Q2VPD4 (BMAL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 84. History...
Names and origin
|Protein names||Recommended name:|
Aryl hydrocarbon receptor nuclear translocator-like protein 2
Brain and muscle ARNT-like 2
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||579 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
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
Nucleus By similarity.
Expressed in the suprachiasmatic nucleus (SCN).
Constitutively expressed in the SCN. Little change throughout day under dark/light cycle. Ref.1
Contains 1 bHLH (basic helix-loop-helix) domain.
Contains 1 PAC (PAS-associated C-terminal) domain.
Contains 2 PAS (PER-ARNT-SIM) domains.
|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
|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 key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 579||579||Aryl hydrocarbon receptor nuclear translocator-like protein 2||PRO_0000273632|
|Domain||48 – 101||54||bHLH|
|Domain||119 – 190||72||PAS 1|
|Domain||296 – 366||71||PAS 2|
|Domain||371 – 414||44||PAC|
|Region||1 – 198||198||Interaction with PER2|
|Motif||4 – 9||6||Nuclear localization signal By similarity|
|Motif||118 – 128||11||Nuclear export signal 1 By similarity|
|Motif||331 – 339||9||Nuclear export signal 2 By similarity|
Amino acid modifications
|Cross-link||226||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3) By similarity|
|Alternative sequence||199||1||T → K in isoform 2.||VSP_022586|
|Alternative sequence||200 – 579||380||Missing in isoform 2.||VSP_022587|
|Sequence conflict||9||1||G → D in AAI08967. Ref.2|
|Sequence conflict||164||1||I → M in AAI08966. Ref.2|
|Sequence conflict||164||1||I → M in AAI08967. Ref.2|
|Sequence conflict||207||1||Y → H in AAI08966. Ref.2|
|Sequence conflict||207||1||Y → H in AAI08967. Ref.2|
|Sequence conflict||213||1||M → V in AAI08966. Ref.2|
|Sequence conflict||213||1||M → V in AAI08967. Ref.2|
|Sequence conflict||423||1||H → Q in AAI08966. Ref.2|
|Sequence conflict||423||1||H → Q in AAI08967. Ref.2|
|Sequence conflict||425 – 426||2||GG → SS in AAI08966. Ref.2|
|Sequence conflict||450||1||V → I in AAI08967. Ref.2|
|Sequence conflict||479||1||S → N in AAI08966. Ref.2|
|Sequence conflict||479||1||S → N in AAI08967. Ref.2|
|Sequence conflict||483||1||Missing in AAI08967. Ref.2|
|Sequence conflict||494||1||N → S in AAI08966. Ref.2|
|Sequence conflict||494||1||N → S in AAI08967. Ref.2|
|Sequence conflict||504||1||P → L in AAI08966. Ref.2|
|Sequence conflict||504||1||P → L in AAI08967. Ref.2|
|Sequence conflict||511||1||E → K in AAI08966. Ref.2|
|Sequence conflict||511||1||E → K in AAI08967. Ref.2|
|Sequence conflict||535||1||G → S in AAI08966. Ref.2|
|Sequence conflict||535||1||G → S in AAI08967. Ref.2|
|Sequence conflict||551||1||I → T in AAI08967. Ref.2|
|Sequence conflict||579||1||L → R in AAI08966. Ref.2|
|||"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.
|||"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).
|||"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.
|||"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.|
|AY005163 mRNA. Translation: AAF88141.1.|
AY014836 mRNA. Translation: AAK12619.1.
BC108965 mRNA. Translation: AAI08966.1.
BC108966 mRNA. Translation: AAI08967.1.
|RefSeq||NP_001276608.1. NM_001289679.1. |
NP_758513.1. NM_172309.2. [Q2VPD4-1]
XP_006507116.1. XM_006507053.1. [Q2VPD4-1]
3D structure databases
|SMR||Q2VPD4. Positions 50-416. |
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000080530; ENSMUSP00000079373; ENSMUSG00000040187. [Q2VPD4-1]|
ENSMUST00000111639; ENSMUSP00000107266; ENSMUSG00000040187. [Q2VPD4-1]
ENSMUST00000129788; ENSMUSP00000121170; ENSMUSG00000040187. [Q2VPD4-2]
|UCSC||uc009esj.1. mouse. [Q2VPD4-1]|
|MGI||MGI:2684845. Arntl2. |
Gene expression databases
Family and domain databases
|Gene3D||4.10.280.10. 1 hit. |
|InterPro||IPR011598. bHLH_dom. |
|Pfam||PF00010. HLH. 1 hit. |
PF00989. PAS. 1 hit.
|PRINTS||PR00785. NCTRNSLOCATR. |
|SMART||SM00353. HLH. 1 hit. |
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
|SUPFAM||SSF47459. SSF47459. 1 hit. |
SSF55785. SSF55785. 2 hits.
|TIGRFAMs||TIGR00229. sensory_box. 1 hit. |
|PROSITE||PS50888. BHLH. 1 hit. |
PS50112. PAS. 2 hits.
|Accession||Primary (citable) accession number: Q2VPD4|
Secondary accession number(s): Q32MV7, Q91XJ5, Q91XJ6
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|