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FLASH GENE
Symbol NOTCH2 contributors: mct/shn - updated : 13-09-2017
HGNC name notch 2
HGNC id 7882
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel   highly Homo sapiens
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
Muscularsmoothvessel predominantly Homo sapiens
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 extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    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
  • Notch signaling through the NOTCH2 receptor is essential for normal biliary tubulogenesis during liver development
  • NOTCH1 and NOTCH2 expression in osteoblast precursors regulates cancellous bone volume and microarchitecture
  • canonical, NOTCH2-dependent signaling plays likely a role in human decidualization
  • NOTCH2 signalling, activated by cell-cell contact of neighbouring distal cell column trophoblasts (dCCTs), could attenuate trophoblast migration
  • NOTCH1 is the primary receptor regulating intestinal stem cell function and NOTCH1 and NOTCH2 together regulate epithelial cell proliferation, cell fate determination, and post-injury regeneration
  • discrete roles for NOTCH2 and NOTCH3 in VSMCs and these roles are linked to specific upstream regulators that control their expression
  • NOTCH2 and NOTCH3 have overlapping roles in promoting development of vascular smooth muscle cells, and together contribute to functional closure of the ductus arteriosus
  • NOTCH2 and NOTCH3 inhibited both cell proliferation and cell apoptosis trophoblast cell lines
  • NOTCH1 and NOTCH2 are the primary NOTCH receptors regulating epithelial cell homoeostasis in human stomach
  • physiologically regulates bone remodeling by inhibiting trabecular bone formation in the appendicular skeleton
  • NOTCH2 signaling is linked to MYC expression and plays a key role in the regulation of Mesenchymal stem/stromal cells (MSCs) proliferation
  • 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
  • NOTCH1 in concert with NOTCH2 contributes to the morphogenesis of renal vesicles into S-shaped bodies in a RBPJ-dependent manner
  • 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)
  • both NOTCH2 and NOTCH3 can promote SDC2 expression in smooth muscle cells
  • potential novel roles of NUMB/NUMBL in regulating heart trabeculation and compaction by inhibiting NOTCH2 and BMP10 signalling
  • receptor-specific function for NOTCH2 in mediating vascular smooth muscle cell growth arrest through CDKN1B
  • NOTCH2 inhibits PDGFB-dependent proliferation and its expression is decreased by PDGFB
  • C8orf4 negatively regulates the self-renewal of liver cancer stem cells (CSCs)via suppression of NOTCH2 signalling
  • CTBP2 and NOTCH2 are possible downstream targets of POU3F4
  • JAG1 and NOTCH2 play a key role in kidney fibrosis development by regulating TFAM expression and metabolic reprogramming
  • LEF1 could activate the critical members (NOTCH1 and NOTCH2) of the NOTCH signaling pathway through directly binding to their promoter regions
  • 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
    tumoral     --over  
    in human hepatocellular carcinoma (HCC) tissues
    tumoral       gain of function
    in liver cancer stem cells (CSCs)
    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
    cancerdigestiveliver
    as a potential therapeutic target for hepatocellular carcinoma
    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
  • mice harboring Notch2 mutations analogous to those in Hajdu-Cheney syndrome (HCS) (Notch2HCS) are severely osteopenic because of enhanced bone resorption