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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

NOTCH1 Gene

protein-coding   GIFtS: 70
GCID: GC09M139388

Notch 1

(Previous names: Notch (Drosophila) homolog 1 (translocation-associated),...)
(Previous symbol: TAN1)
Microbiology & Infectious Diseases Congress
  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)
About This Section

Aliases
Notch 11 2 3     Notch Homolog 1, Translocation-Associated (Drosophila)1
TAN11 2 3 5     Neurogenic Locus Notch Homolog Protein 12
Translocation-Associated Notch Protein TAN-12 3     Notch Homolog 1, Translocation-Associated2
hN12 3     EC 2.1.2.118
Notch (Drosophila) Homolog 1 (Translocation-Associated)1     EC 3.4.21.688

External Ids:    HGNC: 78811   Entrez Gene: 48512   Ensembl: ENSG000001484007   OMIM: 1901985   UniProtKB: P465313   

Export aliases for NOTCH1 gene to outside databases

Previous GC identifers: GC09M130458 GC09M131078 GC09M132829 GC09M134746 GC09M136664 GC09M138508 GC09M108848


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NOTCH1 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
multiple roles during development. (provided by RefSeq, Jul 2008)

GeneCards Summary for NOTCH1 Gene: 
NOTCH1 (notch 1) is a protein-coding gene. Diseases associated with NOTCH1 include left ventricular outflow tract obstruction, and nerve compression syndrome, and among its related super-pathways are Constitutive Signaling by NOTCH1 PEST Domain Mutants and Notch signaling pathway. GO annotations related to this gene include sequence-specific DNA binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is EYS.

UniProtKB/Swiss-Prot: NOTC1_HUMAN, P46531
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 be important for normal
lymphocyte function. In altered form, may contribute to transformation or progression in some T-cell neoplasms.
Involved in the maturation of both CD4+ and CD8+ cells in the thymus. May be important for follicular
differentiation and possibly cell fate selection within the follicle. During cerebellar development, may function
as a receptor for neuronal DNER and may be involved in the differentiation of Bergmann glia. Represses neuronal
and myogenic differentiation. May enhance HIF1A function by sequestering HIF1AN away from HIF1A (By similarity).
Involved in angiogenesis; negatively regulates endothelial cell proliferation, migration and angiogenic sprouting

Gene Wiki entry for NOTCH1 (Notch-1) 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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000009.11  NC_018920.2  NT_024000.16  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the NOTCH1 gene promoter:
         c-Fos   AP-1   ATF-2   c-Jun   NF-kappaB   NF-kappaB1   
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search SABiosciences Chromatin IP Primers for NOTCH1

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NOTCH1


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

Entrez Gene cytogenetic band: 9q34.3   Ensembl cytogenetic band:  9q34.3   HGNC cytogenetic band: 9q34.3

NOTCH1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOTCH1 gene location

GeneLoc information about chromosome 9         GeneLoc Exon Structure

GeneLoc location for GC09M139388:  view genomic region     (about GC identifiers)

Start:
139,388,896 bp from pter      End:
139,440,314 bp from pter
Size:
51,419 bases      Orientation:
minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: NOTC1_HUMAN, P46531 (See protein sequence)
Recommended Name: Neurogenic locus notch homolog protein 1 precursor  
Size: 2555 amino acids; 272505 Da
Subunit: Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by
disulfide bonds. Interacts with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2 and MAML3
which act as transcriptional coactivators for NOTCH1. Notch 1 intracellular domain interacts with SNW1; the
interaction involves multimerized NOTCH1 NICD and is implicated in a formation of an intermediate preactivation
complex which associates with DNA-bound CBF-1/RBPJ. The activated membrane-bound form interacts with AAK1 which
promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and SGK1. Interacts with HIF1AN. HIF1AN
negatively regulates the function of notch intracellular domain (NICD), accelerating myogenic differentiation (By
similarity). Interacts (via NICD) with SNAI1 (via zinc fingers); the interaction induces SNAI1 degradation via
MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via NICD) with MDM2A
Subcellular location: Cell membrane; Single-pass type I membrane protein (By similarity)
Subcellular location: Notch 1 intracellular domain: Nucleus (By similarity). Note=Following proteolytical
processing NICD is translocated to the nucleus (By similarity)
6/12 PDB 3D structures from and Proteopedia for NOTCH1 (see all 12):
1PB5 (3D)        1TOZ (3D)        1YYH (3D)        2F8X (3D)        2F8Y (3D)        2HE0 (3D)    
Secondary accessions: Q59ED8 Q5SXM3

Explore the universe of human proteins at neXtProt for NOTCH1: NX_P46531

Explore proteomics data for NOTCH1 at MOPED 

Post-translational modifications:

  • UniProtKB: 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). Following endocytosis, 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)
  • UniProtKB: Phosphorylated (By similarity)
  • UniProtKB: O-glycosylated on the EGF-like domains. Contains both O-linked fucose and O-linked glucose
  • UniProtKB: Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH. Monoubiquitination at Lys-1759 is
    required for activation by gamma-secretase cleavage, it promotes interaction with AAK1, which stabilizes it.
    Deubiquitination by EIF3F is necessary for nuclear import of activated Notch
  • UniProtKB: Hydroxylated at Asn-1955 by HIF1AN. Hydroxylated at Asn-2022 by HIF1AN (By similarity). Hydroxylation reduces
    affinity for HI1AN and may thus indirectly modulate negative regulation of NICD (By similarity)
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P46531

  • 2 DME Specific Peptides for NOTCH1 (P46531)
     CFNGGTC  INTLGSF 

    NOTCH1 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    NOTCH1 Protein Expression
    REFSEQ proteins: NP_060087.3  
    ENSEMBL proteins: 
     ENSP00000277541  
    Reactome Protein details: P46531
    Human Recombinant Protein Products for NOTCH1: 
    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for NOTCH1 (Notch-1)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for NOTCH1
    OriGene Custom MassSpec 
    OriGene Custom Protein Services for NOTCH1
    GenScript Custom Purified and Recombinant Proteins Services for NOTCH1
    Novus Biologicals NOTCH1 Proteins
    Novus Biologicals NOTCH1 Lysate
    Sino Biological Recombinant Protein for NOTCH1
    Sino Biological Cell Lysate for NOTCH1 
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp. 

    Gene Ontology (GO): 5/12 cellular component terms (GO ID links to tree view) (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane TAS--
    GO:0002193MAML1-RBP-Jkappa- ICN1 complex IDA16510869
    GO:0005576extracellular region TAS--
    GO:0005634nucleus TAS10713164
    GO:0005654nucleoplasm TAS--

    NOTCH1 for ontologies           About GeneDecksing



    NOTCH1 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of NOTCH1
    R&D Systems Antibodies for NOTCH1 (Notch-1)
    Cell Signaling Technology (CST) Antibodies for NOTCH1  (Notch 1)
    OriGene Antibodies for NOTCH1
    OriGene Custom Antibody Services for NOTCH1
    GenScript Superior Antibodies for NOTCH1
    Novus Biologicals NOTCH1 Antibodies
    Abcam antibodies for NOTCH1
    Browse Antibodies at Cloud-Clone Corp. 
    ThermoFisher Antibody for NOTCH1
    LSBio Antibodies in human, mouse, rat for NOTCH1 

    Assay Products for NOTCH1: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for NOTCH1
    R&D Systems ELISAs for NOTCH1 (Notch-1)         (see all)
    GenScript Custom Assay Services for NOTCH1
    Cell Signaling Technology (CST) Sandwich ELISA Kits for NOTCH1 (Notch 1)
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp. 
    Browse CLIAs at Cloud-Clone Corp.


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

    5/13 InterPro protein domains (see all 13):
     IPR022362 Notch_1
     IPR024600 DUF3454_notch
     IPR008297 Notch
     IPR000742 EG-like_dom
     IPR000152 EGF-type_Asp/Asn_hydroxyl_site

    Graphical View of Domain Structure for InterPro Entry P46531

    ProtoNet protein and cluster: P46531

    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: NOTC1_HUMAN, P46531
    Similarity: Belongs to the NOTCH family
    Similarity: Contains 5 ANK repeats
    Similarity: Contains 36 EGF-like domains
    Similarity: Contains 3 LNR (Lin/Notch) repeats


    NOTCH1 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,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NOTC1_HUMAN, P46531
    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 be important for normal
    lymphocyte function. In altered form, may contribute to transformation or progression in some T-cell neoplasms.
    Involved in the maturation of both CD4+ and CD8+ cells in the thymus. May be important for follicular
    differentiation and possibly cell fate selection within the follicle. During cerebellar development, may function
    as a receptor for neuronal DNER and may be involved in the differentiation of Bergmann glia. Represses neuronal
    and myogenic differentiation. May enhance HIF1A function by sequestering HIF1AN away from HIF1A (By similarity).
    Involved in angiogenesis; negatively regulates endothelial cell proliferation, migration and angiogenic sprouting

         Genatlas biochemistry entry for NOTCH1:
    Drosophila Notch homolog 1,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,involved in acute lymphocytic leukemia
    with translocation t(7;9)(q34;q34.3),expressed in CD34+ hematopoietic cells (see TAN1) and in the developing
    cochlear duct,inducing delay of hematopoietic differentiation and alteration of cell cycle kinetics

         Enzyme Numbers (IUBMB): EC 2.1.2.112 EC 3.4.21.682

         Summary:
    During embryonic development, NOTCH1 as signaling molecule is secreted from the following cells: Intermediate Keratinocytes in Embryonic Epidermis, Intervertebral Disc Nucleus Pulposus Cells in Cervical Intervertebral Disc (see all 8).

    It affects the following cells: Arterial Endothelial Cells in Paired Dorsal Aorta, Cardiomyocyte Progenitor Cells in Myocardium (see all 20).

         Gene Ontology (GO): 5/11 molecular function terms (GO ID links to tree view) (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001047core promoter binding ISS--
    GO:0001190RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription ISS--
    GO:0003682chromatin binding ----
    GO:0003700sequence-specific DNA binding transcription factor activity IEA--
    GO:0004857enzyme inhibitor activity ISS--
         
    NOTCH1 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for NOTCH1:
     Synthetic lethal with cisplati 

         15/23 MGI mutant phenotypes (inferred from 14 alleles(MGI details for Notch1) (see all 23):
     cardiovascular system  cellular  craniofacial  digestive/alimentary  embryogenesis 
     endocrine/exocrine gland  growth/size  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism 
     immune system  integument  liver/biliary system  mortality/aging  muscle 

    NOTCH1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for NOTCH1: Notch1tm1Pst Notch1tm1Con Notch1tm1Grid Notch1tm2.1Pst Notch1tm2Agt

       inGenious Targeting Laboratory - Custom generated mouse model solutions for NOTCH1 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for NOTCH1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NOTCH1 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NOTCH1 

    miRNA
    Products:
        
    miRTarBase miRNAs that target NOTCH1:
    hsa-mir-326 (MIRT004424), hsa-mir-30a (MIRT002876), hsa-mir-34a (MIRT002875), hsa-mir-129-5p (MIRT005412), hsa-mir-144 (MIRT005869)

    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NOTCH1
    8/48 QIAGEN miScript miRNA Assays for microRNAs that regulate NOTCH1 (see all 48):
    hsa-miR-3607-3p hsa-miR-429 hsa-miR-548k hsa-miR-25 hsa-miR-139-5p hsa-miR-30d hsa-miR-449a hsa-miR-30a
    SwitchGear 3'UTR luciferase reporter plasmidNOTCH1 3' UTR sequence
    Inhib. RNA
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for NOTCH1
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat NOTCH1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for NOTCH1


    Clone
    Products:
         
    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for NOTCH1 (see all 5)
    OriGene ORF clones in mouse, rat for NOTCH1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: NOTCH1 (NM_017617)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOTCH1
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    Cell Line
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    GenScript Custom overexpressing Cell Line Services for NOTCH1
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    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH1


    (Pathways according to EMD Millipore, 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 SABiosciences, 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 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for NOTCH1 About   (see all 30)                                                                                              See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Signaling by NOTCH1 t(7 9)(NOTCH1:M1580 K2555) Translocation Mutant
    Constitutive Signaling by NOTCH1 PEST Domain Mutants0.89
    Signaling by NOTCH1 in Cancer0.79
    Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants0.89
    Signaling by NOTCH10.79
    Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer0.79
    Signaling by NOTCH1 t(7 9)(NOTCH1:M1580 K2555) Translocation Mutant0.79
    Signaling by NOTCH1 PEST Domain Mutants in Cancer0.79
    Signaling by NOTCH0.74
    2Notch signaling pathway
    Notch signaling pathway0.84
    Delta-Notch Signaling Pathway0.33
    Notch Signaling Pathway0.84
    3Development NOTCH1-mediated pathway for NF-KB activity modulation
    Development NOTCH1-mediated pathway for NF-KB activity modulation0.88
    Development Notch Signaling Pathway0.54
    4Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor
    Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor0.61
    Constitutive Signaling by NOTCH1 t(7 9)(NOTCH1:M1580 K2555) Translocation Mutant0.50
    Constitutive Signaling by NOTCH1 HD Domain Mutants0.61
    5NOTCH2 intracellular domain regulates transcription
    Activated NOTCH1 Transmits Signal to the Nucleus0.59
    Notch-HLH transcription pathway0.32
    NICD traffics to nucleus0.32

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 EMD Millipore Pathway for NOTCH1
        Development Notch Signaling Pathway

    1 R&D Systems Pathway for NOTCH1
        Notch Signaling Pathways

    5 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for NOTCH1
        Notch Signaling
    Molecular Mechanisms of Cancer
    Presenilin-Mediated Signaling
    Epithelial Adherens Junctions
    Pancreatic Adenocarcinoma

    3 Cell Signaling Technology (CST) Pathways for NOTCH1
        Wnt / Hedgehog / Notch
    Angiogenesis
    Neuroscience

    2 GeneGo (Thomson Reuters) Pathways for NOTCH1
        Development NOTCH1-mediated pathway for NF-KB activity modulation
    Development Notch Signaling Pathway

    5/9 BioSystems Pathways for NOTCH1 (see all 9)
        Heart Development
    Notch Signaling Pathway
    Neural Crest Differentiation
    Gastric cancer network 1
    Cardiac Progenitor Differentiation


    5/27        Reactome Pathways for NOTCH1 (see all 27)
        Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
    Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling
    NOTCH1 Intracellular Domain Regulates Transcription
    Pre-NOTCH Expression and Processing
    A third proteolytic cleavage releases NICD


    4         Kegg Pathways  (Kegg details for NOTCH1):
        Dorso-ventral axis formation
    Notch signaling pathway
    Prion diseases
    MicroRNAs in cancer


    NOTCH1 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for NOTCH1

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

    5/150 Interacting proteins for NOTCH1 (P465311, 2, 3 ENSP000002775414) via UniProtKB, MINT, STRING, and/or I2D (see all 150)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    RBPJQ063301, 2, 3, ENSP000003452064EBI-636374,EBI-632552 MINT-8177109 I2D: score=4 STRING: ENSP00000345206
    SNW1Q135731, 3, ENSP000002615314EBI-636374,EBI-632715 I2D: score=4 STRING: ENSP00000261531
    XRCC6P129562, 3, ENSP000003522574MINT-64468 I2D: score=4 STRING: ENSP00000352257
    GFI1BQ5VTD92, 3, ENSP000003447824MINT-2861240 I2D: score=3 STRING: ENSP00000344782
    MAML1Q925852, 3, ENSP000002925994MINT-8177109 I2D: score=3 STRING: ENSP00000292599
    About this table

    Gene Ontology (GO): 5/135 biological process terms (GO ID links to tree view) (see all 135):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter ISS--
    GO:0001701in utero embryonic development IEA--
    GO:0001708cell fate specification IEA--
    GO:0001837epithelial to mesenchymal transition ISS--
    GO:0001889liver development IEA--

    NOTCH1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    NOTCH1 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for NOTCH1 (NOTC1)

    1 HMDB Compound for NOTCH1    About this table
    CompoundSynonyms CAS #PubMed Ids
    CalciumCa (see all 2)7440-70-2--

    10/24 Novoseek inferred chemical compound relationships for NOTCH1 gene (see all 24)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    matrigel 37.9 1 16510599 (1)
    vegf 30 30 18182722 (8), 18056465 (3), 19923082 (3), 16510599 (3) (see all 10)
    asparagine 17.1 1 19245366 (1)
    rapamycin 16.2 3 16651424 (1), 20194733 (1)
    glycogen 9.93 4 10541869 (1), 17234779 (1), 16941152 (1), 19030935 (1)
    threonine 5.51 4 17901244 (1), 19635999 (1), 16282337 (1)
    nitric oxide 5.13 2 15887117 (1), 20147635 (1)
    dexamethasone 4.92 1 16914556 (1)
    oxygen 4.4 5 17179479 (1), 17804701 (1), 19143764 (1), 18924608 (1)
    lipid 2.38 9 18593473 (1), 18991739 (1), 19405120 (1), 19948478 (1) (see all 6)

    Search CenterWatch for drugs/clinical trials and news about NOTCH1 / NOTC1

    (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,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for NOTCH1 gene: 
    NM_017617.3  

    Unigene Cluster for NOTCH1:

    Notch 1
    Hs.495473  [show with all ESTs]
    Unigene Representative Sequence: NM_017617
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000277541(uc004cia.1 uc004chz.3) ENST00000494783 ENST00000491649

    Congresses - knowledge worth sharing:  
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    8/48 QIAGEN miScript miRNA Assays for microRNAs that regulate NOTCH1 (see all 48):
    hsa-miR-3607-3p hsa-miR-429 hsa-miR-548k hsa-miR-25 hsa-miR-139-5p hsa-miR-30d hsa-miR-449a hsa-miR-30a
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    Additional mRNA sequence: 

    AB209873.1 AF308602.1 AK000012.1 BC013208.1 BC039147.1 BC046127.1 BC049843.1 BC063597.1 
    CR457221.1 M73980.1 

    3 DOTS entries:

    DT.116684  DT.101967676  DT.92324288 

    24/207 AceView cDNA sequences (see all 207):

    F04063 BX439805 CB136450 BM549261 AA460357 AI362966 BC039147 F04067 
    CB306580 AW503914 BC049843 BQ636034 AI493630 BF060687 BM975575 BM709403 
    BU633949 NM_017617 AI598175 Z44046 BX281173 AA278939 BU733339 AI364702 

    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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    NOTCH1 expression in normal human tissues (normalized intensities)      NOTCH1 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AGGAACTGTA
    NOTCH1 Expression
    About this image


    NOTCH1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/23 selected tissues (see all 23) fully expand
     
     Brain (Nervous System)    fully expand to see all 14 entries
             Thalamus
             Septum   
     
     Hair
             Fetal Inner Root Sheath Cells Inner Root Sheath
     
     Endothelium (Cardiovascular System)    fully expand to see all 7 entries
             Venous Endothelial Cells Cardinal Veins
     
     Neural Tube (Nervous System)    fully expand to see all 6 entries
             Telencephalon
             spinal cord/lateral wall/ventricular layer   
     
     Cartilage (Muscoskeletal System)    fully expand to see all 6 entries
             Intervertebral Disc Nucleus Pulposus Cells Sacral Intervertebral Disc
             Chondrocyte progenitor cells

    See NOTCH1 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for NOTCH1

    SOURCE GeneReport for Unigene cluster: Hs.495473

    UniProtKB/Swiss-Prot: NOTC1_HUMAN, P46531
    Tissue specificity: In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult
    tissues where it is found mainly in lymphoid tissues

        SABiosciences Expression via Pathway-Focused PCR Arrays including NOTCH1 (see all 16): 
              Neurogenesis in human mouse rat
              Adherens Junctions in human mouse rat
              Stem Cell Signaling in human mouse rat
              Lymphoma in human mouse rat
              Notch Signaling Targets 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)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for NOTCH1 gene from 6/14 species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Notch11 , 5 Notch gene homolog 1 (Drosophila)5
    notch 11
    86.07(n)1
    91.66(a)1
      2 (18.91 cM)5
    181281  NM_008714.31  NP_032740.31 
     264579035 
    chicken
    (Gallus gallus)
    Aves NOTCH11 notch 1 80.05(n)
    81.48(a)
      395655  XM_415420.3  XP_415420.3 
    lizard
    (Anolis carolinensis)
    Reptilia NOTCH16
    Uncharacterized protein
    72(a)
    1 ↔ 1
    AAWZ02036232(2523-29619)
    African clawed frog
    (Xenopus laevis)
    Amphibia notch1-A-prov2 Notch protein 76.65(n)    M33874.1 
    zebrafish
    (Danio rerio)
    Actinopterygii notch1a2 notch homolog 1a 76.68(n)   30718  NM_131441.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta N1 Notch 55.23(n)
    49(a)
      31293  NM_057511.3  NP_476859.2 


    ENSEMBL Gene Tree for NOTCH1 (if available)
    TreeFam Gene Tree for NOTCH1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for NOTCH1 gene
    EYS2  NOTCH42  NOTCH2NL2  NOTCH32  CRB22  NOTCH22  ENSG000002551682  CRB12  
    8 SIMAP similar genes for NOTCH1 using alignment to 8 protein entries:     NOTC1_HUMAN (see all proteins):
    NOTCH2    F9    NOTCH3    CNTNAP2    NOTCH2NL    DLK1
    DKFZp434N181    DLK2

    NOTCH1 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/2267 SNPs in NOTCH1 are shown (see all 2267)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 9 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs413097641,2
    Cpathogenic1139439260(-) CGCAGC/TGACAA 2 R * stg12Minor allele frequency- T:0.00NA 4
    rs29905831,2
    C,A--108901673(+) AGCCCC/TTCCCA 1 -- spa110Minor allele frequency- T:0.32NA CSA WA EA 371
    rs1152296561,2
    F--108901734(+) ACCCTG/CTGCCA 1 -- int11Minor allele frequency- C:0.03WA 118
    rs1923388451,2
    --108901882(+) CCGGCG/TCCCCT 1 -- int10--------
    rs1830986251,2
    --108901944(+) GGGACC/GTAGGA 1 -- int10--------
    rs1879213011,2
    --108901956(+) TGTGGA/GGGCCT 1 -- int10--------
    rs1131209501,2
    C,F--108901983(+) AAACCC/GCAGAG 1 -- int12Minor allele frequency- G:0.03CSA WA 119
    rs1433356551,2
    --108902119(+) CGCCCC/TTGTAG 1 -- int10--------
    rs765656701,2
    F--108902166(+) GAATCT/CGGCCT 1 -- int11Minor allele frequency- C:0.02WA 118
    rs1392003061,2
    --108902226(+) GAGGCA/GCCTGG 1 -- int10--------

    HapMap Linkage Disequilibrium report for NOTCH1 (139388896 - 139440314 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 10/49 variations for NOTCH1 (see all 49):    About this table     
    Variant IDTypeSubtypePubMed ID
    esv2739363CNV Deletion23290073
    esv4392CNV Deletion18987735
    esv2739365CNV Deletion23290073
    esv2677489CNV Deletion23128226
    esv2739364CNV Deletion23290073
    esv2062576CNV Deletion18987734
    dgv1339e201CNV Deletion23290073
    esv2739366CNV Deletion23290073
    nsv6768CNV Insertion18451855
    nsv509334CNV Insertion20534489


    Human Gene Mutation Database (HGMD): NOTCH1
    5/11 SABiosciences Cancer Mutation PCR Assays for NOTCH1 (see all 11):
    Cosmic IdAA Change
    12776p.Q2460*
    12772p.L1575P
    13047p.V1579del
    13048p.L1679P
    13046p.L1586P
    5 SABiosciences Cancer Mutation PCR Arrays containing NOTCH1:
    Tyrosine Kinases & Cell Signaling Pathways Panel 384HT
    Oncogene and Tumor Suppressor Panel 384HT
    Lymphoid Neoplasms
    Cancer Comprehensive Panel 384HT
    Oncogene Panel 384HT
    SeqTarget long-range PCR primers for resequencing NOTCH1
    DNA2.0 Custom Variant and Variant Library Synthesis for NOTCH1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 190198   
    OMIM disorders: 109730  
    UniProtKB/Swiss-Prot: NOTC1_HUMAN, P46531
  • Aortic valve disease 1 (AOVD1) [MIM:109730]: A common defect in the aortic valve in which two rather than
    three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency.
    In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in
    hypoplastic left heart syndrome. Note=The disease is caused by mutations affecting the gene represented in this
    entry

  • 20/136 diseases for NOTCH1 (see all 136):    About MalaCards
    left ventricular outflow tract obstruction    nerve compression syndrome    acute t cell leukemia    acute biphenotypic leukemia
    cadasil    plasmablastic lymphoma    superficial basal cell carcinoma    hajdu-cheney syndrome
    mn1    nodular regenerative hyperplasia    hypoplastic left heart syndrome    alagille syndrome
    spondylocostal dysostosis    osteochondritis dissecans    richter's syndrome    thoracic aortic aneurysm
    ankylosis    dysostosis    tongue cancer    estrogen-receptor negative breast cancer

    16 diseases from the University of Copenhagen DISEASES database for NOTCH1:
    Alagille syndrome     Alzheimer's disease     Leukemia     Cadasil
    Congenital heart defect     Spondylocostal dysostosis     Lymphoma     Heart disease
    Osteochondritis dissecans     Breast cancer     Hypertension     Nerve compression syndrome
    Osteoarthritis     Otosclerosis     Malignant glioma     Cerebrovascular accident

    NOTCH1 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:  
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    10/57 Novoseek inferred disease relationships for NOTCH1 gene (see all 57)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    t-all 90.7 271 15548998 (6), 19245433 (5), 16707600 (5), 18414037 (5) (see all 80)
    leukemogenesis 61.7 17 20194733 (3), 18497996 (2), 15058751 (1), 15694671 (1) (see all 9)
    leukemia t-cell 60.1 13 16954387 (3), 17483057 (2), 19349467 (1), 15231576 (1) (see all 6)
    leukaemia lymphocytic 57.2 15 17008890 (1), 8642337 (1), 11964309 (1), 19091404 (1) (see all 11)
    alagille syndrome 51.3 1 10075489 (1)
    tumors 50.9 183 17874453 (5), 19479935 (5), 11964309 (4), 17344417 (4) (see all 84)
    gastrointestinal carcinoid tumor 50.1 1 16160079 (1)
    leukemia 49.4 56 19794083 (6), 18677410 (5), 18991739 (4), 17008890 (3) (see all 22)
    cancer 41.8 49 17534448 (5), 18184405 (4), 19923082 (3), 19151708 (2) (see all 22)
    lymphoma lymphoblastic 36 1 18663146 (1)

    Genetic Association Database (GAD): NOTCH1
    Human Genome Epidemiology (HuGE) Navigator: NOTCH1 (19 documents)
    Tumor Gene Database (TGDB): NOTCH1

    Export disorders for NOTCH1 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)
    About This Section

    PubMed articles for NOTCH1 gene, integrated from 9 sources (see all 959):
    (articles sorted by number of sources associating them with NOTCH1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. (PubMed id 1831692)1, 2, 3 Ellisen L.W.... Sklar J. (1991)
    2. Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia. (PubMed id 19794083)1, 4, 9 Baldus C.D....Hofmann W.K. (2009)
    3. FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma. (PubMed id 19245433)1, 4, 9 Park M.J....Hayashi Y. (2009)
    4. The impact of NOTCH1, FBW7 and PTEN mutations on prognosis and downstream signaling in pediatric T-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. (PubMed id 19340001)1, 4, 9 Larson Gedman A....Matherly L.H. (2009)
    5. NOTCH1 mutations in T-cell acute lymphoblastic leukemia: prognostic significance and implication in multifactorial leukemogenesis. (PubMed id 16707600)1, 4, 9 Zhu Y.M....Chen S.J. (2006)
    6. NOTCH1/FBXW7 mutation identifies a large subgroup with favourable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a GRAALL study. (PubMed id 19109228)1, 4, 9 Asnafi V....Macintyre E. (2008)
    7. Genetic variation in healthy oldest-old. (PubMed id 19680556)1, 4, 9 Halaschek-Wiener J....Brooks-Wilson A.R. (2009)
    8. Mutations in NOTCH1 cause aortic valve disease. (PubMed id 16025100)1, 2, 9 Garg V.... Srivastava D. (2005)
    9. Serum- and glucocorticoid-inducible kinase 1 (SGK1) c ontrols Notch1 signaling by downregulation of protein stability through Fbw7 ub iquitin ligase. (PubMed id 21147854)1, 2 Mo J.S....Park H.S. (2011)
    10. Notch1 binds and induces degradation of Snail in hepa tocellular carcinoma. (PubMed id 22128911)1, 2 Lim S.O....Jung G. (2011)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     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)
    About This Section
    Entrez Gene: 4851 HGNC: 7881 AceView: NOTCH1 Ensembl:ENSG00000148400 euGenes: HUgn4851
    ECgene: NOTCH1 Kegg: 4851 H-InvDB: NOTCH1

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for NOTCH1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for NOTCH1 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for NOTCH1 gene:
    Search GeneIP for patents involving NOTCH1

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



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    About This Section

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