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NOTCH1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1PB5, 1TOZ, 1YYH, 2F8X, 2F8Y, 2HE0, 2VJ3, 3ETO, 3I08, 3L95, 3NBN, 3V79, 4CUD, 4CUE, 4CUF, 4D0E, 4D0F, 5FM9, 5FMA
Identifiers
Aliases	NOTCH1, Notch1, 9930111A19Rik, Mis6, N1, Tan1, lin-12, AOS5, AOVD1, hN1, notch 1, notch receptor 1
External IDs	OMIM: 190198; MGI: 97363; HomoloGene: 32049; GeneCards: NOTCH1; OMA:NOTCH1 - orthologs
Gene location (Human) Chr. Chromosome 9 (human) Band 9q34.3 Start 136,494,433 bp End 136,546,048 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2 A3|2 18.91 cM Start 26,347,915 bp End 26,406,675 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone epithelium of colon visceral pleura external globus pallidus ganglionic eminence blood gingival epithelium superficial temporal artery granulocyte vulva Top expressed in hair follicle vestibular sensory epithelium vasculature of trunk Rostral migratory stream granulocyte transitional epithelium of urinary bladder conjunctival fornix renal corpuscle skin of back vestibular membrane of cochlear duct More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding DNA-binding transcription factor activity Notch binding enzyme inhibitor activity metal ion binding enzyme binding chromatin binding protein binding sequence-specific DNA binding protein heterodimerization activity chromatin DNA binding transmembrane signaling receptor activity signaling receptor activity RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific Cellular component cytoplasm cytosol membrane adherens junction extracellular region nucleus cell surface apical plasma membrane endoplasmic reticulum integral component of membrane Golgi apparatus receptor complex plasma membrane nucleoplasm MAML1-RBP-Jkappa- ICN1 complex cell periphery endoplasmic reticulum membrane Golgi membrane acrosomal vesicle cytoplasmic vesicle Biological process cardiac vascular smooth muscle cell development endoderm development pulmonary valve morphogenesis positive regulation of endothelial cell differentiation regulation of somitogenesis cell differentiation in spinal cord negative regulation of neuron differentiation regulation of extracellular matrix assembly distal tubule development negative regulation of glial cell proliferation epithelial to mesenchymal transition involved in endocardial cushion formation regulation of transcription by RNA polymerase II aortic valve morphogenesis oligodendrocyte differentiation endocardium morphogenesis negative regulation of osteoblast differentiation negative regulation of stem cell differentiation negative regulation of ossification heart looping negative regulation of photoreceptor cell differentiation arterial endothelial cell differentiation atrioventricular valve morphogenesis Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation humoral immune response foregut morphogenesis negative regulation of oligodendrocyte differentiation positive regulation of cardiac muscle cell proliferation regulation of developmental process mesenchymal cell development animal organ regeneration angiogenesis spermatogenesis negative regulation of pro-B cell differentiation regulation of cardioblast proliferation hair follicle morphogenesis vasculogenesis involved in coronary vascular morphogenesis negative regulation of canonical Wnt signaling pathway regulation of neurogenesis negative regulation of cell population proliferation collecting duct development positive regulation of neuroblast proliferation cilium assembly heart trabecula morphogenesis atrioventricular node development negative regulation of myoblast differentiation cell fate commitment regulation of transcription, DNA-templated cellular response to follicle-stimulating hormone stimulus lung development negative regulation of inner ear auditory receptor cell differentiation cardiac septum morphogenesis ventricular septum morphogenesis negative regulation of cell differentiation coronary artery morphogenesis response to muramyl dipeptide cardiac left ventricle morphogenesis in utero embryonic development negative regulation of cell death endocardial cell differentiation transcription, DNA-templated positive regulation of transcription, DNA-templated heart development prostate gland epithelium morphogenesis embryonic limb morphogenesis growth involved in heart morphogenesis neural tube development pericardium morphogenesis epidermis development cardiac atrium morphogenesis transcription initiation from RNA polymerase II promoter cardiac right atrium morphogenesis negative regulation of cell-substrate adhesion cell migration involved in endocardial cushion formation cell differentiation venous endothelial cell differentiation regulation of inner ear auditory receptor cell differentiation negative regulation of catalytic activity inflammatory response to antigenic stimulus positive regulation of astrocyte differentiation positive regulation of epithelial cell proliferation cardiac right ventricle formation endocardial cushion development cell fate specification positive regulation of keratinocyte differentiation positive regulation of glial cell differentiation negative regulation of neurogenesis glomerular mesangial cell development sprouting angiogenesis glial cell differentiation negative regulation of transcription by RNA polymerase II cardiac muscle cell proliferation secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development positive regulation of epithelial to mesenchymal transition ventricular trabecula myocardium morphogenesis neuronal stem cell population maintenance negative regulation of cell migration involved in sprouting angiogenesis response to lipopolysaccharide compartment pattern specification immune response neuron differentiation epithelial to mesenchymal transition positive regulation of BMP signaling pathway skeletal muscle cell differentiation regulation of gene expression positive regulation of viral genome replication regulation of epithelial cell proliferation involved in prostate gland development negative regulation of transcription, DNA-templated cardiac ventricle morphogenesis branching morphogenesis of an epithelial tube positive regulation of receptor signaling pathway via JAK-STAT negative regulation of anoikis Notch signaling involved in heart development coronary vein morphogenesis apoptotic process involved in embryonic digit morphogenesis regulation of cell migration axonogenesis tissue regeneration positive regulation of cell migration somatic stem cell division cardiac muscle tissue morphogenesis negative regulation of endothelial cell chemotaxis keratinocyte differentiation negative regulation of BMP signaling pathway endocardial cushion morphogenesis endocardium development multicellular organism development auditory receptor cell fate commitment response to corticosteroid tube formation determination of left/right symmetry astrocyte differentiation negative regulation of calcium ion-dependent exocytosis brain development regulation of cell population proliferation positive regulation of cell population proliferation negative regulation of myotube differentiation positive regulation of apoptotic process positive regulation of transcription from RNA polymerase II promoter in response to hypoxia mitral valve formation liver development cardiac chamber formation forebrain development cellular response to vascular endothelial growth factor stimulus neuron fate commitment regulation of epithelial cell proliferation regulation of Notch signaling pathway left/right axis specification positive regulation of transcription by RNA polymerase II cardiac epithelial to mesenchymal transition embryonic hindlimb morphogenesis positive regulation of aorta morphogenesis venous blood vessel morphogenesis Notch signaling pathway negative regulation of gene expression negative regulation of growth rate positive regulation of Ras protein signal transduction positive regulation of ERK1 and ERK2 cascade positive regulation of transcription of Notch receptor target positive regulation of Notch signaling pathway outflow tract morphogenesis coronary sinus valve morphogenesis negative regulation of cell proliferation involved in heart valve morphogenesis negative regulation of extracellular matrix constituent secretion negative regulation of cardiac muscle hypertrophy positive regulation of gene expression homeostasis of number of cells within a tissue negative regulation of biomineral tissue development positive regulation of apoptotic process involved in morphogenesis positive regulation of cardiac epithelial to mesenchymal transition negative regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4851 18128 Ensembl ENSG00000148400 ENSMUSG00000026923 UniProt P46531 Q01705 RefSeq (mRNA) NM_017617 NM_008714 RefSeq (protein) NP_060087 NP_032740 Location (UCSC) Chr 9: 136.49 – 136.55 Mb Chr 2: 26.35 – 26.41 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Neurogenic locus notch homolog protein 1 (Notch 1) is a protein encoded in humans by the NOTCH1 gene. Notch 1 is a single-pass transmembrane receptor.

Function

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 Drosophila, 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 humans, 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 multiple roles during development.

A deficiency can be associated with bicuspid aortic valve.

There is evidence that activated Notch 1 and Notch 3 promote differentiation of progenitor cells into astroglia. Notch 1, when activated before birth, induces radial glia differentiation, but postnatally induces the differentiation into astrocytes. One study shows that Notch-1 cascade is activated by Reelin in an unidentified way. Reelin and Notch1 cooperate in the development of the dentate gyrus, according to another.

Interactions

NOTCH1 has been shown to interact with:

• GSK3B,
• Lck,
• MAML1,
• Mothers against decapentaplegic homolog 3
• NFKB1,
• NOV,
• RBPJ,
• SNW1,
• Ubiquitin C, and
• YY1.
• USP10.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000148400 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000026923 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "NOTCH1 - Neurogenic locus notch homolog protein 1 precursor - Homo sapiens (Human) - NOTCH1 gene & protein". www.uniprot.org. Retrieved 23 May 2022.
6. "Entrez Gene: NOTCH1 Notch homolog 1, translocation-associated (Drosophila)".
7. McKellar SH, Tester DJ, Yagubyan M, Majumdar R, Ackerman MJ, Sundt TM (August 2007). "Novel NOTCH1 mutations in patients with bicuspid aortic valve disease and thoracic aortic aneurysms". J Thorac Cardiovasc Surg. 134 (2): 290–296. doi:10.1016/j.jtcvs.2007.02.041. PMID 17662764.
8. Tanigaki K, Nogaki F, Takahashi J, Tashiro K, Kurooka H, Honjo T (January 2001). "Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate". Neuron. 29 (1): 45–55. doi:10.1016/S0896-6273(01)00179-9. hdl:2433/150564. PMID 11182080. S2CID 17047028.
9. Gaiano N, Nye JS, Fishell G (May 2000). "Radial glial identity is promoted by Notch1 signaling in the murine forebrain". Neuron. 26 (2): 395–404. doi:10.1016/S0896-6273(00)81172-1. PMID 10839358. S2CID 15861936.
10. Chambers CB, Peng Y, Nguyen H, Gaiano N, Fishell G, Nye JS (March 2001). "Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors". Development. 128 (5): 689–702. doi:10.1242/dev.128.5.689. PMID 11171394.
11. Keilani S, Sugaya K (July 2008). "Reelin induces a radial glial phenotype in human neural progenitor cells by activation of Notch-1". BMC Dev. Biol. 8 (1): 69. doi:10.1186/1471-213X-8-69. PMC 2447831. PMID 18593473.
12. Sibbe M, Förster E, Basak O, Taylor V, Frotscher M (July 2009). "Reelin and Notch1 cooperate in the development of the dentate gyrus". J. Neurosci. 29 (26): 8578–85. doi:10.1523/JNEUROSCI.0958-09.2009. PMC 6665659. PMID 19571148.
13. Foltz DR, Santiago MC, Berechid BE, Nye JS (June 2002). "Glycogen synthase kinase-3beta modulates notch signaling and stability". Curr. Biol. 12 (12): 1006–11. Bibcode:2002CBio...12.1006F. doi:10.1016/s0960-9822(02)00888-6. PMID 12123574. S2CID 15884556.
14. Sade H, Krishna S, Sarin A (January 2004). "The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells". J. Biol. Chem. 279 (4): 2937–44. doi:10.1074/jbc.M309924200. PMID 14583609. S2CID 42454311.
15. Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD (December 2000). "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.
16. Wu L, Sun T, Kobayashi K, Gao P, Griffin JD (November 2002). "Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors". Mol. Cell. Biol. 22 (21): 7688–700. doi:10.1128/mcb.22.21.7688-7700.2002. PMC 135662. PMID 12370315.
17. Blokzijl A, Dahlqvist C, Reissmann E, Falk A, Moliner A, Lendahl U, Ibáñez CF (November 2003). "Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3". J. Cell Biol. 163 (4): 723–8. doi:10.1083/jcb.200305112. PMC 2173673. PMID 14638857.
18. Guan E, Wang J, Laborda J, Norcross M, Baeuerle PA, Hoffman T (May 1996). "T cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T cells". J. Exp. Med. 183 (5): 2025–32. doi:10.1084/jem.183.5.2025. PMC 2192574. PMID 8642313.
19. Wang J, Shelly L, Miele L, Boykins R, Norcross MA, Guan E (July 2001). "Human Notch-1 inhibits NF-kappa B activity in the nucleus through a direct interaction involving a novel domain". J. Immunol. 167 (1): 289–95. doi:10.4049/jimmunol.167.1.289. PMID 11418662. S2CID 22399328.
20. Sakamoto K, Yamaguchi S, Ando R, Miyawaki A, Kabasawa Y, Takagi M, Li CL, Perbal B, Katsube K (August 2002). "The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway". J. Biol. Chem. 277 (33): 29399–405. doi:10.1074/jbc.M203727200. PMID 12050162. S2CID 26465428.
21. Nam Y, Weng AP, Aster JC, Blacklow SC (June 2003). "Structural requirements for assembly of the CSL.intracellular Notch1.Mastermind-like 1 transcriptional activation complex". J. Biol. Chem. 278 (23): 21232–9. doi:10.1074/jbc.M301567200. PMID 12644465. S2CID 13637961.
22. Aster JC, Robertson ES, Hasserjian RP, Turner JR, Kieff E, Sklar J (April 1997). "Oncogenic forms of NOTCH1 lacking either the primary binding site for RBP-Jkappa or nuclear localization sequences retain the ability to associate with RBP-Jkappa and activate transcription". J. Biol. Chem. 272 (17): 11336–43. doi:10.1074/jbc.272.17.11336. PMID 9111040. S2CID 36236215.
23. Beatus P, Lundkvist J, Oberg C, Pedersen K, Lendahl U (June 2001). "The origin of the ankyrin repeat region in Notch intracellular domains is critical for regulation of HES promoter activity". Mech. Dev. 104 (1–2): 3–20. doi:10.1016/s0925-4773(01)00373-2. PMID 11404076. S2CID 9526831.
24. Zhou S, Fujimuro M, Hsieh JJ, Chen L, Miyamoto A, Weinmaster G, Hayward SD (April 2000). "SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function". Mol. Cell. Biol. 20 (7): 2400–10. doi:10.1128/mcb.20.7.2400-2410.2000. PMC 85419. PMID 10713164.
25. Chastagner P, Israël A, Brou C (2008). "AIP4/Itch regulates Notch receptor degradation in the absence of ligand". PLOS ONE. 3 (7): e2735. Bibcode:2008PLoSO...3.2735C. doi:10.1371/journal.pone.0002735. PMC 2444042. PMID 18628966.
26. Yeh TS, Lin YM, Hsieh RH, Tseng MJ (October 2003). "Association of transcription factor YY1 with the high molecular weight Notch complex suppresses the transactivation activity of Notch". J. Biol. Chem. 278 (43): 41963–9. doi:10.1074/jbc.M304353200. PMID 12913000. S2CID 23574059.
27. Lim R, Sugino T, Nolte H, Andrade J, Zimmermann B, Shi C, Doddaballapur A, Ong YT, Wilhelm K, Fasse JW, Ernst A, Kaulich M, Husnjak K, Boettger T, Guenther S, Braun T, Krüger M, Benedito R, Dikic I, Potente M (April 2019). "Deubiquitinase USP10 regulates Notch signaling in the endothelium". Science. 364 (6436): 188–193. Bibcode:2019Sci...364..188L. doi:10.1126/science.aat0778. hdl:20.500.12105/9685. PMID 30975888. S2CID 109940358.

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.
• 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. S2CID 1328739.
• Aster JC (2006). "Deregulated NOTCH signaling in acute T-cell lymphoblastic leukemia/lymphoma: new insights, questions, and opportunities". Int. J. Hematol. 82 (4): 295–301. doi:10.1532/IJH97.05096. PMID 16298817. S2CID 32528011.

External links

• NOTCH1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• NOTCH1

• Genes on human chromosome 9