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FLASH GENE
Symbol NOTCH2 contributors: mct/shn - updated : 11/09/2011
HGNC name notch 2
HGNC id 7882
Corresponding disease
ALGS2 Alagille syndrome 2
HJCYS Hajdu-Cheney syndrome
Location 1p11.2      Physical location : 120.454.177 - 120.612.276
Synonym name
  • Notch (Drosophila) homolog 2
  • Notch homolog 2 (Drosophila)
  • Notch homolog 2
  • neurogenic locus notch homolog protein 2
  • Synonym symbol(s) hN2, AGS2, HJCYS
    DNA
    TYPE functioning gene
    STRUCTURE 158.10 kb     34 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map pter - D1S185 - D1S514 - NOTCH2 - cen
    Physical map
    LOC343495 1p11.2 similar to 60S ribosomal protein L6 (TAX-responsive enhancer element binding protein 107) (TAXREB107) (Neoplasm-related protein C140) HAO2 1p13.3-p13.2 hydroxyacid oxidase 2 (long chain) HSD3B2 1p13.1 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 LOC391073 1 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) LOC391074 1 similar to 3 BETA-HYDROXYSTEROID DEHYDROGENASE/DELTA 5-->4-ISOMERASE (3BETA-HSD) LOC391075 1 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) LOC391076 1 similar to 3 BETA-HYDROXYSTEROID DEHYDROGENASE/DELTA 5-->4-ISOMERASE (3BETA-HSD) LOC391077 1 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) HSD3B1 1p13.1 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 LOC391078 1 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) LOC391079 1 similar to 3 BETA-HYDROXYSTEROID DEHYDROGENASE/DELTA 5-->4-ISOMERASE (3BETA-HSD) LOC128102 1p11.2 3-beta-hydroxysteroid dehydrogenase, tissue-type heart LOC391080 1 similar to glyceraldehyde 3-phosphate dehydrogenase LOC391081 1 similar to 3 BETA-HYDROXYSTEROID DEHYDROGENASE/DELTA 5-->4-ISOMERASE (3BETA-HSD) MGC45731 1p11.2 hypothetical protein MGC45731 PHGDH 1p12 phosphoglycerate dehydrogenase HMGCS2 1p12 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (mitochondrial) REG4 1q12-q21 regenerating islet-derived family, member 4 LOC343505 1p11.2 similar to dJ1182A14.5.1 (novel gene (isoform 1)) LOC391082 1 similar to Profilin I ADAM30 1p12-p11 a disintegrin and metalloproteinase domain 30 NOTCH2 1p12-p11 Notch homolog 2 (Drosophila)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    34 splicing 11474 - 2471 - 1994 7698746
    22 splicing 4326 - 1235 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestivecholedoque    
     pancreas exocrine   lowly
    Endocrinepancreas   highly
     thyroid   highly
    Hearing/Equilibriumearinnercochlea highly
    Reproductivefemale systembreastmammary gland highly
     male systemtestis  highly
    Urinarykidney   highly
    Visualeyeanterior segmentcornea highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveacinar
    Skeletonosteoblast
    Visualepithelial cell
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period embryo
    Text atrioventricular cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal peptide
  • 36 extracellular EGF repeats
  • three notch/lin-12 (LNR) repeats
  • two PEST sequences
  • six cdc10/ankyrin (ANK) repeats
  • a RAM23 domain
  • C terminus of the intracellular domain contains a PEST sequence known to mediate proteosomal destruction of the protein
  • mono polymer heteromer , dimer
    isoforms Precursor
    HOMOLOGY
    interspecies ortholog to NOTCH2, Pan troglodytes
    ortholog to notch2, danio rerio
    homolog to Notch2, Rattus norvegicus
    ortholog to Notch2, Mus musculus
    Homologene
    FAMILY
  • NOTCH family
  • CATEGORY regulatory , protooncogene , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,nucleus
    basic FUNCTION
  • receptor for membrane-bound ligands Jagged1, Jagged2, Delta-like1, Delta-like3 and Delta-like4
  • an important element in dental physiological and pathogenic conditions (
  • mediating cell-cell interactions that specify cell fate during development
  • as other Notch family members and ligands, expressed in the human corneal epithelium and appear to play pivotal roles in corneal epithelial cell differentiation
  • central regulator of pancreatic intraepithelial neoplasia progression and malignant transformation
  • essential role of NOTCH2 and MYC in the initiation of a neoplastic transformation program in pancreatic cells
  • play a role in the regulation of red cell differentiation (
  • important role for NOTCH2 signaling in bone homeostasis
  • importance of NOTCH2 in the development and maintenance of the skeleton, and modulate RANKL-induced osteoclastogenesis
  • NOTCH2 and NOTCH3 act together to govern vascular development and smooth muscle differentiation
  • CELLULAR PROCESS cell cycle
    cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    cell communication
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    Notch2 signaling is required for potent antitumor immunity
    a component
  • protein constituent of plasma membrane
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • CBF1 (
  • Delta1, Jagged1, and Jagged2 as ligands for Notch2
  • mastermind-like 1 (Drosophila), MAML1
  • glycogen synthase kinase-3 beta, GSK-3 beta
  • TAT
  • directly controls FOS transcription associated with Marginal zone B (MZB) cells development 5)
  • clear interaction between NOTCH2 and FOS, but the exact role of FOS in forming MZB cells has yet to be determined 5)
  • cell & other
    REGULATION
    activated by delta (DLK1) jagged (JAG*)
    in response to TNF (TNF signaling activates NOTCH2 that sensitizes endothelial cells to apoptosis via modulation of the key apoptosis regulator survivin
    induced by MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH2
    Other undergoing a first proteolytic cleavage by furin (PACE1) in the Golgi during trafficking of Notch to the cell surface,undergoing further cleavage by gamma secretase (see PSEN1) releasing an intracellular domain (NICD) which translocates to the nucleus and modulates transcription of target genes
    modulated by FRINGE (LFNG,MFNG,RFNG) through elongation of linked fucose residues on side chains on some EGF repeats
    ASSOCIATED DISORDERS
    corresponding disease(s) ALGS2 , HJCYS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    with FCER2 in B-cell chronic lymphocytic leukemia
    tumoral   translocation    
    in neoplasia
    constitutional somatic mutation      
  • AGS is a disorder caused by mutations in JAG1 or NOTCH2
  • the vast majority of patients with AGS have mutations in JAG1, with only a small subset showing NOTCH2 mutations
  • tumoral     --over  
    correlated closely with colorectal cancer and may play a role in tumor inhibition in colon carcinogenesis
    constitutional     --low  
    in immune thrombocytopenic purpura
    tumoral germinal mutation     gain of function
    in the pathogenesis of a subset of B-cell lymphoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivepancreas
    ablation of NOTCH2 but not NOTCH1 leads to an abrogation of pancreatic intraepithelial neoplasia progression, and increased survival
    osteoarticularboneostéoporosis
    Notch pathway is a potential target for therapeutic intervention in osteoporosis
    ANIMAL & CELL MODELS
  • Mice homozygous for the Notch2(del1) mutation died perinatally from defects in glomerular development in the kidney while mice heterozygous for both the Notch2(del1) and Jag1(dDSL) mutations exhibit a less severe glomerular defect (
  • mice double mutant for the Notch1 and Notch2 receptors exhibit multiple defects in left-right asymmetry (
  • when Notch2 and Notch3 genes are simultaneously disrupted, mice die in utero at mid-gestation due to severe vascular abnormalities