notch receptor 1 | Notch receptors | IUPHAR Guide to IMMUNOPHARMACOLOGY

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notch receptor 1

  Target has curated data in GtoImmuPdb

Target id: 2861

Nomenclature: notch receptor 1

Family: Notch receptors

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 2555 9q34.3 NOTCH1 notch receptor 1
Mouse 1 2531 2 A3 Notch1 notch 1
Rat 1 2531 3p13 Notch1 notch receptor 1
Previous and Unofficial Names
notch 1 | Notch (Drosophila) homolog 1 (translocation-associated) | TAN1
Database Links
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Inhibitor Comments
CB-103 is a small molecule that binds to the cleaved NOTCH1 receptor intracellular domain (NICD) that translocates to the nucleus and is a component of the functional nuclear NOTCH transcriptional activation complex. By inhibiting NOTCH-mediated transcriptional activation, CB-103 brings about anti-tumour effects in cancer cells that are driven by dominant active NICD.
Immunopharmacology Comments
Activating mutations in NOTCH1 are one of the most frequent somatic alterations detected in chronic lymphocytic leukemia (CLL), and such mutations are associated with poor prognosis [4-6]. The mutations found in CLL generally affect the PEST domain of the receptor, are not ongogenic in isolation and are NOTCH ligand dependent. Different NOTCH1 mutations are found in T-acute lymphoblastic leukemia (T-ALL) [1], and these are more likely to lead to constitutive, ligand-independent NOTCH pathway activation.
Immuno Process Associations
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:2000974 negative regulation of pro-B cell differentiation ISS
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:2000974 negative regulation of pro-B cell differentiation ISS
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:0002437 inflammatory response to antigenic stimulus IEA
Immuno Process:  Tissue repair
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0042246 tissue regeneration IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:0072602 interleukin-4 secretion IEA
General Comments
NOTCH1 is a single-pass transmembrane receptor protein that controls T-cell differentiation. Gain-of-function mutations in NOTCH1 are present in >50% of human T-cell acute lymphoblastic leukemias (T-ALL) [2-3].

References

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1. Belver L, Ferrando A. (2016) The genetics and mechanisms of T cell acute lymphoblastic leukaemia. Nat. Rev. Cancer, 16 (8): 494-507. [PMID:27451956]

2. Bhanushali AA, Babu S, Thangapandi VR, Pillai R, Chheda P, Das BR. (2010) Mutations in the HD and PEST domain of Notch-1 receptor in T-cell acute lymphoblastic leukemia: report of novel mutations from Indian population. Oncol. Res., 19 (2): 99-104. [PMID:21302811]

3. Grabher C, von Boehmer H, Look AT. (2006) Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat. Rev. Cancer, 6 (5): 347-59. [PMID:16612405]

4. Puente XS, Pinyol M, Quesada V, Conde L, Ordóñez GR, Villamor N, Escaramis G, Jares P, Beà S, González-Díaz M et al.. (2011) Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature, 475 (7354): 101-5. [PMID:21642962]

5. Rossi D, Rasi S, Fabbri G, Spina V, Fangazio M, Forconi F, Marasca R, Laurenti L, Bruscaggin A, Cerri M et al.. (2012) Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood, 119 (2): 521-9. [PMID:22077063]

6. Villamor N, Conde L, Martínez-Trillos A, Cazorla M, Navarro A, Beà S, López C, Colomer D, Pinyol M, Aymerich M et al.. (2013) NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia, 27 (5): 1100-6. [PMID:23295735]

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