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NOTCH2 Gene

protein-coding   GIFtS: 70
GCID: GC01M120454

Notch 2

(Previous names: Notch (Drosophila) homolog 2, Notch homolog 2 (Drosophila))
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(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 21 2 3     Notch (Drosophila) Homolog 21
hN22 3     Notch Homolog 2 (Drosophila)1
AGS22 5     Neurogenic Locus Notch Homolog Protein 22
HJCYS2 5     Notch Homolog 22

External Ids:    HGNC: 78821   Entrez Gene: 48532   Ensembl: ENSG000001342507   OMIM: 6002755   UniProtKB: Q047213   

Export aliases for NOTCH2 gene to outside databases

Previous GC identifers: GC01M120900 GC01M119292 GC01M119601 GC01M119800 GC01M120100 GC01M120256 GC01M118312


(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 NOTCH2 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. Two transcript variants encoding different isoforms have been
found for this gene. (provided by RefSeq, Jan 2011)

GeneCards Summary for NOTCH2 Gene:
NOTCH2 (notch 2) is a protein-coding gene. Diseases associated with NOTCH2 include notch2-related alagille syndrome, and alagille syndrome 2. GO annotations related to this gene include receptor activity and calcium ion binding. An important paralog of this gene is DLK2.

UniProtKB/Swiss-Prot: NOTC2_HUMAN, Q04721
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). Involved in bone
remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively
regulates RANKL-induced osteoclast differentiation

Gene Wiki entry for NOTCH2 (Notch-2) 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_000001.11  NT_032977.10  NC_018912.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the NOTCH2 gene promoter:
         Elk-1   AML1a   IRF-1   Tal-1beta   C/EBPalpha   MEF-2A   Nkx6-1   aMEF-2   ITF-2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): NOTCH2 promoter sequence
   Search Chromatin IP Primers for NOTCH2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NOTCH2


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

Entrez Gene cytogenetic band: 1p13-p11   Ensembl cytogenetic band:  1p11.2   HGNC cytogenetic band: 1p13-p11

NOTCH2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOTCH2 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01M120454:  view genomic region     (about GC identifiers)

Start:
120,454,176 bp from pter      End:
120,612,317 bp from pter
Size:
158,142 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, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: NOTC2_HUMAN, Q04721 (See protein sequence)
Recommended Name: Neurogenic locus notch homolog protein 2 precursor  
Size: 2471 amino acids; 265405 Da
Subunit: Heterodimer of a C-terminal fragment N(TM) and an 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 NOTCH2. Interacts with RELA/p65 (By similarity). Interacts with HIF1AN
1 PDB 3D structure from and Proteopedia for NOTCH2:
2OO4 (3D)    
Secondary accessions: Q5T3X7 Q99734 Q9H240

Explore the universe of human proteins at neXtProt for NOTCH2: NX_Q04721

Explore proteomics data for NOTCH2 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
  • Hydroxylated by HIF1AN1
  • Ubiquitination2 at Lys1705
  • Glycosylation2 at Asn46, Asn155, Asn733, Asn1102, Asn1465
  • Modification sites at PhosphoSitePlus

  • See NOTCH2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_001186930.1  NP_077719.2  

    ENSEMBL proteins: 
     ENSP00000256646   ENSP00000473427  
    Reactome Protein details: Q04721

    NOTCH2 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for NOTCH2 (Notch-2)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    Browse OriGene Protein Over-expression Lysates
    OriGene Custom MassSpec
    OriGene Custom Protein Services for NOTCH2
    GenScript Custom Purified and Recombinant Proteins Services for NOTCH2
    Novus Biologicals NOTCH2 Proteins
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for NOTCH2

    NOTCH2 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of NOTCH2
    R&D Systems Antibodies for NOTCH2 (Notch-2)
    Cell Signaling Technology (CST) Antibodies for NOTCH2  (Notch 2)
    OriGene Antibodies for NOTCH2
    OriGene Custom Antibody Services for NOTCH2
    Novus Biologicals NOTCH2 Antibodies
    Abcam antibodies for NOTCH2
    Cloud-Clone Corp. Antibodies for NOTCH2
    ThermoFisher Antibodies for NOTCH2
    LSBio Antibodies in human, mouse, rat for NOTCH2

    NOTCH2 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for NOTCH2
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for NOTCH2
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for NOTCH2
    Cloud-Clone Corp. CLIAs for NOTCH2


    (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 Q04721

    ProtoNet protein and cluster: Q04721

    5 Blocks protein domains:
    IPB000152 Aspartic acid and asparagine hydroxylation site
    IPB000800 LIN-12/notch repeat (LNR) signature
    IPB001438 Type II EGF-like signature
    IPB001881 EGF-like calcium-binding
    IPB002110 Ankyrin repeat signature


    UniProtKB/Swiss-Prot: NOTC2_HUMAN, Q04721
    Similarity: Belongs to the NOTCH family
    Similarity: Contains 6 ANK repeats
    Similarity: Contains 35 EGF-like domains
    Similarity: Contains 3 LNR (Lin/Notch) repeats


    NOTCH2 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: NOTC2_HUMAN, Q04721
    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). Involved in bone
    remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively
    regulates RANKL-induced osteoclast differentiation

         Genatlas biochemistry entry for NOTCH2:
    Drosophila Notch homolog 2,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 neoplasia
    associated translocations

         Summary: 
    During embryonic development, NOTCH2 as signaling molecule is secreted from the following cells:
                
    Ovary: XX Germ Cells (Ovigerous Cord)

    It affects the following cells:
    Ovary: Pre-Granulosa Cells (Primordial Follicle)

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004872receptor activity NAS9244302
    GO:0005509calcium ion binding IEA--
    GO:0005515protein binding IPI10079256
    GO:0038049ligand-activated RNA polymerase II transcription factor binding transcription factor activity TAS9244302
         
    NOTCH2 for ontologies           About GeneDecksing


    Phenotypes:
         Selected MGI mutant phenotypes (inferred from 16 alleles(MGI details for Notch2) (see all 24):
     cardiovascular system  cellular  craniofacial  digestive/alimentary  embryogenesis 
     endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism  immune system 
     integument  liver/biliary system  mortality/aging  muscle  nervous system 

    NOTCH2 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for NOTCH2: Notch2tm3.1Grid Notch2tm2Grid Notch2tm1Grid Notch2tm2Hhi

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NOTCH2
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for NOTCH2

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NOTCH2
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NOTCH2

    miRNA
    Products:
        
    miRTarBase miRNAs that target NOTCH2:
    hsa-mir-16-5p (MIRT001437), hsa-mir-107 (MIRT007156), hsa-mir-183-5p (MIRT025026), hsa-mir-326 (MIRT004425), hsa-mir-92a-3p (MIRT049544), hsa-mir-1 (MIRT001353), hsa-mir-181c-5p (MIRT003209), hsa-mir-744-5p (MIRT037594), hsa-mir-130b-5p (MIRT038296), hsa-mir-106a-5p (MIRT048329), hsa-mir-27b-3p (MIRT046195), hsa-mir-196a-5p (MIRT048264), hsa-let-7c-5p (MIRT051850), hsa-mir-155-5p (MIRT020879), hsa-mir-34a-5p (MIRT005029), hsa-mir-25-3p (MIRT050287), hsa-mir-17-5p (MIRT050936), hsa-mir-181a-5p (MIRT025208)

    Block miRNA regulation of human, mouse, rat NOTCH2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate NOTCH2 (see all 84):
    hsa-miR-548j hsa-miR-579 hsa-miR-146a hsa-miR-15a hsa-miR-218-1* hsa-miR-485-3p hsa-miR-374a hsa-miR-548a-5p
    SwitchGear 3'UTR luciferase reporter plasmidNOTCH2 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for NOTCH2
    Predesigned siRNA for gene silencing in human, mouse, rat NOTCH2

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for NOTCH2

    Clone
    Products:
         
    OriGene clones in human, mouse for NOTCH2 (see all 5)
    OriGene ORF clones in mouse, rat for NOTCH2
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): NOTCH2 (NM_024408)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOTCH2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOTCH2

    Cell Line
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    GenScript Custom overexpressing Cell Line Services for NOTCH2
    Browse ESI BIO Cell Lines and PureStem Progenitors for NOTCH2 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH2


    (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
    NOTC2_HUMAN, Q04721: Cell membrane; Single-pass type I membrane protein
    NOTC2_HUMAN, Q04721: Notch 2 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is
    translocated to the nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    plasma membrane5
    endoplasmic reticulum4
    extracellular4
    golgi apparatus4
    cytoskeleton1

    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 IDA1303260
    GO:0005654nucleoplasm TAS--
    GO:0005789endoplasmic reticulum membrane TAS--

    NOTCH2 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 NOTCH2 About   (see all 18)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Notch signaling pathway (KEGG)
    Notch signaling pathway0.84
    Delta-Notch Signaling Pathway0.33
    Notch Signaling Pathway0.84
    Notch Signaling0.30
    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
    3Signaling by NOTCH2
    NOTCH2 Activation and Transmission of Signal to the Nucleus0.67
    NOTCH2 intracellular domain regulates transcription0.00
    Signaling by NOTCH20.67
    4Gene Expression
    Generic Transcription Pathway0.40
    Gene Expression0.40
    5Signaling by NOTCH1 PEST Domain Mutants in Cancer
    Signaling by NOTCH0.64

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for NOTCH2
        Notch Signaling Pathways

    4 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for NOTCH2
        Notch Signaling
    Molecular Mechanisms of Cancer
    Presenilin-Mediated Signaling
    Epithelial Adherens Junctions

    3 Cell Signaling Technology (CST) Pathways for NOTCH2
        Wnt / Hedgehog / Notch
    Angiogenesis
    Neuroscience

    4 BioSystems Pathways for NOTCH2
        Notch Signaling Pathway
    Neural Crest Differentiation
    Delta-Notch Signaling Pathway
    Notch signaling pathway

    Selected Reactome Pathways for NOTCH2 (see all 6)
        NOTCH2 Activation and Transmission of Signal to the Nucleus
    Pre-NOTCH Processing in Golgi
    Pre-NOTCH Transcription and Translation
    Notch-HLH transcription pathway
    NOTCH2 intracellular domain regulates transcription


    4 Kegg Pathways  (Kegg details for NOTCH2):
        Dorso-ventral axis formation
    Notch signaling pathway
    Thyroid hormone signaling pathway
    MicroRNAs in cancer


    NOTCH2 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NOTCH2 (see all 11): 
              Neurogenesis in human mouse rat
              Stem Cell Transcription Factors in human mouse rat
              Adherens Junctions in human mouse rat
              Stem Cell Signaling in human mouse rat
              Cell Junction PathwayFinder in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for NOTCH2

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

    Selected Interacting proteins for NOTCH2 (Q047212, 3 ENSP000002566464) via UniProtKB, MINT, STRING, and/or I2D (see all 216)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HIST1H3AP684313I2D: score=1 
    HIST1H3BP684313I2D: score=1 
    HIST1H3CP684313I2D: score=1 
    HIST1H3DP684313I2D: score=1 
    HIST1H3EP684313I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 34):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001701in utero embryonic development IEA--
    GO:0001709cell fate determination TAS9244302
    GO:0001890placenta development ----
    GO:0002011morphogenesis of an epithelial sheet IEA--
    GO:0002437inflammatory response to antigenic stimulus IEA--

    NOTCH2 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 NOTCH2 (NOTC2)



    (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,
    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 NOTCH2 gene (2 alternative transcripts): 
    NM_001200001.1  NM_024408.3  

    Unigene Cluster for NOTCH2:

    Notch 2
    Hs.487360  [show with all ESTs]
    Unigene Representative Sequence: NM_024408
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000256646(uc021osy.1 uc001eik.3 uc001eil.3 uc001eim.4)
    ENST00000493703 ENST00000478864 ENST00000479412 ENST00000602566 ENST00000489731


    miRNA
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    Block miRNA regulation of human, mouse, rat NOTCH2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate NOTCH2 (see all 84):
    hsa-miR-548j hsa-miR-579 hsa-miR-146a hsa-miR-15a hsa-miR-218-1* hsa-miR-485-3p hsa-miR-374a hsa-miR-548a-5p
    SwitchGear 3'UTR luciferase reporter plasmidNOTCH2 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat NOTCH2
    Clone
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    OriGene ORF clones in mouse, rat for NOTCH2
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): NOTCH2 (NM_024408)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOTCH2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOTCH2
    Primer
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    OriGene qSTAR qPCR primer pairs in human, mouse for NOTCH2
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat NOTCH2
      QuantiTect SYBR Green Assays in human, mouse, rat NOTCH2
      QuantiFast Probe-based Assays in human, mouse, rat NOTCH2

    Additional mRNA sequence: 

    AF308601.1 AF315356.1 AK027869.1 AK307843.1 AL049386.1 AL133036.1 BC071562.1 GQ231534.1 
    U77493.1 

    22 DOTS entries:

    DT.97837624  DT.453995  DT.97859603  DT.91725275  DT.121448121  DT.95330154  DT.121448068  DT.91639065 
    DT.95118850  DT.95249493  DT.121435635  DT.121448048  DT.100645100  DT.100844596  DT.440461  DT.92468886 
    DT.95113504  DT.121435354  DT.121435400  DT.121435413  DT.121435859  DT.121448099 

    Selected AceView cDNA sequences (see all 379):

    BQ229392 AW771162 BM564476 AL133036 Z39386 AL042063 F10657 CB044930 
    BQ881578 W57968 BF797482 BX117064 NM_024408 AW771066 AL603414 BF887852 
    AW054433 AW151687 AW262638 AW075292 N22407 BM799358 BQ678668 AA827551 

    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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    NOTCH2 expression in normal human tissues (normalized intensities)      NOTCH2 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GACCTCTGTG
    NOTCH2 Expression
    About this image


    NOTCH2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 15) fully expand
     
     Epithelial Cells
             Fetal Inner Root Sheath Cells Inner Root Sheath
     
     Heart (Cardiovascular System)    fully expand to see all 6 entries
             Cardiomyocytes Outflow Tract
     
     Neural Tube (Nervous System)    fully expand to see all 5 entries
             Mesencephalic Ventricular Zone
     
     Tooth (Integumentary System)    fully expand to see all 5 entries
             Inner Enamel Epithelial Cells Dental Enamel
     
     Epidermis (Integumentary System)    fully expand to see all 4 entries
             Intermediate Keratinocytes Embryonic Epidermis
    NOTCH2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NOTCH2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.487360

    UniProtKB/Swiss-Prot: NOTC2_HUMAN, Q04721
    Tissue specificity: Expressed in the brain, heart, kidney, lung, skeletal muscle and liver. Ubiquitously expressed
    in the embryo

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NOTCH2 (see all 11): 
              Neurogenesis in human mouse rat
              Stem Cell Transcription Factors in human mouse rat
              Adherens Junctions in human mouse rat
              Stem Cell Signaling in human mouse rat
              Cell Junction PathwayFinder 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 NOTCH2 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Notch21 , 5 Notch gene homolog 2 (Drosophila)5
    notch 21
    87.14(n)1
    92.59(a)1
      3 (42.42 cM)5
    181291  NM_010928.21  NP_035058.21 
     980135385 
    chicken
    (Gallus gallus)
    Aves NOTCH21 notch 2 74.1(n)
    77.2(a)
      374031  NM_001252033.1  NP_001238962.1 
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia LOC1004863441 neurogenic locus notch homolog protein 2-like 68.89(n)
    70.41(a)
      100486344  XM_002939080.2  XP_002939126.2 
    zebrafish
    (Danio rerio)
    Actinopterygii notch21 notch homolog 2 61.03(n)
    58.99(a)
      58065  NM_001115094.1  NP_001108566.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta N3 determination of glial fate
    transmembrane receptor
    49(a)
    (best of 3)
        --


    ENSEMBL Gene Tree for NOTCH2 (if available)
    TreeFam Gene Tree for NOTCH2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NOTCH2 gene
    DLK22  SNED12  NOTCH42  NOTCH12  DLL32  NOTCH32  JAG22  CRB22  
    DLL42  DLK12  JAG12  DNER2  CRB12  DLL12  
    15 SIMAP similar genes for NOTCH2 using alignment to 4 protein entries:     NOTC2_HUMAN (see all proteins):
    NOTCH2NL    NOTCH1    NOTCH3    F9    CNTNAP2    CUBN
    EFEMP1    PROS1    NOTCH4    UMOD    SNED1    EMR2
    FBLN2    MUC3B    SLIT2

    NOTCH2 for paralogs           About GeneDecksing


    1 Pseudogenes.org Pseudogene for NOTCH2
    PGOHUM00000244876


    (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 NOTCH2 (see all 2734)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0293614
    Alagille syndrome 2 (ALGS2)4--see VAR_0293612 C Y mis40--------
    rs1110336321,2
    Cpathogenic1120581855(-) TGAGTA/GTCTGA 4 Y C mis10--------
    rs38390091,2
    C--120456393(+) GTTTC-/CT    
       A
    /TAC
    TACGT
    2 -- cds10--------
    rs600904681,2
    C--120470149(+) AGGGAT/-TTTTT 1 -- int11Minor allele frequency- -:0.50CSA 2
    rs726972371,2
    C,F--120473425(+) TAATTA/TAAAAA 1 -- int13Minor allele frequency- T:0.21NA WA 240
    rs715866971,2
    C--120501337(+) GAAGATG/-TGTGT 2 -- int11Minor allele frequency- -:0.50NA 2
    rs105607461,2
    C--120501338(+) GAAGA-/TGTG  
            
    TGTGT
    2 -- int10--------
    rs608382891,2
    C--120501338(+) TGTGT-/GT/TC 
            
    CTGTG
    2 -- int11NA 2
    rs1406170361,2
    C--120505803(+) TAGGT-/AGGAA 
     GGAAGGA
    AGGAA
    2 -- cds10--------
    rs670622391,2
    C--120515977(+) TCTGC-/TATGA 
            
    TATAA
    2 -- int10--------

    HapMap Linkage Disequilibrium report for NOTCH2 (120454176 - 120612317 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for NOTCH2 (see all 17):    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv436325CNV Deletion17901297
    nsv820378CNV Duplication20802225
    nsv2610CNV Loss18451855
    nsv524681CNV Gain19592680
    nsv428201CNV Gain18775914
    nsv824331CNV Gain20364138
    nsv872181CNV Gain21882294
    nsv10683CNV Gain18304495
    nsv831226CNV Gain+Loss17160897
    esv22009CNV Gain+Loss19812545

    Human Gene Mutation Database (HGMD): NOTCH2
    Locus Specific Mutation Databases (LSDB): NOTCH2

    1 Site Specific Mutation Identification with PCR Assay for NOTCH2:
    Cosmic IdAA Change
    36210p.R2400*
    3 Site Specific Cancer Mutation PCR Panels containing NOTCH2:
    Tyrosine Kinases & Cell Signaling Pathways Panel 384HT
    Cancer Comprehensive Panel 384HT
    Oncogene Panel 384HT
    SeqTarget long-range PCR primers for resequencing NOTCH2
    DNA2.0 Custom Variant and Variant Library Synthesis for NOTCH2

    (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.)
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    OMIM gene information: 600275   
    OMIM disorders: 610205  102500  
    UniProtKB/Swiss-Prot: NOTC2_HUMAN, Q04721
  • Alagille syndrome 2 (ALGS2) [MIM:610205]: A form of Alagille syndrome, an autosomal dominant multisystem
    disorder. It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac,
    skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical
    involvement of the renal and vascular systems. Note=The disease is caused by mutations affecting the gene
    represented in this entry
  • Hajdu-Cheney syndrome (HJCYS) [MIM:102500]: A rare skeletal disorder characterized by the association of
    facial anomalies, acro-osteolysis, general osteoporosis, insufficient ossification of the skull, and periodontal
    disease (premature loss of permanent teeth). Other features include cleft palate, congenital heart defects,
    polycystic kidneys, orthopedic problems and anomalies of the genitalia, intestines and eyes. Note=The disease is
    caused by mutations affecting the gene represented in this entry. NOTCH2 mutations associated with Hajdu-Cheney
    syndrome cluster to the last coding exon of the gene. This suggests that the mutant mRNA products may escape
    nonsense-mediated decay and the resulting truncated NOTCH2 proteins act in a gain-of-function manner

  • Selected diseases for NOTCH2 (see all 68):    About MalaCards
    notch2-related alagille syndrome    alagille syndrome 2    serpentine fibula polycystic kidney syndrome    hajdu-cheney syndrome
    alagille syndrome    nodular regenerative hyperplasia    splenic marginal zone lymphoma    lung squamous cell carcinoma
    cutaneous malignant melanoma    congenital heart defect    arteriosclerosis    hepatitis
    pharyngitis    cholestasis    oligodendroglioma    hemangioma
    sjogren's syndrome    hepatoblastoma    periodontal disease    purpura

    3 diseases from the University of Copenhagen DISEASES database for NOTCH2:
    Alagille syndrome     Hajdu-Cheney syndrome     Cancer

    NOTCH2 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    6 Novoseek inferred disease relationships for NOTCH2 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    alagille syndrome 78.1 8 11861489 (3), 19914235 (1), 19551907 (1)
    lymphocytic leukemia chronic b-cell 33.9 1 15621797 (1)
    cholestasis 28.5 1 15307138 (1)
    tumors 13.6 18 17675579 (2), 15520184 (2), 18087195 (2), 19904829 (1) (see all 8)
    cancer 0.41 2 17675579 (1), 19445024 (1)
    breast cancer 0 12 15492845 (5), 18087195 (3), 17675579 (2)

    GeneTests: NOTCH2
    GeneReviews: NOTCH2
    Genetic Association Database (GAD): NOTCH2
    Human Genome Epidemiology (HuGE) Navigator: NOTCH2 (44 documents)

    Export disorders for NOTCH2 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 NOTCH2 gene, integrated from 10 sources (see all 237):
    (articles sorted by number of sources associating them with NOTCH2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Analysis of coding-polymorphisms in NOTCH-related genes reveals NUMBL poly-glutamine repeat to be associated with schizophrenia in Brazilian and Danish subjects. (PubMed id 16899352)1, 4, 9 Passos Gregorio S....Dias-Neto E. (Schizophr. Res. 2006)
    2. Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis. (PubMed id 21378989)1, 2 Isidor B....Le Caignec C. (Nat. Genet. 2011)
    3. Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. (PubMed id 21378985)1, 2 Simpson M.A.... Trembath R.C. (Nat. Genet. 2011)
    4. Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population. (PubMed id 20571754)1, 4 Fontaine-Bisson B....Franks P.W. (Diabetologia 2010)
    5. Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function. (PubMed id 19833888)1, 4 Simonis-Bik A.M....'t Hart L.M. (Diabetes 2010)
    6. Obesity and diabetes genetic variants associated with gestational weight gain. (PubMed id 20816152)1, 4 Stuebe A.M....Siega-Riz A.M. (Am. J. Obstet. Gynecol. 2010)
    7. Examination of all type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI. (PubMed id 19933996)1, 4 Zhao J....Grant S.F. (Diabetes 2010)
    8. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (Mol. Med. 2010)
    9. Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study. (PubMed id 20075150)1, 4 Talmud P.J....Humphries S.E. (BMJ 2010)
    10. Polygenic risk variants for type 2 diabetes susceptibility modify age at diagnosis in monogenic HNF1A diabetes. (PubMed id 19794065)1, 4 Lango Allen H....Weedon M.N. (Diabetes 2010)

    (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: 4853 HGNC: 7882 AceView: NOTCH2 Ensembl:ENSG00000134250 euGenes: HUgn4853
    ECgene: NOTCH2 Kegg: 4853 H-InvDB: NOTCH2

    (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 NOTCH2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for NOTCH2 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=NOTCH2[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 NOTCH2 gene:
    Search GeneIP for patents involving NOTCH2

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



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