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NOTCH4 Gene

protein-coding   GIFtS: 67
GCID: GC06M032166

Notch 4

(Previous names: Notch (Drosophila) homolog 4, Notch homolog 4 (Drosophila))
(Previous symbol: INT3)
  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 41 2 3     NOTCH32
INT31 2 3 5     Neurogenic Locus Notch Homolog Protein 42
Notch (Drosophila) Homolog 41     Notch Homolog 42
Notch Homolog 4 (Drosophila)1     hNotch43

External Ids:    HGNC: 78841   Entrez Gene: 48552   Ensembl: ENSG000002043017   OMIM: 1649515   UniProtKB: Q994663   

Export aliases for NOTCH4 gene to outside databases

Previous GC identifers: GC06M032185 GC06M031933 GC06M032234 GC06M032231 GC06M032270


(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 NOTCH4 Gene:
This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share
structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like
(EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members
play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling
network is an evolutionarily conserved intercellular signaling pathway which regulates interactions between
physically adjacent cells. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate)
establishes an intercellular signaling pathway that plays a key role in development. Homologues of the
notch-ligands have also been identified in human, but precise interactions between these ligands and the human
notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on
the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play
a role in vascular, renal and hepatic development. This gene may be associated with susceptibility to
schizophrenia in a small portion of cases. An alternative splice variant has been described but its biological
nature has not been determined. (provided by RefSeq, Jul 2008)

GeneCards Summary for NOTCH4 Gene:
NOTCH4 (notch 4) is a protein-coding gene. Diseases associated with NOTCH4 include pseudobulbar palsy, and schizoaffective disorder. GO annotations related to this gene include receptor activity and calcium ion binding. An important paralog of this gene is DLK2.

UniProtKB/Swiss-Prot: NOTC4_HUMAN, Q99466
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. May regulate branching morphogenesis
in the developing vascular system (By similarity)

Gene Wiki entry for NOTCH4 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_000006.12  NC_018917.2  NT_007592.16  NT_113891.3  NT_167244.2  NT_167246.2  NT_167247.2  NT_167248.2  
NT_167249.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the NOTCH4 gene promoter:
         p53   MyoD   Tal-1beta   PPAR-alpha   HEN1   Ik-2   NF-kappaB1   ITF-2   ATF6   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): NOTCH4 promoter sequence
   Search Chromatin IP Primers for NOTCH4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NOTCH4


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

Entrez Gene cytogenetic band: 6p21.3   Ensembl cytogenetic band:  6p21.32   HGNC cytogenetic band: 6p21.3

NOTCH4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOTCH4 gene location

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06M032166:  view genomic region     (about GC identifiers)

Start:
32,162,620 bp from pter      End:
32,191,844 bp from pter
Size:
29,225 bases      Orientation:
minus strand

6 alternative locations:
Chr6-,NT_167244 3,477,358-3,486,924      Chr6-,NT_167246 3,505,441-3,534,689      Chr6-,NT_167249 3,510,346-3,539,573     
Chr6-,NT_167247 3,542,444-3,571,691      Chr6-,NT_167248 3,423,638-3,452,865      Chr6-,NT_113891.2 3,633,298-3,662,520     

(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: NOTC4_HUMAN, Q99466 (See protein sequence)
Recommended Name: Neurogenic locus notch homolog protein 4 precursor  
Size: 2003 amino acids; 209622 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 NOTCH4
Sequence caution: Sequence=BAA09708.1; Type=Frameshift; Positions=1438, 1463;
Secondary accessions: B0V183 B0V1X5 O00306 Q5SSY7 Q99458 Q99940 Q9H3S8 Q9UII9 Q9UIJ0
Alternative splicing: 3 isoforms:  Q99466-1   Q99466-2   Q99466-3   

Explore the universe of human proteins at neXtProt for NOTCH4: NX_Q99466

Explore proteomics data for NOTCH4 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
  • Glycosylation2 at Asn664, Asn714, Asn964, Asn1143
  • Modification sites at PhosphoSitePlus

  • See NOTCH4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_004548.3  
    ENSEMBL proteins: 
     ENSP00000364163   ENSP00000398123  
    Reactome Protein details: Q99466

    NOTCH4 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
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    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for NOTCH4
    OriGene Custom MassSpec
    OriGene Custom Protein Services for NOTCH4
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    Novus Biologicals NOTCH4 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for NOTCH4

    NOTCH4 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of NOTCH4
    R&D Systems Antibodies for NOTCH4 (Notch-4)
    Cell Signaling Technology (CST) Antibodies for NOTCH4 
    OriGene Antibodies for NOTCH4
    OriGene Custom Antibody Services for NOTCH4
    Novus Biologicals NOTCH4 Antibodies
    Abcam antibodies for NOTCH4
    Cloud-Clone Corp. Antibodies for NOTCH4
    ThermoFisher Antibodies for NOTCH4
    LSBio Antibodies in human, mouse, rat for NOTCH4

    NOTCH4 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    GenScript Custom Assay Services for NOTCH4
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for NOTCH4
    Cloud-Clone Corp. CLIAs for NOTCH4


    (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 12):
     IPR001881 EGF-like_Ca-bd_dom
     IPR008297 Notch
     IPR000742 EG-like_dom
     IPR009030 Growth_fac_rcpt_N_dom
     IPR000800 Notch_dom

    Graphical View of Domain Structure for InterPro Entry Q99466

    ProtoNet protein and cluster: Q99466

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


    UniProtKB/Swiss-Prot: NOTC4_HUMAN, Q99466
    Similarity: Belongs to the NOTCH family
    Similarity: Contains 5 ANK repeats
    Similarity: Contains 29 EGF-like domains
    Similarity: Contains 3 LNR (Lin/Notch) repeats


    NOTCH4 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: NOTC4_HUMAN, Q99466
    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. May regulate branching morphogenesis
    in the developing vascular system (By similarity)

         Genatlas biochemistry entry for NOTCH4:
    Drosophila Notch homolog 4,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,homologous to MMTV integration site
    int-3,containing a (CTG)n repeats polymorphism,with 2 isoforms L and S

         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004872receptor activity TAS11823422
    GO:0005509calcium ion binding TAS11823422
    GO:0005515protein binding IPI11101851
    GO:0046982protein heterodimerization activity TAS8681805
         
    NOTCH4 for ontologies           About GeneDecksing


    Phenotypes:
         6 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Notch4):
     cardiovascular system  embryogenesis  growth/size/body  homeostasis/metabolism  nervous system 
     normal 

    NOTCH4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Notch4tm1Grid for NOTCH4

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NOTCH4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for NOTCH4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NOTCH4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NOTCH4

    miRNA
    Products:
        
    miRTarBase miRNAs that target NOTCH4:
    hsa-mir-34c-5p (MIRT006192), hsa-mir-18a-3p (MIRT040767), hsa-mir-181c-5p (MIRT003211)

    Block miRNA regulation of human, mouse, rat NOTCH4 using miScript Target Protectors
    6 qRT-PCR Assays for microRNAs that regulate NOTCH4:
    hsa-miR-221* hsa-miR-4265 hsa-miR-607 hsa-miR-218-1* hsa-miR-3945 hsa-miR-4296
    SwitchGear 3'UTR luciferase reporter plasmidNOTCH4 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for NOTCH4
    Predesigned siRNA for gene silencing in human, mouse, rat NOTCH4

    Gene Editing
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    DNA2.0 Custom Protein Engineering Service for NOTCH4

    Clone
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    OriGene clones in human, mouse for NOTCH4 (see all 5)
    OriGene ORF clones in mouse, rat for NOTCH4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: NOTCH4 (NM_004557)
    Sino Biological Human cDNA Clone for NOTCH4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOTCH4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOTCH4

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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH4


    (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
    NOTC4_HUMAN, Q99466: Cell membrane; Single-pass type I membrane protein
    NOTC4_HUMAN, Q99466: Notch 4 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 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane TAS--
    GO:0005576extracellular region TAS--
    GO:0005634nucleus TAS8681805
    GO:0005654nucleoplasm TAS--
    GO:0005789endoplasmic reticulum membrane TAS--

    NOTCH4 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 NOTCH4 About   (see all 18)  
    See pathways by source

    SuperPathContained pathways About
    1Notch signaling pathway (KEGG)
    Notch signaling pathway0.84
    Notch Signaling0.30
    Notch Signaling Pathway0.84
    Signaling by NOTCH40.00
    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 NOTCH4
        Notch Signaling Pathways

    4 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for NOTCH4
        Notch Signaling
    Molecular Mechanisms of Cancer
    Presenilin-Mediated Signaling
    Epithelial Adherens Junctions

    3 Cell Signaling Technology (CST) Pathways for NOTCH4
        Wnt / Hedgehog / Notch
    Angiogenesis
    Neuroscience

    4 BioSystems Pathways for NOTCH4
        Notch Signaling Pathway
    Neural Crest Differentiation
    Delta-Notch Signaling Pathway
    Notch signaling pathway


    5 Reactome Pathways for NOTCH4
        Pre-NOTCH Processing in Golgi
    Pre-NOTCH Transcription and Translation
    Notch-HLH transcription pathway
    Signaling by NOTCH4
    Pre-NOTCH Processing in the Endoplasmic Reticulum


    4 Kegg Pathways  (Kegg details for NOTCH4):
        Dorso-ventral axis formation
    Notch signaling pathway
    Thyroid hormone signaling pathway
    MicroRNAs in cancer


    NOTCH4 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NOTCH4 (see all 7): 
              Adherens Junctions in human mouse rat
              Stem Cell Signaling in human mouse rat
              Neurotoxicity in human mouse rat
              Cell Junction PathwayFinder in human mouse rat
              Angiogenesis in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for NOTCH4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 12)

    Selected Interacting proteins for NOTCH4 (Q994662, 3 ENSP000003641634) via UniProtKB, MINT, STRING, and/or I2D (see all 19)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SMAD2Q157963, ENSP000002621604I2D: score=3 STRING: ENSP00000262160
    SMAD3P840223, ENSP000003329734I2D: score=3 STRING: ENSP00000332973
    MAML1Q925853, ENSP000002925994I2D: score=2 STRING: ENSP00000292599
    DLL4Q9NR613, ENSP000002497494I2D: score=1 STRING: ENSP00000249749
    PSEN1P497683, ENSP000003263664I2D: score=1 STRING: ENSP00000326366
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 19):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001569patterning of blood vessels ISS--
    GO:0001709cell fate determination TAS11823422
    GO:0001763morphogenesis of a branching structure ISS--
    GO:0001886endothelial cell morphogenesis IEA--
    GO:0006367transcription initiation from RNA polymerase II promoter TAS--

    NOTCH4 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 NOTCH4 (NOTC4)

    2 Novoseek inferred chemical compound relationships for NOTCH4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    snp 2 74.2 3 11239712 (2), 15653273 (1)
    vegf 29.9 5 16951162 (3), 18671974 (1), 17955263 (1)



    NOTCH4 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 NOTCH4 gene: 
    NM_004557.3  

    Unigene Cluster for NOTCH4:

    Notch 4
    Hs.436100  [show with all ESTs]
    Unigene Representative Sequence: NM_004557
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000491215 ENST00000474612(uc011dpt.2 uc003oba.3 uc011dpw.1)
    ENST00000375023(uc003obb.3 uc011dpu.2 uc011dpv.2) ENST00000465528
    ENST00000473562(uc003obc.3) ENST00000443903
    miRNA
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    6 qRT-PCR Assays for microRNAs that regulate NOTCH4:
    hsa-miR-221* hsa-miR-4265 hsa-miR-607 hsa-miR-218-1* hsa-miR-3945 hsa-miR-4296
    SwitchGear 3'UTR luciferase reporter plasmidNOTCH4 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat NOTCH4
    Clone
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    GenScript: all cDNA clones in your preferred vector: NOTCH4 (NM_004557)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOTCH4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOTCH4
    Primer
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    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat NOTCH4
      QuantiTect SYBR Green Assays in human, mouse, rat NOTCH4
      QuantiFast Probe-based Assays in human, mouse, rat NOTCH4

    Additional mRNA sequence: 

    AK131314.1 AK290785.1 AK293692.1 AK294161.1 BC033869.1 BC063815.1 BC140782.1 BC144540.1 
    BC144541.1 D63395.1 U95299.1 

    6 DOTS entries:

    DT.443558  DT.97785448  DT.40281802  DT.121378239  DT.99962397  DT.91906043 

    Selected AceView cDNA sequences (see all 222):

    NM_022107 AI673445 AI880212 AL705928 BQ183096 BU682631 BG743359 CR604341 
    BP340382 BC063815 BQ011648 BU172121 AI300614 BG490215 AW572963 AI355714 
    CK821917 BU149977 BQ053714 CA307082 BU855923 AI244789 BI769793 BQ711693 

    GeneLoc Exon Structure


    (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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    NOTCH4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GTAGGGAGGA
    NOTCH4 Expression
    About this image


    NOTCH4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 6) fully expand
     
     Endothelium (Cardiovascular System)    fully expand to see all 3 entries
             Angioblasts Embryonic Blood Islands
     
     Lateral Plate Mesoderm (Gastrulation Derivatives)    fully expand to see all 3 entries
             Angioblasts Embryonic Blood Islands
     
     Blood (Cardiovascular System)    fully expand to see all 2 entries
             Granulocytes Peripheral Blood
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 2 entries
             Myoblasts Mandibular Arch Muscles
     
     Placenta (Extraembryonic Tissues)
             Extravillous Cytotrophoblast Cells Extravillous Cytotrophoblast Layer
    NOTCH4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NOTCH4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.436100

    UniProtKB/Swiss-Prot: NOTC4_HUMAN, Q99466
    Tissue specificity: Highly expressed in the heart, moderately in the lung and placenta and at low levels in the
    liver, skeletal muscle, kidney, pancreas, spleen, lymph node, thymus, bone marrow and fetal liver. No expression
    was seen in adult brain or peripheral blood leukocytes

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NOTCH4 (see all 7): 
              Adherens Junctions in human mouse rat
              Stem Cell Signaling in human mouse rat
              Neurotoxicity in human mouse rat
              Cell Junction PathwayFinder in human mouse rat
              Angiogenesis 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 NOTCH4 gene from Selected species (see all 11)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Notch41 , 5 Notch gene homolog 4 (Drosophila)5
    notch 41
    83.21(n)1
    82.4(a)1
      17 (18.15 cM)5
    181321  NM_010929.21  NP_035059.21 
     345642685 
    lizard
    (Anolis carolinensis)
    Reptilia NOTCH46
    notch 4
    38(a)
    1 ↔ 1
    2(198816928-198859587)
    fruit fly
    (Drosophila melanogaster)
    Insecta CG153883   -- 39(a)
    (best of 2)
      22E1   --


    ENSEMBL Gene Tree for NOTCH4 (if available)
    TreeFam Gene Tree for NOTCH4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NOTCH4 gene
    DLK22  SNED12  NOTCH12  DLL32  NOTCH32  JAG22  CRB22  DLL42  
    DLK12  NOTCH22  JAG12  DNER2  CRB12  DLL12  
    7 SIMAP similar genes for NOTCH4 using alignment to 4 protein entries:     NOTC4_HUMAN (see all proteins):
    F9    NOTCH3    NOTCH2    DKFZp761E1322    MTPN    NOTCH1
    CRB1

    NOTCH4 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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    Polymorphic Variants from UniProtKB/Swiss-Prot
    NOTC4_HUMAN, Q99466: The poly-Leu region of NOTCH4 (in the signal peptide) is polymorphic and the number of Leu varies in
    the population (from 6 to 12)


    Selected SNPs for NOTCH4 (see all 868)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs615808651,2
    C--31947501(+) TTTTT-/TT/TTT
            
    GAGAC
    2 -- us2k1 cds10--------
    rs1463951611,2
    --32079741(+) GCGACA/GGAGGG 1 -- ds50010--------
    rs1816602001,2
    --32079751(+) GCTGGA/TTTCAG 1 -- ds50010--------
    rs1384577081,2
    --32079791(+) GCATTA/GGATTC 1 -- ds50010--------
    rs1415752601,2
    --32079793(+) ATTAGA/CTTCCC 1 -- ds50010--------
    rs1389861661,2
    C--32079889(+) CTGAC-/AGGAGGTG 1 -- ds50010--------
    rs1863157841,2
    --32080133(+) ATGCTA/GAGCCA 1 -- ds50010--------
    rs455920331,2
    C,F--32080155(+) TGCTGA/GCATTA 1 -- ds50013Minor allele frequency- G:0.05WA NA EA 358
    rs31809631,2
    C--32080275(-) CCACTC/GCTATC 1 -- ut31 ese30--------
    rs728463051,2
    C--32080290(+) AAGAAA/GCGCTT 1 -- ut310--------

    HapMap Linkage Disequilibrium report for NOTCH4 (32162620 - 32191844 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 10 variations for NOTCH4:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2677748CNV Deletion23128226
    dgv6643n71CNV Loss21882294
    nsv884712CNV Loss21882294
    dgv6645n71CNV Loss21882294
    nsv830629CNV Loss17160897
    nsv10826CNV Loss18304495
    dgv6644n71CNV Loss21882294
    nsv884715CNV Loss21882294
    nsv462877CNV Loss19166990
    dgv1929e1CNV Complex17122850

    Human Gene Mutation Database (HGMD): NOTCH4
    Site Specific Mutation Identification with PCR Assays
    1 Copy Number PCR Panel containing NOTCH4:
    Pancreatic Cancer
    SeqTarget long-range PCR primers for resequencing NOTCH4
    DNA2.0 Custom Variant and Variant Library Synthesis for NOTCH4

    (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: 164951    OMIM disorders: --

    Selected diseases for NOTCH4 (see all 63):    
    About MalaCards
    pseudobulbar palsy    schizoaffective disorder    cadasil    klippel-trenaunay syndrome
    tongue cancer    arteriovenous malformation    alopecia areata    schizophrenia
    inclusion body myositis    plasmacytoma    alopecia    vascular dementia
    myositis    hepatitis    arteriosclerosis    kawasaki disease
    cervical squamous cell carcinoma    hemangioma    mood disorder    narcolepsy

    5 diseases from the University of Copenhagen DISEASES database for NOTCH4:
    Cadasil     Migraine     Vascular dementia     Cerebrovascular accident
    Pseudobulbar palsy

    NOTCH4 for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for NOTCH4 gene (see all 14)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    schizophrenia 54.1 83 12873802 (6), 12627456 (5), 16894623 (5), 11407996 (5) (see all 26)
    mammary tumor 39.3 3 9243759 (1), 15288259 (1)
    schizoaffective disorder 24.8 4 11239712 (4)
    tumors 18.5 42 18339869 (3), 9243759 (3), 16778208 (3), 17675579 (2) (see all 18)
    hepatocellular carcinoma 16.5 8 16951162 (2), 17696940 (1), 17920003 (1), 19304334 (1)
    breast cancer 16.1 5 17158237 (2), 18339869 (2)
    cancer 15 6 18184405 (2), 17158237 (1), 15867348 (1), 17804716 (1)
    ovarian cancer 11.1 11 18974129 (2), 18632624 (2), 16778208 (1)
    leukemia 0 1 9461376 (1)
    carcinoma squamous cell 0 1 20359736 (1)

    Genetic Association Database (GAD): NOTCH4
    Human Genome Epidemiology (HuGE) Navigator: NOTCH4 (42 documents)
    Tumor Gene Database (TGDB): NOTCH4

    Export disorders for NOTCH4 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 NOTCH4 gene, integrated from 10 sources (see all 221):
    (articles sorted by number of sources associating them with NOTCH4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Gene organization of human NOTCH4 and (CTG)n polymorphism in this human counterpart gene of mouse proto-oncogene Int3. (PubMed id 9168133)1, 2, 9 Sugaya K.... Mita K. (Gene 1997)
    2. A review and re-evaluation of an association between the NOTCH4 locus and schizophrenia. (PubMed id 16894623)1, 4, 9 Wang Z....Shen Y. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2006)
    3. Association evidence of schizophrenia with distal genomic region of NOTCH4 in Taiwanese families. (PubMed id 17054719)1, 4, 9 Liu C.M....Hwu H.G. (Genes Brain Behav. 2007)
    4. No evidence for association between NOTCH4 and schizophrenia in a large family-based and case-control association analysis. (PubMed id 16969274)1, 4, 9 Ivo R....Cichon S. (Psychiatr. Genet. 2006)
    5. Family-based association study of the NOTCH4 gene in schizophrenia using Japanese and Chinese samples. (PubMed id 12873802)1, 4, 9 Takahashi S....Tsuang M.T. (Biol. Psychiatry 2003)
    6. NOTCH4 gene polymorphism and susceptibility to schizophrenia and schizoaffective disorder. (PubMed id 11239712)1, 4, 9 Ujike H....Kuroda S. (Neurosci. Lett. 2001)
    7. A NOTCH4 association with multiple sclerosis is secondary to HLA-DR*1501. (PubMed id 14651518)1, 4, 9 Duvefelt K....Hillert J. (Tissue Antigens 2004)
    8. NOTCH4 gene haplotype is associated with schizophrenia in African Americans. (PubMed id 14732589)1, 4, 9 Luo X....Gelernter J. (Biol. Psychiatry 2004)
    9. NOTCH4 and the frontal lobe in schizophrenia. (PubMed id 12627456)1, 4, 9 Wassink T.H....Andreasen N.C. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2003)
    10. Two NOTCH4 polymorphisms and their relation to schizophrenia susceptibility and different personality traits. (PubMed id 12605097)1, 4, 9 Carmine A....Olson L. (Psychiatr. Genet. 2003)

    (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: 4855 HGNC: 7884 AceView: NOTCH4 Ensembl:ENSG00000204301 euGenes: HUgn4855
    ECgene: NOTCH4 Kegg: 4855 H-InvDB: NOTCH4

    (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 NOTCH4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for NOTCH4 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for NOTCH4 gene:
    Search GeneIP for patents involving NOTCH4

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



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