, complete cds.
AB000812 - Homo sapiens mRNA for BMAL1b, complete cds.
AB527546 - Synthetic construct DNA, clone: pF1KB6124, Homo sapiens ARNTL gene for aryl hydrocarbon receptor nuclear translocator-like, without stop codon, in Flexi system.
EU446463 - Synthetic construct Homo sapiens clone IMAGE:100070312; IMAGE:100011672; FLH257242.01L aryl hydrocarbon receptor nuclear translocator-like (ARNTL) gene, encodes complete protein.
JF432385 - Synthetic construct Homo sapiens clone IMAGE:100073586 aryl hydrocarbon receptor nuclear translocator-like (ARNTL) gene, encodes complete protein.
KJ890711 - Synthetic construct Homo sapiens clone ccsbBroadEn_00105 ARNTL gene, encodes complete protein.
D89722 - Homo sapiens mRNA for BMAL1a, complete cds.
BC016674 - Homo sapiens aryl hydrocarbon receptor nuclear translocator-like, mRNA (cDNA clone MGC:21285 IMAGE:3921870), complete cds.
KJ905690 - Synthetic construct Homo sapiens clone ccsbBroadEn_15360 ARNTL gene, encodes complete protein.
U51627 - Homo sapiens MOP3 mRNA, complete cds.
JD236053 - Sequence 217077 from Patent EP1572962.
JD305803 - Sequence 286827 from Patent EP1572962.
CU691964 - Synthetic construct Homo sapiens gateway clone IMAGE:100021258 5' read ARNTL mRNA.
AB000814 - Homo sapiens mRNA for BMAL1f, partial cds.
AK128317 - Homo sapiens cDNA FLJ46458 fis, clone THYMU3020869.
JD293041 - Sequence 274065 from Patent EP1572962.
JD060442 - Sequence 41466 from Patent EP1572962.
JD174966 - Sequence 155990 from Patent EP1572962.
JD046515 - Sequence 27539 from Patent EP1572962.
JD363251 - Sequence 344275 from Patent EP1572962.
JD346828 - Sequence 327852 from Patent EP1572962.
JD253280 - Sequence 234304 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04710 - Circadian rhythm - mammal

BioCarta from NCI Cancer Genome Anatomy Project
h_circadianPathway - Circadian Rhythms

Reactome (by CSHL, EBI, and GO)

Protein O00327 (Reactome details) participates in the following event(s):

R-HSA-400228 BMAL1 binds CLOCK,NPAS2 forming BMAL1:CLOCK,NPAS2 heterodimer
R-HSA-549355 CRY proteins stabilize unphosphorylated BMAL1:CLOCK,NPAS2
R-HSA-400256 CRY:PER heterodimer binds the BMAL1:CLOCK/NPAS2 heterodimer
R-HSA-5663105 p-BMAL1:p-CLOCK,NPAS2 binds BHLHE41 (DEC2) gene
R-HSA-5663118 p-BMAL1:p-CLOCK,NPAS2 binds PER2 gene
R-HSA-5663120 p-BMAL1:p-CLOCK,NPAS2 binds CRY1 gene
R-HSA-5663122 p-BMAL1:p-CLOCK,NPAS2 binds NAMPT gene
R-HSA-5663124 p-BMAL1:p-CLOCK,NPAS2 binds SERPINE1 gene
R-HSA-5663127 p-BMAL1:p-CLOCK,NPAS2 binds F7 gene
R-HSA-5663132 p-BMAL1:p-CLOCK,NPAS2 binds DBP gene
R-HSA-5663138 p-BMAL1:p-CLOCK,NPAS2 binds CCRN4L (NOCTURNIN) gene
R-HSA-5663155 p-BMAL1:p-CLOCK,NPAS2 binds NR1D1 gene
R-HSA-5663156 p-BMAL1:p-CLOCK,NPAS2 binds PPARA gene
R-HSA-5663165 p-BMAL1:p-CLOCK,NPAS2 binds AVP gene
R-HSA-5663170 p-BMAL1:p-CLOCK,NPAS2 binds BHLHE40 gene
R-HSA-5663174 p-BMAL1:p-CLOCK,NPAS2 binds PER1 gene
R-HSA-5669302 p-BMAL1:p-CLOCK,NPAS2 binds RORA gene
R-HSA-8878702 p-BMAL1:p-CLOCK,NPAS2 binds KLF15 gene
R-HSA-400253 Circadian Clock
R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian gene expression

-  Other Names for This Gene
  Alternate Gene Symbols: A2I2N6, A8K645, ARNTL, B5ME11, B7WPG7, BHLHE5, BMAL1_HUMAN, D3DQW6, ENST00000389707.1, ENST00000389707.2, ENST00000389707.3, ENST00000389707.4, ENST00000389707.5, ENST00000389707.6, ENST00000389707.7, MOP3, NM_001351815, O00313, O00314, O00315, O00316, O00317, O00327, PASD3, Q4G136, Q8IUT4, Q99631, Q99649, uc001mkp.1, uc001mkp.2, uc001mkp.3, uc001mkp.4
UCSC ID: ENST00000389707.8
RefSeq Accession: NM_001297719
Protein: O00327 (aka BMAL1_HUMAN or BMAL_HUMAN)
CCDS: CCDS31430.1, CCDS73259.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.