Free for academic non-profit institutions. Other users need a Commercial license
This gene encodes a member of the NOTCH family of proteins. Members of this Type I 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 signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor plays a role in the development of numerous cell and tissue types. Mutations in this gene are associated with aortic valve disease, Adams-Oliver syndrome, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and head and neck squamous cell carcinoma. [provided by RefSeq, Jan 2016]
NOTCH1 is one of four known genes encoding the NOTCH family of proteins, a group of receptors involved in the Notch signaling pathway. NOTCH proteins are characterized by N-terminal EGF-like repeats followed by LNR domains which form a complex with ligands to prevent signaling. The Notch signaling pathway is involved in processes related to cell fate specification, differentiation, proliferation, and survival. Activation of Notch has been shown to be correlative with mammary tumorgenesis in mice and increased expression of Notch receptors has been observed in a variety of cancer types including cervical, colon, head and neck, lung, renal, pancreatic, leukemia, and breast cancer. A number of treatment modalities have been explored related to Notch inhibition especially in breast cancer with mixed results.
NOTCH1 (Notch Receptor 1) is a Protein Coding gene. Diseases associated with NOTCH1 include Aortic Valve Disease 1 and Adams-Oliver Syndrome 5. Among its related pathways are Neuroscience and Gene regulatory network modelling somitogenesis. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is NOTCH2.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000978 | RNA polymerase II proximal promoter sequence-specific DNA binding | IEA,ISS | -- |
GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | IEA,ISS | -- |
GO:0003682 | chromatin binding | IEA | -- |
GO:0003700 | DNA-binding transcription factor activity | IEA | -- |
GO:0004857 | enzyme inhibitor activity | IEA,ISS | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000139 | Golgi membrane | TAS | -- |
GO:0001669 | acrosomal vesicle | IEA | -- |
GO:0002193 | MAML1-RBP-Jkappa- ICN1 complex | IDA | 16510869 |
GO:0005576 | extracellular region | TAS | -- |
GO:0005634 | nucleus | TAS | 10713164 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Signaling by NOTCH1 | ||
2 | Pre-NOTCH Expression and Processing | ||
3 | Notch Signaling Pathway (WikiPathways) | ||
4 | NOTCH2 Activation and Transmission of Signal to the Nucleus | ||
5 | HIV Life Cycle |
.45
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000122 | negative regulation of transcription by RNA polymerase II | IEA,ISS | -- |
GO:0001525 | angiogenesis | IEA | -- |
GO:0001701 | in utero embryonic development | IEA | -- |
GO:0001708 | cell fate specification | IEA | -- |
GO:0001837 | epithelial to mesenchymal transition | IEA,ISS | -- |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
Compound | Action | Cas Number |
---|---|---|
FLI-06 | 313967-18-9 | |
LY3039478 | Notch inhibitor, novel and potent | 1421438-81-4 |
PF-03084014 | γ-secretase inhibitor | 865773-15-5 |
Z-Ile-Leu-aldehyde | 161710-10-7 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | NOTCH1 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | NOTCH1 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | NOTCH1 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Notch1 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Notch1 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | NOTCH1 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | NOTCH1 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | NOTCH1 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | NOTCH1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | notch1 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | notch1-A-prov 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | notch1b 30 31 |
|
OneToMany | |
notch1a 30 31 |
|
OneToMany | |||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.10327 30 |
|
||
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP001015 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | N 30 31 |
|
OneToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 09 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
636418 | Uncertain Significance: not provided | 136,497,290(-) | T/C | MISSENSE_VARIANT | |
636419 | Conflicting Interpretations: not provided | 136,508,390(-) | G/A | INTRON_VARIANT | |
636452 | Uncertain Significance: not provided | 136,506,571(-) | C/A | MISSENSE_VARIANT | |
636512 | Uncertain Significance: not provided | 136,513,125(-) | C/A | MISSENSE_VARIANT | |
636578 | Uncertain Significance: not provided | 136,513,042(-) | T/C | MISSENSE_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
aortic valve disease 1 |
|
|
adams-oliver syndrome 5 |
|
|
adams-oliver syndrome |
|
|
tetralogy of fallot |
|
|
familial thoracic aortic aneurysm and aortic dissection |
|