BMAL2_MOUSE
ID BMAL2_MOUSE Reviewed; 579 AA.
AC Q2VPD4; Q32MV7; Q91XJ5; Q91XJ6;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Aryl hydrocarbon receptor nuclear translocator-like protein 2;
DE AltName: Full=Brain and muscle ARNT-like 2;
GN Name=Arntl2; Synonyms=Bmal2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND INDUCTION.
RC STRAIN=C57BL/6J; TISSUE=Midbrain;
RX PubMed=11207387; DOI=10.1016/s0304-3940(01)01581-6;
RA Okano T., Sasaki M., Fukada Y.;
RT "Cloning of mouse BMAL2 and its daily expression profile in the
RT suprachiasmatic nucleus: a remarkable acceleration of Bmal2 sequence
RT divergence after Bmal gene duplication.";
RL Neurosci. Lett. 300:111-114(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND INTERACTION WITH PER2.
RX PubMed=19605937; DOI=10.1074/jbc.m109.040758;
RA Sasaki M., Yoshitane H., Du N.H., Okano T., Fukada Y.;
RT "Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its
RT negative role and a positive role of BMAL2 in the circadian
RT transcription.";
RL J. Biol. Chem. 284:25149-25159(2009).
RN [4]
RP FUNCTION.
RX PubMed=20153195; DOI=10.1016/j.cub.2009.12.034;
RA Shi S., Hida A., McGuinness O.P., Wasserman D.H., Yamazaki S.,
RA Johnson C.H.;
RT "Circadian clock gene Bmal1 is not essential; functional replacement with
RT its paralog, Bmal2.";
RL Curr. Biol. 20:316-321(2010).
CC -!- FUNCTION: Transcriptional activator which forms a core component of the
CC circadian clock. The circadian clock, an internal time-keeping system,
CC regulates various physiological processes through the generation of
CC approximately 24 hour circadian rhythms in gene expression, which are
CC translated into rhythms in metabolism and behavior. It is derived from
CC the Latin roots 'circa' (about) and 'diem' (day) and acts as an
CC important regulator of a wide array of physiological functions
CC including metabolism, sleep, body temperature, blood pressure,
CC endocrine, immune, cardiovascular, and renal function. Consists of two
CC major components: the central clock, residing in the suprachiasmatic
CC nucleus (SCN) of the brain, and the peripheral clocks that are present
CC in nearly every tissue and organ system. Both the central and
CC peripheral clocks can be reset by environmental cues, also known as
CC Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the
CC central clock is light, which is sensed by retina and signals directly
CC to the SCN. The central clock entrains the peripheral clocks through
CC neuronal and hormonal signals, body temperature and feeding-related
CC cues, aligning all clocks with the external light/dark cycle. Circadian
CC rhythms allow an organism to achieve temporal homeostasis with its
CC environment at the molecular level by regulating gene expression to
CC create a peak of protein expression once every 24 hours to control when
CC a particular physiological process is most active with respect to the
CC solar day. Transcription and translation of core clock components
CC (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and
CC CRY2) plays a critical role in rhythm generation, whereas delays
CC imposed by post-translational modifications (PTMs) are important for
CC determining the period (tau) of the rhythms (tau refers to the period
CC of a rhythm and is the length, in time, of one complete cycle). A
CC diurnal rhythm is synchronized with the day/night cycle, while the
CC ultradian and infradian rhythms have a period shorter and longer than
CC 24 hours, respectively. Disruptions in the circadian rhythms contribute
CC to the pathology of cardiovascular diseases, cancer, metabolic
CC syndromes and aging. A transcription/translation feedback loop (TTFL)
CC forms the core of the molecular circadian clock mechanism.
CC Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2,
CC form the positive limb of the feedback loop, act in the form of a
CC heterodimer and activate the transcription of core clock genes and
CC clock-controlled genes (involved in key metabolic processes), harboring
CC E-box elements (5'-CACGTG-3') within their promoters. The core clock
CC genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form
CC the negative limb of the feedback loop and interact with the
CC CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its
CC activity and thereby negatively regulating their own expression. This
CC heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G,
CC which form a second feedback loop and which activate and repress
CC ARNTL/BMAL1 transcription, respectively. The CLOCK-ARNTL2/BMAL2
CC heterodimer activates the transcription of SERPINE1/PAI1 and
CC BHLHE40/DEC1. {ECO:0000269|PubMed:19605937,
CC ECO:0000269|PubMed:20153195}.
CC -!- SUBUNIT: Component of the circadian core oscillator, which includes the
CC CRY proteins, CLOCK, or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D
CC and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with
CC CLOCK to form the ARNTL2/BMAL2-CLOCK transactivator. Can form
CC heterodimers or homodimers which interact directly with CLOCK to form
CC the transcription activator. Interacts with NPAS2 and HIF1A (By
CC similarity). Interacts with PER2. {ECO:0000250|UniProtKB:Q8WYA1,
CC ECO:0000269|PubMed:19605937}.
CC -!- INTERACTION:
CC Q2VPD4; P97784: Cry1; NbExp=3; IntAct=EBI-9696862, EBI-1266607;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=BMAL2a;
CC IsoId=Q2VPD4-1; Sequence=Displayed;
CC Name=2; Synonyms=BMAL2b;
CC IsoId=Q2VPD4-2; Sequence=VSP_022586, VSP_022587;
CC -!- TISSUE SPECIFICITY: Expressed in the suprachiasmatic nucleus (SCN).
CC -!- INDUCTION: Constitutively expressed in the SCN. Little change
CC throughout day under dark/light cycle. {ECO:0000269|PubMed:11207387}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
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DR EMBL; AY005163; AAF88141.1; -; mRNA.
DR EMBL; AY014836; AAK12619.1; -; mRNA.
DR EMBL; BC108965; AAI08966.1; -; mRNA.
DR EMBL; BC108966; AAI08967.1; -; mRNA.
DR CCDS; CCDS20702.1; -. [Q2VPD4-1]
DR RefSeq; NP_001276608.1; NM_001289679.1.
DR RefSeq; NP_001276609.1; NM_001289680.1.
DR RefSeq; NP_001276610.1; NM_001289681.1.
DR RefSeq; NP_758513.1; NM_172309.2. [Q2VPD4-1]
DR RefSeq; XP_006507116.1; XM_006507053.3. [Q2VPD4-1]
DR AlphaFoldDB; Q2VPD4; -.
DR SMR; Q2VPD4; -.
DR ComplexPortal; CPX-3228; CLOCK-BMAL2 transcription complex.
DR DIP; DIP-60819N; -.
DR IntAct; Q2VPD4; 6.
DR STRING; 10090.ENSMUSP00000107266; -.
DR PhosphoSitePlus; Q2VPD4; -.
DR PaxDb; Q2VPD4; -.
DR PRIDE; Q2VPD4; -.
DR Antibodypedia; 12657; 118 antibodies from 22 providers.
DR DNASU; 272322; -.
DR Ensembl; ENSMUST00000080530; ENSMUSP00000079373; ENSMUSG00000040187. [Q2VPD4-1]
DR Ensembl; ENSMUST00000111639; ENSMUSP00000107266; ENSMUSG00000040187. [Q2VPD4-1]
DR Ensembl; ENSMUST00000129788; ENSMUSP00000121170; ENSMUSG00000040187. [Q2VPD4-2]
DR GeneID; 272322; -.
DR KEGG; mmu:272322; -.
DR UCSC; uc009esj.2; mouse. [Q2VPD4-1]
DR CTD; 56938; -.
DR MGI; MGI:2684845; Arntl2.
DR VEuPathDB; HostDB:ENSMUSG00000040187; -.
DR eggNOG; KOG3561; Eukaryota.
DR GeneTree; ENSGT00940000160423; -.
DR HOGENOM; CLU_1371797_0_0_1; -.
DR InParanoid; Q2VPD4; -.
DR OMA; YVGDNYR; -.
DR OrthoDB; 331262at2759; -.
DR PhylomeDB; Q2VPD4; -.
DR TreeFam; TF319983; -.
DR BioGRID-ORCS; 272322; 1 hit in 74 CRISPR screens.
DR PRO; PR:Q2VPD4; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q2VPD4; protein.
DR Bgee; ENSMUSG00000040187; Expressed in animal zygote and 161 other tissues.
DR ExpressionAtlas; Q2VPD4; baseline and differential.
DR Genevisible; Q2VPD4; MM.
DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; IBA:GO_Central.
DR GO; GO:1990513; C:CLOCK-BMAL transcription complex; IPI:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISO:MGI.
DR GO; GO:0007623; P:circadian rhythm; ISO:MGI.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:MGI.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001067; Nuc_translocat.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF00989; PAS; 1.
DR PRINTS; PR00785; NCTRNSLOCATR.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR TIGRFAMs; TIGR00229; sensory_box; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Biological rhythms; DNA-binding;
KW Isopeptide bond; Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..579
FT /note="Aryl hydrocarbon receptor nuclear translocator-like
FT protein 2"
FT /id="PRO_0000273632"
FT DOMAIN 48..101
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 119..190
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 296..366
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 371..414
FT /note="PAC"
FT REGION 1..198
FT /note="Interaction with PER2"
FT /evidence="ECO:0000269|PubMed:19605937"
FT REGION 40..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 186..213
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 469..536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4..9
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT MOTIF 118..128
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT MOTIF 331..339
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT CROSSLNK 226
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2 and SUMO3)"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT CROSSLNK 233
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8WYA1"
FT VAR_SEQ 199
FT /note="T -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11207387"
FT /id="VSP_022586"
FT VAR_SEQ 200..579
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11207387"
FT /id="VSP_022587"
FT CONFLICT 9
FT /note="G -> D (in Ref. 2; AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="I -> M (in Ref. 2; AAI08966/AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="Y -> H (in Ref. 2; AAI08966/AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="M -> V (in Ref. 2; AAI08966/AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 423
FT /note="H -> Q (in Ref. 2; AAI08966/AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 425..426
FT /note="GG -> SS (in Ref. 2; AAI08966)"
FT /evidence="ECO:0000305"
FT CONFLICT 450
FT /note="V -> I (in Ref. 2; AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 479
FT /note="S -> N (in Ref. 2; AAI08966/AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 483
FT /note="Missing (in Ref. 2; AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 494
FT /note="N -> S (in Ref. 2; AAI08966/AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 504
FT /note="P -> L (in Ref. 2; AAI08966/AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="E -> K (in Ref. 2; AAI08966/AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 535
FT /note="G -> S (in Ref. 2; AAI08966/AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 551
FT /note="I -> T (in Ref. 2; AAI08967)"
FT /evidence="ECO:0000305"
FT CONFLICT 579
FT /note="L -> R (in Ref. 2; AAI08966)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 579 AA; 64399 MW; D73F04B16CA0A363 CRC64;
MEFPRKRRGR DSQPLQSEFM TDTTVESLPQ NPFASLLSTR TGVSAPSGIR EAHSQMEKRR
RDKMNHLIQK LSSMIPPHIP TAHKLDKLSV LRRAVQYLRS LRGMTELYLG ENSKPSFIQD
KELSHLILKA AEGFLFVVGC ERGRIFYVSK SVSKTLRYDQ ASLIGQNLFD FLHPKDVAKV
KEQLSCDGSP REKPIDTKTS QVYSHPYTGR PRMHSGSRRS FFFRMKSCTV PVKEEQPCSS
CSKKKDHRKF HTVHCTGYLR SWPLNVVGME KESGGGKDSG PLTCLVAMGR LHPYIVPQKS
GKINVRPAEF ITRFAMNGKF VYVDQRATAI LGYLPQELLG TSCYEYFHQD DHSSLTDKHK
AVLQSKEKIL TDSYKFRVKD GAFVTLKSEW FSFTNPWTKE LEYIVSVNTL VLGRSETRLS
LLHCGGSSQS SEDSFRQSCI NVPGVSTGTV LGAGSIGTDI ANEVLSLQRL HSSSPEDASP
SEEVRDDCSV NGGNAYGPAS TREPFAVSPS ETEVLEAARQ HQSTEPAHPH GPLPGDSAQL
GFDVLCDSDS IDMAAFMNYL EAEGGLGDPG DFSDIQWAL
