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Q2VPD4 (BMAL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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 2
Alternative name(s):
Brain and muscle ARNT-like 2
Gene names
Name:Arntl2
Synonyms:Bmal2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length579 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. The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. Ref.3 Ref.4

Subunit structure

Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with CLOCK to form the ARNTL2/BMAL2-CLOCK transactivator. Can form heterodimers or homodimers which interact directly with CLOCK to form the transcription activator. Also interacts with NPAS2 and HIF1A By similarity. Interacts with PER2. Ref.3

Subcellular location

Nucleus By similarity.

Tissue specificity

Expressed in the suprachiasmatic nucleus (SCN).

Induction

Constitutively expressed in the SCN. Little change throughout day under dark/light cycle. Ref.1

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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q2VPD4-1)

Also known as: BMAL2a;

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: Q2VPD4-2)

Also known as: BMAL2b;

The sequence of this isoform differs from the canonical sequence as follows:
     199-199: T → K
     200-579: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 579579Aryl hydrocarbon receptor nuclear translocator-like protein 2
PRO_0000273632

Regions

Domain48 – 10154bHLH
Domain119 – 19072PAS 1
Domain296 – 36671PAS 2
Domain371 – 41444PAC
Region1 – 198198Interaction with PER2
Motif4 – 96Nuclear localization signal By similarity
Motif118 – 12811Nuclear export signal 1 By similarity
Motif331 – 3399Nuclear export signal 2 By similarity

Amino acid modifications

Cross-link226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3) By similarity

Natural variations

Alternative sequence1991T → K in isoform 2.
VSP_022586
Alternative sequence200 – 579380Missing in isoform 2.
VSP_022587

Experimental info

Sequence conflict91G → D in AAI08967. Ref.2
Sequence conflict1641I → M in AAI08966. Ref.2
Sequence conflict1641I → M in AAI08967. Ref.2
Sequence conflict2071Y → H in AAI08966. Ref.2
Sequence conflict2071Y → H in AAI08967. Ref.2
Sequence conflict2131M → V in AAI08966. Ref.2
Sequence conflict2131M → V in AAI08967. Ref.2
Sequence conflict4231H → Q in AAI08966. Ref.2
Sequence conflict4231H → Q in AAI08967. Ref.2
Sequence conflict425 – 4262GG → SS in AAI08966. Ref.2
Sequence conflict4501V → I in AAI08967. Ref.2
Sequence conflict4791S → N in AAI08966. Ref.2
Sequence conflict4791S → N in AAI08967. Ref.2
Sequence conflict4831Missing in AAI08967. Ref.2
Sequence conflict4941N → S in AAI08966. Ref.2
Sequence conflict4941N → S in AAI08967. Ref.2
Sequence conflict5041P → L in AAI08966. Ref.2
Sequence conflict5041P → L in AAI08967. Ref.2
Sequence conflict5111E → K in AAI08966. Ref.2
Sequence conflict5111E → K in AAI08967. Ref.2
Sequence conflict5351G → S in AAI08966. Ref.2
Sequence conflict5351G → S in AAI08967. Ref.2
Sequence conflict5511I → T in AAI08967. Ref.2
Sequence conflict5791L → R in AAI08966. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (BMAL2a) [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: D73F04B16CA0A363

FASTA57964,399
        10         20         30         40         50         60 
MEFPRKRRGR DSQPLQSEFM TDTTVESLPQ NPFASLLSTR TGVSAPSGIR EAHSQMEKRR 

        70         80         90        100        110        120 
RDKMNHLIQK LSSMIPPHIP TAHKLDKLSV LRRAVQYLRS LRGMTELYLG ENSKPSFIQD 

       130        140        150        160        170        180 
KELSHLILKA AEGFLFVVGC ERGRIFYVSK SVSKTLRYDQ ASLIGQNLFD FLHPKDVAKV 

       190        200        210        220        230        240 
KEQLSCDGSP REKPIDTKTS QVYSHPYTGR PRMHSGSRRS FFFRMKSCTV PVKEEQPCSS 

       250        260        270        280        290        300 
CSKKKDHRKF HTVHCTGYLR SWPLNVVGME KESGGGKDSG PLTCLVAMGR LHPYIVPQKS 

       310        320        330        340        350        360 
GKINVRPAEF ITRFAMNGKF VYVDQRATAI LGYLPQELLG TSCYEYFHQD DHSSLTDKHK 

       370        380        390        400        410        420 
AVLQSKEKIL TDSYKFRVKD GAFVTLKSEW FSFTNPWTKE LEYIVSVNTL VLGRSETRLS 

       430        440        450        460        470        480 
LLHCGGSSQS SEDSFRQSCI NVPGVSTGTV LGAGSIGTDI ANEVLSLQRL HSSSPEDASP 

       490        500        510        520        530        540 
SEEVRDDCSV NGGNAYGPAS TREPFAVSPS ETEVLEAARQ HQSTEPAHPH GPLPGDSAQL 

       550        560        570 
GFDVLCDSDS IDMAAFMNYL EAEGGLGDPG DFSDIQWAL 

« Hide

Isoform 2 (BMAL2b) [UniParc].

Checksum: 81927B4F8778237A
Show »

FASTA19922,697

References

« Hide 'large scale' references
[1]"Cloning of mouse BMAL2 and its daily expression profile in the suprachiasmatic nucleus: a remarkable acceleration of Bmal2 sequence divergence after Bmal gene duplication."
Okano T., Sasaki M., Fukada Y.
Neurosci. Lett. 300:111-114(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INDUCTION.
Strain: C57BL/6.
Tissue: Midbrain.
[2]"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] (ISOFORM 1).
[3]"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.
[4]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY005163 mRNA. Translation: AAF88141.1.
AY014836 mRNA. Translation: AAK12619.1.
BC108965 mRNA. Translation: AAI08966.1.
BC108966 mRNA. Translation: AAI08967.1.
CCDSCCDS20702.1. [Q2VPD4-1]
RefSeqNP_001276608.1. NM_001289679.1.
NP_001276609.1. NM_001289680.1.
NP_001276610.1. NM_001289681.1.
NP_758513.1. NM_172309.2. [Q2VPD4-1]
XP_006507116.1. XM_006507053.1. [Q2VPD4-1]
UniGeneMm.333500.
Mm.442075.

3D structure databases

ProteinModelPortalQ2VPD4.
SMRQ2VPD4. Positions 50-416.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ2VPD4.

Proteomic databases

PRIDEQ2VPD4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000080530; ENSMUSP00000079373; ENSMUSG00000040187. [Q2VPD4-1]
ENSMUST00000111639; ENSMUSP00000107266; ENSMUSG00000040187. [Q2VPD4-1]
ENSMUST00000129788; ENSMUSP00000121170; ENSMUSG00000040187. [Q2VPD4-2]
GeneID272322.
KEGGmmu:272322.
UCSCuc009esj.1. mouse. [Q2VPD4-1]

Organism-specific databases

CTD56938.
MGIMGI:2684845. Arntl2.

Phylogenomic databases

eggNOGNOG288887.
GeneTreeENSGT00650000092935.
HOGENOMHOG000234379.
HOVERGENHBG107503.
InParanoidQ2VPD4.
KOK09099.
OMASAMIPQC.
OrthoDBEOG7V1FQ8.
PhylomeDBQ2VPD4.
TreeFamTF319983.

Gene expression databases

BgeeQ2VPD4.
GenevestigatorQ2VPD4.

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. 2 hits.
TIGRFAMsTIGR00229. sensory_box. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio393555.
PROQ2VPD4.
SOURCESearch...

Entry information

Entry nameBMAL2_MOUSE
AccessionPrimary (citable) accession number: Q2VPD4
Secondary accession number(s): Q32MV7, Q91XJ5, Q91XJ6
Entry history
Integrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 84 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

MGD cross-references

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