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NOTCH4 notch receptor 4 [ Homo sapiens (human) ]

Gene ID: 4855, updated on 29-Mar-2020

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
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

Genomic context

See NOTCH4 in Genome Data Viewer
Location:
6p21.32
Exon count:
31
Annotation release Status Assembly Chr Location
109.20200228 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (32194843..32224067, complement)
105 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 advanced glycosylation end-product specific receptor Neighboring gene PBX homeobox 2 Neighboring gene G protein signaling modulator 3 Neighboring gene TSBP1 and BTNL2 antisense RNA 1 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

NHGRI GWAS Catalog

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ16302, MGC74442

Gene Ontology Provided by GOA

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

General protein information

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

NCBI Reference Sequences (RefSeq)

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
    Q99466
    UniProtKB/TrEMBL
    A0A1U9X983
    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: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

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

Reference GRCh38.p13 ALT_REF_LOCI_1

Genomic

  1. NT_167244.2 Reference GRCh38.p13 ALT_REF_LOCI_1

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

Reference GRCh38.p13 ALT_REF_LOCI_2

Genomic

  1. NT_113891.3 Reference GRCh38.p13 ALT_REF_LOCI_2

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

Reference GRCh38.p13 ALT_REF_LOCI_4

Genomic

  1. NT_167246.2 Reference GRCh38.p13 ALT_REF_LOCI_4

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

Reference GRCh38.p13 ALT_REF_LOCI_5

Genomic

  1. NT_167247.2 Reference GRCh38.p13 ALT_REF_LOCI_5

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

Reference GRCh38.p13 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p13 ALT_REF_LOCI_6

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

Reference GRCh38.p13 ALT_REF_LOCI_7

Genomic

  1. NT_167249.2 Reference GRCh38.p13 ALT_REF_LOCI_7

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