Notch Homolog 3 (NOTCH3)

CADASIL; CASIL; Neurogenic locus notch homolog protein 3

SPN	N240
HGNC	7883
MGI	99460
PubMed	24743243
RGD	620761
UniProt	Q9UM47
Wiki	Notch_3

NOTCH3 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).

Reference

"Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia."
Nature 383:707-710(1996) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and biology of human chromosome 19."
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]

"Human ligands of the Notch receptor."
Am. J. Pathol. 154:785-794(1999) [PubMed] [Europe PMC] [Abstract]

"MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors."
Nat. Genet. 26:484-489(2000) [PubMed] [Europe PMC] [Abstract]

"Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors."
Mol. Cell. Biol. 22:7688-7700(2002) [PubMed] [Europe PMC] [Abstract]

"Conserved signal peptide of Notch3 inhibits interaction with proteasome."
Biochem. Biophys. Res. Commun. 355:245-251(2007) [PubMed] [Europe PMC] [Abstract]

"Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor."
J. Biol. Chem. 282:24027-24038(2007) [PubMed] [Europe PMC] [Abstract]

"Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways."
Proc. Natl. Acad. Sci. U.S.A. 105:3368-3373(2008) [PubMed] [Europe PMC] [Abstract]

"Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients."
Lancet 350:1511-1515(1997) [PubMed] [Europe PMC] [Abstract]

"Quantitative MRI in CADASIL: correlation with disability and cognitive performance."
Neurology 52:1361-1367(1999) [PubMed] [Europe PMC] [Abstract]

"Diagnostic Notch3 sequence analysis in CADASIL: three new mutations in Dutch patients. Dutch CADASIL Research Group."
Neurology 52:1913-1915(1999) [PubMed] [Europe PMC] [Abstract]

"Small in-frame deletions and missense mutations in CADASIL: 3D models predict misfolding of Notch3 EGF-like repeat domains."
Eur. J. Hum. Genet. 8:280-285(2000) [PubMed] [Europe PMC] [Abstract]

"Identification of a novel mutation C144F in the Notch3 gene in an Australian CADASIL pedigree."
Hum. Mutat. 16:449-450(2000) [PubMed] [Europe PMC] [Abstract]

"Evaluation of DHPLC analysis in mutational scanning of Notch3, a gene with a high G-C content."
Hum. Mutat. 16:518-526(2000) [PubMed] [Europe PMC] [Abstract]

"Splice site mutation causing a seven amino acid Notch3 in-frame deletion in CADASIL."
Neurology 54:1874-1875(2000) [PubMed] [Europe PMC] [Abstract]

"A novel mutation in the Notch3 gene in an Italian family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: genetic and magnetic resonance spectroscopic findings."
Arch. Neurol. 58:1418-1422(2001) [PubMed] [Europe PMC] [Abstract]

"Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis."
Lancet 358:2049-2051(2001) [PubMed] [Europe PMC] [Abstract]

"Reversible coma with raised intracranial pressure: an unusual clinical manifestation of CADASIL."
Acta Neuropathol. 103:188-192(2002) [PubMed] [Europe PMC] [Abstract]

"CADASIL: a common form of hereditary arteriopathy causing brain infarcts and dementia."
Brain Pathol. 12:371-384(2002) [PubMed] [Europe PMC] [Abstract]

"C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke."
Neurology 59:277-279(2002) [PubMed] [Europe PMC] [Abstract]

"A novel mutation (C67Y)in the NOTCH3 gene in a Korean CADASIL patient."
J. Korean Med. Sci. 18:141-144(2003) [PubMed] [Europe PMC] [Abstract]

"Genetic, clinical and pathological studies of CADASIL in Japan: a partial contribution of Notch3 mutations and implications of smooth muscle cell degeneration for the pathogenesis."
J. Neurol. Sci. 212:79-84(2003) [PubMed] [Europe PMC] [Abstract]

"The influence of genetic and cardiovascular risk factors on the CADASIL phenotype."
Brain 127:2031-2038(2004) [PubMed] [Europe PMC] [Abstract]

"Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients."
Brain 127:2533-2539(2004) [PubMed] [Europe PMC] [Abstract]

"Detection of the founder effect in Finnish CADASIL families."
Eur. J. Hum. Genet. 12:813-819(2004) [PubMed] [Europe PMC] [Abstract]

"Gene symbol: NOTCH3. Disease: CADASIL."
Hum. Genet. 115:175-175(2004) [PubMed] [Europe PMC] [Abstract]

"Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies."
Arch. Neurol. 62:1091-1094(2005) [PubMed] [Europe PMC] [Abstract]

"Gene symbol: NOTCH3. Disease: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy."
Hum. Genet. 116:242-242(2005) [PubMed] [Europe PMC] [Abstract]

"Activating NOTCH3 mutation in a patient with small-vessel-disease of the brain."
Hum. Mutat. 29:452-452(2008) [PubMed] [Europe PMC] [Abstract]

"Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis."
Am. J. Hum. Genet. 92:1001-1007(2013) [PubMed] [Europe PMC] [Abstract]

"Hypomorphic NOTCH3 alleles do not cause CADASIL in humans."
Hum. Mutat. 34:1486-1489(2013) [PubMed] [Europe PMC] [Abstract]