UniProtKB - Q2VPD4 (BMAL2_MOUSE)
Aryl hydrocarbon receptor nuclear translocator-like protein 2
Arntl2
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 PublicationsGO - Molecular functioni
- DNA-binding transcription factor activity Source: MGI
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: MGI
- E-box binding Source: UniProtKB
- protein dimerization activity Source: InterPro
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
GO - Biological processi
- circadian regulation of gene expression Source: Ensembl
- circadian rhythm Source: MGI
- positive regulation of circadian rhythm Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: MGI
- regulation of transcription by RNA polymerase II Source: MGI
Keywordsi
Molecular function | Activator, DNA-binding |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Names & Taxonomyi
Protein namesi | Recommended name: Aryl hydrocarbon receptor nuclear translocator-like protein 2Alternative name(s): Brain and muscle ARNT-like 2 |
Gene namesi | Name:Arntl2 Synonyms:Bmal2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2684845, Arntl2 |
VEuPathDBi | HostDB:ENSMUSG00000040187 |
Subcellular locationi
Nucleus
- Nucleus PROSITE-ProRule annotation
Nucleus
- CLOCK-BMAL transcription complex Source: ComplexPortal
- nucleolus Source: MGI
- nucleoplasm Source: MGI
- nucleus Source: ComplexPortal
Other locations
- aryl hydrocarbon receptor complex Source: GO_Central
- cytoplasm Source: InterPro
Keywords - Cellular componenti
NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000273632 | 1 – 579 | Aryl hydrocarbon receptor nuclear translocator-like protein 2Add BLAST | 579 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 226 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3)By similarity | ||
Cross-linki | 233 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity |
Keywords - PTMi
Isopeptide bond, Ubl conjugationProteomic databases
PaxDbi | Q2VPD4 |
PRIDEi | Q2VPD4 |
PTM databases
PhosphoSitePlusi | Q2VPD4 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000040187, Expressed in secondary oocyte and 204 other tissues |
ExpressionAtlasi | Q2VPD4, baseline and differential |
Genevisiblei | Q2VPD4, 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 PublicationBinary interactionsi
Q2VPD4
With | #Exp. | IntAct |
---|---|---|
Cry1 [P97784] | 3 | EBI-9696862,EBI-1266607 |
GO - Molecular functioni
- protein dimerization activity Source: InterPro
Protein-protein interaction databases
ComplexPortali | CPX-3228, CLOCK-BMAL2 transcription complex |
DIPi | DIP-60819N |
IntActi | Q2VPD4, 6 interactors |
STRINGi | 10090.ENSMUSP00000107266 |
Miscellaneous databases
RNActi | Q2VPD4, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 48 – 101 | bHLHPROSITE-ProRule annotationAdd BLAST | 54 | |
Domaini | 119 – 190 | PAS 1PROSITE-ProRule annotationAdd BLAST | 72 | |
Domaini | 296 – 366 | PAS 2PROSITE-ProRule annotationAdd BLAST | 71 | |
Domaini | 371 – 414 | PACAdd BLAST | 44 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 198 | Interaction with PER21 PublicationAdd BLAST | 198 | |
Regioni | 40 – 61 | DisorderedSequence analysisAdd BLAST | 22 | |
Regioni | 186 – 213 | DisorderedSequence analysisAdd BLAST | 28 | |
Regioni | 469 – 536 | DisorderedSequence analysisAdd BLAST | 68 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 4 – 9 | Nuclear localization signalBy similarity | 6 | |
Motifi | 118 – 128 | Nuclear export signal 1By similarityAdd BLAST | 11 | |
Motifi | 331 – 339 | Nuclear export signal 2By similarity | 9 |
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG3561, Eukaryota |
GeneTreei | ENSGT00940000160423 |
HOGENOMi | CLU_1371797_0_0_1 |
InParanoidi | Q2VPD4 |
OMAi | IPQCNPV |
OrthoDBi | 331262at2759 |
PhylomeDBi | Q2VPD4 |
TreeFami | TF319983 |
Family and domain databases
CDDi | cd00130, PAS, 2 hits |
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf IPR001067, Nuc_translocat IPR000014, PAS IPR035965, PAS-like_dom_sf IPR013767, PAS_fold |
Pfami | View protein in Pfam PF00010, HLH, 1 hit PF00989, PAS, 1 hit |
PRINTSi | PR00785, NCTRNSLOCATR |
SMARTi | View protein in SMART SM00353, HLH, 1 hit SM00091, PAS, 2 hits |
SUPFAMi | SSF47459, SSF47459, 1 hit SSF55785, SSF55785, 2 hits |
TIGRFAMsi | TIGR00229, sensory_box, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit PS50112, PAS, 2 hits |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
The sequence of this isoform differs from the canonical sequence as follows:
199-199: T → K
200-579: Missing.
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9Q994 | E9Q994_MOUSE | Aryl hydrocarbon receptor nuclear t... | Arntl2 | 570 | Annotation score: | ||
E9Q993 | E9Q993_MOUSE | Aryl hydrocarbon receptor nuclear t... | Arntl2 | 569 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 9 | G → D in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 164 | I → M in AAI08966 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 164 | I → M in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 207 | Y → H in AAI08966 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 207 | Y → H in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 213 | M → V in AAI08966 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 213 | M → V in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 423 | H → Q in AAI08966 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 423 | H → Q in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 425 – 426 | GG → SS in AAI08966 (PubMed:15489334).Curated | 2 | |
Sequence conflicti | 450 | V → I in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 479 | S → N in AAI08966 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 479 | S → N in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 483 | Missing in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 494 | N → S in AAI08966 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 494 | N → S in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 504 | P → L in AAI08966 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 504 | P → L in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 511 | E → K in AAI08966 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 511 | E → K in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 535 | G → S in AAI08966 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 535 | G → S in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 551 | I → T in AAI08967 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 579 | L → R in AAI08966 (PubMed:15489334).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_022586 | 199 | T → K in isoform 2. 1 Publication | 1 | |
Alternative sequenceiVSP_022587 | 200 – 579 | Missing in isoform 2. 1 PublicationAdd BLAST | 380 |
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 |
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_006507053.3 [Q2VPD4-1] |
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.2, mouse [Q2VPD4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
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_006507053.3 [Q2VPD4-1] |
3D structure databases
SMRi | Q2VPD4 |
ModBasei | Search... |
Protein-protein interaction databases
ComplexPortali | CPX-3228, CLOCK-BMAL2 transcription complex |
DIPi | DIP-60819N |
IntActi | Q2VPD4, 6 interactors |
STRINGi | 10090.ENSMUSP00000107266 |
PTM databases
PhosphoSitePlusi | Q2VPD4 |
Proteomic databases
PaxDbi | Q2VPD4 |
PRIDEi | Q2VPD4 |
Protocols and materials databases
Antibodypediai | 12657, 117 antibodies from 22 providers |
DNASUi | 272322 |
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.2, mouse [Q2VPD4-1] |
Organism-specific databases
CTDi | 56938 |
MGIi | MGI:2684845, Arntl2 |
VEuPathDBi | HostDB:ENSMUSG00000040187 |
Phylogenomic databases
eggNOGi | KOG3561, Eukaryota |
GeneTreei | ENSGT00940000160423 |
HOGENOMi | CLU_1371797_0_0_1 |
InParanoidi | Q2VPD4 |
OMAi | IPQCNPV |
OrthoDBi | 331262at2759 |
PhylomeDBi | Q2VPD4 |
TreeFami | TF319983 |
Miscellaneous databases
BioGRID-ORCSi | 272322, 1 hit in 64 CRISPR screens |
PROi | PR:Q2VPD4 |
RNActi | Q2VPD4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000040187, Expressed in secondary oocyte and 204 other tissues |
ExpressionAtlasi | Q2VPD4, baseline and differential |
Genevisiblei | Q2VPD4, MM |
Family and domain databases
CDDi | cd00130, PAS, 2 hits |
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf IPR001067, Nuc_translocat IPR000014, PAS IPR035965, PAS-like_dom_sf IPR013767, PAS_fold |
Pfami | View protein in Pfam PF00010, HLH, 1 hit PF00989, PAS, 1 hit |
PRINTSi | PR00785, NCTRNSLOCATR |
SMARTi | View protein in SMART SM00353, HLH, 1 hit SM00091, PAS, 2 hits |
SUPFAMi | SSF47459, SSF47459, 1 hit SSF55785, SSF55785, 2 hits |
TIGRFAMsi | TIGR00229, sensory_box, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit PS50112, PAS, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | BMAL2_MOUSE | |
Accessioni | Q2VPD4Primary (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: | February 23, 2022 | |
This is version 127 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot