Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol NPAS2 contributors: mct - updated : 19-12-2016
HGNC name neuronal PAS domain protein 2
HGNC id 7895
Location 2q11.2      Physical location : 101.436.612 - 101.613.287
Synonym name
  • member of PAS superfamily 4
  • basic-helix-loop-helix-PAS protein MOP4
  • class E basic helix-loop-helix protein 9
  • Synonym symbol(s) MOP4, FLJ23138, EVI34, PASD4, MGC71151
    DNA
    TYPE functioning gene
    STRUCTURE 176.68 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    Physical map
    LOC129530 2q11.2 hypothetical protein LOC129530 APACD 2q11.2 ATP binding protein associated with cell differentiation IF2 2p11.1-q11.1 ATP binding protein associated with cell differentiation REV1L 2q11.1-q11.2 REV1-like (yeast) LAF4 2q11.2-q12 lymphoid nuclear protein related to AF4 LOC389009 2 LOC389009 FLJ45273 2q12.1 FLJ45273 protein HCP7 2q11.2 cytochrome c, somatic pseudogene CHST10 2p11.2 carbohydrate sulfotransferase 10 LOC129522 2q12.1 similar to RalA binding protein 1 (RalBP1) (Ral interacting protein 1) (76-kDa Ral-interacting protein) (Dinitrophenyl S-glutathione ATPase) (DNP-SG ATPase) LOC129521 2q12.1 similar to hypothetical protein VIAF1 2q12.1 IAP-associated factor VIAF1 LOC150580 2q12.1 similar to hypothetical protein FLJ39426 LOC389010 2 LOC389010 NPAS2 2p11.2-q12 neuronal PAS domain protein 2 RPL31 2q12.1 ribosomal protein L31 TBC1D8 2q12.1 TBC1 domain family, member 8 (with GRAM domain) C40 2q12.1 hypothetical protein C40 LOC389011 2 LOC389011 LOC391410 2 similar to peptidyl-Pro cis trans isomerase RNF149 2q12.1 ring finger protein 149 CREG2 2q11.2 ring finger protein 149 LOC389012 2 similar to hypothetical protein MGC33442 LOC389013 2 LOC389013 LOC389014 2 LOC389014 LOC391411 2 similar to ribosomal protein S6 LOC391412 2 similar to Lysosomal Pro-X carboxypeptidase precursor (Prolylcarboxypeptidase) (PRCP) (Proline carboxypeptidase) (Angiotensinase C) (Lysosomal carboxypeptidase C) MAP4K4 2q11.2 mitogen-activated protein kinase kinase kinase kinase 4 FLJ20373 2q12.1 hypothetical protein FLJ20373 IL1R2 2q12 interleukin 1 receptor, type II IL1R1 2q12 interleukin 1 receptor, type I IL1RL2 2q12 interleukin 1 receptor-like 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 4004 - 824 - 1997 9012850
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestine  highly
    Endocrineadrenal gland   highly
    Nervousbrainforebrain   
    Reproductivemale systemprostate  highly
    Respiratorylung   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmooth   
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal 1-61 AAs of NPAS2 are sufficient to sense NAD(P)H
  • BHLH-PAS-A domain binding specifically to the E-box DNA sequence in the presence, but not in the absence, of heme
  • two heme-binding sites on two PAS domains, a stretch of approximately 300AA, termed the PAS (Per - ARNT - Sim) domain
  • a heme domain, has been suggested to act as a sensor for carbon monoxide
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to murine Npas2
    intraspecies homolog to CLOCK
    Homologene
    FAMILY basic helix-loop-helix PAS family
    CATEGORY transcription factor , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • acting as a transcription factor that regulates the mammalian circadian rhythm
  • overlapping role of CLOCK and NPAS2 transcription factors in liver circadian oscillators
  • is likely required for effective control of a food-entrainable oscillator
  • is not required for detection of or behavioral responses to a variety of acute or chronic metabolic deficits, but is more likely to be involved in effective synchronization of feeding behavior with scheduled food availability
  • with ARNTL were associated with reproduction and with seasonal variation
  • DNA-binding of NPAS2 and ARNTL to PER2 was decreased by sleep deprivation (SD), although SD is known to increase PER2 expression in the cortex (PMId: 22039518)
  • transcription factor that regulates mammalian circadian rhythms
  • its DNA-binding activity is specifically enhanced by NAD(P)H independently of NAD(P)(+)
  • essential role for NPAS2 in programming the peripheral circadian response and hepatic metabolism
  • controlled the circadian rhythm of NR0B2 expression by binding rhythmically to the NR0B2 promoter, which was enhanced by nicotinamide adenine dinucleotide
  • important role for the circadian protein, NPAS2, in the nucleus accumbens (NAc) in the regulation of dopamine receptor expression and drug reward
  • suprachiasmatic nucleus (SCN)-specific role for NPAS2 in the molecular circadian clock, and the core loops of SCN neuron and peripheral cell circadian clocks are fundamentally similar
  • NPAS2 can compensate for loss of CLOCK in peripheral cells as well as in suprachiasmatic nucleus (SCN)
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS circadian
    PATHWAY
    metabolism
    signaling
    a component
  • component of an heterodimer with BMAL1, can independently heterodimerize with BMAL1 in the hypothalamic suprachiasmatic nuclei to maintain molecular and behavioral rhythmicity
  • ARNTL in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • RARA
  • RXRA
  • structural changes of the heme domain are responsible for heterodimer formation with ARNTL
  • lack of NR1D1 increased ARNTL, NPAS2, CLOCK, and FABP7 expression, confirming the direct regulation of these genes by NR1D1 also in the brain
  • cell & other
    REGULATION
    induced by DNA binding of the NPAS2-ARNTL (BMAL1) dimer is induced by reduced form of NAD and NADP (inhibited by oxidized form)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in colo-rectal tumor tissues
    Susceptibility to chronic fatigue syndrome (CFS)
    Variant & Polymorphism SNP
  • T allele of rs356653 (NPAS2) were more likely to have CFS and NPAS2 expression was increased in those with CFS
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    could serve as a promising target and potential prognostic indicator for colorectal cancer
    ANIMAL & CELL MODELS
    impaired cued and contextual memory in NPAS2-deficient mice