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Q9WTL8 (BMAL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aryl hydrocarbon receptor nuclear translocator-like protein 1
Alternative name(s):
Arnt3
Brain and muscle ARNT-like 1
Gene names
Name:Arntl
Synonyms:Bmal1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length632 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1, NR1D2, RORA, RORB and RORG, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. ARNTL/BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. The CLOCK-ARNTL/BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2 and also genes implicated in glucose and lipid metabolism. Represses glucocorticoid receptor (GR)-induced transcriptional activity by reducing the association of GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. May play a role in spermatogenesis; contributes to the chromatoid body assembly and physiology. Ref.12 Ref.15 Ref.16 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.35 Ref.36 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.45 Ref.46 Ref.47 Ref.48 Ref.49 Ref.51

Subunit structure

Component of the circadian clock oscillator which includes the CRY1/2 proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER1/2/3 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/BMAL1. 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. Interacts with PER2, CRY1 and CRY2. Interaction with PER and CRY proteins requires translocation to the nucleus. Interaction of the CLOCK-ARNTL/BMAL1 heterodimer with PER or CRY inhibits transcription activation. Interacts with CIART. Interacts with DDX4, SUMO3, OGT, EED, EZH2 and SUZ12. The CLOCK-ARNTL/BMAL1 heterodimer interacts with GSK3B. Ref.4 Ref.8 Ref.11 Ref.13 Ref.14 Ref.16 Ref.18 Ref.20 Ref.24 Ref.26 Ref.33 Ref.37 Ref.45 Ref.49 Ref.51

Subcellular location

Nucleus. Cytoplasm. NucleusPML body. Note: Shuttles between the nucleus and the cytoplasm and this nucleocytoplasmic shuttling is essential for the nuclear accumulation of CLOCK, target gene transcription and the degradation of the CLOCK-ARNTL/BMAL1 heterodimer. The sumoylated form localizes in the PML body. Ref.5 Ref.6 Ref.8 Ref.13 Ref.18 Ref.26 Ref.33

Tissue specificity

Expressed in liver and testis (at protein level). Ref.9 Ref.33

Induction

In liver, exhibits circadian rhythm expression. Ref.9

Post-translational modification

Ubiquitinated, leading to its proteasomal degradation. Ref.8 Ref.13 Ref.38

O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-ARNTL/BMAL1 heterodimer thereby increasing CLOCK-ARNTL/BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2/3 and CRY1/2. Ref.37 Ref.38

Acetylated on Lys-544 upon dimerization with CLOCK. Acetylation facilitates CRY1-mediated repression. Ref.10

Phosphorylated upon dimerization with CLOCK. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the CLOCK-ARNTL/BMAL1 heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver with a peak between CT10 to CT14. Phosphorylation at Ser-97 by CK2 is essential for its nuclear localization, its interaction with CLOCK and controls CLOCK nuclear entry. Ref.5 Ref.6 Ref.14 Ref.17 Ref.18 Ref.24

Sumoylated on Lys-266 upon dimerization with CLOCK. Predominantly conjugated to poly-SUMO2/3 rather than SUMO1 and the level of these conjugates undergo rhythmic variation, peaking at CT9-CT12. Sumoylation localizes it exclusively to the PML body and promotes its ubiquitination in the PML body, ubiquitin-dependent proteasomal degradation and the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer. Ref.7 Ref.13

Disruption phenotype

Mice are characterized by reduced lifespan, and the presence of a number of pathologies characteristic of pre-mature aging and increased oxidative stress. They show impaired functional connectivity, increased oxidative damage and severe astrogliosis in the brain. They also exhibit accelerated thrombosis with elevated levels of thrombogenic factors, including VWF, SERPINE1/PAI1, and fibrinogen. Both male and female mice are infertile and male mice have low testosterone and high luteinizing hormone serum levels and a significant decrease in sperm count. Ref.12 Ref.27 Ref.41 Ref.46

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 1 PAC (PAS-associated C-terminal) domain.

Contains 2 PAS (PER-ARNT-SIM) domains.

Ontologies

Keywords
   Biological processBiological rhythms
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Glycoprotein
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcircadian regulation of gene expression

Inferred from direct assay Ref.51. Source: UniProtKB

circadian rhythm

Inferred from direct assay PubMed 12024206PubMed 12150932PubMed 12843397Ref.6. Source: MGI

negative regulation of fat cell differentiation

Inferred from mutant phenotype Ref.31. Source: UniProtKB

oxidative stress-induced premature senescence

Inferred from mutant phenotype Ref.27. Source: UniProtKB

positive regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype Ref.31Ref.40. Source: UniProtKB

positive regulation of skeletal muscle cell differentiation

Inferred from mutant phenotype Ref.40. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 14672706PubMed 15147242PubMed 15193144. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype. Source: UniProtKB

protein import into nucleus, translocation

Inferred from direct assay Ref.6. Source: MGI

regulation of cell cycle

Inferred from mutant phenotype Ref.39. Source: UniProtKB

regulation of cellular senescence

Inferred from mutant phenotype Ref.27. Source: UniProtKB

regulation of hair cycle

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of neurogenesis

Inferred from mutant phenotype Ref.39. Source: UniProtKB

regulation of protein catabolic process

Inferred from direct assay Ref.6. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay Ref.51. Source: UniProtKB

spermatogenesis

Inferred from mutant phenotype Ref.33. Source: UniProtKB

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15147242. Source: GOC

   Cellular_componentchromatoid body

Inferred from direct assay Ref.33. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nuclear body

Inferred from direct assay Ref.13. Source: MGI

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.6. Source: MGI

transcription factor complex

Inferred from direct assay Ref.51. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from physical interaction Ref.2. Source: MGI

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 15147242. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred by curator PubMed 14672706. Source: BHF-UCL

RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription

Inferred from direct assay PubMed 15560782. Source: BHF-UCL

bHLH transcription factor binding

Inferred from physical interaction PubMed 12397359PubMed 15193144PubMed 15560782. Source: BHF-UCL

core promoter binding

Inferred from direct assay Ref.49. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction PubMed 12397359PubMed 15193144. Source: BHF-UCL

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12024206Ref.2. Source: MGI

signal transducer activity

Inferred from electronic annotation. Source: InterPro

transcription factor binding

Inferred from sequence alignment PubMed 11707566. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9WTL8-1)

Also known as: b';

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9WTL8-2)

Also known as: b;

The sequence of this isoform differs from the canonical sequence as follows:
     48-54: Missing.
Isoform 3 (identifier: Q9WTL8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     49-68: Missing.
     280-280: K → KA
Isoform 4 (identifier: Q9WTL8-4)

The sequence of this isoform differs from the canonical sequence as follows:
     48-54: Missing.
     280-280: K → KA
Isoform 5 (identifier: Q9WTL8-5)

Also known as: g';

The sequence of this isoform differs from the canonical sequence as follows:
     48-54: Missing.
     161-483: AADGFLFVVG...PSGEGGPKRT → DVTEGRSSLS...PRLDFRLKRI
     484-632: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 632632Aryl hydrocarbon receptor nuclear translocator-like protein 1
PRO_0000127158

Regions

Domain79 – 13254bHLH
Domain150 – 22273PAS 1
Domain333 – 40371PAS 2
Domain408 – 45144PAC
Motif36 – 416Nuclear localization signal Ref.8
Motif149 – 15911Nuclear export signal 1
Motif367 – 3759Nuclear export signal 2

Amino acid modifications

Modified residue171Phosphoserine; by GSK3-beta Ref.24
Modified residue211Phosphothreonine; by GSK3-beta Ref.24
Modified residue971Phosphoserine; by CK2 Ref.18
Modified residue5441N6-acetyllysine Ref.10
Cross-link259Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3) Ref.13
Cross-link266Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.7

Natural variations

Alternative sequence48 – 547Missing in isoform 2, isoform 4 and isoform 5.
VSP_007992
Alternative sequence49 – 6820Missing in isoform 3.
VSP_007993
Alternative sequence161 – 483323AADGF…GPKRT → DVTEGRSSLSPSLSSRSSII ARMTLLARACLTTCIQKILP KLRNSYLPRTLRPGSDSLMP RLDFRLKRI in isoform 5.
VSP_007995
Alternative sequence2801K → KA in isoform 3 and isoform 4.
VSP_007994
Alternative sequence484 – 632149Missing in isoform 5.
VSP_007996

Experimental info

Mutagenesis38 – 392KR → AA: Loss of nuclear localization.
Mutagenesis971S → A: Impaired nuclear accumulation, decreased interaction with CLOCK and disruption of circadain clock function. Ref.18
Mutagenesis1021L → E: Reduced CLOCK binding. Abolishes transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. Ref.51
Mutagenesis1221L → E: Reduced CLOCK binding. Abolishes transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. Ref.51
Mutagenesis1541L → A: Significant reduction in nucleocytoplasmic shuttling; when associated with A-157. Ref.8
Mutagenesis1571L → A: Significant reduction in nucleocytoplasmic shuttling; when associated with A-154. Ref.8
Mutagenesis2301K → R: No effect on sumoylation. Ref.7
Mutagenesis2361K → R: No effect on sumoylation. Ref.7
Mutagenesis2591K → R: Significant decrease in; transcriptional activity, localization in PML body, ubiquitination and proteasome-mediated proteolysis. Ref.13
Mutagenesis2661K → R: Abolishes sumoylation. Ref.7
Mutagenesis2791K → R: No effect on sumoylation. Ref.7
Mutagenesis3231I → D: Reduced CLOCK binding. Slightly reduced transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. Impairs regulation of circadian clock. Ref.51
Mutagenesis3701L → A: Significant reduction in nucleocytoplasmic shuttling; when associated with A-374. Ref.8
Mutagenesis3741L → A: Significant reduction in nucleocytoplasmic shuttling; when associated with A-370. Ref.8
Mutagenesis4181S → A: Decreases without abolishing O-GlcNAcylation. Ref.38
Sequence conflict2541F → L in BAA76414. Ref.1
Sequence conflict2541F → L in BAA81898. Ref.1

Secondary structure

.................................................. 632
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (b') [UniParc].

Last modified August 15, 2003. Version 2.
Checksum: 9669C3712A95C2DE

FASTA63269,452
        10         20         30         40         50         60 
MADQRMDISS TISDFMSPGP TDLLSGSLGT SGVDCNRKRK GSATDYQLDD FAFEESMDTD 

        70         80         90        100        110        120 
KDDPHGRLEY AEHQGRIKNA REAHSQIEKR RRDKMNSFID ELASLVPTCN AMSRKLDKLT 

       130        140        150        160        170        180 
VLRMAVQHMK TLRGATNPYT EANYKPTFLS DDELKHLILR AADGFLFVVG CDRGKILFVS 

       190        200        210        220        230        240 
ESVFKILNYS QNDLIGQSLF DYLHPKDIAK VKEQLSSSDT APRERLIDAK TGLPVKTDIT 

       250        260        270        280        290        300 
PGPSRLCSGA RRSFFCRMKC NRPSVKVEDK DFASTCSKKK DRKSFCTIHS TGYLKSWPPT 

       310        320        330        340        350        360 
KMGLDEDNEP DNEGCNLSCL VAIGRLHSHM VPQPANGEIR VKSMEYVSRH AIDGKFVFVD 

       370        380        390        400        410        420 
QRATAILAYL PQELLGTSCY EYFHQDDIGH LAECHRQVLQ TREKITTNCY KFKIKDGSFI 

       430        440        450        460        470        480 
TLRSRWFSFM NPWTKEVEYI VSTNTVVLAN VLEGGDPTFP QLTAPPHSMD SMLPSGEGGP 

       490        500        510        520        530        540 
KRTHPTVPGI PGGTRAGAGK IGRMIAEEIM EIHRIRGSSP SSCGSSPLNI TSTPPPDASS 

       550        560        570        580        590        600 
PGGKKILNGG TPDIPSTGLL PGQAQETPGY PYSDSSSILG ENPHIGIDMI DNDQGSSSPS 

       610        620        630 
NDEAAMAVIM SLLEADAGLG GPVDFSDLPW PL 

« Hide

Isoform 2 (b) [UniParc].

Checksum: 5A99555F851260CF
Show »

FASTA62568,614
Isoform 3 [UniParc].

Checksum: 24B91BA2E81D1A25
Show »

FASTA61367,200
Isoform 4 [UniParc].

Checksum: 837330EF65406CE4
Show »

FASTA62668,685
Isoform 5 (g') [UniParc].

Checksum: 9AE175BE7F6A446C
Show »

FASTA22225,061

References

« Hide 'large scale' references
[1]"Characterization of three splice variants and genomic organization of the mouse BMAL1 gene."
Yu W., Ikeda M., Abe H., Honma S., Ebisawa T., Yamauchi T., Honma K., Nomura M.
Biochem. Biophys. Res. Commun. 260:760-767(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 5).
Tissue: Brain.
[2]"Transcriptionally active heterodimer formation of an Arnt-like PAS protein, Arnt3, with HIF-1a, HLF, and clock."
Takahata S., Sogawa K., Kobayashi A., Ema M., Mimura J., Ozaki N., Fujii-Kuriyama Y.
Biochem. Biophys. Res. Commun. 248:789-794(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
[4]"Role of the CLOCK protein in the mammalian circadian mechanism."
Gekakis N., Staknis D., Nguyen H.B., Davis F.C., Wilsbacher L.D., King D.P., Takahashi J.S., Weitz C.J.
Science 280:1564-1569(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLOCK.
[5]"Posttranslational mechanisms regulate the mammalian circadian clock."
Lee C., Etchegaray J.-P., Cagampang F.R.A., Loudon A.S.I., Reppert S.M.
Cell 107:855-867(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION.
[6]"BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system."
Kondratov R.V., Chernov M.V., Kondratova A.A., Gorbacheva V.Y., Gudkov A.V., Antoch M.P.
Genes Dev. 17:1921-1932(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION.
[7]"Circadian clock control by SUMOylation of BMAL1."
Cardone L., Hirayama J., Giordano F., Tamaru T., Palvimo J.J., Sassone-Corsi P.
Science 309:1390-1394(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-266, MUTAGENESIS OF LYS-230; LYS-236; LYS-266 AND LYS-279.
[8]"BMAL1 shuttling controls transactivation and degradation of the CLOCK/BMAL1 heterodimer."
Kwon I., Lee J., Chang S.H., Jung N.C., Lee B.J., Son G.H., Kim K., Lee K.H.
Mol. Cell. Biol. 26:7318-7330(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, NUCLEAR EXPORT SIGNAL, INTERACTION WITH CLOCK, MUTAGENESIS OF 38-LYS-ARG-39; LEU-154; LEU-157; LEU-370 AND LEU-374, UBIQUITINATION, PROTEASOMAL DEGRADATION.
[9]"Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5."
Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.
Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
[10]"CLOCK-mediated acetylation of BMAL1 controls circadian function."
Hirayama J., Sahar S., Grimaldi B., Tamaru T., Takamatsu K., Nakahata Y., Sassone-Corsi P.
Nature 450:1086-1090(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-544.
[11]"Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK."
Langmesser S., Tallone T., Bordon A., Rusconi S., Albrecht U.
BMC Mol. Biol. 9:41-41(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CRY1; CRY2 AND PER2.
[12]"The circadian clock protein BMAL1 is necessary for fertility and proper testosterone production in mice."
Alvarez J.D., Hansen A., Ord T., Bebas P., Chappell P.E., Giebultowicz J.M., Williams C., Moss S., Sehgal A.
J. Biol. Rhythms 23:26-36(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[13]"Dual modification of BMAL1 by SUMO2/3 and ubiquitin promotes circadian activation of the CLOCK/BMAL1 complex."
Lee J., Lee Y., Lee M.J., Park E., Kang S.H., Chung C.H., Lee K.H., Kim K.
Mol. Cell. Biol. 28:6056-6065(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-259, SUBCELLULAR LOCATION, INTERACTION WITH SUMO3, MUTAGENESIS OF LYS-259, UBIQUITINATION, PROTEASOMAL DEGRADATION.
[14]"A serine cluster mediates BMAL1-dependent CLOCK phosphorylation and degradation."
Spengler M.L., Kuropatwinski K.K., Schumer M., Antoch M.P.
Cell Cycle 8:4138-4146(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GSK3B AND CLOCK, PHOSPHORYLATION.
[15]"Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications."
Nader N., Chrousos G.P., Kino T.
FASEB J. 23:1572-1583(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its negative role and a positive role of BMAL2 in the circadian transcription."
Sasaki M., Yoshitane H., Du N.H., Okano T., Fukada Y.
J. Biol. Chem. 284:25149-25159(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PER2.
[17]"Roles of CLOCK phosphorylation in suppression of E-box-dependent transcription."
Yoshitane H., Takao T., Satomi Y., Du N.H., Okano T., Fukada Y.
Mol. Cell. Biol. 29:3675-3686(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[18]"CK2alpha phosphorylates BMAL1 to regulate the mammalian clock."
Tamaru T., Hirayama J., Isojima Y., Nagai K., Norioka S., Takamatsu K., Sassone-Corsi P.
Nat. Struct. Mol. Biol. 16:446-448(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-97, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-97, INTERACTION WITH CLOCK.
[19]"Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1."
Nakahata Y., Sahar S., Astarita G., Kaluzova M., Sassone-Corsi P.
Science 324:654-657(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"Identification of two amino acids in the C-terminal domain of mouse CRY2 essential for PER2 interaction."
Ozber N., Baris I., Tatlici G., Gur I., Kilinc S., Unal E.B., Kavakli I.H.
BMC Mol. Biol. 11:69-69(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CRY2.
[21]"Circadian clock gene Bmal1 is not essential; functional replacement with its paralog, Bmal2."
Shi S., Hida A., McGuinness O.P., Wasserman D.H., Yamazaki S., Johnson C.H.
Curr. Biol. 20:316-321(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[22]"CLOCK regulates circadian rhythms of hepatic glycogen synthesis through transcriptional activation of Gys2."
Doi R., Oishi K., Ishida N.
J. Biol. Chem. 285:22114-22121(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[23]"Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes."
Marcheva B., Ramsey K.M., Buhr E.D., Kobayashi Y., Su H., Ko C.H., Ivanova G., Omura C., Mo S., Vitaterna M.H., Lopez J.P., Philipson L.H., Bradfield C.A., Crosby S.D., Je Bailey L., Wang X., Takahashi J.S., Bass J.
Nature 466:627-631(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[24]"Regulation of BMAL1 protein stability and circadian function by GSK3beta-mediated phosphorylation."
Sahar S., Zocchi L., Kinoshita C., Borrelli E., Sassone-Corsi P.
PLoS ONE 5:E8561-E8561(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-17 AND THR-21, INTERACTION WITH GSK3B.
[25]"CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function."
Andrews J.L., Zhang X., McCarthy J.J., McDearmon E.L., Hornberger T.A., Russell B., Campbell K.S., Arbogast S., Reid M.B., Walker J.R., Hogenesch J.B., Takahashi J.S., Esser K.A.
Proc. Natl. Acad. Sci. U.S.A. 107:19090-19095(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[26]"Identification of RACK1 and protein kinase Calpha as integral components of the mammalian circadian clock."
Robles M.S., Boyault C., Knutti D., Padmanabhan K., Weitz C.J.
Science 327:463-466(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNB2L1 AND PRKCA, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[27]"Circadian clock protein BMAL1 regulates cellular senescence in vivo."
Khapre R.V., Kondratova A.A., Susova O., Kondratov R.V.
Cell Cycle 10:4162-4169(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[28]"Loss of Bmal1 leads to uncoupling and impaired glucose-stimulated insulin secretion in beta-cells."
Lee J., Kim M.S., Li R., Liu V.Y., Fu L., Moore D.D., Ma K., Yechoor V.K.
Islets 3:381-388(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[29]"Deficiency in core circadian protein Bmal1 is associated with a prothrombotic and vascular phenotype."
Somanath P.R., Podrez E.A., Chen J., Ma Y., Marchant K., Antoch M., Byzova T.V.
J. Cell. Physiol. 226:132-140(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[30]"Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces dyslipidemia and ectopic fat formation."
Shimba S., Ogawa T., Hitosugi S., Ichihashi Y., Nakadaira Y., Kobayashi M., Tezuka M., Kosuge Y., Ishige K., Ito Y., Komiyama K., Okamatsu-Ogura Y., Kimura K., Saito M.
PLoS ONE 6:E25231-E25231(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[31]"The clock gene, brain and muscle Arnt-like 1, regulates adipogenesis via Wnt signaling pathway."
Guo B., Chatterjee S., Li L., Kim J.M., Lee J., Yechoor V.K., Minze L.J., Hsueh W., Ma K.
FASEB J. 26:3453-3463(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[32]"Circadian Dbp transcription relies on highly dynamic BMAL1-CLOCK interaction with E boxes and requires the proteasome."
Stratmann M., Suter D.M., Molina N., Naef F., Schibler U.
Mol. Cell 48:277-287(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[33]"Circadian proteins CLOCK and BMAL1 in the chromatoid body, a RNA processing granule of male germ cells."
Peruquetti R.L., de Mateo S., Sassone-Corsi P.
PLoS ONE 7:E42695-E42695(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH DDX4.
[34]"Mechanism of the circadian clock in physiology."
Richards J., Gumz M.L.
Am. J. Physiol. 304:R1053-R1064(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[35]"The clock gene brain and muscle Arnt-like protein-1 (BMAL1) is involved in hair growth."
Watabe Y., Tomioka M., Watabe A., Aihara M., Shimba S., Inoue H.
Arch. Dermatol. Res. 305:755-761(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[36]"The molecular clock regulates circadian transcription of tissue factor gene."
Oishi K., Koyanagi S., Ohkura N.
Biochem. Biophys. Res. Commun. 431:332-335(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[37]"O-GlcNAcylation of BMAL1 regulates circadian rhythms in NIH3T3 fibroblasts."
Ma Y.T., Luo H., Guan W.J., Zhang H., Chen C., Wang Z., Li J.D.
Biochem. Biophys. Res. Commun. 431:382-387(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION, INTERACTION WITH OGT.
[38]"O-GlcNAc signaling entrains the circadian clock by inhibiting BMAL1/CLOCK ubiquitination."
Li M.D., Ruan H.B., Hughes M.E., Lee J.S., Singh J.P., Jones S.P., Nitabach M.N., Yang X.
Cell Metab. 17:303-310(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION, UBIQUITINATION, MUTAGENESIS OF SER-418.
[39]"The circadian molecular clock regulates adult hippocampal neurogenesis by controlling the timing of cell-cycle entry and exit."
Bouchard-Cannon P., Mendoza-Viveros L., Yuen A., Kaern M., Cheng H.Y.
Cell Rep. 5:961-973(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[40]"Brain and muscle Arnt-like 1 is a key regulator of myogenesis."
Chatterjee S., Nam D., Guo B., Kim J.M., Winnier G.E., Lee J., Berdeaux R., Yechoor V.K., Ma K.
J. Cell Sci. 126:2213-2224(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[41]"Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration."
Musiek E.S., Lim M.M., Yang G., Bauer A.Q., Qi L., Lee Y., Roh J.H., Ortiz-Gonzalez X., Dearborn J.T., Culver J.P., Herzog E.D., Hogenesch J.B., Wozniak D.F., Dikranian K., Giasson B.I., Weaver D.R., Holtzman D.M., Fitzgerald G.A.
J. Clin. Invest. 123:5389-5400(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[42]"Bmal1 and beta-cell clock are required for adaptation to circadian disruption, and their loss of function leads to oxidative stress-induced beta-cell failure in mice."
Lee J., Moulik M., Fang Z., Saha P., Zou F., Xu Y., Nelson D.L., Ma K., Moore D.D., Yechoor V.K.
Mol. Cell. Biol. 33:2327-2338(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[43]"Global loss of Bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism."
Kennaway D.J., Varcoe T.J., Voultsios A., Boden M.J.
PLoS ONE 8:E65255-E65255(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[44]"Metabolism and the circadian clock converge."
Eckel-Mahan K., Sassone-Corsi P.
Physiol. Rev. 93:107-135(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[45]"Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory monocytes."
Nguyen K.D., Fentress S.J., Qiu Y., Yun K., Cox J.S., Chawla A.
Science 341:1483-1488(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CLOCK; EED; EZH2 AND SUZ12.
[46]"BMAL1-dependent regulation of the mTOR signaling pathway delays aging."
Khapre R.V., Kondratova A.A., Patel S., Dubrovsky Y., Wrobel M., Antoch M.P., Kondratov R.V.
Aging (Albany NY) 6:48-57(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[47]"CLOCK:BMAL1 is a pioneer-like transcription factor."
Menet J.S., Pescatore S., Rosbash M.
Genes Dev. 28:8-13(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[48]"CLOCK/BMAL1 regulates circadian change of mouse hepatic insulin sensitivity via SIRT1."
Zhou B., Zhang Y., Zhang F., Xia Y., Liu J., Huang R., Wang Y., Hu Y., Wu J., Dai C., Wang H., Tu Y., Peng X., Wang Y., Zhai Q.
Hepatology 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[49]"Gene model 129 (Gm129) encodes a novel transcriptional repressor that modulates circadian gene expression."
Annayev Y., Adar S., Chiou Y.Y., Lieb J., Sancar A., Ye R.
J. Biol. Chem. 289:5013-5024(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CIART.
[50]"Molecular architecture of the mammalian circadian clock."
Partch C.L., Green C.B., Takahashi J.S.
Trends Cell Biol. 24:90-99(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[51]"Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex."
Huang N., Chelliah Y., Shan Y., Taylor C.A., Yoo S.H., Partch C., Green C.B., Zhang H., Takahashi J.S.
Science 337:189-194(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 69-453 IN COMPLEX WITH CLOCK, FUNCTION, INTERACTION WITH CLOCK, MUTAGENESIS OF LEU-102; LEU-122 AND ILE-323.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB012601 mRNA. Translation: BAA76414.1.
AB015203 mRNA. Translation: BAA81898.1.
AB012602 mRNA. Translation: BAA76415.1.
AB014494 mRNA. Translation: BAA32208.1.
BC025973 mRNA. Translation: AAH25973.1.
BC011080 mRNA. Translation: AAH11080.1.
PIRJE0270.
RefSeqNP_001229977.1. NM_001243048.1.
NP_031515.1. NM_007489.4.
XP_006507314.1. XM_006507251.1.
UniGeneMm.440371.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4F3LX-ray2.27B69-453[»]
DisProtDP00735.
ProteinModelPortalQ9WTL8.
SMRQ9WTL8. Positions 76-448.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198207. 16 interactions.
DIPDIP-43977N.
IntActQ9WTL8. 20 interactions.
MINTMINT-1657344.

PTM databases

PhosphoSiteQ9WTL8.

Proteomic databases

PaxDbQ9WTL8.
PRIDEQ9WTL8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000047321; ENSMUSP00000046235; ENSMUSG00000055116. [Q9WTL8-4]
GeneID11865.
KEGGmmu:11865.
UCSCuc009jhf.2. mouse. [Q9WTL8-3]
uc009jhi.2. mouse. [Q9WTL8-2]
uc009jhj.2. mouse. [Q9WTL8-1]

Organism-specific databases

CTD406.
MGIMGI:1096381. Arntl.

Phylogenomic databases

eggNOGNOG293303.
GeneTreeENSGT00650000092935.
HOGENOMHOG000234379.
HOVERGENHBG107503.
InParanoidQ9WTL8.
KOK02296.
OMAEKINTNC.
OrthoDBEOG7V1FQ8.
PhylomeDBQ9WTL8.
TreeFamTF319983.

Enzyme and pathway databases

ReactomeREACT_109335. Circadian Clock.
REACT_24972. Circadian Clock.

Gene expression databases

ArrayExpressQ9WTL8.
BgeeQ9WTL8.
GenevestigatorQ9WTL8.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamPF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view]
PRINTSPR00785. NCTRNSLOCATR.
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 3 hits.
TIGRFAMsTIGR00229. sensory_box. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio279875.
PROQ9WTL8.
SOURCESearch...

Entry information

Entry nameBMAL1_MOUSE
AccessionPrimary (citable) accession number: Q9WTL8
Secondary accession number(s): O88295 expand/collapse secondary AC list , Q921S4, Q9R0U2, Q9WTL9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: August 15, 2003
Last modified: April 16, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot