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Q9WTL8 (BMAL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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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 lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

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

General annotation (Comments)

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. Ref.9 Ref.11

Subunit structure

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 By similarity. 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 CRY2. Interacts with CLOCK; the heterodimer binds DNA. Ref.4 Ref.9 Ref.10 Ref.11

Subcellular location

Nucleus Ref.5 Ref.6 Ref.10.

Post-translational modification

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

Phosphorylated upon dimerization with CLOCK. Ref.5 Ref.6

Sumoylated on Lys-266 upon dimerization with CLOCK. Ref.7

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 componentNucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
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.11. Source: UniProtKB

protein import into nucleus, translocation

Inferred from direct assay Ref.6. Source: MGI

regulation of protein catabolic process

Inferred from direct assay Ref.6. Source: MGI

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nuclear body

Inferred from direct assay PubMed 18644859. Source: MGI

transcription factor complex

Inferred from direct assay Ref.11. 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 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

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

Amino acid modifications

Modified residue5441N6-acetyllysine Ref.8
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

Mutagenesis1021L → E: Reduced CLOCK binding. Abolishes transcriptional activation by the CLOCK-ARNTL heterodimer. Ref.11
Mutagenesis1221L → E: Reduced CLOCK binding. Abolishes transcriptional activation by the CLOCK-ARNTL heterodimer. Ref.11
Mutagenesis2301K → R: No effect on sumoylation. Ref.7
Mutagenesis2361K → R: No effect on sumoylation. Ref.7
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 heterodimer. Impairs regulation of circadian clock. Ref.11
Sequence conflict2541F → L in BAA76414. Ref.1
Sequence conflict2541F → L in BAA81898. Ref.1

Secondary structure

1 .................................................. 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]"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.
[9]"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.
[10]"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.
[11]"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.
IPIIPI00403502.
IPI00462286.
IPI00474434.
IPI00474567.
IPI00875930.
PIRJE0270.
RefSeqNP_001229977.1. NM_001243048.1.
NP_031515.1. NM_007489.4.
UniGeneMm.440371.

3D structure databases

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

Protein-protein interaction databases

DIPDIP-43977N.
IntActQ9WTL8. 18 interactions.
MINTMINT-1657344.

PTM databases

PhosphoSiteQ9WTL8.

Proteomic databases

PaxDbQ9WTL8.
PRIDEQ9WTL8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000047321; ENSMUSP00000046235; ENSMUSG00000055116.
GeneID11865.
KEGGmmu:11865.
UCSCuc009jhf.1. mouse.
uc009jhi.1. mouse.
uc009jhj.1. mouse.

Organism-specific databases

CTD406.
MGIMGI:1096381. Arntl.

Phylogenomic databases

eggNOGNOG293303.
GeneTreeENSGT00650000092935.
HOGENOMHOG000234379.
HOVERGENHBG107503.
InParanoidQ9WTL8.
KOK02296.
OMAEKINTNC.
OrthoDBEOG4NS3B2.

Enzyme and pathway databases

ReactomeREACT_109335. Circadian Clock.
REACT_24972. Circadian Clock (mouse).

Gene expression databases

ArrayExpressQ9WTL8.
BgeeQ9WTL8.
GenevestigatorQ9WTL8.
GermOnlineENSMUSG00000055116. Mus musculus.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR013655. PAS_fold_3.
[Graphical view]
PfamPF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
PF08447. PAS_3. 1 hit.
[Graphical view]
PRINTSPR00785. NCTRNSLOCATR.
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF47459. HLH_basic. 1 hit.
TIGRFAMsTIGR00229. sensory_box. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS50113. PAC. False negative.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio279875.
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: May 1, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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