Notch-2

From Wikipedia, the free encyclopedia
  (Redirected from NOTCH2)
Jump to: navigation, search
Notch 2
Protein NOTCH2 PDB 2oo4.png
PDB rendering based on 2oo4.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols NOTCH2 ; AGS2; HJCYS; hN2
External IDs OMIM600275 MGI97364 HomoloGene7865 GeneCards: NOTCH2 Gene
RNA expression pattern
PBB GE NOTCH2 212377 s at tn.png
PBB GE NOTCH2 202443 x at tn.png
PBB GE NOTCH2 202445 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4853 18129
Ensembl ENSG00000134250 ENSMUSG00000027878
UniProt Q04721 O35516
RefSeq (mRNA) NM_001200001 NM_010928
RefSeq (protein) NP_001186930 NP_035058
Location (UCSC) Chr 1:
120.45 – 120.61 Mb
Chr 3:
98.01 – 98.15 Mb
PubMed search [1] [2]

Neurogenic locus notch homolog protein 2 also known as notch 2 is a protein that in humans is encoded by the NOTCH2 gene.[1]

NOTCH2 is associated with Alagille syndrome[2] and Hajdu–Cheney syndrome.[3]

Function[edit]

Notch 2 is 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 Drosophilia, 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 a role in vascular, renal and hepatic development.[4]

Mutations within the last coding exon of Notch2 that remove the PEST domain and escape the nonsense-mediated mRNA decay have been shown to be the main cause of the Hajdu-Cheney syndrome.[5][6][7]

Interactions[edit]

NOTCH2 has been shown to interact with JAG1,[8][9][10] JAG2,[10] Delta-like 1[8][10][11] and GSK3B.[12]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ "Entrez Gene: NOTCH2 Notch homolog 2 (Drosophila)". 
  5. ^ A Simpson, Michael; Irving, Melita D; Asilmaz, Esra; Gray, Mary J; Dafou, Dimitra; Elmslie, Frances V; Mansour, Sahar; Holder, Sue E et al. (2011). "Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss". Nature Genetics 43 (4): 303–305. doi:10.1038/ng.779. PMID 21378985. Retrieved 2011-03-07. 
  6. ^ Isidor, Bertrand; Pierre Lindenbaum (2011). "Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis". Nature Genetics 43 (4): 306–8. doi:10.1038/ng.778. PMID 21378989. 
  7. ^ Majewski, J; Schwartzentruber, Jeremy A.; Caqueret, Aurore; Patry, Lysanne; Marcadier, Janet; Fryns, Jean-Pierre; Boycott, Kym M.; Ste-Marie, Louis-Georges; McKiernan, Fergus E.; Marik, Ivo; Van Esch, Hilde; Michaud, Jacques L.; Samuels, Mark E. (2011). "Mutations in NOTCH2 in families with Hajdu-Cheney syndrome". Hum Mutat 32 (10): 1114–7. doi:10.1002/humu.21546. PMID 21681853. 
  8. ^ a b Shimizu, K; Chiba S, Saito T, Kumano K, Takahashi T, Hirai H (July 2001). "Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation". J. Biol. Chem. (United States) 276 (28): 25753–8. doi:10.1074/jbc.M103473200. ISSN 0021-9258. PMID 11346656. 
  9. ^ Shimizu, K; Chiba S, Kumano K, Hosoya N, Takahashi T, Kanda Y, Hamada Y, Yazaki Y, Hirai H (November 1999). "Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods". J. Biol. Chem. (UNITED STATES) 274 (46): 32961–9. doi:10.1074/jbc.274.46.32961. ISSN 0021-9258. PMID 10551863. 
  10. ^ a b c Shimizu, K; Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, Kanda Y, Hamada Y, Hirai H (September 2000). "Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2". Mol. Cell. Biol. (UNITED STATES) 20 (18): 6913–22. doi:10.1128/MCB.20.18.6913-6922.2000. ISSN 0270-7306. PMC 88767. PMID 10958687. 
  11. ^ Blaumueller, C M; Qi H, Zagouras P, Artavanis-Tsakonas S (July 1997). "Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane". Cell (UNITED STATES) 90 (2): 281–91. doi:10.1016/S0092-8674(00)80336-0. ISSN 0092-8674. PMID 9244302. 
  12. ^ Espinosa, Lluís; Inglés-Esteve Julia, Aguilera Cristina, Bigas Anna (August 2003). "Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways". J. Biol. Chem. (United States) 278 (34): 32227–35. doi:10.1074/jbc.M304001200. ISSN 0021-9258. PMID 12794074. 

Further reading[edit]

External links[edit]