Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q2VPD4

- BMAL2_MOUSE

UniProt

Q2VPD4 - BMAL2_MOUSE

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 86 (01 Oct 2014)
      Sequence version 2 (23 Jan 2007)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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, 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/DEC1.2 Publications

    GO - Molecular functioni

    1. E-box binding Source: UniProtKB
    2. protein binding Source: UniProtKB
    3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity Source: Ensembl
    4. 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

    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. nucleus Source: UniProtKB-SubCell
    3. transcription factor complex Source: InterPro

    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.
    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. Also 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 PER2Add
    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.
    GeneTreeiENSGT00650000092935.
    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

    MEFPRKRRGR DSQPLQSEFM TDTTVESLPQ NPFASLLSTR TGVSAPSGIR    50
    EAHSQMEKRR RDKMNHLIQK LSSMIPPHIP TAHKLDKLSV LRRAVQYLRS 100
    LRGMTELYLG ENSKPSFIQD KELSHLILKA AEGFLFVVGC ERGRIFYVSK 150
    SVSKTLRYDQ ASLIGQNLFD FLHPKDVAKV KEQLSCDGSP REKPIDTKTS 200
    QVYSHPYTGR PRMHSGSRRS FFFRMKSCTV PVKEEQPCSS CSKKKDHRKF 250
    HTVHCTGYLR SWPLNVVGME KESGGGKDSG PLTCLVAMGR LHPYIVPQKS 300
    GKINVRPAEF ITRFAMNGKF VYVDQRATAI LGYLPQELLG TSCYEYFHQD 350
    DHSSLTDKHK AVLQSKEKIL TDSYKFRVKD GAFVTLKSEW FSFTNPWTKE 400
    LEYIVSVNTL VLGRSETRLS LLHCGGSSQS SEDSFRQSCI NVPGVSTGTV 450
    LGAGSIGTDI ANEVLSLQRL HSSSPEDASP SEEVRDDCSV NGGNAYGPAS 500
    TREPFAVSPS ETEVLEAARQ HQSTEPAHPH GPLPGDSAQL GFDVLCDSDS 550
    IDMAAFMNYL EAEGGLGDPG DFSDIQWAL 579
    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 ENSGT00650000092935.
    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.
    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

    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 1, 2014
    This is version 86 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