NOTCH4

Notch 4
Identifiers
Symbols	NOTCH4; FLJ16302; INT3; MGC74442; NOTCH3
External IDs	OMIM: 164951 MGI: 107471 HomoloGene: 3351 GeneCards: NOTCH4 Gene
Gene Ontology Molecular function • receptor activity • calcium ion binding • protein binding • protein heterodimerization activity Cellular component • extracellular region • nucleus • nucleoplasm • endoplasmic reticulum lumen • Golgi lumen • cytosol • plasma membrane • integral to plasma membrane • cell surface Biological process • patterning of blood vessels • cell fate determination • morphogenesis of a branching structure • endothelial cell morphogenesis • Notch signaling pathway • Notch receptor processing • embryo development • gene expression • hemopoiesis • cell differentiation • mammary gland development • negative regulation of cell differentiation • negative regulation of endothelial cell differentiation • positive regulation of transcription, DNA-dependent • regulation of developmental process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4855	18132
Ensembl	n/a	ENSMUSG00000015468
UniProt	Q99466	P31695
RefSeq (mRNA)	NM_004557.3	NM_010929.2
RefSeq (protein)	NP_004548.3	NP_035059.2
Location (UCSC)	n/a	Chr 17: 34.7 – 34.73 Mb
PubMed search	[1]	[2]

Neurogenic locus notch homolog protein 4 is a protein that in humans is encoded by the NOTCH4 gene.^[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 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. This gene may be associated with susceptibility to schizophrenia in a small portion of cases. An alternative splice variant has been described but its biological nature has not been determined.^[2]

References

1. ^ 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. PMID 7835890. 
2. ^ "Entrez Gene: NOTCH4 Notch homolog 4 (Drosophila)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4855. 

Further reading

• Artavanis-Tsakonas S, Rand MD, Lake RJ (1999). "Notch signaling: cell fate control and signal integration in development.". Science 284 (5415): 770–6. Bibcode 1999Sci...284..770A. doi:10.1126/science.284.5415.770. PMID 10221902. 
• Mumm JS, Kopan R (2001). "Notch signaling: from the outside in.". Dev. Biol. 228 (2): 151–65. doi:10.1006/dbio.2000.9960. PMID 11112321. 
• Kojika S, Griffin JD (2001). "Notch receptors and hematopoiesis.". Exp. Hematol. 29 (9): 1041–52. doi:10.1016/S0301-472X(01)00676-2. PMID 11532344. 
• Allenspach EJ, Maillard I, Aster JC, Pear WS (2003). "Notch signaling in cancer.". Cancer Biol. Ther. 1 (5): 466–76. PMID 12496471. 
• 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. PMID 16894623. 
• 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. PMID 7671825. 
• 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. PMID 8681805. 
• 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. PMID 9168133. 
• 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. PMID 9576833. 
• 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. PMID 9693032. 
• Gray GE, Mann RS, Mitsiadis E, et al. (1999). "Human ligands of the Notch receptor.". Am. J. Pathol. 154 (3): 785–94. doi:10.1016/S0002-9440(10)65325-4. PMC 1866435. PMID 10079256. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1866435. 
• 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. PMID 10645000. 
• Wei J, Hemmings GP (2000). "The NOTCH4 locus is associated with susceptibility to schizophrenia.". Nat. Genet. 25 (4): 376–7. doi:10.1038/78044. PMID 10932176. 
• 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. PMID 11078798. 
• 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. PMID 11101851. 
• Kusano S, Raab-Traub N (2001). "An Epstein-Barr virus protein interacts with Notch.". J. Virol. 75 (1): 384–95. doi:10.1128/JVI.75.1.384-395.2001. PMC 113931. PMID 11119607. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=113931. 
• 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. PMID 11381257. 

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