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Aliases for ARNTL2 Gene

Aliases for ARNTL2 Gene

  • Aryl Hydrocarbon Receptor Nuclear Translocator-Like 2 2 3
  • BMAL2 3 4 6
  • CLIF 3 4 6
  • Class E Basic Helix-Loop-Helix Protein 6 3 4
  • Basic-Helix-Loop-Helix-PAS Protein MOP9 3 4
  • PAS Domain-Containing Protein 9 3 4
  • Brain And Muscle ARNT-Like 2 3 4
  • Member Of PAS Protein 9 3 4
  • CYCLE-Like Factor 3 4
  • BHLHe6 3 4
  • PASD9 3 4
  • MOP9 3 4
  • Aryl Hydrocarbon Receptor Nuclear Translocator-Like Protein 2 3
  • Transcription Factor BMAL2 3

External Ids for ARNTL2 Gene

Summaries for ARNTL2 Gene

Entrez Gene Summary for ARNTL2 Gene

  • This gene encodes a basic helix-loop-helix transcription factor belonging to the PAS (PER, ARNT, SIM) superfamily. The PAS proteins play important roles in adaptation to low atmospheric and cellular oxygen levels, exposure to certain environmental pollutants, and diurnal oscillations in light and temperature. This protein forms a transcriptionally active heterodimer with the circadian CLOCK protein, the structurally related MOP4, and hypoxia-inducible factors, such as HIF1alpha. Consistent with its role as a biologically relevant partner of circadian and hypoxia factors, this protein is coexpressed in regions of the brain such as the thalamus, hypothalamus, and amygdala. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

GeneCards Summary for ARNTL2 Gene

ARNTL2 (Aryl Hydrocarbon Receptor Nuclear Translocator-Like 2) is a Protein Coding gene. Diseases associated with ARNTL2 include hypoxia. Among its related pathways are Circadian Clock and Circadian Clock. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and protein dimerization activity. An important paralog of this gene is AHRR.

UniProtKB/Swiss-Prot for ARNTL2 Gene

  • 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.

Gene Wiki entry for ARNTL2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ARNTL2 Gene

Genomics for ARNTL2 Gene

Genomic Location for ARNTL2 Gene

Start:
27,332,854 bp from pter
End:
27,425,813 bp from pter
Size:
92,960 bases
Orientation:
Plus strand

Genomic View for ARNTL2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for ARNTL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ARNTL2 Gene

Regulatory Elements for ARNTL2 Gene

Proteins for ARNTL2 Gene

  • Protein details for ARNTL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WYA1-BMAL2_HUMAN
    Recommended name:
    Aryl hydrocarbon receptor nuclear translocator-like protein 2
    Protein Accession:
    Q8WYA1
    Secondary Accessions:
    • B7Z429
    • F5H402
    • Q8WYA2
    • Q8WYA3
    • Q8WYA4
    • Q96J63
    • Q9H2M4
    • Q9NS70
    • Q9NYQ4
    • Q9NYQ5

    Protein attributes for ARNTL2 Gene

    Size:
    636 amino acids
    Molecular mass:
    70887 Da
    Quaternary structure:
    • 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. Interacts with PER2 (By similarity).

    Three dimensional structures from OCA and Proteopedia for ARNTL2 Gene

    Alternative splice isoforms for ARNTL2 Gene

neXtProt entry for ARNTL2 Gene

Proteomics data for ARNTL2 Gene at MOPED

Post-translational modifications for ARNTL2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for ARNTL2 Gene

Domains for ARNTL2 Gene

Gene Families for ARNTL2 Gene

HGNC:
  • bHLH :Basic helix-loop-helix proteins

Suggested Antigen Peptide Sequences for ARNTL2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8WYA1

UniProtKB/Swiss-Prot:

BMAL2_HUMAN
Domain:
  • Contains 1 bHLH (basic helix-loop-helix) domain.:
    • Q8WYA1
  • Contains 1 PAC (PAS-associated C-terminal) domain.:
    • Q8WYA1
  • Contains 2 PAS (PER-ARNT-SIM) domains.:
    • Q8WYA1
genes like me logo Genes that share domains with ARNTL2: view

Function for ARNTL2 Gene

Molecular function for ARNTL2 Gene

UniProtKB/Swiss-Prot Function: 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.
UniProtKB/Swiss-Prot Induction: Constitutively expressed. Has no circadian rhythm expression pattern.

Gene Ontology (GO) - Molecular Function for ARNTL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000982 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity IDA 15147242
GO:0003700 sequence-specific DNA binding transcription factor activity NAS 11018023
GO:0004871 signal transducer activity IEA --
GO:0005515 protein binding --
GO:0046983 protein dimerization activity IEA --
genes like me logo Genes that share ontologies with ARNTL2: view

miRNA for ARNTL2 Gene

miRTarBase miRNAs that target ARNTL2

No data available for Enzyme Numbers (IUBMB) , Phenotypes , Animal Models , Transcription Factor Targeting and HOMER Transcription for ARNTL2 Gene

Localization for ARNTL2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ARNTL2 Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for ARNTL2 Gene COMPARTMENTS Subcellular localization image for ARNTL2 gene
Compartment Confidence
nucleus 5

Gene Ontology (GO) - Cellular Components for ARNTL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus NAS 11018023
GO:0005667 transcription factor complex IEA --
GO:0005730 nucleolus IDA --
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with ARNTL2: view

Pathways for ARNTL2 Gene

genes like me logo Genes that share pathways with ARNTL2: view

Pathways by source for ARNTL2 Gene

Gene Ontology (GO) - Biological Process for ARNTL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006355 regulation of transcription, DNA-templated NAS 11018023
GO:0006357 regulation of transcription from RNA polymerase II promoter IDA 12055078
GO:0006366 transcription from RNA polymerase II promoter IDA 15147242
GO:0007165 signal transduction IEA --
GO:0007623 circadian rhythm IDA 10864977
genes like me logo Genes that share ontologies with ARNTL2: view

Transcripts for ARNTL2 Gene

mRNA/cDNA for ARNTL2 Gene

Unigene Clusters for ARNTL2 Gene

Aryl hydrocarbon receptor nuclear translocator-like 2:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for ARNTL2 Gene

No ASD Table

Relevant External Links for ARNTL2 Gene

GeneLoc Exon Structure for
ARNTL2
ECgene alternative splicing isoforms for
ARNTL2

Expression for ARNTL2 Gene

mRNA expression in normal human tissues for ARNTL2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ARNTL2 Gene

This gene is overexpressed in Esophagus - Mucosa (7.5).

Integrated Proteomics: protein expression from ProteomicsDB, MOPED, and MaxQB for ARNTL2 Gene

SOURCE GeneReport for Unigene cluster for ARNTL2 Gene Hs.434269

mRNA Expression by UniProt/SwissProt for ARNTL2 Gene

Q8WYA1-BMAL2_HUMAN
Tissue specificity: Expressed in fetal brain. Highly expressed in brain and placenta. Lower levels in heart, liver, thymus, kidney and lung. Located to endothelial cells and neuronal cells of the suprachiasmatic nucleus (SCN). Also detected in endothelial cells of the heart, lung and kidney. In the brain, specifically expressed in the thalamus, hippocampus and amygdala.
genes like me logo Genes that share expressions with ARNTL2: view

Orthologs for ARNTL2 Gene

This gene was present in the common ancestor of animals.

Orthologs for ARNTL2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ARNTL2 35
  • 99.74 (n)
  • 99.69 (a)
ARNTL2 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia ARNTL2 35
  • 88.29 (n)
  • 83.31 (a)
ARNTL2 36
  • 83 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ARNTL2 35
  • 88.41 (n)
  • 85.42 (a)
ARNTL2 36
  • 85 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Arntl2 35
  • 77.33 (n)
  • 73.08 (a)
Arntl2 16
Arntl2 36
  • 72 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ARNTL2 36
  • 76 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 49 (a)
ManyToMany
rat
(Rattus norvegicus)
Mammalia Arntl2 35
  • 77.32 (n)
  • 70.87 (a)
chicken
(Gallus gallus)
Aves ARNTL2 35
  • 73.49 (n)
  • 69.88 (a)
ARNTL2 36
  • 67 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ARNTL2 36
  • 67 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100124875 35
  • 61.8 (n)
  • 60 (a)
zebrafish
(Danio rerio)
Actinopterygii arntl2 35
  • 59.64 (n)
  • 55.27 (a)
fruit fly
(Drosophila melanogaster)
Insecta cyc 36
  • 48 (a)
OneToMany
cyc 37
  • 50 (a)
Species with no ortholog for ARNTL2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for ARNTL2 Gene

ENSEMBL:
Gene Tree for ARNTL2 (if available)
TreeFam:
Gene Tree for ARNTL2 (if available)

Paralogs for ARNTL2 Gene

Paralogs for ARNTL2 Gene

Selected SIMAP similar genes for ARNTL2 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with ARNTL2: view

Variants for ARNTL2 Gene

Sequence variations from dbSNP and Humsavar for ARNTL2 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type MAF
rs922270 -- 27,352,018(+) TATCA(C/T)TGCAC intron-variant
rs922271 -- 27,352,239(+) AACAT(C/T)ATATA intron-variant
rs922272 -- 27,355,307(+) AATTC(A/G)CTGCA intron-variant
rs1037923 -- 27,344,977(+) AGTGA(C/T)GTCGT intron-variant
rs1037924 -- 27,345,174(+) TGTTT(A/G)TAGAT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for ARNTL2 Gene

Variant ID Type Subtype PubMed ID
esv2745664 CNV Deletion 23290073
dgv271e199 CNV Deletion 23128226
nsv521872 CNV Gain 19592680
nsv898940 CNV Loss 21882294
nsv436825 CNV Insertion 17901297
nsv469175 CNV Loss 19166990
esv270213 CNV Insertion 20981092
esv272753 CNV Insertion 20981092
nsv832357 CNV Gain 17160897
nsv650 CNV Insertion 18451855

Relevant External Links for ARNTL2 Gene

HapMap Linkage Disequilibrium report
ARNTL2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ARNTL2 Gene

Disorders for ARNTL2 Gene

(1) MalaCards Diseases for ARNTL2 Gene

Search for ARNTL2 Gene in MalaCards »

(1) University of Copenhagen DISEASES for ARNTL2 Gene

Relevant External Links for ARNTL2

Genetic Association Database (GAD)
ARNTL2
Human Genome Epidemiology (HuGE) Navigator
ARNTL2
genes like me logo Genes that share disorders with ARNTL2: view

No data available for UniProtKB/Swiss-Prot for ARNTL2 Gene

Publications for ARNTL2 Gene

  1. The basic helix-loop-helix-PAS protein MOP9 is a brain-specific heterodimeric partner of circadian and hypoxia factors. (PMID: 10864977) Hogenesch J.B. … Bradfield C.A. (J. Neurosci. 2000) 2 3 4
  2. cDNA cloning of a novel bHLH-PAS transcription factor superfamily gene, BMAL2; Its mRNA expression, subcellular distribution, and chromosomal localization. (PMID: 10964693) Ikeda M. … Nomura M. (Biochem. Biophys. Res. Commun. 2000) 2 3 4
  3. CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression. (PMID: 11018023) Maemura K. … Lee M.-E. (J. Biol. Chem. 2000) 3 4
  4. Chicken pineal clock genes: implication of BMAL2 as a bidirectional regulator in circadian clock oscillation. (PMID: 11554928) Okano T. … Fukada Y. (Genes Cells 2001) 3 4
  5. Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2. (PMID: 12738229) Schoenhard J.A. … Vaughan D.E. (J. Mol. Cell. Cardiol. 2003) 3 4

Products for ARNTL2 Gene

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat
  • Pathway & Disease-focused RT² Profiler PCR Arrays
  • QIAGEN qRT-PCR Assays for microRNAs that regulate ARNTL2
    • QuantiTect SYBR Green Assays in human,mouse,rat
    • Pre-validated RT² qPCR Primer Assay in human,mouse,rat
    • QuantiFast Probe-based Assays in human,mouse,rat
    • Predesigned siRNA for gene silencing in human,mouse,rat for ARNTL2
    • Block miRNA regulation of ARNTL2 using miScript Target Protectors

    Sources for ARNTL2 Gene

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