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Q2VPD4

- BMAL2_MOUSE

UniProt

Q2VPD4 - BMAL2_MOUSE

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Protein

Aryl hydrocarbon receptor nuclear translocator-like protein 2

Gene

Arntl2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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 NR1D1/2 and RORA/B/G, 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/DEC1.2 Publications

GO - Molecular functioni

  1. E-box binding Source: UniProtKB
  2. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity Source: Ensembl
  3. signal transducer activity Source: InterPro

GO - Biological processi

  1. circadian rhythm Source: Ensembl
  2. positive regulation of circadian rhythm Source: UniProtKB
  3. positive regulation of transcription, DNA-templated Source: UniProtKB
  4. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_198620. BMAL1:CLOCK,NPAS2 activates circadian gene expression.

Names & Taxonomyi

Protein namesi
Recommended name:
Aryl hydrocarbon receptor nuclear translocator-like protein 2
Alternative name(s):
Brain and muscle ARNT-like 2
Gene namesi
Name:Arntl2
Synonyms:Bmal2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 6

Organism-specific databases

MGIiMGI:2684845. Arntl2.

Subcellular locationi

Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  1. cytoplasm Source: InterPro
  2. nucleolus Source: Ensembl
  3. transcription factor complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 579579Aryl hydrocarbon receptor nuclear translocator-like protein 2PRO_0000273632Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki226 – 226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3)By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PRIDEiQ2VPD4.

PTM databases

PhosphoSiteiQ2VPD4.

Expressioni

Tissue specificityi

Expressed in the suprachiasmatic nucleus (SCN).

Inductioni

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

Gene expression databases

BgeeiQ2VPD4.
ExpressionAtlasiQ2VPD4. baseline and differential.
GenevestigatoriQ2VPD4.

Interactioni

Subunit structurei

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. Interacts with NPAS2 and HIF1A (By similarity). Interacts with PER2.By similarity1 Publication

Protein-protein interaction databases

DIPiDIP-60819N.

Structurei

3D structure databases

ProteinModelPortaliQ2VPD4.
SMRiQ2VPD4. Positions 50-416.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini48 – 10154bHLHPROSITE-ProRule annotationAdd
BLAST
Domaini119 – 19072PAS 1PROSITE-ProRule annotationAdd
BLAST
Domaini296 – 36671PAS 2PROSITE-ProRule annotationAdd
BLAST
Domaini371 – 41444PACAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 198198Interaction with PER21 PublicationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi4 – 96Nuclear localization signalBy similarity
Motifi118 – 12811Nuclear export signal 1By similarityAdd
BLAST
Motifi331 – 3399Nuclear export signal 2By similarity

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
Contains 2 PAS (PER-ARNT-SIM) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG288887.
GeneTreeiENSGT00760000118788.
HOGENOMiHOG000234379.
HOVERGENiHBG107503.
InParanoidiQ2VPD4.
KOiK09099.
OMAiSAMIPQC.
OrthoDBiEOG7V1FQ8.
PhylomeDBiQ2VPD4.
TreeFamiTF319983.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view]
PRINTSiPR00785. NCTRNSLOCATR.
SMARTiSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
TIGRFAMsiTIGR00229. sensory_box. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q2VPD4-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MEFPRKRRGR DSQPLQSEFM TDTTVESLPQ NPFASLLSTR TGVSAPSGIR
60 70 80 90 100
EAHSQMEKRR RDKMNHLIQK LSSMIPPHIP TAHKLDKLSV LRRAVQYLRS
110 120 130 140 150
LRGMTELYLG ENSKPSFIQD KELSHLILKA AEGFLFVVGC ERGRIFYVSK
160 170 180 190 200
SVSKTLRYDQ ASLIGQNLFD FLHPKDVAKV KEQLSCDGSP REKPIDTKTS
210 220 230 240 250
QVYSHPYTGR PRMHSGSRRS FFFRMKSCTV PVKEEQPCSS CSKKKDHRKF
260 270 280 290 300
HTVHCTGYLR SWPLNVVGME KESGGGKDSG PLTCLVAMGR LHPYIVPQKS
310 320 330 340 350
GKINVRPAEF ITRFAMNGKF VYVDQRATAI LGYLPQELLG TSCYEYFHQD
360 370 380 390 400
DHSSLTDKHK AVLQSKEKIL TDSYKFRVKD GAFVTLKSEW FSFTNPWTKE
410 420 430 440 450
LEYIVSVNTL VLGRSETRLS LLHCGGSSQS SEDSFRQSCI NVPGVSTGTV
460 470 480 490 500
LGAGSIGTDI ANEVLSLQRL HSSSPEDASP SEEVRDDCSV NGGNAYGPAS
510 520 530 540 550
TREPFAVSPS ETEVLEAARQ HQSTEPAHPH GPLPGDSAQL GFDVLCDSDS
560 570
IDMAAFMNYL EAEGGLGDPG DFSDIQWAL
Length:579
Mass (Da):64,399
Last modified:January 23, 2007 - v2
Checksum:iD73F04B16CA0A363
GO
Isoform 2 (identifier: Q2VPD4-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:199
Mass (Da):22,697
Checksum:i81927B4F8778237A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti9 – 91G → D in AAI08967. (PubMed:15489334)Curated
Sequence conflicti164 – 1641I → M in AAI08966. (PubMed:15489334)Curated
Sequence conflicti164 – 1641I → M in AAI08967. (PubMed:15489334)Curated
Sequence conflicti207 – 2071Y → H in AAI08966. (PubMed:15489334)Curated
Sequence conflicti207 – 2071Y → H in AAI08967. (PubMed:15489334)Curated
Sequence conflicti213 – 2131M → V in AAI08966. (PubMed:15489334)Curated
Sequence conflicti213 – 2131M → V in AAI08967. (PubMed:15489334)Curated
Sequence conflicti423 – 4231H → Q in AAI08966. (PubMed:15489334)Curated
Sequence conflicti423 – 4231H → Q in AAI08967. (PubMed:15489334)Curated
Sequence conflicti425 – 4262GG → SS in AAI08966. (PubMed:15489334)Curated
Sequence conflicti450 – 4501V → I in AAI08967. (PubMed:15489334)Curated
Sequence conflicti479 – 4791S → N in AAI08966. (PubMed:15489334)Curated
Sequence conflicti479 – 4791S → N in AAI08967. (PubMed:15489334)Curated
Sequence conflicti483 – 4831Missing in AAI08967. (PubMed:15489334)Curated
Sequence conflicti494 – 4941N → S in AAI08966. (PubMed:15489334)Curated
Sequence conflicti494 – 4941N → S in AAI08967. (PubMed:15489334)Curated
Sequence conflicti504 – 5041P → L in AAI08966. (PubMed:15489334)Curated
Sequence conflicti504 – 5041P → L in AAI08967. (PubMed:15489334)Curated
Sequence conflicti511 – 5111E → K in AAI08966. (PubMed:15489334)Curated
Sequence conflicti511 – 5111E → K in AAI08967. (PubMed:15489334)Curated
Sequence conflicti535 – 5351G → S in AAI08966. (PubMed:15489334)Curated
Sequence conflicti535 – 5351G → S in AAI08967. (PubMed:15489334)Curated
Sequence conflicti551 – 5511I → T in AAI08967. (PubMed:15489334)Curated
Sequence conflicti579 – 5791L → R in AAI08966. (PubMed:15489334)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei199 – 1991T → K in isoform 2. 1 PublicationVSP_022586
Alternative sequencei200 – 579380Missing in isoform 2. 1 PublicationVSP_022587Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY005163 mRNA. Translation: AAF88141.1.
AY014836 mRNA. Translation: AAK12619.1.
BC108965 mRNA. Translation: AAI08966.1.
BC108966 mRNA. Translation: AAI08967.1.
CCDSiCCDS20702.1. [Q2VPD4-1]
RefSeqiNP_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]
UniGeneiMm.333500.
Mm.442075.

Genome annotation databases

EnsembliENSMUST00000080530; ENSMUSP00000079373; ENSMUSG00000040187. [Q2VPD4-1]
ENSMUST00000111639; ENSMUSP00000107266; ENSMUSG00000040187. [Q2VPD4-1]
ENSMUST00000129788; ENSMUSP00000121170; ENSMUSG00000040187. [Q2VPD4-2]
GeneIDi272322.
KEGGimmu:272322.
UCSCiuc009esj.1. mouse. [Q2VPD4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY005163 mRNA. Translation: AAF88141.1 .
AY014836 mRNA. Translation: AAK12619.1 .
BC108965 mRNA. Translation: AAI08966.1 .
BC108966 mRNA. Translation: AAI08967.1 .
CCDSi CCDS20702.1. [Q2VPD4-1 ]
RefSeqi NP_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 ]
UniGenei Mm.333500.
Mm.442075.

3D structure databases

ProteinModelPortali Q2VPD4.
SMRi Q2VPD4. Positions 50-416.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-60819N.

PTM databases

PhosphoSitei Q2VPD4.

Proteomic databases

PRIDEi Q2VPD4.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000080530 ; ENSMUSP00000079373 ; ENSMUSG00000040187 . [Q2VPD4-1 ]
ENSMUST00000111639 ; ENSMUSP00000107266 ; ENSMUSG00000040187 . [Q2VPD4-1 ]
ENSMUST00000129788 ; ENSMUSP00000121170 ; ENSMUSG00000040187 . [Q2VPD4-2 ]
GeneIDi 272322.
KEGGi mmu:272322.
UCSCi uc009esj.1. mouse. [Q2VPD4-1 ]

Organism-specific databases

CTDi 56938.
MGIi MGI:2684845. Arntl2.

Phylogenomic databases

eggNOGi NOG288887.
GeneTreei ENSGT00760000118788.
HOGENOMi HOG000234379.
HOVERGENi HBG107503.
InParanoidi Q2VPD4.
KOi K09099.
OMAi SAMIPQC.
OrthoDBi EOG7V1FQ8.
PhylomeDBi Q2VPD4.
TreeFami TF319983.

Enzyme and pathway databases

Reactomei REACT_198620. BMAL1:CLOCK,NPAS2 activates circadian gene expression.

Miscellaneous databases

NextBioi 393555.
PROi Q2VPD4.
SOURCEi Search...

Gene expression databases

Bgeei Q2VPD4.
ExpressionAtlasi Q2VPD4. baseline and differential.
Genevestigatori Q2VPD4.

Family and domain databases

Gene3Di 4.10.280.10. 1 hit.
InterProi IPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view ]
Pfami PF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view ]
PRINTSi PR00785. NCTRNSLOCATR.
SMARTi SM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view ]
SUPFAMi SSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
TIGRFAMsi TIGR00229. sensory_box. 1 hit.
PROSITEi PS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiBMAL2_MOUSE
AccessioniPrimary (citable) accession number: Q2VPD4
Secondary accession number(s): Q32MV7, Q91XJ5, Q91XJ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: January 23, 2007
Last modified: October 29, 2014
This is version 87 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3