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NOTCH3 notch receptor 3 [ Homo sapiens (human) ]

Gene ID: 4854, updated on 8-Apr-2024

Summary

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Official Symbol
NOTCH3provided by HGNC
Official Full Name
notch receptor 3provided by HGNC
Primary source
HGNC:HGNC:7883
See related
Ensembl:ENSG00000074181 MIM:600276; AllianceGenome:HGNC:7883
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
IMF2; LMNS; CASIL; CADASIL; CADASIL1
Summary
This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [provided by RefSeq, Jul 2008]
Expression
Broad expression in fat (RPKM 35.4), placenta (RPKM 33.8) and 22 other tissues See more
Orthologs
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Genomic context

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Location:
19p13.12
Exon count:
33
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (15159038..15200995, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (15283989..15325912, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (15269849..15311806, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 782, pseudogene Neighboring gene olfactory receptor family 10 subfamily B member 1 pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15281145-15281735 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10267 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15291996-15292515 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15292516-15293034 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15296283-15296783 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15305376-15305876 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15305877-15306377 Neighboring gene microRNA 6795 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:15310876-15311102 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15311689-15312190 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15312191-15312690 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15333321-15334017 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10268 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15343009-15343510 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10269 Neighboring gene epoxide hydrolase 3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15361355-15362226 Neighboring gene bromodomain containing 4 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:15373316-15373494 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:15374509-15375008 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15376180-15376680 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:15385287-15385786 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14182 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14183 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15409795-15410322 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15410749-15411456 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10270 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10271 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10273 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10272 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10274 Neighboring gene uncharacterized LOC124904643 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:15443616-15444232 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10276 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14184 Neighboring gene A-kinase anchoring protein 8

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. [Mechanism of Notch3 signaling pathway regulating the differentiation of aortic dissection vascular stem cells into smooth muscle cells]. Han Y, et al. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2023 May. PMID 37308231
  2. Structural changes in NOTCH3 induced by CADASIL mutations: Role of cysteine and non-cysteine alterations. Lee SJ, et al. J Biol Chem, 2023 Jun. PMID 37209821, Free PMC Article
  3. Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment. Huang K, et al. BMC Cancer, 2023 Jan 16. PMID 36647017, Free PMC Article
  4. Phenotypic variability in 446 CADASIL patients: Impact of NOTCH3 gene mutation location in addition to the effects of age, sex and vascular risk factors. Dupé C, et al. J Cereb Blood Flow Metab, 2023 Jan. PMID 36254369, Free PMC Article
  5. Clinical features and spectrum of NOTCH3 variants in Finnish patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Mönkäre S, et al. Acta Neurol Scand, 2022 Nov. PMID 36086804, Free PMC Article

See all (480) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.
    Title: Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.
  2. NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway.
    Title: NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway.
  3. LncRNA WWTR1-AS1 upregulates Notch3 through miR-136 to increase cancer cell stemness in cervical squamous cell carcinoma.
    Title: LncRNA WWTR1-AS1 upregulates Notch3 through miR-136 to increase cancer cell stemness in cervical squamous cell carcinoma.
  4. Progress to Clarify How NOTCH3 Mutations Lead to CADASIL, a Hereditary Cerebral Small Vessel Disease.
    Title: Progress to Clarify How NOTCH3 Mutations Lead to CADASIL, a Hereditary Cerebral Small Vessel Disease.
  5. DLL4/Notch3/WNT5B axis mediates bidirectional prometastatic crosstalk between melanoma and lymphatic endothelial cells.
    Title: DLL4/Notch3/WNT5B axis mediates bidirectional prometastatic crosstalk between melanoma and lymphatic endothelial cells.
  6. Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.
    Title: Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.
  7. Association of NOTCH3 Variant Position With Stroke Onset and Other Clinical Features Among Patients With CADASIL.
    Title: Association of NOTCH3 Variant Position With Stroke Onset and Other Clinical Features Among Patients With CADASIL.
  8. The m6A reader IGF2BP3 preserves NOTCH3 mRNA stability to sustain Notch3 signaling and promote tumor metastasis in nasopharyngeal carcinoma.
    Title: The m6A reader IGF2BP3 preserves NOTCH3 mRNA stability to sustain Notch3 signaling and promote tumor metastasis in nasopharyngeal carcinoma.
  9. The cysteine-altering p.R544C variant in the NOTCH3 gene is a probable candidate for blood pressure and relevant traits in the Taiwan Biobank.
    Title: The cysteine-altering p.R544C variant in the NOTCH3 gene is a probable candidate for blood pressure and relevant traits in the Taiwan Biobank.
  10. HIV-1 subtype B Tat enhances NOTCH3 signaling in astrocytes to mediate oxidative stress, inflammatory response, and neuronal apoptosis.
    Title: HIV-1 subtype B Tat enhances NOTCH3 signaling in astrocytes to mediate oxidative stress, inflammatory response, and neuronal apoptosis.
Submit: New GeneRIF Correction See all GeneRIFs (427)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cadherin binding HDA PubMed 
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables enzyme binding IEA
Inferred from Electronic Annotation
more info
  
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables signaling receptor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in Notch signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in artery morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in axon guidance IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in forebrain development IEA
Inferred from Electronic Annotation
more info
  
involved_in glomerular capillary formation IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of neuron differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
  
involved_in neuroblast differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in neuron fate commitment IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of miRNA transcription IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of smooth muscle cell proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in Golgi membrane TAS
Traceable Author Statement
more info
  
is_active_in cell surface IBA
Inferred from Biological aspect of Ancestor
more info
  
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 IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
part_of receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of receptor complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
neurogenic locus notch homolog protein 3
Names
Notch homolog 3
notch 3

NCBI Reference Sequences (RefSeq)

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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_009819.1 RefSeqGene

    Range
    4987..46944
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000435.3 → NP_000426.2  neurogenic locus notch homolog protein 3 precursor

    See identical proteins and their annotated locations for NP_000426.2

    Status: REVIEWED

    Source sequence(s)
    AC004257, AC004663, U97669
    Consensus CDS
    CCDS12326.1
    UniProtKB/Swiss-Prot
    Q9UEB3, Q9UM47, Q9UPL3, Q9Y6L8
    Related
    ENSP00000263388.1, ENST00000263388.7
    Conserved Domains (11) summary
    smart00179
    Location:657 → 686
    EGF_CA; Calcium-binding EGF-like domain
    COG0666
    Location:1777 → 1893
    ANKYR; Ankyrin repeat [Signal transduction mechanisms]
    cd00054
    Location:158 → 195
    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:1866 → 1992
    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 ...
    pfam00066
    Location:1425 → 1459
    Notch; LNR domain
    pfam06816
    Location:1508 → 1557
    NOD; NOTCH protein
    pfam07684
    Location:1578 → 1637
    NODP; NOTCH protein
    pfam11936
    Location:2212 → 2273
    DUF3454; Domain of unknown function (DUF3454)
    pfam12796
    Location:1910 → 2002
    Ank_2; Ankyrin repeats (3 copies)
    pfam13857
    Location:1858 → 1913
    Ank_5; Ankyrin repeats (many copies)
    sd00045
    Location:1905 → 1936
    ANK; ANK repeat [structural motif]

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_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    15159038..15200995 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005259924.5 → XP_005259981.1  neurogenic locus notch homolog protein 3 isoform X1

    Conserved Domains (10) summary
    COG0666
    Location:1725 → 1841
    ANKYR; Ankyrin repeat [Signal transduction mechanisms]
    cd00054
    Location:158 → 195
    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:1814 → 1940
    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 ...
    pfam00066
    Location:1373 → 1407
    Notch; LNR domain
    pfam06816
    Location:1456 → 1505
    NOD; NOTCH protein
    pfam07684
    Location:1526 → 1585
    NODP; NOTCH protein
    pfam11936
    Location:2160 → 2221
    DUF3454; Domain of unknown function (DUF3454)
    pfam12796
    Location:1858 → 1950
    Ank_2; Ankyrin repeats (3 copies)
    pfam13857
    Location:1806 → 1861
    Ank_5; Ankyrin repeats (many copies)
    sd00045
    Location:1853 → 1884
    ANK; ANK repeat [structural motif]

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    15283989..15325912 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054321104.1 → XP_054177079.1  neurogenic locus notch homolog protein 3 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UM47.2 GenPept UniProtKB/Swiss-Prot:Q9UM47

Gene LinkOut

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