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Aliases for NOTCH3 Gene

Aliases for NOTCH3 Gene

  • Notch 3 2 3 4 5
  • Notch (Drosophila) Homolog 3 2
  • Notch Homolog 3 (Drosophila) 2
  • Notch Homolog 3 3
  • CADASIL1 3
  • CADASIL 3
  • CASIL 3
  • IMF2 3
  • LMNS 3

External Ids for NOTCH3 Gene

Previous HGNC Symbols for NOTCH3 Gene

  • CADASIL

Previous GeneCards Identifiers for NOTCH3 Gene

  • GC19M015649
  • GC19M015115
  • GC19M015270
  • GC19M014839

Summaries for NOTCH3 Gene

Entrez Gene Summary for NOTCH3 Gene

  • 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]

GeneCards Summary for NOTCH3 Gene

NOTCH3 (Notch 3) is a Protein Coding gene. Diseases associated with NOTCH3 include myofibromatosis, infantile 2 and cerebral arteriopathy with subcortical infarcts and leukoencephalopathy. Among its related pathways are Gene Expression and Signaling by GPCR. GO annotations related to this gene include calcium ion binding and enzyme binding. An important paralog of this gene is JAG1.

UniProtKB/Swiss-Prot for NOTCH3 Gene

  • Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity).

Gene Wiki entry for NOTCH3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NOTCH3 Gene

Genomics for NOTCH3 Gene

Regulatory Elements for NOTCH3 Gene

Promoters for NOTCH3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around NOTCH3 on UCSC Golden Path with GeneCards custom track

Genomic Location for NOTCH3 Gene

Chromosome:
19
Start:
15,159,038 bp from pter
End:
15,200,981 bp from pter
Size:
41,944 bases
Orientation:
Minus strand

Genomic View for NOTCH3 Gene

Genes around NOTCH3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NOTCH3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NOTCH3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NOTCH3 Gene

Proteins for NOTCH3 Gene

  • Protein details for NOTCH3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UM47-NOTC3_HUMAN
    Recommended name:
    Neurogenic locus notch homolog protein 3
    Protein Accession:
    Q9UM47
    Secondary Accessions:
    • Q9UEB3
    • Q9UPL3
    • Q9Y6L8

    Protein attributes for NOTCH3 Gene

    Size:
    2321 amino acids
    Molecular mass:
    243631 Da
    Quaternary structure:
    • Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by disulfide bonds (By similarity). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH3. Interacts with PSMA1. Interacts with HIF1AN.

    Three dimensional structures from OCA and Proteopedia for NOTCH3 Gene

neXtProt entry for NOTCH3 Gene

Proteomics data for NOTCH3 Gene at MOPED

Post-translational modifications for NOTCH3 Gene

  • Hydroxylated by HIF1AN.
  • Phosphorylated.
  • Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity).
  • Ubiquitination at Lys 521, Lys 1473, and Lys 1684
  • Glycosylation at Asn 1179, Asn 1336, and Asn 1438
  • Modification sites at PhosphoSitePlus

Other Protein References for NOTCH3 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for NOTCH3 (NOTCH3)
  • Cloud-Clone Corp. Antibodies for NOTCH3

No data available for DME Specific Peptides for NOTCH3 Gene

Domains & Families for NOTCH3 Gene

Gene Families for NOTCH3 Gene

Suggested Antigen Peptide Sequences for NOTCH3 Gene

Graphical View of Domain Structure for InterPro Entry

Q9UM47

UniProtKB/Swiss-Prot:

NOTC3_HUMAN :
  • Contains 34 EGF-like domains.
  • Belongs to the NOTCH family.
  • Contains 5 ANK repeats.
Domain:
  • Contains 34 EGF-like domains.
Family:
  • Belongs to the NOTCH family.
Similarity:
  • Contains 5 ANK repeats.
  • Contains 3 LNR (Lin/Notch) repeats.
genes like me logo Genes that share domains with NOTCH3: view

Function for NOTCH3 Gene

Molecular function for NOTCH3 Gene

GENATLAS Biochemistry:
Drosophila Notch homolog 3,mediating cell-cell interactions that specify cell fate during development,undergoing a first proteolytic cleavage by furin (PACE1) in the Golgi during trafficking of Notch to the cell surface,undergoing further cleavage by gamma secretase (see PSEN1) releasing an intracellular domain (NICD) which translocates to the nucleus and modulates transcription of target genes,putatively involved in translocation with acute lymphoblastic/myeloblastic leukemia and in the decision between the endocrine and exocrine fates in the developing pancreas
UniProtKB/Swiss-Prot Function:
Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity).
genes like me logo Genes that share phenotypes with NOTCH3: view

Human Phenotype Ontology for NOTCH3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NOTCH3 Gene

MGI Knock Outs for NOTCH3:

Animal Model Products

  • Taconic Biosciences Mouse Models for NOTCH3

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Transcription Factor Targets and HOMER Transcription for NOTCH3 Gene

Localization for NOTCH3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NOTCH3 Gene

Cell membrane; Single-pass type I membrane protein.
Notch 3 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NOTCH3 Gene COMPARTMENTS Subcellular localization image for NOTCH3 gene
Compartment Confidence
cytoskeleton 5
cytosol 5
endoplasmic reticulum 5
extracellular 5
golgi apparatus 5
nucleus 5
plasma membrane 5
lysosome 1
mitochondrion 1
vacuole 1

Gene Ontology (GO) - Cellular Components for NOTCH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005737 cytoplasm IDA --
GO:0005789 endoplasmic reticulum membrane TAS --
GO:0005829 cytosol TAS --
GO:0015629 actin cytoskeleton IDA --
genes like me logo Genes that share ontologies with NOTCH3: view

Pathways & Interactions for NOTCH3 Gene

genes like me logo Genes that share pathways with NOTCH3: view

SIGNOR curated interactions for NOTCH3 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for NOTCH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007219 Notch signaling pathway IEA,TAS --
GO:0007220 Notch receptor processing TAS --
GO:0030154 cell differentiation IEA --
GO:0030900 forebrain development IEA --
GO:0045665 negative regulation of neuron differentiation IEA --
genes like me logo Genes that share ontologies with NOTCH3: view

Drugs & Compounds for NOTCH3 Gene

(9) Drugs for NOTCH3 Gene - From: DGIdb, ApexBio, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
FLI-06 Pharma 0
MK0752 Pharma inhibitor, other Notch signaling pathway inhibitor, Other 0
OMP-59R5 Pharma 0
PF-03084014 Pharma other Other 0
REGN421 Pharma other, Inhibitor Other, Notch pathway inhibitors 0
genes like me logo Genes that share compounds with NOTCH3: view

Transcripts for NOTCH3 Gene

Unigene Clusters for NOTCH3 Gene

Notch 3:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for NOTCH3 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20a · 20b ^ 21 ^ 22 ^ 23a · 23b ^ 24 ^
SP1: -
SP2: - -
SP3:

ExUns: 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32
SP1:
SP2:
SP3:

Relevant External Links for NOTCH3 Gene

GeneLoc Exon Structure for
NOTCH3
ECgene alternative splicing isoforms for
NOTCH3

Expression for NOTCH3 Gene

mRNA expression in normal human tissues for NOTCH3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NOTCH3 Gene

This gene is overexpressed in Artery - Tibial (x7.3) and Artery - Coronary (x4.5).

Protein differential expression in normal tissues from HIPED for NOTCH3 Gene

This gene is overexpressed in Plasma (25.0), Placenta (12.0), Gallbladder (11.9), and Pancreatic juice (10.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for NOTCH3 Gene



SOURCE GeneReport for Unigene cluster for NOTCH3 Gene Hs.8546

mRNA Expression by UniProt/SwissProt for NOTCH3 Gene

Q9UM47-NOTC3_HUMAN
Tissue specificity: Ubiquitously expressed in fetal and adult tissues.
genes like me logo Genes that share expression patterns with NOTCH3: view

Primer Products

In Situ Assay Products

No data available for Protein tissue co-expression partners for NOTCH3 Gene

Orthologs for NOTCH3 Gene

This gene was present in the common ancestor of animals.

Orthologs for NOTCH3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NOTCH3 36
  • 100 (a)
OneToOne
NOTCH3 35
  • 99.35 (n)
  • 99.87 (a)
cow
(Bos Taurus)
Mammalia NOTCH3 35
  • 88.4 (n)
  • 93.43 (a)
NOTCH3 36
  • 93 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NOTCH3 36
  • 93 (a)
OneToOne
NOTCH3 35
  • 87.2 (n)
  • 91.77 (a)
mouse
(Mus musculus)
Mammalia Notch3 16
Notch3 36
  • 91 (a)
OneToOne
Notch3 35
  • 84.32 (n)
  • 90.99 (a)
oppossum
(Monodelphis domestica)
Mammalia NOTCH3 36
  • 77 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NOTCH3 36
  • 73 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Notch3 35
  • 84.56 (n)
  • 91.47 (a)
lizard
(Anolis carolinensis)
Reptilia NOTCH3 36
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia notch2 35
  • 63.66 (n)
  • 64.28 (a)
zebrafish
(Danio rerio)
Actinopterygii -- 35
notch3 36
  • 57 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta N 36
  • 38 (a)
OneToMany
SP1070 37
  • 38 (a)
CG15388 37
  • 37 (a)
worm
(Caenorhabditis elegans)
Secernentea Y69H2.2 37
  • 28 (a)
Y69H2.12 37
  • 27 (a)
Y69H2.11 37
  • 27 (a)
W02C12.1 37
  • 37 (a)
R05G6.9 37
  • 28 (a)
lin-12 37
  • 24 (a)
F55H12.3 37
  • 29 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 40 (a)
ManyToMany
Species with no ortholog for NOTCH3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NOTCH3 Gene

ENSEMBL:
Gene Tree for NOTCH3 (if available)
TreeFam:
Gene Tree for NOTCH3 (if available)

Paralogs for NOTCH3 Gene

Paralogs for NOTCH3 Gene

genes like me logo Genes that share paralogs with NOTCH3: view

Variants for NOTCH3 Gene

Sequence variations from dbSNP and Humsavar for NOTCH3 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
VAR_012871 Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)
rs28937321 Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL) 15,192,504(-) GGCTG(G/T)GTGGG reference, missense
VAR_012873 Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)
VAR_012874 Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)
VAR_012876 Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)

Structural Variations from Database of Genomic Variants (DGV) for NOTCH3 Gene

Variant ID Type Subtype PubMed ID
esv34154 CNV Loss 18971310
nsv911131 CNV Loss 21882294
nsv911132 CNV Loss 21882294
esv997404 CNV Loss 20482838
nsv521424 CNV Loss 19592680
esv2718225 CNV Deletion 23290073

Variation tolerance for NOTCH3 Gene

Residual Variation Intolerance Score: 39.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.21; 84.90% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NOTCH3 Gene

HapMap Linkage Disequilibrium report
NOTCH3
Human Gene Mutation Database (HGMD)
NOTCH3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NOTCH3 Gene

Disorders for NOTCH3 Gene

MalaCards: The human disease database

(29) MalaCards diseases for NOTCH3 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
myofibromatosis, infantile 2
  • imf2
cerebral arteriopathy with subcortical infarcts and leukoencephalopathy
  • cadasil
lateral meningocele syndrome
  • lehman syndrome
cadasil
  • cerebral arteriopathy with subcortical infarcts and leukoencephalopathy
myofibromatosis, infantile, 1
  • congenital generalized fibromatosis
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

NOTC3_HUMAN
  • Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL) [MIM:125310]: A cerebrovascular disease characterized by multiple subcortical infarcts, pseudobulbar palsy, dementia, and the presence of granular deposits in small cerebral arteries producing ischemic stroke. {ECO:0000269 PubMed:10227618, ECO:0000269 PubMed:10371548, ECO:0000269 PubMed:10802807, ECO:0000269 PubMed:10854111, ECO:0000269 PubMed:11058919, ECO:0000269 PubMed:11102981, ECO:0000269 PubMed:11559313, ECO:0000269 PubMed:11755616, ECO:0000269 PubMed:11810186, ECO:0000269 PubMed:12136071, ECO:0000269 PubMed:12146805, ECO:0000269 PubMed:12589106, ECO:0000269 PubMed:12810003, ECO:0000269 PubMed:15229130, ECO:0000269 PubMed:15300988, ECO:0000269 PubMed:15364702, ECO:0000269 PubMed:15378071, ECO:0000269 PubMed:15818833, ECO:0000269 PubMed:16009764, ECO:0000269 PubMed:24000151, ECO:0000269 PubMed:9388399}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Myofibromatosis, infantile 2 (IMF2) [MIM:615293]: A rare mesenchymal disorder characterized by the development of benign tumors in the skin, striated muscles, bones, and, more rarely, visceral organs. Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular lesions occur in about half of the patients. Lesions may be solitary or multicentric, and they may be present at birth or become apparent in early infancy or occasionally in adult life. Visceral lesions are associated with high morbidity and mortality. {ECO:0000269 PubMed:23731542}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for NOTCH3

Genetic Association Database (GAD)
NOTCH3
Human Genome Epidemiology (HuGE) Navigator
NOTCH3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NOTCH3
genes like me logo Genes that share disorders with NOTCH3: view

No data available for Genatlas for NOTCH3 Gene

Publications for NOTCH3 Gene

  1. Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies. (PMID: 16009764) Peters N. … Dichgans M. (Arch. Neurol. 2005) 3 4 23 48 67
  2. Mutations in NOTCH3 cause the formation and retention of aggregates in the endoplasmic reticulum, leading to impaired cell proliferation. (PMID: 19825845) Takahashi K. … Watanabe A. (Hum. Mol. Genet. 2010) 3 23
  3. Differential subcellular localization regulates c-Cbl E3 ligase activity upon Notch3 protein in T-cell leukemia. (PMID: 19966856) Checquolo S. … Screpanti I. (Oncogene 2010) 3 23
  4. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy and right-to-left shunt: lack of evidence for an association in a prevalence study. (PMID: 18948701) Mazzucco S. … Rizzuto N. (Eur. Neurol. 2009) 3 23
  5. CADASIL: extended polymorphisms and mutational analysis of the NOTCH3 gene. (PMID: 19006080) Ungaro C. … Quattrone A. (J. Neurosci. Res. 2009) 3 23

Products for NOTCH3 Gene

Sources for NOTCH3 Gene

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