Notch 4

NOTCH4
Identifiers
Aliases	NOTCH4, INT3, notch 4, notch receptor 4
External IDs	OMIM: 164951; MGI: 107471; HomoloGene: 3351; GeneCards: NOTCH4; OMA:NOTCH4 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) Band 6p21.32 Start 32,194,843 bp End 32,224,067 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17 B1|17 18.15 cM Start 34,783,242 bp End 34,807,477 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart right lung subcutaneous adipose tissue upper lobe of left lung lactiferous gland left ventricle right auricle right lobe of thyroid gland left lobe of thyroid gland myometrium Top expressed in external carotid artery tail of embryo gastrula internal carotid artery right lung right lung lobe left lung lumbar subsegment of spinal cord myocardium of ventricle left lung lobe More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding protein heterodimerization activity calcium ion binding signaling receptor activity Notch binding Cellular component integral component of membrane cytosol endoplasmic reticulum membrane membrane Golgi membrane integral component of plasma membrane nucleoplasm extracellular region cell surface nucleus plasma membrane Biological process regulation of transcription, DNA-templated negative regulation of cell differentiation endothelial cell morphogenesis negative regulation of endothelial cell differentiation morphogenesis of a branching structure transcription, DNA-templated mammary gland development positive regulation of transcription, DNA-templated multicellular organism development positive regulation of transcription of Notch receptor target branching involved in blood vessel morphogenesis cell fate determination endothelial cell differentiation transcription initiation from RNA polymerase II promoter Notch signaling pathway cell differentiation regulation of developmental process vasculature development wound healing hemopoiesis miRNA-mediated gene silencing by inhibition of translation positive regulation of Notch signaling pathway negative regulation of Notch signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4855 18132 Ensembl ENSG00000234876 ENSG00000238196 ENSG00000204301 ENSG00000232339 ENSG00000223355 ENSG00000235396 ENSG00000206312 ENSMUSG00000015468 UniProt Q99466 P31695 RefSeq (mRNA) NM_004557 NM_010929 RefSeq (protein) NP_004548 NP_035059 Location (UCSC) Chr 6: 32.19 – 32.22 Mb Chr 17: 34.78 – 34.81 Mb PubMed search
Wikidata
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Neurogenic locus notch homolog 4 (Notch 4) is a protein that in humans is encoded by the NOTCH4 gene located on chromosome 6.

Gene

An alternative splice variant of the NOTCH4 gene has been described, but its biological significance has not been determined.

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.

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. doi:10.4161/cbt.1.5.159. 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. S2CID 29260869.
• 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. doi:10.1242/dev.121.8.2633. 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. doi:10.1242/dev.122.7.2251. 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.
• 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. S2CID 34510337.
• 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. 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. S2CID 23335042.
• 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.
• 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. S2CID 41566662.