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   24-JAN-2024, entry version 137.
DE   RecName: Full=Basic helix-loop-helix ARNT-like protein 2;
DE   AltName: Full=Aryl hydrocarbon receptor nuclear translocator-like protein 2;
DE   AltName: Full=Brain and muscle ARNT-like 2;
GN   Name=Bmal2; Synonyms=Arntl2;
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, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a
CC       critical role in rhythm generation, whereas delays imposed by post-
CC       translational modifications (PTMs) are important for determining the
CC       period (tau) of the rhythms (tau refers to the period of a rhythm and
CC       is the length, in time, of one complete cycle). A diurnal rhythm is
CC       synchronized with the day/night cycle, while the ultradian and
CC       infradian rhythms have a period shorter and longer than 24 hours,
CC       respectively. Disruptions in the circadian rhythms contribute to the
CC       pathology of cardiovascular diseases, cancer, metabolic syndromes and
CC       aging. A transcription/translation feedback loop (TTFL) forms the core
CC       of the molecular circadian clock mechanism. Transcription factors,
CC       CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the
CC       feedback loop, act in the form of a heterodimer and activate the
CC       transcription of core clock genes and clock-controlled genes (involved
CC       in key metabolic processes), harboring E-box elements (5'-CACGTG-3')
CC       within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which
CC       are transcriptional repressors form the negative limb of the feedback
CC       loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer
CC       inhibiting its activity and thereby negatively regulating their own
CC       expression. This heterodimer also activates nuclear receptors NR1D1/2
CC       and RORA/B/G, which form a second feedback loop and which activate and
CC       repress BMAL1 transcription, respectively. The CLOCK-BMAL2 heterodimer
CC       activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1.
CC       {ECO:0000269|PubMed:19605937, ECO:0000269|PubMed:20153195}.
CC   -!- SUBUNIT: Component of the circadian core oscillator, which includes the
CC       CRY proteins, CLOCK, or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E,
CC       TIMELESS and the PER proteins. Interacts directly with CLOCK to form
CC       the BMAL2-CLOCK transactivator. Can form heterodimers or homodimers
CC       which interact directly with CLOCK to form the transcription activator.
CC       Interacts with NPAS2 and HIF1A (By similarity). Interacts with PER2.
CC       {ECO:0000250|UniProtKB:Q8WYA1, 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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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; 10090-ENSMUSP00000107266; -.
DR   Antibodypedia; 12657; 159 antibodies from 23 providers.
DR   DNASU; 272322; -.
DR   Ensembl; ENSMUST00000080530.6; ENSMUSP00000079373.5; ENSMUSG00000040187.16. [Q2VPD4-1]
DR   Ensembl; ENSMUST00000111639.8; ENSMUSP00000107266.2; ENSMUSG00000040187.16. [Q2VPD4-1]
DR   Ensembl; ENSMUST00000129788.8; ENSMUSP00000121170.2; ENSMUSG00000040187.16. [Q2VPD4-2]
DR   GeneID; 272322; -.
DR   KEGG; mmu:272322; -.
DR   UCSC; uc009esj.2; mouse. [Q2VPD4-1]
DR   AGR; MGI:2684845; -.
DR   CTD; 56938; -.
DR   MGI; MGI:2684845; Bmal2.
DR   VEuPathDB; HostDB:ENSMUSG00000040187; -.
DR   eggNOG; KOG3561; Eukaryota.
DR   GeneTree; ENSGT00940000160423; -.
DR   HOGENOM; CLU_1371797_0_0_1; -.
DR   InParanoid; Q2VPD4; -.
DR   OMA; RIKCSRI; -.
DR   OrthoDB; 2872674at2759; -.
DR   PhylomeDB; Q2VPD4; -.
DR   TreeFam; TF319983; -.
DR   BioGRID-ORCS; 272322; 1 hit in 79 CRISPR screens.
DR   PRO; PR:Q2VPD4; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; Q2VPD4; Protein.
DR   Bgee; ENSMUSG00000040187; Expressed in animal zygote and 164 other cell types or tissues.
DR   ExpressionAtlas; Q2VPD4; baseline and differential.
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:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
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; Helix-loop-helix DNA-binding domain; 1.
DR   Gene3D; 3.30.450.20; PAS domain; 2.
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   NCBIfam; TIGR00229; sensory_box; 1.
DR   PANTHER; PTHR23042:SF48; ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR-LIKE PROTEIN 2; 1.
DR   PANTHER; PTHR23042; CIRCADIAN PROTEIN CLOCK/ARNT/BMAL/PAS; 1.
DR   Pfam; PF00010; HLH; 1.
DR   Pfam; PF00989; PAS; 1.
DR   Pfam; PF14598; PAS_11; 1.
DR   PRINTS; PR00785; NCTRNSLOCATR.
DR   SMART; SM00353; HLH; 1.
DR   SMART; SM00091; PAS; 2.
DR   SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR   SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 2.
DR   PROSITE; PS50888; BHLH; 1.
DR   PROSITE; PS50112; PAS; 2.
DR   Genevisible; Q2VPD4; MM.
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="Basic helix-loop-helix ARNT-like 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
//