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Aliases for NPAS2 Gene

Aliases for NPAS2 Gene

  • Neuronal PAS Domain Protein 2 2 3
  • MOP4 3 4 6
  • Class E Basic Helix-Loop-Helix Protein 9 3 4
  • Basic-Helix-Loop-Helix-PAS Protein MOP4 3 4
  • PAS Domain-Containing Protein 4 3 4
  • Member Of PAS Protein 4 3 4
  • Neuronal PAS2 3 4
  • BHLHe9 3 4
  • PASD4 3 4
  • Neuronal PAS Domain-Containing Protein 2 3
  • Member Of PAS Superfamily 4 3

External Ids for NPAS2 Gene

Summaries for NPAS2 Gene

Entrez Gene Summary for NPAS2 Gene

  • The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors. A similar mouse protein may play a regulatory role in the acquisition of specific types of memory. It also may function as a part of a molecular clock operative in the mammalian forebrain. [provided by RefSeq, Jul 2008]

GeneCards Summary for NPAS2 Gene

NPAS2 (Neuronal PAS Domain Protein 2) is a Protein Coding gene. Among its related pathways are Metabolism and Metabolism. 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 NPAS2 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 NPAS2-ARNTL/BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. NPAS2 plays an important role in sleep homeostasis and in maintaining circadian behaviors in normal light/dark and feeding conditions and in the effective synchronization of feeding behavior with scheduled food availability. Regulates the gene transcription of key metabolic pathways in the liver and is involved in DNA damage response by regulating several cell cycle and DNA repair genes.

Gene Wiki entry for NPAS2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NPAS2 Gene

Genomics for NPAS2 Gene

Genomic Location for NPAS2 Gene

Start:
100,820,151 bp from pter
End:
100,996,829 bp from pter
Size:
176,679 bases
Orientation:
Plus strand

Genomic View for NPAS2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NPAS2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NPAS2 Gene

Regulatory Elements for NPAS2 Gene

Proteins for NPAS2 Gene

  • Protein details for NPAS2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99743-NPAS2_HUMAN
    Recommended name:
    Neuronal PAS domain-containing protein 2
    Protein Accession:
    Q99743
    Secondary Accessions:
    • Q4ZFV9
    • Q53SQ3
    • Q86V96
    • Q99629

    Protein attributes for NPAS2 Gene

    Size:
    824 amino acids
    Molecular mass:
    91791 Da
    Cofactor:
    Name=heme; Xref=ChEBI:CHEBI:30413;
    Quaternary structure:
    • Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with ARNTL/BMAL1 and this heterodimerization is required for E-box-dependent transactivation. Interacts with NCOA3, KAT2B, CREBBP and EP300.

neXtProt entry for NPAS2 Gene

Proteomics data for NPAS2 Gene at MOPED

Post-translational modifications for NPAS2 Gene

No Post-translational modifications

Other Protein References for NPAS2 Gene

No data available for DME Specific Peptides for NPAS2 Gene

Domains for NPAS2 Gene

Gene Families for NPAS2 Gene

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

UniProtKB/Swiss-Prot:

NPAS2_HUMAN
Domain:
  • Contains 1 bHLH (basic helix-loop-helix) domain.:
    • Q99743
  • Contains 1 PAC (PAS-associated C-terminal) domain.:
    • Q99743
  • Contains 2 PAS (PER-ARNT-SIM) domains.:
    • Q99743
genes like me logo Genes that share domains with NPAS2: view

Function for NPAS2 Gene

Molecular function for NPAS2 Gene

GENATLAS Biochemistry: neuronal PAS domain protein 2,expressed in the central nervous system
UniProtKB/Swiss-Prot EnzymeRegulation: Carbon monoxide (CO) and the redox state of the cell can modulate the transcriptional activity of the NPAS2-ARNTL/BMAL1 heterodimer. NADH and NADPH enhance the DNA-binding activity of the heterodimer whereas CO binds the heme group in NPAS2 and inhibits the DNA-binding activity of the heterodimer.
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 NPAS2-ARNTL/BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. NPAS2 plays an important role in sleep homeostasis and in maintaining circadian behaviors in normal light/dark and feeding conditions and in the effective synchronization of feeding behavior with scheduled food availability. Regulates the gene transcription of key metabolic pathways in the liver and is involved in DNA damage response by regulating several cell cycle and DNA repair genes.

Gene Ontology (GO) - Molecular Function for NPAS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001047 core promoter binding ISS --
GO:0003677 DNA binding IPI 9576906
GO:0003700 sequence-specific DNA binding transcription factor activity IEA --
GO:0004871 signal transducer activity IEA --
GO:0005515 protein binding IPI 14645221
genes like me logo Genes that share ontologies with NPAS2: view
genes like me logo Genes that share phenotypes with NPAS2: view

miRNA for NPAS2 Gene

miRTarBase miRNAs that target NPAS2
Targeting motifs for NPAS2 Gene
HOMER Transcription Factor Regulatory Elements motif NPAS2
  • Consensus sequence: KCCACGTGAC Submotif: canonical Cell Type: Liver GeoId: GSE39860

No data available for Enzyme Numbers (IUBMB) , Animal Models and Transcription Factor Targeting for NPAS2 Gene

Localization for NPAS2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NPAS2 Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NPAS2 Gene COMPARTMENTS Subcellular localization image for NPAS2 gene
Compartment Confidence
cytosol 4
nucleus 4
plasma membrane 1

Gene Ontology (GO) - Cellular Components for NPAS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 14645221
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IPI 9576906
GO:0005737 cytoplasm --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with NPAS2: view

Pathways for NPAS2 Gene

genes like me logo Genes that share pathways with NPAS2: view

Pathways by source for NPAS2 Gene

Gene Ontology (GO) - Biological Process for NPAS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated --
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0007165 signal transduction IEA --
GO:0007417 central nervous system development TAS 9012850
genes like me logo Genes that share ontologies with NPAS2: view

Transcripts for NPAS2 Gene

mRNA/cDNA for NPAS2 Gene

(9) REFSEQ mRNAs :
(12) Additional mRNA sequences :
(1) Selected AceView cDNA sequences:
(12) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for NPAS2 Gene

Neuronal PAS domain protein 2:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for NPAS2 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b · 13c ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b · 18c ^ 19 ^
SP1: - - -
SP2: - - - - -
SP3:
SP4:
SP5:
SP6:

ExUns: 20 ^ 21a · 21b
SP1:
SP2:
SP3:
SP4:
SP5: -
SP6:

Relevant External Links for NPAS2 Gene

GeneLoc Exon Structure for
NPAS2
ECgene alternative splicing isoforms for
NPAS2

Expression for NPAS2 Gene

mRNA expression in normal human tissues for NPAS2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for NPAS2 Gene

SOURCE GeneReport for Unigene cluster for NPAS2 Gene Hs.156832

genes like me logo Genes that share expressions with NPAS2: view

Orthologs for NPAS2 Gene

This gene was present in the common ancestor of animals.

Orthologs for NPAS2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NPAS2 36
  • 99.72 (n)
  • 99.76 (a)
NPAS2 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NPAS2 36
  • 88.43 (n)
  • 90.42 (a)
NPAS2 37
  • 90 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NPAS2 36
  • 89.41 (n)
  • 90.34 (a)
NPAS2 37
  • 85 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Npas2 36
  • 86.9 (n)
  • 88.55 (a)
Npas2 16
Npas2 37
  • 88 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NPAS2 37
  • 68 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NPAS2 37
  • 59 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Npas2 36
  • 86.74 (n)
  • 88.42 (a)
chicken
(Gallus gallus)
Aves NPAS2 36
  • 75.56 (n)
  • 75.19 (a)
NPAS2 37
  • 74 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NPAS2 37
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia npas2 36
  • 64.85 (n)
  • 61.72 (a)
zebrafish
(Danio rerio)
Actinopterygii -- 36
npas2 37
  • 46 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Clk 37
  • 27 (a)
OneToMany
Clk 38
  • 50 (a)
Species with no ortholog for NPAS2:
  • 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 NPAS2 Gene

ENSEMBL:
Gene Tree for NPAS2 (if available)
TreeFam:
Gene Tree for NPAS2 (if available)

Paralogs for NPAS2 Gene

Paralogs for NPAS2 Gene

genes like me logo Genes that share paralogs with NPAS2: view

Variants for NPAS2 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for NPAS2 Gene

Q99743-NPAS2_HUMAN
Variants in NPAS2 show a susceptibility to seasonal affective disorder (SAD) [MIM:608516]. SAD is a depressive condition resulting from seasonal changes, and with diurnal preference

Sequence variations from dbSNP and Humsavar for NPAS2 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type MAF
rs9223 -- 100,993,365(+) CAGAC(C/T)GTGTT reference, synonymous-codon
rs74106 -- 100,929,093(-) acccc(A/G)tcttc intron-variant
rs184817 -- 100,931,294(-) ATGAG(C/T)CTTTG intron-variant, upstream-variant-2KB
rs356641 -- 100,921,732(+) ttcaA(C/T)GGCTA intron-variant
rs356642 -- 100,920,976(+) GGAAC(A/G)CAAAC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NPAS2 Gene

Variant ID Type Subtype PubMed ID
nsv834315 CNV Gain 17160897
nsv829584 CNV Gain 20364138
nsv834316 CNV Gain 17160897
esv2667827 CNV Deletion 23128226
esv2720445 CNV Deletion 23290073

Relevant External Links for NPAS2 Gene

HapMap Linkage Disequilibrium report
NPAS2
Human Gene Mutation Database (HGMD)
NPAS2

Disorders for NPAS2 Gene

Relevant External Links for NPAS2

Genetic Association Database (GAD)
NPAS2
Human Genome Epidemiology (HuGE) Navigator
NPAS2
genes like me logo Genes that share disorders with NPAS2: view

No data available for UniProtKB/Swiss-Prot for NPAS2 Gene

Publications for NPAS2 Gene

  1. Ala394Thr polymorphism in the clock gene NPAS2: a circadian modifier for the risk of non-Hodgkin's lymphoma. (PMID: 17096334) Zhu Y. … Zheng T. (Int. J. Cancer 2007) 3 4 23 49
  2. Non-synonymous polymorphisms in the circadian gene NPAS2 and breast cancer risk. (PMID: 17453337) Zhu Y. … Zheng T. (Breast Cancer Res. Treat. 2008) 3 4 23 49
  3. The circadian gene NPAS2, a putative tumor suppressor, is involved in DNA damage response. (PMID: 18819933) Hoffman A.E. … Zhu Y. (Mol. Cancer Res. 2008) 3 4 23
  4. The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer. (PMID: 19649706) Yi C. … Katsaro D. (Breast Cancer Res. Treat. 2010) 3 23 49
  5. Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system. (PMID: 9012850) Zhou Y.-D. … McKnight S.L. (Proc. Natl. Acad. Sci. U.S.A. 1997) 2 3 4

Products for NPAS2 Gene

Sources for NPAS2 Gene

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