Notch 3

NOTCH3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ZLP, 5CZX, 5CZV
Identifiers
Aliases	NOTCH3, CADASIL, CASIL, IMF2, LMNS, CADASIL1, notch 3
External IDs	OMIM: 600276 MGI: 99460 HomoloGene: 376 GeneCards: NOTCH3
Gene ontology Molecular function • calcium ion binding • protein binding • enzyme binding • cadherin binding involved in cell-cell adhesion • receptor activity Cellular component • cytoplasm • integral component of membrane • cytosol • endoplasmic reticulum membrane • membrane • Golgi membrane • receptor complex • plasma membrane • nucleoplasm • extracellular region • actin cytoskeleton • nucleus • cell-cell adherens junction Biological process • Notch signaling pathway • cell differentiation • regulation of transcription, DNA-templated • negative regulation of neuron differentiation • negative regulation of cell differentiation • glomerular capillary formation • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • multicellular organism development • artery morphogenesis • Notch receptor processing • forebrain development • neuron fate commitment • transcription initiation from RNA polymerase II promoter • positive regulation of transcription from RNA polymerase II promoter • positive regulation of smooth muscle cell proliferation • cell-cell adhesion Sources:Amigo / QuickGO
RNA expression pattern
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_000426.2	NP_032742.1
Location (UCSC)	Chr 19: 15.16 – 15.2 Mb	Chr 17: 32.12 – 32.17 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

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Neurogenic locus notch homolog protein 3 is a protein that in humans is encoded by the NOTCH3 gene.^[3][4]

Function

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).^[4] Mutations in NOTCH3 have also been identified in a Turkish family with Alzheimer's disease.^[5] Adult Notch3 knock-out mice show incomplete neuronal maturation in the spinal cord dorsal horn, resulting in permanently increased nociceptive sensitivity.^[6] Mutations in NOTCH3 are associated to lateral meningocele syndrome .^[7]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Sugaya K, Fukagawa T, Matsumoto K, Mita K, Takahashi E, Ando A, Inoko H, Ikemura T (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. Check date values in: |year= / |date= mismatch (help)
4. "Entrez Gene: NOTCH3 Notch homolog 3 (Drosophila)".
5. Guerreiro RJ, Lohmann E, Kinsella E, Brás JM, Luu N, Gurunlian N, Dursun B, Bilgic B, Santana I, Hanagasi H, Gurvit H, Gibbs JR, Oliveira C, Emre M, Singleton A (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.
6. 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.
7. Gripp KW, Robbins KM, Sobreira NL, Witmer PD, Bird LM, Avela K, Makitie O, Alves D, Hogue JS, Zackai EH, Doheny KF, Stabley DL, Sol-Church K (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

• 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 (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 GM, Chabriat H, Mas JL, Cabanis EA, Baudrimont M, Maciazek J (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, Alamowitch S, Domenga V, Cécillion M, Marechal E, Maciazek J, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach JF, Bousser MG, Tournier-Lasserve E (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, Cruaud C, Maciazek J, Weissenbach J, Bousser MG, Bach JF, Tournier-Lasserve E (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, Henrique D, Carcangiu ML, Banks A, Leiman J, Ward D, Ish-Horowitz D, Artavanis-Tsakonas S (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, Piga N, Chapon F, Godfrain C, Tournier-Lasserve E (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 DD, Parisi JE, Cecillon M, Tournier-Lasserve E, Bousser MG (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 MM, Lucas C, Leys D, Bousser MG, Tournier-Lasserve E (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 JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD (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 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, Mazzei R, Labate A, Conforti FL, Patitucci A, Gabriele AL, Tagarelli G, Magariello A, Zappia M, Gambardella A, Federico A, Quattrone A (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

• NOTCH3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)