Browse NOTCH4

Summary
SymbolNOTCH4
Namenotch 4
Aliases Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location6p21.3
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 Cell membrane; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: Notch 4 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus.
Domain PF00023 Ankyrin repeat
PF12796 Ankyrin repeats (3 copies)
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. May regulate branching morphogenesis in the developing vascular system (By similarity).

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0001569 patterning of blood vessels
GO:0001709 cell fate determination
GO:0001763 morphogenesis of a branching structure
GO:0001885 endothelial cell development
GO:0001886 endothelial cell morphogenesis
GO:0002064 epithelial cell development
GO:0003158 endothelium development
GO:0003382 epithelial cell morphogenesis
GO:0006352 DNA-templated transcription, initiation
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0007219 Notch signaling pathway
GO:0007220 Notch receptor processing
GO:0007221 positive regulation of transcription of Notch receptor target
GO:0007389 pattern specification process
GO:0030856 regulation of epithelial cell differentiation
GO:0030857 negative regulation of epithelial cell differentiation
GO:0030879 mammary gland development
GO:0035239 tube morphogenesis
GO:0045165 cell fate commitment
GO:0045446 endothelial cell differentiation
GO:0045601 regulation of endothelial cell differentiation
GO:0045602 negative regulation of endothelial cell differentiation
GO:0048514 blood vessel morphogenesis
GO:0048732 gland development
GO:0048754 branching morphogenesis of an epithelial tube
GO:0060562 epithelial tube morphogenesis
GO:0061138 morphogenesis of a branching epithelium
Molecular Function GO:0046982 protein heterodimerization activity
Cellular Component -
> 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-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-1980150: Signaling by NOTCH4
Summary
SymbolNOTCH4
Namenotch 4
Aliases Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between NOTCH4 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
 

There is no record.

Summary
SymbolNOTCH4
Namenotch 4
Aliases Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location6p21.3
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 NOTCH4 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
SymbolNOTCH4
Namenotch 4
Aliases Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location6p21.3
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 NOTCH4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)141201
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)6501
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)8701
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.050.883
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.0520.983
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.0420.989
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.3360.334
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.4480.651
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1750.878
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.1270.449
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.9990.327
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.4753.02e-05
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of NOTCH4 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) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277329.65.524.10.0026
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275929.66.822.80.0077
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 382710.5010.50.135
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221313.6013.60.279
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.109.10.458
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 6116.7016.71
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolNOTCH4
Namenotch 4
Aliases Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NOTCH4. 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
SymbolNOTCH4
Namenotch 4
Aliases Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NOTCH4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NOTCH4.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolNOTCH4
Namenotch 4
Aliases Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NOTCH4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolNOTCH4
Namenotch 4
Aliases Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of NOTCH4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolNOTCH4
Namenotch 4
Aliases Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between NOTCH4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolNOTCH4
Namenotch 4
Aliases Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting NOTCH4 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.