Notch proteins

Notch (LNR) domain

Structure of a Prototype LNR Module from Human Notch1.[1]
Identifiers
Symbol Notch
Pfam PF00066
InterPro IPR000800
SMART SM00004
PROSITE PS50258

Notch (DSL) proteins are a family of transmembrane proteins with repeated extracellular EGF domains and the notch (or DSL) domains. These proteins are involved in lateral inhibition in embryogenesis.

The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. In Drosophila, Notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. This same pathway operates to mediate binary cell fate decisions in C. elegans development.[2][3] Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play a role in vascular, renal and hepatic development.[4]

Human proteins containing this domain

Notch-1

Main article: Notch-1

Function

This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth-like factor (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. In Drosophila, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play multiple roles during development.[5] A deficiency can be associated with bicuspid aortic valve.[6]

There is evidence that activated Notch 1 and Notch 3 promote differentiation of progenitor cells into astroglia.[7] Notch 1, then activated before birth, induces radial glia differentiation,[8] but postnatally induces the differentiation into astrocytes.[9] One study shows that Notch-1 cascade is activated by Reelin in an unidentified way.[10] Reelin and Notch1 cooperate in the development of the dentate gyrus, according to another.[11]

Notch-2

Main article: Notch-2

Notch-2 (Neurogenic locus notch homolog protein 2) is a protein that in humans is encoded by the NOTCH2 gene.[12]

NOTCH2 is associated with Alagille syndrome[13] and Hajdu–Cheney syndrome.[14]

Notch-3

Main article: NOTCH3

Notch-4

Main article: NOTCH4

See also

Notes

  1. ↑ Vardar D, North CL, Sanchez-Irizarry C, Aster JC, Blacklow SC (Jun 2003). "Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat module from human Notch1". Biochemistry. 42 (23): 7061–7. doi:10.1021/bi034156y. PMID 12795601.
  2. ↑ Greenwald IS, Sternberg PW, Horvitz HR (Sep 1983). "The lin-12 locus specifies cell fates in Caenorhabditis elegans". Cell. 34 (2): 435–44. doi:10.1016/0092-8674(83)90377-X. PMID 6616618.
  3. ↑ Greenwald I (Jul 2012). "Notch and the awesome power of genetics". Genetics. 191 (3): 655–69. doi:10.1534/genetics.112.141812. PMID 22785620.
  4. ↑ "Entrez Gene: NOTCH2 Notch homolog 2 (Drosophila)".
  5. ↑ "Entrez Gene: NOTCH1 Notch homolog 1, translocation-associated (Drosophila)".
  6. ↑ McKellar SH, Tester DJ, Yagubyan M, Majumdar R, Ackerman MJ, Sundt TM (Aug 2007). "Novel NOTCH1 mutations in patients with bicuspid aortic valve disease and thoracic aortic aneurysms". The Journal of Thoracic and Cardiovascular Surgery. 134 (2): 290–6. doi:10.1016/j.jtcvs.2007.02.041. PMID 17662764.
  7. ↑ Tanigaki K, Nogaki F, Takahashi J, Tashiro K, Kurooka H, Honjo T (Jan 2001). "Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate". Neuron. 29 (1): 45–55. doi:10.1016/S0896-6273(01)00179-9. PMID 11182080.
  8. ↑ Gaiano N, Nye JS, Fishell G (May 2000). "Radial glial identity is promoted by Notch1 signaling in the murine forebrain". Neuron. 26 (2): 395–404. doi:10.1016/S0896-6273(00)81172-1. PMID 10839358.
  9. ↑ Chambers CB, Peng Y, Nguyen H, Gaiano N, Fishell G, Nye JS (Mar 2001). "Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors". Development. 128 (5): 689–702. PMID 11171394.
  10. ↑ Keilani S, Sugaya K (July 2008). "Reelin induces a radial glial phenotype in human neural progenitor cells by activation of Notch-1". BMC Developmental Biology. 8 (1): 69. doi:10.1186/1471-213X-8-69. PMC 2447831Freely accessible. PMID 18593473.
  11. ↑ Sibbe M, Förster E, Basak O, Taylor V, Frotscher M (Jul 2009). "Reelin and Notch1 cooperate in the development of the dentate gyrus". The Journal of Neuroscience. 29 (26): 8578–85. doi:10.1523/JNEUROSCI.0958-09.2009. PMID 19571148.
  12. ↑ Larsson C, Lardelli M, White I, Lendahl U (Nov 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.
  13. ↑ Samejima H, Torii C, Kosaki R, Kurosawa K, Yoshihashi H, Muroya K, Okamoto N, Watanabe Y, Kosho T, Kubota M, Matsuda O, Goto M, Izumi K, Takahashi T, Kosaki K (2007). "Screening for Alagille syndrome mutations in the JAG1 and NOTCH2 genes using denaturing high-performance liquid chromatography". Genetic Testing. 11 (3): 216–27. doi:10.1089/gte.2006.0519. PMID 17949281.
  14. ↑ Simpson MA, Irving MD, Asilmaz E, Gray MJ, Dafou D, Elmslie FV, Mansour S, Holder SE, Brain CE, Burton BK, Kim KH, Pauli RM, Aftimos S, Stewart H, Kim CA, Holder-Espinasse M, Robertson SP, Drake WM, Trembath RC (Apr 2011). "Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss". Nature Genetics. 43 (4): 303–5. doi:10.1038/ng.779. PMID 21378985.

References

This article incorporates text from the public domain Pfam and InterPro IPR000800

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