Notch proteins

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Notch (LNR) domain
PDB 1pb5 EBI.jpg
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. 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. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. 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.[2]

Human proteins containing this domain[edit]

Notch-1[edit]

Main article: Notch-1

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 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. 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.[3] A deficiency can be associated with bicuspid aortic valve.[4]

There is evidence that activated Notch 1 and Notch 3 promote differentiation of progenitor cells into astroglia.[5] Interestingliy, Notch 1, then activated before birth, induces radial glia differentiation,[6] but postnatally induces the differentiation into astrocytes.[7] One study shows that Notch-1 cascade is activated by Reelin in an unidentified way.[8] Reelin and Notch1 cooperate in the development of the dentate gyrus, according to another.[9]

Notch-2[edit]

Main article: Notch-2

Notch-2 (Neurogenic locus notch homolog protein 2) is a protein that in humans is encoded by the NOTCH2 gene.[10]

NOTCH2 is associated with Alagille syndrome[11] and Hajdu–Cheney syndrome.[12]

Notch-3[edit]

Main article: NOTCH3

Notch-4[edit]

Main article: NOTCH4

See also[edit]

Notes[edit]

  1. ^ Vardar D, North CL, Sanchez-Irizarry C, Aster JC, Blacklow SC (June 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. ^ "Entrez Gene: NOTCH2 Notch homolog 2 (Drosophila)". 
  3. ^ "Entrez Gene: NOTCH1 Notch homolog 1, translocation-associated (Drosophila)". 
  4. ^ Stephen H. McKellar MD (August 2007). "Novel NOTCH1 mutations in patients with bicuspid aortic valve disease and thoracic aortic aneurysms". J Thorac Cardiovasc Surg 134 (2): 290–296. doi:10.1016/j.jtcvs.2007.02.041. PMID 17662764. 
  5. ^ Tanigaki K, Nogaki F, Takahashi J, Tashiro K, Kurooka H, Honjo T (January 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. 
  6. ^ 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. 
  7. ^ Chambers CB, Peng Y, Nguyen H, Gaiano N, Fishell G, Nye JS (March 2001). "Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors". Development 128 (5): 689–702. PMID 11171394. 
  8. ^ Keilani S, Sugaya K (July 2008). "Reelin induces a radial glial phenotype in human neural progenitor cells by activation of Notch-1". BMC Dev. Biol. 8 (1): 69. doi:10.1186/1471-213X-8-69. PMC 2447831. PMID 18593473. 
  9. ^ Sibbe M, Förster E, Basak O, Taylor V, Frotscher M (July 2009). "Reelin and Notch1 cooperate in the development of the dentate gyrus". J. Neurosci. 29 (26): 8578–85. doi:10.1523/JNEUROSCI.0958-09.2009. PMID 19571148. 
  10. ^ Larsson C, Lardelli M, White I, Lendahl U (May 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. 
  11. ^ Samejima H, Torii C, Kosaki R et al. (2007). "Screening for Alagille syndrome mutations in the JAG1 and NOTCH2 genes using denaturing high-performance liquid chromatography". Genet. Test. 11 (3): 216–27. doi:10.1089/gte.2006.0519. PMID 17949281. 
  12. ^ 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 (2011-03-06). "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[edit]

  • Tax FE, Yeargers JJ, Thomas JH (1994). "Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with Delta and Serrate of Drosophila". Nature 368 (6467): 150–154. doi:10.1038/368150a0. PMID 8139658. 
  • Lindsell CE, Shawber CJ, Boulter J, Weinmaster G (1995). "Jagged: a mammalian ligand that activates Notch1". Cell 80 (6): 909–91. doi:10.1016/0092-8674(95)90294-5. PMID 7697721. 
  • Kelley MR, Kidd S, Deutsch WA, Young MW (1987). "Mutations altering the structure of epidermal growth factor-like coding sequences at the Drosophila Notch locus". Cell 51 (4): 539–548. doi:10.1016/0092-8674(87)90123-1. PMID 3119223. 

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