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    NOTCH2 notch 2 [ Homo sapiens (human) ]

    Gene ID: 4853, updated on 22-Apr-2017
    Official Symbol
    NOTCH2provided by HGNC
    Official Full Name
    notch 2provided by HGNC
    Primary source
    HGNC:HGNC:7882
    See related
    Ensembl:ENSG00000134250 MIM:600275; Vega:OTTHUMG00000012177
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    hN2; AGS2; HJCYS
    Summary
    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]
    Orthologs
    Location:
    1p12
    Exon count:
    38
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 1 NC_000001.11 (119911553..120073449, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (120454176..120639880, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene notch 2 pseudogene 1 Neighboring gene ADAM metallopeptidase domain 30 Neighboring gene uncharacterized LOC101929178 Neighboring gene uncharacterized LOC105378939 Neighboring gene uncharacterized LOC105378940 Neighboring gene RNA, U6 small nuclear 465, pseudogene

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Alagille syndrome 2
    MedGen: C1857761 OMIM: 610205 GeneReviews: Alagille Syndrome
    Compare labs
    Hajdu-Cheney syndrome
    MedGen: C0917715 OMIM: 102500 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated (2014-07-17)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated (2014-07-17)

    ClinGen Genome Curation Page

    NHGRI GWAS Catalog

    Description
    Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
    NHGRI GWA Catalog

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat interacts with the EGF-like repeats 1-6 (amino acids 26-256) of Human Notch2, suggesting Tat might modulate Notch2 function, thus affecting various AIDS-associated pathologies PubMed

    Go to the HIV-1, Human Interaction Database

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    • Diseases of glycosylation, organism-specific biosystem (from REACTOME)
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    • Dorso-ventral axis formation, organism-specific biosystem (from KEGG)
      Dorso-ventral axis formation, organism-specific biosystem
      Dorso-ventral axis formation
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    • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
      Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
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    • NOTCH2 Activation and Transmission of Signal to the Nucleus, organism-specific biosystem (from REACTOME)
      NOTCH2 Activation and Transmission of Signal to the Nucleus, organism-specific biosystemSimilar to NOTCH1, NOTCH2 is activated by Delta-like and Jagged ligands (DLL/JAG) expressed in trans on a neighboring cell (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004...
    • NOTCH2 intracellular domain regulates transcription, organism-specific biosystem (from REACTOME)
      NOTCH2 intracellular domain regulates transcription, organism-specific biosystemIn the nucleus, NICD2 forms a complex with RBPJ (CBF1, CSL) and MAML (mastermind). NICD2:RBPJ:MAML complex activates transcription from RBPJ-binding promoter elements (RBEs) (Wu et al. 2000). Besides...
    • Neural Crest Differentiation, organism-specific biosystem (from WikiPathways)
      Neural Crest Differentiation, organism-specific biosystemGene regulatory network model of cranial neural crest cell (CNCC) development, adaped from PMID: 19575671. Most interactions in the model are proposed to regulate transcription of core factors involv...
    • Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Notch Signaling Pathway, organism-specific biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
    • Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
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    • Notch signaling, organism-specific biosystem (from KEGG)
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      Notch signaling pathway, organism-specific biosystem
      Notch signaling pathway
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    • Pre-NOTCH Expression and Processing, organism-specific biosystem (from REACTOME)
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    • Pre-NOTCH Processing in Golgi, organism-specific biosystem (from REACTOME)
      Pre-NOTCH Processing in Golgi, organism-specific biosystemNOTCH undergoes final posttranslational processing in the Golgi apparatus (Lardelli et al. 1994, Blaumueller et al. 1997, Weinmaster et al. 1991, Weinmaster et al. 1992, Uyttendaele et al. 1996). Mov...
    • Pre-NOTCH Processing in the Endoplasmic Reticulum, organism-specific biosystem (from REACTOME)
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    • Pre-NOTCH Transcription and Translation, organism-specific biosystem (from REACTOME)
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    • Signal Transduction, organism-specific biosystem (from REACTOME)
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    • Signaling by NOTCH, organism-specific biosystem (from REACTOME)
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    • Signaling by NOTCH2, organism-specific biosystem (from REACTOME)
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    • Th1 and Th2 cell differentiation, organism-specific biosystem (from KEGG)
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    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    receptor activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    transcription factor activity, ligand-activated RNA polymerase II transcription factor binding TAS
    Traceable Author Statement
    more info
    PubMed 
    Process Evidence Code Pubs
    Notch signaling involved in heart development IC
    Inferred by Curator
    more info
    PubMed 
    Notch signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Notch signaling pathway TAS
    Traceable Author Statement
    more info
     
    animal organ morphogenesis IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    apoptotic process TAS
    Traceable Author Statement
    more info
    PubMed 
    atrial septum morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    bone remodeling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cell cycle arrest IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell fate determination TAS
    Traceable Author Statement
    more info
    PubMed 
    cell growth IDA
    Inferred from Direct Assay
    more info
    PubMed 
    hemopoiesis TAS
    Traceable Author Statement
    more info
    PubMed 
    intracellular receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    marginal zone B cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    multicellular organism development NAS
    Non-traceable Author Statement
    more info
    PubMed 
    negative regulation of apoptotic process TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nervous system development NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of Ras protein signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    pulmonary valve morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of developmental process IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of transcription, DNA-templated TAS
    Traceable Author Statement
    more info
    PubMed 
    stem cell population maintenance TAS
    Traceable Author Statement
    more info
    PubMed 
    transcription initiation from RNA polymerase II promoter TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    Golgi membrane TAS
    Traceable Author Statement
    more info
     
    cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
     
    extracellular region TAS
    Traceable Author Statement
    more info
     
    integral component of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane IDA
    Inferred from Direct Assay
    more info
     
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    receptor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    neurogenic locus notch homolog protein 2
    Names
    Notch homolog 2

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008163.1 RefSeqGene

      Range
      4960..163101
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001200001.1NP_001186930.1  neurogenic locus notch homolog protein 2 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AF315356, BC071562, DB290699
      UniProtKB/Swiss-Prot
      Q04721
      UniProtKB/TrEMBL
      Q6IQ50
      Conserved Domains (2) summary
      PHA02887
      Location:629681
      PHA02887; EGF-like protein; Provisional
      cd00054
      Location:182218
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    2. NM_024408.3NP_077719.2  neurogenic locus notch homolog protein 2 isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_077719.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AF315356, AL133036, BC071562, DB290699
      Consensus CDS
      CCDS908.1
      UniProtKB/Swiss-Prot
      Q04721
      UniProtKB/TrEMBL
      Q6IQ50, Q9UFD5
      Related
      ENSP00000256646.2, OTTHUMP00000014035, ENST00000256646.6, OTTHUMT00000033679
      Conserved Domains (9) summary
      cd00054
      Location:182218
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      cd00204
      Location:19382062
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam05387
      Location:22922421
      Chorion_3; Chorion family 3
      pfam00066
      Location:14231456
      Notch; LNR domain
      pfam06816
      Location:15401591
      NOD; NOTCH protein
      pfam07684
      Location:16201673
      NODP; NOTCH protein
      pfam11936
      Location:23812444
      DUF3454; Domain of unknown function (DUF3454)
      pfam12796
      Location:19482040
      Ank_2; Ankyrin repeats (3 copies)
      sd00045
      Location:19431974
      ANK; ANK repeat [structural motif]

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p7 Primary Assembly

      Range
      119911553..120073449 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017001372.1XP_016856861.1  neurogenic locus notch homolog protein 2 isoform X2

    2. XM_011541520.2XP_011539822.1  neurogenic locus notch homolog protein 2 isoform X3

      See identical proteins and their annotated locations for XP_011539822.1

      Conserved Domains (9) summary
      cd00054
      Location:143179
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      cd00204
      Location:18992023
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam05387
      Location:22532382
      Chorion_3; Chorion family 3
      pfam00066
      Location:13841417
      Notch; LNR domain
      pfam06816
      Location:15011552
      NOD; NOTCH protein
      pfam07684
      Location:15811634
      NODP; NOTCH protein
      pfam11936
      Location:23422405
      DUF3454; Domain of unknown function (DUF3454)
      pfam12796
      Location:19092001
      Ank_2; Ankyrin repeats (3 copies)
      sd00045
      Location:19041935
      ANK; ANK repeat [structural motif]
    3. XM_005270901.3XP_005270958.1  neurogenic locus notch homolog protein 2 isoform X3

      See identical proteins and their annotated locations for XP_005270958.1

      Conserved Domains (9) summary
      cd00054
      Location:143179
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      cd00204
      Location:18992023
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam05387
      Location:22532382
      Chorion_3; Chorion family 3
      pfam00066
      Location:13841417
      Notch; LNR domain
      pfam06816
      Location:15011552
      NOD; NOTCH protein
      pfam07684
      Location:15811634
      NODP; NOTCH protein
      pfam11936
      Location:23422405
      DUF3454; Domain of unknown function (DUF3454)
      pfam12796
      Location:19092001
      Ank_2; Ankyrin repeats (3 copies)
      sd00045
      Location:19041935
      ANK; ANK repeat [structural motif]
    4. XM_011541519.2XP_011539821.1  neurogenic locus notch homolog protein 2 isoform X1

      Conserved Domains (9) summary
      cd00054
      Location:178214
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      cd00204
      Location:19342058
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam05387
      Location:22882417
      Chorion_3; Chorion family 3
      pfam00066
      Location:14191452
      Notch; LNR domain
      pfam06816
      Location:15361587
      NOD; NOTCH protein
      pfam07684
      Location:16161669
      NODP; NOTCH protein
      pfam11936
      Location:23772440
      DUF3454; Domain of unknown function (DUF3454)
      pfam12796
      Location:19442036
      Ank_2; Ankyrin repeats (3 copies)
      sd00045
      Location:19391970
      ANK; ANK repeat [structural motif]
    5. XM_017001373.1XP_016856862.1  neurogenic locus notch homolog protein 2 isoform X3

      Conserved Domains (9) summary
      cd00054
      Location:143179
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      cd00204
      Location:18992023
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam05387
      Location:22532382
      Chorion_3; Chorion family 3
      pfam00066
      Location:13841417
      Notch; LNR domain
      pfam06816
      Location:15011552
      NOD; NOTCH protein
      pfam07684
      Location:15811634
      NODP; NOTCH protein
      pfam11936
      Location:23422405
      DUF3454; Domain of unknown function (DUF3454)
      pfam12796
      Location:19092001
      Ank_2; Ankyrin repeats (3 copies)
      sd00045
      Location:19041935
      ANK; ANK repeat [structural motif]

    Alternate CHM1_1.1

    Genomic

    1. NC_018912.2 Alternate CHM1_1.1

      Range
      120569670..120727793 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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