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UniProtKB - Q2VPD4 (BMAL2_MOUSE)

Protein

Aryl hydrocarbon receptor nuclear translocator-like protein 2

Gene

Arntl2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator, DNA-binding
Biological processBiological rhythms, Transcription, Transcription regulation

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:2684845 Arntl2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002736321 – 579Aryl hydrocarbon receptor nuclear translocator-like protein 2Add BLAST579

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3)By similarity
Cross-linki233Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiQ2VPD4
PRIDEiQ2VPD4

PTM databases

PhosphoSitePlusiQ2VPD4

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

BgeeiENSMUSG00000040187 Expressed in 167 organ(s), highest expression level in secondary oocyte
ExpressionAtlasiQ2VPD4 baseline and differential
GenevisibleiQ2VPD4 MM

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

Binary interactionsi

WithEntry#Exp.IntActNotes
Cry1P977843EBI-9696862,EBI-1266607

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

ComplexPortaliCPX-3228 CLOCK-BMAL2 transcription complex
DIPiDIP-60819N
IntActiQ2VPD4, 6 interactors
STRINGi10090.ENSMUSP00000079373

Structurei

3D structure databases

ProteinModelPortaliQ2VPD4
SMRiQ2VPD4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini48 – 101bHLHPROSITE-ProRule annotationAdd BLAST54
Domaini119 – 190PAS 1PROSITE-ProRule annotationAdd BLAST72
Domaini296 – 366PAS 2PROSITE-ProRule annotationAdd BLAST71
Domaini371 – 414PACAdd BLAST44

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 198Interaction with PER21 PublicationAdd BLAST198

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi4 – 9Nuclear localization signalBy similarity6
Motifi118 – 128Nuclear export signal 1By similarityAdd BLAST11
Motifi331 – 339Nuclear export signal 2By similarity9

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3561 Eukaryota
ENOG410XRJI LUCA
GeneTreeiENSGT00760000118788
HOGENOMiHOG000234379
HOVERGENiHBG107503
InParanoidiQ2VPD4
KOiK09099
OrthoDBiEOG091G126J
PhylomeDBiQ2VPD4
TreeFamiTF319983

Family and domain databases

CDDicd00083 HLH, 1 hit
cd00130 PAS, 2 hits
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR001067 Nuc_translocat
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold
PfamiView protein in Pfam
PF00010 HLH, 1 hit
PF00989 PAS, 1 hit
PRINTSiPR00785 NCTRNSLOCATR
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SM00091 PAS, 2 hits
SUPFAMiSSF47459 SSF47459, 1 hit
SSF55785 SSF55785, 2 hits
TIGRFAMsiTIGR00229 sensory_box, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
PS50112 PAS, 2 hits

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9Q994E9Q994_MOUSE
Aryl hydrocarbon receptor nuclear t...
Arntl2
570Annotation score:
E9Q993E9Q993_MOUSE
Aryl hydrocarbon receptor nuclear t...
Arntl2
569Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9G → D in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti164I → M in AAI08966 (PubMed:15489334).Curated1
Sequence conflicti164I → M in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti207Y → H in AAI08966 (PubMed:15489334).Curated1
Sequence conflicti207Y → H in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti213M → V in AAI08966 (PubMed:15489334).Curated1
Sequence conflicti213M → V in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti423H → Q in AAI08966 (PubMed:15489334).Curated1
Sequence conflicti423H → Q in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti425 – 426GG → SS in AAI08966 (PubMed:15489334).Curated2
Sequence conflicti450V → I in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti479S → N in AAI08966 (PubMed:15489334).Curated1
Sequence conflicti479S → N in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti483Missing in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti494N → S in AAI08966 (PubMed:15489334).Curated1
Sequence conflicti494N → S in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti504P → L in AAI08966 (PubMed:15489334).Curated1
Sequence conflicti504P → L in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti511E → K in AAI08966 (PubMed:15489334).Curated1
Sequence conflicti511E → K in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti535G → S in AAI08966 (PubMed:15489334).Curated1
Sequence conflicti535G → S in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti551I → T in AAI08967 (PubMed:15489334).Curated1
Sequence conflicti579L → R in AAI08966 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_022586199T → K in isoform 2. 1 Publication1
Alternative sequenceiVSP_022587200 – 579Missing in isoform 2. 1 PublicationAdd BLAST380

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006507053.3 [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.2 mouse [Q2VPD4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006507053.3 [Q2VPD4-1]
UniGeneiMm.333500
Mm.442075

3D structure databases

ProteinModelPortaliQ2VPD4
SMRiQ2VPD4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

ComplexPortaliCPX-3228 CLOCK-BMAL2 transcription complex
DIPiDIP-60819N
IntActiQ2VPD4, 6 interactors
STRINGi10090.ENSMUSP00000079373

PTM databases

PhosphoSitePlusiQ2VPD4

Proteomic databases

PaxDbiQ2VPD4
PRIDEiQ2VPD4

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi56938
MGIiMGI:2684845 Arntl2

Phylogenomic databases

eggNOGiKOG3561 Eukaryota
ENOG410XRJI LUCA
GeneTreeiENSGT00760000118788
HOGENOMiHOG000234379
HOVERGENiHBG107503
InParanoidiQ2VPD4
KOiK09099
OrthoDBiEOG091G126J
PhylomeDBiQ2VPD4
TreeFamiTF319983

Miscellaneous databases

PROiPR:Q2VPD4
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000040187 Expressed in 167 organ(s), highest expression level in secondary oocyte
ExpressionAtlasiQ2VPD4 baseline and differential
GenevisibleiQ2VPD4 MM

Family and domain databases

CDDicd00083 HLH, 1 hit
cd00130 PAS, 2 hits
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR001067 Nuc_translocat
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold
PfamiView protein in Pfam
PF00010 HLH, 1 hit
PF00989 PAS, 1 hit
PRINTSiPR00785 NCTRNSLOCATR
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SM00091 PAS, 2 hits
SUPFAMiSSF47459 SSF47459, 1 hit
SSF55785 SSF55785, 2 hits
TIGRFAMsiTIGR00229 sensory_box, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
PS50112 PAS, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiBMAL2_MOUSE
AccessioniPrimary (citable) accession number: Q2VPD4
Secondary accession number(s): Q32MV7, Q91XJ5, Q91XJ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 110 of the entry and version 2 of the sequence. See 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
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