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NOTCH4 notch receptor 4 [ Homo sapiens (human) ]

Gene ID: 4855, updated on 10-Oct-2019

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
109.20190905 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 BioSystems

  • Breast cancer, organism-specific biosystem (from KEGG)
    Breast cancer, organism-specific biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Breast cancer, conserved biosystem (from KEGG)
    Breast cancer, conserved biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Canonical and Non-canonical Notch signaling, organism-specific biosystem (from WikiPathways)
    Canonical and Non-canonical Notch signaling, organism-specific biosystemThis pathway is based on figure 1 of "Alteration of Notch signaling in skeletal development and disease" (see bibliography). In the NOTCH signaling pathway, mammals have 11 ligands (JAG, DLL, DLK, et...
  • Defective LFNG causes SCDO3, organism-specific biosystem (from REACTOME)
    Defective LFNG causes SCDO3, organism-specific biosystemThe Fringe family (CAZy family GT31) of glycosyltransferases in mammals includes LFNG (lunatic fringe; MIM:602576), MFNG (manic fringe; MIM:602577) and RFNG (radical fringe; MIM:602578). Fringe enzym...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Diseases associated with O-glycosylation of proteins, organism-specific biosystem (from REACTOME)
    Diseases associated with O-glycosylation of proteins, organism-specific biosystemGlycosylation is the most abundant modification of proteins, variations of which occur in all living cells. Glycosylation can be further categorized into N-linked (where the oligosaccharide is conjug...
  • Diseases of glycosylation, organism-specific biosystem (from REACTOME)
    Diseases of glycosylation, organism-specific biosystemDiseases of glycosylation, usually referred to as congenital disorders of glycosylation (CDG), are rare inherited disorders ascribing defects of nucleotide-sugar biosynthesis and transport, glycosylt...
  • Dorso-ventral axis formation, organism-specific biosystem (from KEGG)
    Dorso-ventral axis formation, organism-specific biosystem
    Dorso-ventral axis formation
  • Dorso-ventral axis formation, conserved biosystem (from KEGG)
    Dorso-ventral axis formation, conserved biosystem
    Dorso-ventral axis formation
  • Endocrine resistance, organism-specific biosystem (from KEGG)
    Endocrine resistance, organism-specific biosystemEndocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. The most commonly used endocrine therapy agents are selective estrogen receptor modulators (SER...
  • Endocrine resistance, conserved biosystem (from KEGG)
    Endocrine resistance, conserved biosystemEndocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. The most commonly used endocrine therapy agents are selective estrogen receptor modulators (SER...
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • 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...
  • MicroRNAs in cancer, organism-specific biosystem (from KEGG)
    MicroRNAs in cancer, organism-specific biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...
  • MicroRNAs in cancer, conserved biosystem (from KEGG)
    MicroRNAs in cancer, conserved biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...
  • 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)
    Notch Signaling Pathway, organism-specific biosystemThe Notch pathway is an evolutionally conserved signaling pathway which plays an important role in diverse developmental and physiological processes. These include cell-fate determination, tissue pat...
  • Notch signaling, organism-specific biosystem (from KEGG)
    Notch signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
  • Notch signaling, conserved biosystem (from KEGG)
    Notch signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
  • Notch signaling pathway, organism-specific biosystem (from KEGG)
    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 Pathway Interaction Database)
    Notch signaling pathway, organism-specific biosystem
    Notch signaling pathway
  • Notch signaling pathway, conserved biosystem (from KEGG)
    Notch signaling pathway, conserved 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-HLH transcription pathway, organism-specific biosystem (from REACTOME)
    Notch-HLH transcription pathway, organism-specific biosystemTHE NOTCH-HLH TRANSCRIPTION PATHWAY: Notch signaling was first identified in Drosophila, where it has been studied in detail at the genetic, molecular, biochemical and cellular levels (reviewed in ...
  • Pre-NOTCH Expression and Processing, organism-specific biosystem (from REACTOME)
    Pre-NOTCH Expression and Processing, organism-specific biosystemIn humans and other mammals the NOTCH gene family has four members, NOTCH1, NOTCH2, NOTCH3 and NOTCH4, encoded on four different chromosomes. Their transcription is developmentally regulated and tiss...
  • 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)
    Pre-NOTCH Processing in the Endoplasmic Reticulum, organism-specific biosystemIn the endoplasmic reticulum, glycosyl transferases modify NOTCH precursors by glycosylating conserved serine and threonine residues in EGF repeats of NOTCH. O-fucosyl transferase POFUT1 fucosylates...
  • Pre-NOTCH Transcription and Translation, organism-specific biosystem (from REACTOME)
    Pre-NOTCH Transcription and Translation, organism-specific biosystemIn humans, the NOTCH protein family has four members: NOTCH1, NOTCH2, NOTCH3 and NOTCH4. NOTCH1 protein was identified first, as the product of a chromosome 9 gene translocated in T-cell acute lympho...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by NOTCH, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH, organism-specific biosystemThe Notch Signaling Pathway (NSP) is a highly conserved pathway for cell-cell communication. NSP is involved in the regulation of cellular differentiation, proliferation, and specification. For exam...
  • Signaling by NOTCH4, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH4, organism-specific biosystemSimilar to NOTCH1, NOTCH4 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH4, first by ADAM10 at the S2 cleav...
  • Thyroid hormone signaling pathway, organism-specific biosystem (from KEGG)
    Thyroid hormone signaling pathway, organism-specific biosystemThe thyroid hormones (THs) are important regulators of growth, development and metabolism. The action of TH is mainly mediated by T3 (3,5,3'-triiodo-L-thyronine). Thyroid hormones, L-thyroxine (T4) a...

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 
protein heterodimerization activity TAS
Traceable Author Statement
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
 
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 differentiation NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of endothelial cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
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 Annotation Release 109.20190905

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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