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NOTCH3 Gene

protein-coding   GIFtS: 69
GCID: GC19M015270

Notch 3

(Previous names: Notch (Drosophila) homolog 3, Notch homolog 3 (Drosophila))
(Previous symbol: CADASIL)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Notch 31 2 3     Notch (Drosophila) Homolog 31
CADASIL1 2 5     Notch Homolog 3 (Drosophila)1
CASIL2 5     Neurogenic Locus Notch Homolog Protein 32
IMF22 5     Notch Homolog 32

External Ids:    HGNC: 78831   Entrez Gene: 48542   Ensembl: ENSG000000741817   OMIM: 6002765   UniProtKB: Q9UM473   

Export aliases for NOTCH3 gene to outside databases

Previous GC identifers: GC19M015649 GC19M015115 GC19M015131 GC19M014839


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for NOTCH3 Gene:
This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein
notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an
intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands
have also been identified in human, but precise interactions between these ligands and the human notch homologues
remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal
dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). (provided by RefSeq, Jul 2008)

GeneCards Summary for NOTCH3 Gene:
NOTCH3 (notch 3) is a protein-coding gene. Diseases associated with NOTCH3 include myofibromatosis, infantile 2, and balo's concentric sclerosis. GO annotations related to this gene include enzyme binding and calcium ion binding. An important paralog of this gene is DLK2.

UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47
Function: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate
determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a
transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects
the implementation of differentiation, proliferation and apoptotic programs (By similarity)

Gene Wiki entry for NOTCH3 (Notch 3) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000019.10  NT_011295.12  NC_018930.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the NOTCH3 gene promoter:
         AP-2gamma   GATA-2   C/EBPalpha   CHOP-10   Pax-3   COMP1   STAT3   AP-2beta   AP-2alpha   AP-2alphaA   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidNOTCH3 promoter sequence
   Search Chromatin IP Primers for NOTCH3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NOTCH3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19p13.2-p13.1   Ensembl cytogenetic band:  19p13.12   HGNC cytogenetic band: 19p13.2-p13.1

NOTCH3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOTCH3 gene location

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19M015270:  view genomic region     (about GC identifiers)

Start:
15,270,444 bp from pter      End:
15,311,792 bp from pter
Size:
41,349 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47 (See protein sequence)
Recommended Name: Neurogenic locus notch homolog protein 3 precursor  
Size: 2321 amino acids; 243631 Da
Subunit: Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by
disulfide bonds (By similarity). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators
for NOTCH3. Interacts with PSMA1. Interacts with HIF1AN
Secondary accessions: Q9UEB3 Q9UPL3 Q9Y6L8

Explore the universe of human proteins at neXtProt for NOTCH3: NX_Q9UM47

Explore proteomics data for NOTCH3 at MOPED

Post-translational modifications: 

  • Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like
    convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible
    form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding,
    it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called
    notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to
    release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity)1
  • Phosphorylated (By similarity)1
  • Hydroxylated by HIF1AN1
  • Ubiquitination2 at Lys521, Lys1473, Lys1684
  • Glycosylation2 at Asn1179, Asn1336, Asn1438
  • Modification sites at PhosphoSitePlus

  • See NOTCH3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_000426.2  
    ENSEMBL proteins: 
     ENSP00000263388   ENSP00000470661   ENSP00000468879   ENSP00000473138  
    Reactome Protein details: Q9UM47

    NOTCH3 Human Recombinant Protein Products:

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    Browse OriGene Protein Over-expression Lysates
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    Novus Biologicals NOTCH3 Protein
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    Browse Sino Biological Cell Lysates
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    Cloud-Clone Corp. Proteins for NOTCH3

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    NOTCH3 Assay Products:

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    Cloud-Clone Corp. ELISAs for NOTCH3
    Cloud-Clone Corp. CLIAs for NOTCH3


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    ANKRD: Ankyrin repeat domain containing

    Selected InterPro protein domains (see all 14):
     IPR010660 Notch_NOD_dom
     IPR024600 DUF3454_notch
     IPR001881 EGF-like_Ca-bd_dom
     IPR008297 Notch
     IPR000742 EG-like_dom

    Graphical View of Domain Structure for InterPro Entry Q9UM47

    ProtoNet protein and cluster: Q9UM47

    5 Blocks protein domains:
    IPB000152 Aspartic acid and asparagine hydroxylation site
    IPB000800 LIN-12/notch repeat (LNR) signature
    IPB001881 EGF-like calcium-binding
    IPB002049 Laminin-type EGF-like domain
    IPB002110 Ankyrin repeat signature


    UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47
    Similarity: Belongs to the NOTCH family
    Similarity: Contains 5 ANK repeats
    Similarity: Contains 34 EGF-like domains
    Similarity: Contains 3 LNR (Lin/Notch) repeats


    NOTCH3 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NOTC3_HUMAN, Q9UM47
    Function: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate
    determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a
    transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects
    the implementation of differentiation, proliferation and apoptotic programs (By similarity)

         Genatlas biochemistry entry for NOTCH3:
    Drosophila Notch homolog 3,mediating cell-cell interactions that specify cell fate during development,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,putatively involved in translocation with
    acute lymphoblastic/myeloblastic leukemia and in the decision between the endocrine and exocrine fates in the
    developing pancreas

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005509calcium ion binding IEA--
    GO:0005515protein binding IPI11101851
    GO:0019899enzyme binding IEA--
         
    NOTCH3 for ontologies           About GeneDecksing


    Phenotypes:
         Selected MGI mutant phenotypes (inferred from 7 alleles(MGI details for Notch3) (see all 20):
     behavior/neurological  cardiovascular system  cellular  embryogenesis  endocrine/exocrine gland 
     growth/size/body  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism  immune system 
     integument  mortality/aging  muscle  nervous system  normal 

    NOTCH3 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for NOTCH3: Notch3tm1Khan Notch3tm1Grid

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NOTCH3
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for NOTCH3

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NOTCH3
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NOTCH3

    miRNA
    Products:
        
    miRTarBase miRNAs that target NOTCH3:
    hsa-mir-1 (MIRT006550), hsa-mir-335-5p (MIRT017387), hsa-mir-484 (MIRT042194), hsa-mir-150-5p (MIRT007016), hsa-mir-206 (MIRT000665)

    Block miRNA regulation of human, mouse, rat NOTCH3 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate NOTCH3 (see all 25):
    hsa-miR-26a-2* hsa-miR-875-3p hsa-miR-3673 hsa-miR-136 hsa-miR-520d-5p hsa-miR-1263 hsa-miR-300 hsa-miR-24-1*
    SwitchGear 3'UTR luciferase reporter plasmidNOTCH3 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for NOTCH3
    Predesigned siRNA for gene silencing in human, mouse, rat NOTCH3

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for NOTCH3

    Clone
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    OriGene clones in human, mouse for NOTCH3 (see all 5)
    OriGene ORF clones in mouse, rat for NOTCH3
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    GenScript: all cDNA clones in your preferred vector: NOTCH3 (NM_000435)
    Browse Sino Biological Human cDNA Clones
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    Search Vector BioLabs for ready-to-use adenovirus/AAV for human, mouse, rat NOTCH3

    Cell Line
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    Browse ESI BIO Cell Lines and PureStem Progenitors for NOTCH3 
    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH3


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    NOTC3_HUMAN, Q9UM47: Cell membrane; Single-pass type I membrane protein
    NOTC3_HUMAN, Q9UM47: Notch 3 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is
    translocated to the nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    plasma membrane5
    cytosol4
    endoplasmic reticulum4
    extracellular4
    golgi apparatus4
    cytoskeleton1
    lysosome1
    mitochondrion1

    Gene Ontology (GO): Selected cellular component terms (see all 13):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane TAS--
    GO:0005576extracellular region TAS--
    GO:0005634nucleus IDA--
    GO:0005654nucleoplasm TAS--
    GO:0005730NOT nucleolus IDA--

    NOTCH3 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for NOTCH3 About   (see all 17)  
    See pathways by source

    SuperPathContained pathways About
    1Notch signaling pathway (KEGG)
    Notch signaling pathway0.84
    Notch Signaling0.30
    Notch Signaling Pathway0.84
    Signaling by NOTCH30.00
    Delta-Notch Signaling Pathway0.33
    2Pre-NOTCH Expression and Processing
    Pre-NOTCH Expression and Processing0.62
    Notch-HLH transcription pathway0.00
    Pre-NOTCH Transcription and Translation0.62
    Pre-NOTCH Processing in the Endoplasmic Reticulum0.00
    Pre-NOTCH Processing in Golgi0.00
    3Gene Expression
    Generic Transcription Pathway0.40
    Gene Expression0.40
    4Signaling by NOTCH1 PEST Domain Mutants in Cancer
    Signaling by NOTCH0.64
    5Signaling by GPCR
    Signal Transduction0.58

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for NOTCH3
        Notch Signaling Pathways

    4 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for NOTCH3
        Notch Signaling
    Molecular Mechanisms of Cancer
    Presenilin-Mediated Signaling
    Epithelial Adherens Junctions

    3 Cell Signaling Technology (CST) Pathways for NOTCH3
        Wnt / Hedgehog / Notch
    Angiogenesis
    Neuroscience

    4 BioSystems Pathways for NOTCH3
        Notch Signaling Pathway
    Neural Crest Differentiation
    Delta-Notch Signaling Pathway
    Notch signaling pathway

    5 Reactome Pathways for NOTCH3
        Pre-NOTCH Processing in Golgi
    Pre-NOTCH Transcription and Translation
    Notch-HLH transcription pathway
    Pre-NOTCH Processing in the Endoplasmic Reticulum
    Signaling by NOTCH3


    4 Kegg Pathways  (Kegg details for NOTCH3):
        Dorso-ventral axis formation
    Notch signaling pathway
    Thyroid hormone signaling pathway
    MicroRNAs in cancer


    NOTCH3 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NOTCH3: 
              Notch Signaling Targets in human mouse rat
              Adherens Junctions in human mouse rat
              Stem Cell Signaling in human mouse rat
              Cell Junction PathwayFinder in human mouse rat
              Notch Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for NOTCH3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for NOTCH3 (Q9UM471, 2, 3 ENSP000002633884) via UniProtKB, MINT, STRING, and/or I2D (see all 199)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CSNK2BP678702, 3MINT-8253473 I2D: score=2 
    ENSG00000206406P678702, 3MINT-8253473 I2D: score=2 
    ENSG00000224398P678702, 3MINT-8253473 I2D: score=2 
    ENSG00000224774P678702, 3MINT-8253473 I2D: score=2 
    ENSG00000228875P678702, 3MINT-8253473 I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006355regulation of transcription, DNA-templated IEA--
    GO:0006367transcription initiation from RNA polymerase II promoter TAS--
    GO:0007219Notch signaling pathway TAS--
    GO:0007220Notch receptor processing TAS--
    GO:0007275multicellular organismal development ----

    NOTCH3 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for NOTCH3 (NOTC3)

    3 Novoseek inferred chemical compound relationships for NOTCH3 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cysteine 58.1 29 19043263 (2), 16256149 (2), 15714997 (1), 17331978 (1) (see all 18)
    arginine 14.1 3 15714997 (1), 11559313 (1)
    calcium 1.73 1 10024441 (1)



    NOTCH3 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for NOTCH3 gene: 
    NM_000435.2  

    Unigene Cluster for NOTCH3:

    Notch 3
    Hs.8546  [show with all ESTs]
    Unigene Representative Sequence: U97669
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000263388(uc002nan.3 uc002nao.1) ENST00000595514 ENST00000597756
    ENST00000601011 ENST00000600841 ENST00000595045
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate NOTCH3 (see all 25):
    hsa-miR-26a-2* hsa-miR-875-3p hsa-miR-3673 hsa-miR-136 hsa-miR-520d-5p hsa-miR-1263 hsa-miR-300 hsa-miR-24-1*
    SwitchGear 3'UTR luciferase reporter plasmidNOTCH3 3' UTR sequence
    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector: NOTCH3 (NM_000435)
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    Search Vector BioLabs for ready-to-use adenovirus/AAV for human, mouse, rat NOTCH3
    Primer
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      QuantiTect SYBR Green Assays in human, mouse, rat NOTCH3
      QuantiFast Probe-based Assays in human, mouse, rat NOTCH3

    Additional mRNA sequence: 

    AB209447.1 U97669.1 

    5 DOTS entries:

    DT.217396  DT.91963540  DT.100815125  DT.75121130  DT.91646701 

    Selected AceView cDNA sequences (see all 277):

    BI523794 BU553672 BQ919557 AI274902 T63511 BE764071 BI052410 CA433198 
    BF435534 CA446395 AW194070 AI091531 AI559175 AI473478 AI921030 AA301460 
    BU846477 BU956081 BM841037 CK904462 AI969777 BM021466 CB270591 CN483616 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for NOTCH3    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20a · 20b ^ 21 ^ 22 ^ 23a · 23b ^ 24 ^
    SP1:                                                                                                                    -                                       
    SP2:                                                                                      -                             -                                       
    SP3:                                                                                                                                                            

    ExUns: 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32
    SP1:                                                
    SP2:                                                
    SP3:                                                


    ECgene alternative splicing isoforms for NOTCH3

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    NOTCH3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GCAGAATAGA
    NOTCH3 Expression
    About this image


    NOTCH3 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 13) fully expand
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 40 entries
             Myoblasts Cervical Hypaxial Myotome
     
     Somite (Muscoskeletal System)    fully expand to see all 32 entries
             Myoblasts Cervical Hypaxial Myotome
     
     Limb (Muscoskeletal System)    fully expand to see all 8 entries
             Myoblasts Forelimb Ventral Muscles
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Midbrain tegmentum
     
     Neural Tube (Nervous System)    fully expand to see all 3 entries
             Telencephalon
    NOTCH3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NOTCH3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.8546

    UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47
    Tissue specificity: Ubiquitously expressed in fetal and adult tissues

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NOTCH3: 
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              Cell Junction PathwayFinder in human mouse rat
              Notch Signaling Pathway in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for NOTCH3 gene from 13 species (see representative species )    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    chimpanzee
    (Pan troglodytes)
    Mammalia NOTCH31 notch 3 99.35(n)
    99.87(a)
      455792  XM_003316164.1  XP_003316212.1 
    mouse
    (Mus musculus)
    Mammalia Notch31 , 5 Notch gene homolog 3 (Drosophila)5
    notch 31
    84.32(n)1
    90.99(a)1
      17 (17.37 cM)5
    181311  NM_008716.21  NP_032742.11 
     321208205 
    rat
    (Rattus norvegicus)
    Mammalia Notch31 notch 3 84.56(n)
    91.47(a)
      56761  NM_020087.2  NP_064472.2 
    cow
    (Bos taurus)
    Mammalia NOTCH31 notch 3 88.4(n)
    93.43(a)
      789485  XM_003586246.2  XP_003586294.1 
    dog
    (Canis familiaris)
    Mammalia NOTCH31 notch 3 87.2(n)
    91.77(a)
      610439  XM_005633201.1  XP_005633258.1 
    oppossum
    (Monodelphis domestica)
    Mammalia NOTCH36
    notch 3
    77(a)
    1 ↔ 1
    3(477582725-477612416)
    platypus
    (Ornithorhynchus anatinus)
    Mammalia NOTCH36
    notch 3
    73(a)
    1 ↔ 1
    Contig12531(1906-14314)
    lizard
    (Anolis carolinensis)
    Reptilia NOTCH36
    notch 3
    63(a)
    1 ↔ 1
    2(103176116-103239023)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia 1420334872   -- 76.95(n)    142033487 
    zebrafish
    (Danio rerio)
    Actinopterygii AF152001.12   -- 75.66(n)   58066  AF152001.1 
    sea squirt
    (Ciona savignyi)
    Ascidiacea --
    Uncharacterized protein
    40(a)
    many ↔ many
    reftig_370(131384-180972)
    fruit fly
    (Drosophila melanogaster)
    Insecta SP10703 Notch binding 38(a)
    (best of 2)
      27D2   --
    worm
    (Caenorhabditis elegans)
    Secernentea W02C12.13 EGF-like protein 37(a)
    (best of 7)
      IV(4008218-4014159)   --
            Species with no ortholog for NOTCH3

    ENSEMBL Gene Tree for NOTCH3 (if available)
    TreeFam Gene Tree for NOTCH3 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NOTCH3 gene
    DLK22  SNED12  NOTCH42  NOTCH12  DLL32  DLL42  JAG22  CRB22  
    DLK12  NOTCH22  JAG12  DNER2  CRB12  DLL12  
    Selected SIMAP similar genes for NOTCH3 using alignment to 5 protein entries:     NOTC3_HUMAN (see all proteins) (see all similar genes):
    F9 p22    factor IX F9    CRB1    F9    SVEP1    SLIT3
    NOTCH2    PPP1R12A    SLIT2    FBLN7    NOTCH1    PROS1
    VCAN    DLL3    ACAN    GABPB1    SNED1    ANKRD44

    NOTCH3 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for NOTCH3 (see all 1322)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs2011180341,2,,4
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4 --15229476(+) GTTGCA/GATCAC 2 R C mis10--------
    rs289336981,2,,4
    CCerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4 pathogenic115231165(-) TCACCC/TGTATC 2 R C mis1 ese30--------
    rs289336971,2,,4
    CCerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4 pathogenic115234256(-) CCTTCC/TGCTGC 2 R C mis1 ese30--------
    rs289336961,2,,4
    CCerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4 pathogenic115234295(-) CCTGCC/TGCCAT 2 R C mis1 ese30--------
    VAR_0443044
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0443042 C Y mis40--------
    VAR_0442344
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0442342 C S mis40--------
    VAR_0128904
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0128902 C Y mis40--------
    VAR_0128964
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0128962 R C mis40--------
    VAR_0442864
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0442862 C R mis40--------
    VAR_0443134
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0443132 C R mis40--------

    HapMap Linkage Disequilibrium report for NOTCH3 (15270444 - 15311792 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for NOTCH3:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2718225CNV Deletion23290073
    nsv911131CNV Loss21882294
    esv997404CNV Loss20482838
    esv34154CNV Loss18971310
    nsv521424CNV Loss19592680
    nsv911132CNV Loss21882294

    Human Gene Mutation Database (HGMD): NOTCH3
    Locus Specific Mutation Databases (LSDB): NOTCH3

    Site Specific Mutation Identification with PCR Assays
    1 Copy Number PCR Panel containing NOTCH3:
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600276   
    OMIM disorders: 125310  615293  
    UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47
  • Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)
    [MIM:125310]: A cerebrovascular disease characterized by multiple subcortical infarcts, pseudobulbar palsy,
    dementia, and the presence of granular deposits in small cerebral arteries producing ischemic stroke. Note=The
    disease is caused by mutations affecting the gene represented in this entry
  • Myofibromatosis, infantile 2 (IMF2) [MIM:615293]: A rare mesenchymal disorder characterized by the
    development of benign tumors in the skin, striated muscles, bones, and, more rarely, visceral organs.
    Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular
    lesions occur in about half of the patients. Lesions may be solitary or multicentric, and they may be present at
    birth or become apparent in early infancy or occasionally in adult life. Visceral lesions are associated with
    high morbidity and mortality. Note=The disease is caused by mutations affecting the gene represented in this
    entry

  • Selected diseases for NOTCH3 (see all 69):    
    About MalaCards
    myofibromatosis, infantile 2    balo's concentric sclerosis    cadasil    cerebrovascular disease
    myofibromatosis, infantile, 1    pseudobulbar palsy    hemiplegic migraine    varicose veins
    vascular dementia    migraine with aura    cerebritis    familial hemiplegic migraine
    migraine    ossifying fibroma    lymphoblastic lymphoma    dementia
    ductal carcinoma in situ    abdominal aortic aneurysm    cervical squamous cell carcinoma    vascular disease

    5 diseases from the University of Copenhagen DISEASES database for NOTCH3:
    Cadasil     Migraine     Vascular dementia     Cerebrovascular accident
    Pseudobulbar palsy

    NOTCH3 for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for NOTCH3 gene (see all 27)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cadasil 99.3 380 15857853 (5), 10766655 (5), 11391502 (5), 16580020 (5) (see all 99)
    infarct 87.7 115 18572291 (2), 12417361 (2), 16949066 (2), 16580020 (2) (see all 99)
    migraine 83 26 16492242 (6), 16426270 (3), 19018300 (2), 15313840 (1) (see all 12)
    dementia vascular 82 11 11757773 (1), 11706120 (1), 11102981 (1), 15857853 (1) (see all 10)
    dementia 76.1 27 11391502 (3), 11591842 (1), 10712431 (1), 10716263 (1) (see all 24)
    subcortical infarction 74.7 3 16580020 (1), 19242647 (1)
    infarction lacunar 74 2 17239802 (1), 12511775 (1)
    stroke 73.4 33 7783868 (2), 11591842 (1), 11757773 (1), 10712431 (1) (see all 31)
    cerebrovascular disease 66.2 13 11861701 (2), 11578869 (1), 19139365 (1), 12480758 (1) (see all 10)
    t-all 60.4 10 11891328 (2), 12524208 (1), 18032925 (1), 16838279 (1) (see all 7)

    GeneTests: NOTCH3
    GeneReviews: NOTCH3
    Genetic Association Database (GAD): NOTCH3
    Human Genome Epidemiology (HuGE) Navigator: NOTCH3 (67 documents)

    Export disorders for NOTCH3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for NOTCH3 gene, integrated from 10 sources (see all 366):
    (articles sorted by number of sources associating them with NOTCH3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies. (PubMed id 16009764)1, 2, 4, 9 Peters N.... Dichgans M. (Arch. Neurol. 2005)
    2. CADASIL: extended polymorphisms and mutational analysis of the NOTCH3 gene. (PubMed id 19006080)1, 4, 9 Ungaro C....Quattrone A. (J. Neurosci. Res. 2009)
    3. Investigating the association between Notch3 polymorphism and migraine. (PubMed id 16492242)1, 4, 9 Borroni B....Padovani A. (Headache 2006)
    4. Genetic, clinical and pathological studies of CADASIL in Japan: a partial contribution of Notch3 mutations and implications of smooth muscle cell degeneration for the pathogenesis. (PubMed id 12810003)1, 2, 9 Santa Y....Tabira T. (J. Neurol. Sci. 2003)
    5. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. (PubMed id 9388399)1, 2, 9 Joutel A.... Tournier-Lasserve E. (Lancet 1997)
    6. Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese. (PubMed id 19242647)1, 4, 9 Lee Y.C....Soong B.W. (J. Neurol. 2009)
    7. Notch3 gene polymorphism and ischaemic cerebrovascular disease. (PubMed id 11861701)1, 4, 9 Ito D....Fukuuchi Y. (J. Neurol. Neurosurg. Psychiatr. 2002)
    8. Investigation of the NOTCH3 and TNFSF7 genes on C19p13 as candidates for migraine. (PubMed id 19018300)1, 4, 9 Smith R.A....Griffiths L. (Open Neurol J 2008)
    9. Genetic variants of the NOTCH3 gene in migraine--a mutation analysis and association study. (PubMed id 16426270)1, 4, 9 Schwaag S....KuhlenbAoumer G. (Cephalalgia 2006)
    10. A novel mutation in the Notch3 gene in an Italian family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: genetic and magnetic resonance spectroscopic findings. (PubMed id 11559313)1, 2, 9 Oliveri R.L.... Quattrone A. (Arch. Neurol. 2001)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 4854 HGNC: 7883 AceView: NOTCH3 Ensembl:ENSG00000074181 euGenes: HUgn4854
    ECgene: NOTCH3 Kegg: 4854 H-InvDB: NOTCH3

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for NOTCH3 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for NOTCH3 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=NOTCH3[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for NOTCH3 gene:
    Search GeneIP for patents involving NOTCH3

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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