Notch 3

Notch 3
Identifiers
Symbols	NOTCH3; CADASIL; CASIL
External IDs	OMIM: 600276 MGI: 99460 HomoloGene: 376 GeneCards: NOTCH3 Gene
Gene Ontology Molecular function • receptor activity • calcium ion binding • protein binding Cellular component • extracellular region • nucleus • nucleoplasm • endoplasmic reticulum lumen • Golgi lumen • cytosol • plasma membrane • integral to membrane Biological process • regulation of transcription, DNA-dependent • Notch signaling pathway • Notch receptor processing • multicellular organismal development • gene expression • forebrain development • tissue regeneration • negative regulation of neuron differentiation • neuron fate commitment • regulation of developmental process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4854	18131
Ensembl	ENSG00000074181	ENSMUSG00000038146
UniProt	Q9UM47	n/a
RefSeq (mRNA)	NM_000435.2	NM_008716.2
RefSeq (protein)	NP_000426.2	NP_032742.1
Location (UCSC)	Chr 19: 15.27 – 15.31 Mb	Chr 17: 32.26 – 32.3 Mb
PubMed search	[1]	[2]

Neurogenic locus notch homolog protein 3 is a protein that in humans is encoded by the 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.

Pathology

Micrograph showing CADASIL with a Notch 3 immunostain.

Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Further reading

• Lewis J (1996). "Neurogenic genes and vertebrate neurogenesis.". Curr. Opin. Neurobiol. 6 (1): 3–10. doi:10.1016/S0959-4388(96)80002-X. PMID 8794055. 
• Joutel A, Tournier-Lasserve E (2002). "[Molecular basis and physiopathogenic mechanisms of CADASIL: a model of small vessel diseases of the brain]". J. Soc. Biol. 196 (1): 109–15. PMID 12134625. 
• Guidetti D, Casali B, Mazzei RL, Dotti MT (2006). "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.". Clin. Exp. Hypertens. 28 (3–4): 271–7. doi:10.1080/10641960600549223. PMID 16833034. 
• Beleil OM, Mickey MR, Terasaki PI (1972). "Comparison of male and female kidney transplant survival rates". Transplantation 13 (5): 493–500. doi:10.1097/00007890-197205000-00008. PMID 4557798. 
• Larsson C, Lardelli M, White I, Lendahl U (1995). "The human NOTCH1, 2, and 3 genes are located at chromosome positions 9q34, 1p13-p11, and 19p13.2-p13.1 in regions of neoplasia-associated translocation". Genomics 24 (2): 253–8. doi:10.1006/geno.1994.1613. PMID 7698746. 
• Tournier-Lasserve E, Joutel A, Melki J, et al. (1993). "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12". Nat. Genet. 3 (3): 256–9. doi:10.1038/ng0393-256. PMID 8485581. 
• Joutel A, Corpechot C, Ducros A, et al. (1996). "Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia". Nature 383 (6602): 707–10. doi:10.1038/383707a0. PMID 8878478. 
• Joutel A, Vahedi K, Corpechot C, et al. (1997). "Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients". Lancet 350 (9090): 1511–5. doi:10.1016/S0140-6736(97)08083-5. PMID 9388399. 
• Gray GE, Mann RS, Mitsiadis E, et al. (1999). "Human ligands of the Notch receptor". Am. J. Pathol. 154 (3): 785–94. doi:10.1016/S0002-9440(10)65325-4. PMC 1866435. PMID 10079256. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1866435. 
• Joutel A, Andreux F, Gaulis S, et al. (2000). "The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients". J. Clin. Invest. 105 (5): 597–605. doi:10.1172/JCI8047. PMC 289174. PMID 10712431. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=289174. 
• Joutel A, Dodick DD, Parisi JE, et al. (2000). "De novo mutation in the Notch3 gene causing CADASIL". Ann. Neurol. 47 (3): 388–91. doi:10.1002/1531-8249(200003)47:3<388::AID-ANA19>3.0.CO;2-Q. PMID 10716263. 
• Joutel A, Chabriat H, Vahedi K, et al. (2000). "Splice site mutation causing a seven amino acid Notch3 in-frame deletion in CADASIL". Neurology 54 (9): 1874–5. PMID 10802807. 
• Shimizu K, Chiba S, Saito T, et al. (2000). "Physical interaction of Delta1, Jagged1, and Jagged2 with Notch1 and Notch3 receptors". Biochem. Biophys. Res. Commun. 276 (1): 385–9. doi:10.1006/bbrc.2000.3469. PMID 11006133. 
• Wu L, Aster JC, Blacklow SC, et al. (2001). "MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors". Nat. Genet. 26 (4): 484–9. doi:10.1038/82644. PMID 11101851. 
• Beatus P, Lundkvist J, Oberg C, et al. (2001). "The origin of the ankyrin repeat region in Notch intracellular domains is critical for regulation of HES promoter activity". Mech. Dev. 104 (1–2): 3–20. doi:10.1016/S0925-4773(01)00373-2. PMID 11404076. 
• Saxena MT, Schroeter EH, Mumm JS, Kopan R (2001). "Murine notch homologs (N1-4) undergo presenilin-dependent proteolysis". J. Biol. Chem. 276 (43): 40268–73. doi:10.1074/jbc.M107234200. PMID 11518718. 
• Oliveri RL, Muglia M, De Stefano N, et al. (2001). "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 (9): 1418–22. doi:10.1001/archneur.58.9.1418. PMID 11559313. 
• Dichgans M, Herzog J, Gasser T (2001). "NOTCH3 mutation involving three cysteine residues in a family with typical CADASIL". Neurology 57 (9): 1714–7. PMID 11706120. 

External links

• MeSH NOTCH3+protein,+human