TISIDB

Summary
Symbol	NOTCH4
Name	notch 4
Aliases	Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location	6p21.3
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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

> KEGG and Reactome Pathway

[ TOP ]

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
Symbol	NOTCH4
Name	notch 4
Aliases	Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location	6p21.3
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 [ TOP ]
There is no record.

Summary
Symbol	NOTCH4
Name	notch 4
Aliases	Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location	6p21.3
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

[ TOP ]

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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	NOTCH4
Name	notch 4
Aliases	Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location	6p21.3
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

[ TOP ]

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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.05	0.883
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.052	0.983
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.042	0.989
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.336	0.334
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.448	0.651
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.175	0.878
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.127	0.449
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.999	0.327
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.475	3.02e-05

> Mutation difference between responders and non-responders

[ TOP ]

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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	29.6	5.5	24.1	0.0026
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	29.6	6.8	22.8	0.0077
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	10.5	0	10.5	0.135
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	0	13.6	0.279
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	16.7	0	16.7	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	NOTCH4
Name	notch 4
Aliases	Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location	6p21.3
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 [ TOP ]

Summary
Symbol	NOTCH4
Name	notch 4
Aliases	Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location	6p21.3
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NOTCH4
Name	notch 4
Aliases	Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location	6p21.3
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	NOTCH4
Name	notch 4
Aliases	Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NOTCH4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NOTCH4
Name	notch 4
Aliases	Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NOTCH4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NOTCH4
Name	notch 4
Aliases	Notch (Drosophila) homolog 4; Notch homolog 4 (Drosophila); Notch homolog 4; hNotch4; Neurogenic locus notch ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NOTCH4 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse NOTCH4