Notch 4
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
Neurogenic locus notch homolog 4 (Notch 4) is a protein that in humans is encoded by the NOTCH4 gene located on chromosome 6.{{cite journal |vauthors=Sugaya K, Fukagawa T, Matsumoto K, Mita K, Takahashi E, Ando A, Inoko H, Ikemura T | title = 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 | journal = Genomics | volume = 23 | issue = 2 | pages = 408–19 |date=Feb 1995 | pmid = 7835890 | doi =10.1006/geno.1994.1517 }}
Gene
An alternative splice variant of the NOTCH4 gene has been described, but its biological significance has not been determined.{{cite web | title = Entrez Gene: NOTCH4 Notch homolog 4 (Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4855}}
Structure
The neurogenic locus notch homolog 4 protein is a member of the Notch family. Members of this type 1 transmembrane protein family share structural characteristics. These include an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain that consists of multiple, but different, domain types.
Function
Notch protein family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling pathway is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells
In Drosophila, notch interacts with its cell-bound ligands (delta and serrate), and establishes an intercellular signaling pathway that then plays a key role in development. Homologues of the notch-ligands have also been identified in humans, but precise interactions between these ligands and the human notch homologues remain to be determined. The notch protein is cleaved in the trans-Golgi network, and then presented on the cell surface as a heterodimer. The protein functions as a receptor for membrane bound ligands, and may play a role in vascular, renal, and hepatic development.
Clinical significance
Mutations in the notch4 gene may be associated with susceptibility to schizophrenia in a small portion of cases.{{cite journal |vauthors=Shayevitz C, Cohen OS, Faraone SV, Glatt SJ | title = A re-review of the association between the NOTCH4 locus and schizophrenia | journal = Am. J. Med. Genet. B Neuropsychiatr. Genet. | volume = 159B | issue = 5 | pages = 477–83 |date=July 2012 | pmid = 22488909 | doi = 10.1002/ajmg.b.32050 | s2cid = 28027007 }}
References
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Further reading
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- {{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=Mumm JS, Kopan R |title=Notch signaling: from the outside in. |journal=Dev. Biol. |volume=228 |issue= 2 |pages= 151–65 |year= 2001 |pmid= 11112321 |doi= 10.1006/dbio.2000.9960 |doi-access= free }}
- {{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 |doi-access=free }}
- {{cite journal |vauthors=Allenspach EJ, Maillard I, Aster JC, Pear WS |title=Notch signaling in cancer. |journal=Cancer Biol. Ther. |volume=1 |issue= 5 |pages= 466–76 |year= 2003 |pmid= 12496471 |doi= 10.4161/cbt.1.5.159|doi-access=free }}
- {{cite journal |vauthors=Wang Z, Wei J, Zhang X, etal |title=A review and re-evaluation of an association between the NOTCH4 locus and schizophrenia. |journal=Am. J. Med. Genet. B Neuropsychiatr. Genet. |volume=141 |issue= 8 |pages= 902–6 |year= 2007 |pmid= 16894623 |doi= 10.1002/ajmg.b.30383 |s2cid=29260869 }}
- {{cite journal |vauthors=Matsuno K, Diederich RJ, Go MJ, etal |title=Deltex acts as a positive regulator of Notch signaling through interactions with the Notch ankyrin repeats. |journal=Development |volume=121 |issue= 8 |pages= 2633–44 |year= 1995 |doi=10.1242/dev.121.8.2633 |pmid= 7671825 }}
- {{cite journal |vauthors=Uyttendaele H, Marazzi G, Wu G, etal |title=Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific mammalian Notch gene. |journal=Development |volume=122 |issue= 7 |pages= 2251–9 |year= 1996 |doi=10.1242/dev.122.7.2251 |pmid= 8681805 }}
- {{cite journal |vauthors=Sugaya K, Sasanuma S, Nohata J, etal |title=Gene organization of human NOTCH4 and (CTG)n polymorphism in this human counterpart gene of mouse proto-oncogene Int3. |journal=Gene |volume=189 |issue= 2 |pages= 235–44 |year= 1997 |pmid= 9168133 |doi=10.1016/S0378-1119(96)00857-8 }}
- {{cite journal |vauthors=Uyttendaele H, Soriano JV, Montesano R, Kitajewski J |title=Notch4 and Wnt-1 proteins function to regulate branching morphogenesis of mammary epithelial cells in an opposing fashion. |journal=Dev. Biol. |volume=196 |issue= 2 |pages= 204–17 |year= 1998 |pmid= 9576833 |doi= 10.1006/dbio.1998.8863 |doi-access= free }}
- {{cite journal |vauthors=Li L, Huang GM, Banta AB, etal |title=Cloning, characterization, and the complete 56.8-kilobase DNA sequence of the human NOTCH4 gene. |journal=Genomics |volume=51 |issue= 1 |pages= 45–58 |year= 1998 |pmid= 9693032 |doi= 10.1006/geno.1998.5330 }}
- {{cite journal |vauthors=Gray GE, Mann RS, Mitsiadis E, etal |title=Human ligands of the Notch receptor. |journal=Am. J. Pathol. |volume=154 |issue= 3 |pages= 785–94 |year= 1999 |pmid= 10079256 |doi= 10.1016/S0002-9440(10)65325-4| pmc=1866435 }}
- {{cite journal |vauthors=Imatani A, Callahan R |title=Identification of a novel NOTCH-4/INT-3 RNA species encoding an activated gene product in certain human tumor cell lines. |journal=Oncogene |volume=19 |issue= 2 |pages= 223–31 |year= 2000 |pmid= 10645000 |doi= 10.1038/sj.onc.1203295 |doi-access= free }}
- {{cite journal |vauthors=Wei J, Hemmings GP |title=The NOTCH4 locus is associated with susceptibility to schizophrenia. |journal=Nat. Genet. |volume=25 |issue= 4 |pages= 376–7 |year= 2000 |pmid= 10932176 |doi= 10.1038/78044 |s2cid=34510337 }}
- {{cite journal |vauthors=Suzuki T, Aoki D, Susumu N, etal |title=Imbalanced expression of TAN-1 and human Notch4 in endometrial cancers. |journal=Int. J. Oncol. |volume=17 |issue= 6 |pages= 1131–9 |year= 2001 |pmid= 11078798 |doi= 10.3892/ijo.17.6.1131}}
- {{cite journal |vauthors=Wu L, Aster JC, Blacklow SC, etal |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 |s2cid=23335042 }}
- {{cite journal |vauthors=Kusano S, Raab-Traub N |title=An Epstein-Barr virus protein interacts with Notch. |journal=J. Virol. |volume=75 |issue= 1 |pages= 384–95 |year= 2001 |pmid= 11119607 |doi= 10.1128/JVI.75.1.384-395.2001 | pmc=113931 }}
- {{cite journal |vauthors=Sklar P, Schwab SG, Williams NM, etal |title=Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls. |journal=Nat. Genet. |volume=28 |issue= 2 |pages= 126–8 |year= 2001 |pmid= 11381257 |doi= 10.1038/88836 |s2cid=41566662 }}
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{{Notch signaling pathway}}