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词条 Notch 2
释义

  1. Function

  2. Interactions

  3. References

  4. Further reading

  5. External links

{{Infobox_gene}}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

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

NOTCH2 has been shown to interact with:

  • Delta-like 1[8][9][8]
  • GSK3B,[9]
  • JAG1,[10][11][12] and
  • JAG2.[11]

References

1. ^{{cite journal | vauthors = Larsson C, Lardelli M, White I, Lendahl U | title = 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 | journal = Genomics | volume = 24 | issue = 2 | pages = 253–8 | date = May 1995 | pmid = 7698746 | pmc = | doi = 10.1006/geno.1994.1613 }}
2. ^{{cite journal | vauthors = 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 | title = Screening for Alagille syndrome mutations in the JAG1 and NOTCH2 genes using denaturing high-performance liquid chromatography | journal = Genet. Test. | volume = 11 | issue = 3 | pages = 216–27 | year = 2007 | pmid = 17949281 | doi = 10.1089/gte.2006.0519 }}
3. ^{{cite journal | vauthors = 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 | title = Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. | journal = Nature Genetics | volume = 43 | issue = 4 | pages = 303–5 | date = 2011-03-06 | pmid = 21378985 | doi = 10.1038/ng.779 }}
4. ^{{cite web | title = Entrez Gene: NOTCH2 Notch homolog 2 (Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4853| accessdate = }}
5. ^{{cite journal | vauthors = 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 | title = Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss | journal = Nature Genetics | volume = 43 | issue = 4 | pages = 303–305 | year = 2011 | pmid = 21378985 | doi = 10.1038/ng.779 | url = http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.779.html | display-authors = 8 | accessdate = 2011-03-07}}
6. ^{{cite journal | vauthors = Isidor B, Lindenbaum P, Pichon O, Bézieau S, Dina C, Jacquemont S, Martin-Coignard D, Thauvin-Robinet C, Le Merrer M, Mandel JL, David A, Faivre L, Cormier-Daire V, Redon R, Le Caignec C | title = Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis | journal = Nature Genetics | volume = 43 | issue = 4 | pages = 306–8 | year = 2011 | pmid = 21378989 | doi = 10.1038/ng.778 | url = http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.778.html | accessdate = }}
7. ^{{cite journal | vauthors = Majewski J, Schwartzentruber JA, Caqueret A, Patry L, Marcadier J, Fryns JP, Boycott KM, Ste-Marie LG, McKiernan FE, Marik I, Van Esch H, Michaud JL, Samuels ME | title = Mutations in NOTCH2 in families with Hajdu-Cheney syndrome | journal = Hum Mutat | volume = 32 | issue = 10 | pages = 1114–7 | year = 2011 | pmid = 21681853 | doi = 10.1002/humu.21546}}
8. ^{{cite journal | vauthors = Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S | title = Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane | journal = Cell | volume = 90 | issue = 2 | pages = 281–91 | date = July 1997 | pmid = 9244302 | doi = 10.1016/s0092-8674(00)80336-0}}
9. ^{{cite journal | vauthors = Espinosa L, Inglés-Esteve J, Aguilera C, Bigas A | title = Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways | journal = J. Biol. Chem. | volume = 278 | issue = 34 | pages = 32227–35 | date = August 2003 | pmid = 12794074 | doi = 10.1074/jbc.M304001200 }}
10. ^1 {{cite journal | vauthors = Shimizu K, Chiba S, Saito T, Kumano K, Takahashi T, Hirai H | title = Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation | journal = J. Biol. Chem. | volume = 276 | issue = 28 | pages = 25753–8 | date = July 2001 | pmid = 11346656 | doi = 10.1074/jbc.M103473200 }}
11. ^1 2 {{cite journal | vauthors = Shimizu K, Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, Kanda Y, Hamada Y, Hirai H | title = Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2 | journal = Mol. Cell. Biol. | volume = 20 | issue = 18 | pages = 6913–22 | date = September 2000 | pmid = 10958687 | pmc = 88767 | doi = 10.1128/mcb.20.18.6913-6922.2000}}
12. ^{{cite journal | vauthors = Shimizu K, Chiba S, Kumano K, Hosoya N, Takahashi T, Kanda Y, Hamada Y, Yazaki Y, Hirai H | title = Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods | journal = J. Biol. Chem. | volume = 274 | issue = 46 | pages = 32961–9 | date = November 1999 | pmid = 10551863 | doi = 10.1074/jbc.274.46.32961}}

Further reading

{{refbegin | 2}}
  • {{cite journal | vauthors = Artavanis-Tsakonas S, Rand MD, Lake RJ | title = Notch signaling: cell fate control and signal integration in development | journal = Science | volume = 284 | issue = 5415 | pages = 770–6 | year = 1999 | pmid = 10221902 | doi = 10.1126/science.284.5415.770 | bibcode = 1999Sci...284..770A}}
  • {{cite journal | vauthors = Kojika S, Griffin JD | title = Notch receptors and hematopoiesis | journal = Exp. Hematol. | volume = 29 | issue = 9 | pages = 1041–52 | year = 2001 | pmid = 11532344 | doi = 10.1016/S0301-472X(01)00676-2 }}
  • {{cite journal | vauthors = Schwarzmeier JD, Hubmann R, Düchler M, Jäger U, Shehata M | title = Regulation of CD23 expression by Notch2 in B-cell chronic lymphocytic leukemia | journal = Leuk. Lymphoma | volume = 46 | issue = 2 | pages = 157–65 | year = 2005 | pmid = 15621797 | doi = 10.1080/10428190400010742 }}
  • {{cite journal | vauthors = Stifani S, Blaumueller CM, Redhead NJ, Hill RE, Artavanis-Tsakonas S | title = Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins | journal = Nat. Genet. | volume = 2 | issue = 2 | pages = 119–27 | year = 1993 | pmid = 1303260 | doi = 10.1038/ng1092-119 }}
  • {{cite journal | vauthors = Katsanis N, Fitzgibbon J, Fisher EM | title = Paralogy mapping: identification of a region in the human MHC triplicated onto human chromosomes 1 and 9 allows the prediction and isolation of novel PBX and NOTCH loci | journal = Genomics | volume = 35 | issue = 1 | pages = 101–8 | year = 1996 | pmid = 8661110 | doi = 10.1006/geno.1996.0328 }}
  • {{cite journal | vauthors = Hsieh JJ, Nofziger DE, Weinmaster G, Hayward SD | title = Epstein-Barr virus immortalization: Notch2 interacts with CBF1 and blocks differentiation | journal = J. Virol. | volume = 71 | issue = 3 | pages = 1938–45 | year = 1997 | pmid = 9032325 | pmc = 191274 | doi = }}
  • {{cite journal | vauthors = Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S | title = Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane | journal = Cell | volume = 90 | issue = 2 | pages = 281–91 | year = 1997 | pmid = 9244302 | doi = 10.1016/S0092-8674(00)80336-0 }}
  • {{cite journal | vauthors = Bigas A, Martin DI, Milner LA | title = Notch1 and Notch2 inhibit myeloid differentiation in response to different cytokines | journal = Mol. Cell. Biol. | volume = 18 | issue = 4 | pages = 2324–33 | year = 1998 | pmid = 9528802 | pmc = 121486 | doi = }}
  • {{cite journal | vauthors = Berezovska O, Xia MQ, Hyman BT | title = Notch is expressed in adult brain, is coexpressed with presenilin-1, and is altered in Alzheimer disease | journal = J. Neuropathol. Exp. Neurol. | volume = 57 | issue = 8 | pages = 738–45 | year = 1998 | pmid = 9720489 | doi = 10.1097/00005072-199808000-00003 }}
  • {{cite journal | vauthors = Gray GE, Mann RS, Mitsiadis E, Henrique D, Carcangiu ML, Banks A, Leiman J, Ward D, Ish-Horowitz D, Artavanis-Tsakonas S | title = Human ligands of the Notch receptor | journal = Am. J. Pathol. | volume = 154 | issue = 3 | pages = 785–94 | year = 1999 | pmid = 10079256 | pmc = 1866435 | doi = 10.1016/S0002-9440(10)65325-4 }}
  • {{cite journal | vauthors = Shimizu K, Chiba S, Kumano K, Hosoya N, Takahashi T, Kanda Y, Hamada Y, Yazaki Y, Hirai H | title = Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods | journal = J. Biol. Chem. | volume = 274 | issue = 46 | pages = 32961–9 | year = 2000 | pmid = 10551863 | doi = 10.1074/jbc.274.46.32961 }}
  • {{cite journal | vauthors = Shimizu K, Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, Kanda Y, Hamada Y, Hirai H | title = Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2 | journal = Mol. Cell. Biol. | volume = 20 | issue = 18 | pages = 6913–22 | year = 2000 | pmid = 10958687 | pmc = 88767 | doi = 10.1128/MCB.20.18.6913-6922.2000 }}
  • {{cite journal | vauthors = Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD | title = MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors | journal = Nat. Genet. | volume = 26 | issue = 4 | pages = 484–9 | year = 2001 | pmid = 11101851 | doi = 10.1038/82644 }}
  • {{cite journal | vauthors = Sriuranpong V, Borges MW, Ravi RK, Arnold DR, Nelkin BD, Baylin SB, Ball DW | title = Notch signaling induces cell cycle arrest in small cell lung cancer cells | journal = Cancer Res. | volume = 61 | issue = 7 | pages = 3200–5 | year = 2001 | pmid = 11306509 | doi = }}
  • {{cite journal | vauthors = Shimizu K, Chiba S, Saito T, Kumano K, Takahashi T, Hirai H | title = Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation | journal = J. Biol. Chem. | volume = 276 | issue = 28 | pages = 25753–8 | year = 2001 | pmid = 11346656 | doi = 10.1074/jbc.M103473200 }}
  • {{cite journal | vauthors = Saxena MT, Schroeter EH, Mumm JS, Kopan R | title = Murine notch homologs (N1-4) undergo presenilin-dependent proteolysis | journal = J. Biol. Chem. | volume = 276 | issue = 43 | pages = 40268–73 | year = 2001 | pmid = 11518718 | doi = 10.1074/jbc.M107234200 }}
  • {{cite journal | vauthors = Inglés-Esteve J, Espinosa L, Milner LA, Caelles C, Bigas A | title = Phosphorylation of Ser2078 modulates the Notch2 function in 32D cell differentiation | journal = J. Biol. Chem. | volume = 276 | issue = 48 | pages = 44873–80 | year = 2002 | pmid = 11577080 | doi = 10.1074/jbc.M104703200 }}
{{refend}}

External links

  • [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=alagille GeneReviews/NCBI/UW/NIH entry on Alagille syndrome]
  • [https://www.ncbi.nlm.nih.gov/omim/118450,600275,601920,610205,118450,600275,601920,610205 OMIM entries on Alagille syndrome]
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