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    NOTCH4 notch receptor 4 [ Homo sapiens (human) ]

    Gene ID: 4855, updated on 17-Jun-2024

    Summary

    Official Symbol
    NOTCH4provided by HGNC
    Official Full Name
    notch receptor 4provided by HGNC
    Primary source
    HGNC:HGNC:7884
    See related
    Ensembl:ENSG00000204301 MIM:164951; AllianceGenome:HGNC:7884
    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
    INT3
    Summary
    This gene encodes a member of the NOTCH family of proteins. Members of this Type I 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 signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor may play a role in vascular, renal and hepatic development. Mutations in this gene may be associated with schizophrenia. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]
    Expression
    Broad expression in fat (RPKM 20.5), lung (RPKM 16.6) and 21 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See NOTCH4 in Genome Data Viewer
    Location:
    6p21.32
    Exon count:
    31
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (32194843..32224067, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (32048032..32077265, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (32162620..32191844, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:32150105-32150623 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:32150624-32151141 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:32156057-32156613 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:32157766-32158334 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:32158721-32158899 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:32163365-32164145 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:32164146-32164927 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:32164928-32165708 Neighboring gene advanced glycosylation end-product specific receptor Neighboring gene PBX homeobox 2 Neighboring gene G protein signaling modulator 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:32222789-32223446 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:32223447-32224103 Neighboring gene TSBP1 and BTNL2 antisense RNA 1 Neighboring gene MPRA-validated peak5754 silencer Neighboring gene testis expressed basic protein 1 Neighboring gene heterogeneous nuclear ribonucleoprotein A1 pseudogene 2 Neighboring gene RNA, U6 small nuclear 603, pseudogene

    Genomic regions, transcripts, and products

    Expression

    • 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 Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    EBI GWAS Catalog

    Description
    A comprehensive family-based replication study of schizophrenia genes.
    EBI GWAS Catalog
    A genome-wide association study identifies 2 susceptibility Loci for Crohn's disease in a Japanese population.
    EBI GWAS Catalog
    A genome-wide integrative genomic study localizes genetic factors influencing antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA-1).
    EBI GWAS Catalog
    Common genetic variation and the control of HIV-1 in humans.
    EBI GWAS Catalog
    Common variants conferring risk of schizophrenia.
    EBI GWAS Catalog
    Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production.
    EBI GWAS Catalog
    Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia.
    EBI GWAS Catalog
    Genome-wide association scan in north Indians reveals three novel HLA-independent risk loci for ulcerative colitis.
    EBI GWAS Catalog
    Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.
    EBI GWAS Catalog
    Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis.
    EBI GWAS Catalog
    Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population.
    EBI GWAS Catalog
    Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.
    EBI GWAS Catalog
    Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis.
    EBI GWAS Catalog
    Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens.
    EBI GWAS Catalog
    Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
    EBI GWAS Catalog
    Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ16302, MGC74442

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables Notch binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables calcium ion binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables cis-regulatory region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables signaling receptor activity TAS
    Traceable Author Statement
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in branching involved in blood vessel morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cell differentiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in cell fate determination TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in epithelial to mesenchymal transition IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in hemopoiesis TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in mammary gland development IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in morphogenesis of a branching structure ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of cell adhesion molecule production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of cell differentiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of cell-cell adhesion mediated by cadherin IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of endothelial cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of DNA-templated transcription TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of smooth muscle cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of transcription of Notch receptor target TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in vasculature development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in wound healing IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    located_in Golgi membrane TAS
    Traceable Author Statement
    more info
     
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
     
    located_in extracellular region TAS
    Traceable Author Statement
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    located_in nucleus TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 

    General protein information

    Preferred Names
    neurogenic locus notch homolog protein 4
    Names
    Notch homolog 4
    notch 4

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_028190.1 RefSeqGene

      Range
      5001..34225
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_004557.4NP_004548.3  neurogenic locus notch homolog protein 4 preproprotein

      See identical proteins and their annotated locations for NP_004548.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the protein.
      Source sequence(s)
      AL705928, BQ023880, D63395, U95299
      Consensus CDS
      CCDS34420.1
      UniProtKB/Swiss-Prot
      B0V183, B0V1X5, O00306, Q5SSY7, Q99458, Q99466, Q99940, Q9H3S8, Q9UII9, Q9UIJ0
      UniProtKB/TrEMBL
      A0A1U9X938, A0A1U9X983, A0A1U9X986, B2RTR4
      Related
      ENSP00000364163.3, ENST00000375023.3
      Conserved Domains (8) summary
      smart00004
      Location:12071245
      NL; Domain found in Notch and Lin-12
      cd00054
      Location:432473
      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:16611787
      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 ...
      sd00045
      Location:16341664
      ANK; ANK repeat [structural motif]
      pfam00066
      Location:12491285
      Notch; LNR domain
      pfam07684
      Location:13801420
      NODP; NOTCH protein
      cl02419
      Location:11651203
      Notch; LNR domain
      cl26072
      Location:17531851
      Ank_5; Ankyrin repeats (many copies)

    RNA

    1. NR_134949.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes an alternate internal exon and lacks an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK290785, AL662884, BC033869, BC144540, U95299
    2. NR_134950.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate internal exon and uses an alternate splice site at an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK290785, BC033869, BC144540, BC144541, U95299

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      32194843..32224067 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_167244.2 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      3527442..3537008 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_2

    Genomic

    1. NT_113891.3 Reference GRCh38.p14 ALT_REF_LOCI_2

      Range
      3633192..3662414 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_4

    Genomic

    1. NT_167246.2 Reference GRCh38.p14 ALT_REF_LOCI_4

      Range
      3499821..3529069 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_5

    Genomic

    1. NT_167247.2 Reference GRCh38.p14 ALT_REF_LOCI_5

      Range
      3536859..3566106 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_6

    Genomic

    1. NT_167248.2 Reference GRCh38.p14 ALT_REF_LOCI_6

      Range
      3418042..3447269 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_7

    Genomic

    1. NT_167249.2 Reference GRCh38.p14 ALT_REF_LOCI_7

      Range
      3511048..3540275 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      32048032..32077265 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)