An alternative splice variant of the NOTCH4 gene has been described, but its biological significance has not been determined.[2]
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 Drosophilia, 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.[2]
Clinical significance
Mutations in the notch4 gene may be associated with susceptibility to schizophrenia in a small portion of cases.[3]
References
↑Sugaya K, Fukagawa T, Matsumoto K, Mita K, Takahashi E, Ando A, Inoko H, Ikemura T (Feb 1995). "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". Genomics. 23 (2): 408–19. doi:10.1006/geno.1994.1517. PMID7835890.
↑Shayevitz C, Cohen OS, Faraone SV, Glatt SJ (July 2012). "A re-review of the association between the NOTCH4 locus and schizophrenia". Am. J. Med. Genet. B Neuropsychiatr. Genet. 159B (5): 477–83. doi:10.1002/ajmg.b.32050. PMID22488909.
Allenspach EJ, Maillard I, Aster JC, Pear WS (2003). "Notch signaling in cancer". Cancer Biol. Ther. 1 (5): 466–76. doi:10.4161/cbt.1.5.159. PMID12496471.
Wang Z, Wei J, Zhang X, et al. (2007). "A review and re-evaluation of an association between the NOTCH4 locus and schizophrenia". Am. J. Med. Genet. B Neuropsychiatr. Genet. 141 (8): 902–6. doi:10.1002/ajmg.b.30383. PMID16894623.
Matsuno K, Diederich RJ, Go MJ, et al. (1995). "Deltex acts as a positive regulator of Notch signaling through interactions with the Notch ankyrin repeats". Development. 121 (8): 2633–44. PMID7671825.
Uyttendaele H, Marazzi G, Wu G, et al. (1996). "Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific mammalian Notch gene". Development. 122 (7): 2251–9. PMID8681805.
Sugaya K, Sasanuma S, Nohata J, et al. (1997). "Gene organization of human NOTCH4 and (CTG)n polymorphism in this human counterpart gene of mouse proto-oncogene Int3". Gene. 189 (2): 235–44. doi:10.1016/S0378-1119(96)00857-8. PMID9168133.
Uyttendaele H, Soriano JV, Montesano R, Kitajewski J (1998). "Notch4 and Wnt-1 proteins function to regulate branching morphogenesis of mammary epithelial cells in an opposing fashion". Dev. Biol. 196 (2): 204–17. doi:10.1006/dbio.1998.8863. PMID9576833.
Li L, Huang GM, Banta AB, et al. (1998). "Cloning, characterization, and the complete 56.8-kilobase DNA sequence of the human NOTCH4 gene". Genomics. 51 (1): 45–58. doi:10.1006/geno.1998.5330. PMID9693032.
Imatani A, Callahan R (2000). "Identification of a novel NOTCH-4/INT-3 RNA species encoding an activated gene product in certain human tumor cell lines". Oncogene. 19 (2): 223–31. doi:10.1038/sj.onc.1203295. PMID10645000.
Wei J, Hemmings GP (2000). "The NOTCH4 locus is associated with susceptibility to schizophrenia". Nat. Genet. 25 (4): 376–7. doi:10.1038/78044. PMID10932176.
Suzuki T, Aoki D, Susumu N, et al. (2001). "Imbalanced expression of TAN-1 and human Notch4 in endometrial cancers". Int. J. Oncol. 17 (6): 1131–9. doi:10.3892/ijo.17.6.1131. PMID11078798.
Wu L, Aster JC, Blacklow SC, et al. (2001). "MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors". Nat. Genet. 26 (4): 484–9. doi:10.1038/82644. PMID11101851.
Sklar P, Schwab SG, Williams NM, et al. (2001). "Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls". Nat. Genet. 28 (2): 126–8. doi:10.1038/88836. PMID11381257.
