Browse NOTCH2

Summary
SymbolNOTCH2
Namenotch 2
Aliases Notch (Drosophila) homolog 2; Notch homolog 2 (Drosophila); HJCYS; Notch homolog 2; Neurogenic locus notch h ......
Chromosomal Location1p13-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Notch 2 extracellular truncation: Cell membrane Single-pass type I membrane protein ; SUBCELLULAR LOCATION: Notch 2 intracellular domain: Nucleus Cytoplasm Note=Following proteolytical processing NICD is translocated to the nucleus. Retained at the cytoplasm by TCIM (PubMed:25985737).
Domain PF12796 Ankyrin repeats (3 copies)
PF11936 Domain of unknown function (DUF3454)
PF00008 EGF-like domain
PF07645 Calcium-binding EGF domain
PF12661 Human growth factor-like EGF
PF06816 NOTCH protein
PF07684 NOTCH protein
PF00066 LNR domain
Function

Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation (PubMed:29149593). Positively regulates self-renewal of liver cancer cells (PubMed:25985737).

> Gene Ontology
 
Biological Process GO:0001709 cell fate determination
GO:0002263 cell activation involved in immune response
GO:0002285 lymphocyte activation involved in immune response
GO:0002312 B cell activation involved in immune response
GO:0002313 mature B cell differentiation involved in immune response
GO:0002315 marginal zone B cell differentiation
GO:0002335 mature B cell differentiation
GO:0002366 leukocyte activation involved in immune response
GO:0002521 leukocyte differentiation
GO:0003007 heart morphogenesis
GO:0003170 heart valve development
GO:0003177 pulmonary valve development
GO:0003179 heart valve morphogenesis
GO:0003184 pulmonary valve morphogenesis
GO:0003205 cardiac chamber development
GO:0003206 cardiac chamber morphogenesis
GO:0003209 cardiac atrium morphogenesis
GO:0003230 cardiac atrium development
GO:0003279 cardiac septum development
GO:0003283 atrial septum development
GO:0006352 DNA-templated transcription, initiation
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0007050 cell cycle arrest
GO:0007219 Notch signaling pathway
GO:0007265 Ras protein signal transduction
GO:0007507 heart development
GO:0016049 cell growth
GO:0019827 stem cell population maintenance
GO:0030098 lymphocyte differentiation
GO:0030183 B cell differentiation
GO:0030522 intracellular receptor signaling pathway
GO:0042113 B cell activation
GO:0045165 cell fate commitment
GO:0045786 negative regulation of cell cycle
GO:0046578 regulation of Ras protein signal transduction
GO:0046579 positive regulation of Ras protein signal transduction
GO:0046849 bone remodeling
GO:0048771 tissue remodeling
GO:0051056 regulation of small GTPase mediated signal transduction
GO:0051057 positive regulation of small GTPase mediated signal transduction
GO:0060411 cardiac septum morphogenesis
GO:0060413 atrial septum morphogenesis
GO:0061311 cell surface receptor signaling pathway involved in heart development
GO:0061314 Notch signaling involved in heart development
GO:0098727 maintenance of cell number
GO:1905314 semi-lunar valve development
Molecular Function GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding
GO:0038049 transcription factor activity, ligand-activated RNA polymerase II transcription factor binding
Cellular Component GO:0043235 receptor complex
> KEGG and Reactome Pathway
 
KEGG hsa04320 Dorso-ventral axis formation
hsa04330 Notch signaling pathway
hsa04919 Thyroid hormone signaling pathway
Reactome R-HSA-157212: A third proteolytic cleavage releases NICD
R-HSA-5083630: Defective LFNG causes SCDO3
R-HSA-1643685: Disease
R-HSA-3906995: Diseases associated with O-glycosylation of proteins
R-HSA-3781865: Diseases of glycosylation
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-157052: NICD traffics to nucleus
R-HSA-2979096: NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-2197563: NOTCH2 intracellular domain regulates transcription
R-HSA-350054: Notch-HLH transcription pathway
R-HSA-1912422: Pre-NOTCH Expression and Processing
R-HSA-1912420: Pre-NOTCH Processing in Golgi
R-HSA-1912399: Pre-NOTCH Processing in the Endoplasmic Reticulum
R-HSA-1912408: Pre-NOTCH Transcription and Translation
R-HSA-156988: Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor
R-HSA-162582: Signal Transduction
R-HSA-157118: Signaling by NOTCH
R-HSA-1980145: Signaling by NOTCH2
Summary
SymbolNOTCH2
Namenotch 2
Aliases Notch (Drosophila) homolog 2; Notch homolog 2 (Drosophila); HJCYS; Notch homolog 2; Neurogenic locus notch h ......
Chromosomal Location1p13-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between NOTCH2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between NOTCH2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
20351182ThymomaPromote immunityNotch2(flox/flox) mice crossed with E8I-cre transgenic (N2F/F-E8I) mice, in which the Notch2 gene is absent only in CD8(+) T cells, die earlier than control mice after inoculation with OVA-expressing EG7 thymoma cells. In contrast, Notch1(flox/flox) mice crossed with E8I-cre transgenic mice inoculated with EG7 cells die comparable to control mice, indicating that Notch2 is crucial for exerting antitumor CTL responses. These findings indicate that Notch2 signaling in CD8(+) T cells is required for generating potent antitumor CTLs, thus providing a crucial target for augmenting tumor immune responses.
Summary
SymbolNOTCH2
Namenotch 2
Aliases Notch (Drosophila) homolog 2; Notch homolog 2 (Drosophila); HJCYS; Notch homolog 2; Neurogenic locus notch h ......
Chromosomal Location1p13-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of NOTCH2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolNOTCH2
Namenotch 2
Aliases Notch (Drosophila) homolog 2; Notch homolog 2 (Drosophila); HJCYS; Notch homolog 2; Neurogenic locus notch h ......
Chromosomal Location1p13-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of NOTCH2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0160.952
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2730.888
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1670.901
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1560.586
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.0360.99
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3140.934
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1560.747
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.0470.982
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.360.88
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.7330.556
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.3450.461
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.150.073
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of NOTCH2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141714.35.98.40.576
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103200201
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277314.816.4-1.61
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 014014.3-14.31
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275914.816.9-2.11
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.16.24.91
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 472514.310.71
1329033130MelanomaallAnti-PD-1 (nivolumab) 38277.93.74.20.636
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221313.6013.60.279
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolNOTCH2
Namenotch 2
Aliases Notch (Drosophila) homolog 2; Notch homolog 2 (Drosophila); HJCYS; Notch homolog 2; Neurogenic locus notch h ......
Chromosomal Location1p13-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NOTCH2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolNOTCH2
Namenotch 2
Aliases Notch (Drosophila) homolog 2; Notch homolog 2 (Drosophila); HJCYS; Notch homolog 2; Neurogenic locus notch h ......
Chromosomal Location1p13-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NOTCH2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NOTCH2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolNOTCH2
Namenotch 2
Aliases Notch (Drosophila) homolog 2; Notch homolog 2 (Drosophila); HJCYS; Notch homolog 2; Neurogenic locus notch h ......
Chromosomal Location1p13-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NOTCH2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolNOTCH2
Namenotch 2
Aliases Notch (Drosophila) homolog 2; Notch homolog 2 (Drosophila); HJCYS; Notch homolog 2; Neurogenic locus notch h ......
Chromosomal Location1p13-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of NOTCH2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolNOTCH2
Namenotch 2
Aliases Notch (Drosophila) homolog 2; Notch homolog 2 (Drosophila); HJCYS; Notch homolog 2; Neurogenic locus notch h ......
Chromosomal Location1p13-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between NOTCH2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolNOTCH2
Namenotch 2
Aliases Notch (Drosophila) homolog 2; Notch homolog 2 (Drosophila); HJCYS; Notch homolog 2; Neurogenic locus notch h ......
Chromosomal Location1p13-p11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting NOTCH2 collected from DrugBank database.
> Drugs from DrugBank database
 

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