Notch 3

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Notch 3
Identifiers
Symbols NOTCH3 ; CADASIL; CASIL; IMF2
External IDs OMIM600276 MGI99460 HomoloGene376 GeneCards: NOTCH3 Gene
RNA expression pattern
PBB GE NOTCH3 203238 s at tn.png
PBB GE NOTCH3 203237 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4854 18131
Ensembl ENSG00000074181 ENSMUSG00000038146
UniProt Q9UM47 Q61982
RefSeq (mRNA) NM_000435 NM_008716
RefSeq (protein) NP_000426 NP_032742
Location (UCSC) Chr 19:
15.27 – 15.31 Mb
Chr 17:
32.12 – 32.17 Mb
PubMed search [1] [2]

Neurogenic locus notch homolog protein 3 is a protein that in humans is encoded by the NOTCH3 gene.[1][2]

Function[edit]

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[edit]

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).[2] Mutations in NOTCH3 have also been identified in a Turkish family with Alzheimer's disease.[3] Adult Notch3 knock-out mice show incomplete neuronal maturation in the spinal cord dorsal horn, resulting in permanently increased nociceptive sensitivity.[4] Mutations in NOTCH3 are associated to lateral meningocele syndrome .[5]

References[edit]

  1. ^ Sugaya K, Fukagawa T, Matsumoto K, Mita K, Takahashi E, Ando A et al. (Feb 1995). "Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3". Genomics 23 (2): 408–19. doi:10.1006/geno.1994.1517. PMID 7835890. 
  2. ^ a b "Entrez Gene: NOTCH3 Notch homolog 3 (Drosophila)". 
  3. ^ Guerreiro R, Lohmann E, Kinsella E, Brás J, Luu N, Gurunlian N et al. (2012). "Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3 mutation in a Turkish family with Alzheimer's disease". Neurobiol. Aging 33 (5): 1008.e17–23. doi:10.1016/j.neurobiolaging.2011.10.009. PMC 3306507. PMID 22153900. 
  4. ^ Rusanescu G, Mao J (2014). "Notch3 is necessary for neuronal differentiation and maturation in the adult spinal cord". J. Cell. Mol. Med. 18 (10): 2103–16. doi:10.1111/jcmm.12362. PMC 4244024. PMID 25164209. 
  5. ^ Gripp K, Robbins K, Sobreira N, Witmer P, Bird L, Avela K et al. (2014). "Truncating mutations in the last exon of NOTCH3 cause lateral meningocele syndrome". Am. J. Med. Genet. A. doi:10.1002/ajmg.a.36863. PMID 25394726. 

Further reading[edit]

  • 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 R, Dotti M (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 O, Mickey M, Terasaki P (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 (1994). "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, Weissenbach J, Lathrop G, Chabriat H 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, Vahedi K, Chabriat H, Mouton P 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, Troesch A, Chabriat H, Vayssière 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 G, Mann R, Mitsiadis E, Henrique D, Carcangiu M, Banks A 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. 
  • Joutel A, Andreux F, Gaulis S, Domenga V, Cecillon M, Battail N 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. 
  • Joutel A, Dodick D, Parisi J, Cecillon M, Tournier-Lasserve E, Bousser M (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, Domenga V, Vayssière C, Ruchoux M et al. (2000). "Splice site mutation causing a seven amino acid Notch3 in-frame deletion in CADASIL". Neurology 54 (9): 1874–5. doi:10.1212/wnl.54.9.1874. PMID 10802807. 
  • Shimizu K, Chiba S, Saito T, Kumano K, Hirai H (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 J, Blacklow S, Lake R, Artavanis-Tsakonas S, Griffin J (2000). "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, Pedersen K, Lendahl U (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 M, Schroeter E, Mumm J, 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 R, Muglia M, De Stefano N, Mazzei R, Labate A, Conforti F 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. doi:10.1212/wnl.57.9.1714. PMID 11706120. 

External links[edit]