Browse DLL4

Summary
SymbolDLL4
Namedelta-like 4 (Drosophila)
Aliases delta-like 4 homolog (Drosophila); hdelta2; delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 prot ......
Chromosomal Location15q14
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
Domain PF01414 Delta serrate ligand
PF00008 EGF-like domain
PF07657 N terminus of Notch ligand
Function

Involved in the Notch signaling pathway as Notch ligand (PubMed:11134954). Activates NOTCH1 and NOTCH4. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting (PubMed:20616313). Essential for retinal progenitor proliferation. Required for suppressing rod fates in late retinal progenitors as well as for proper generation of other retinal cell types (By similarity). During spinal cord neurogenesis, inhibits V2a interneuron fate (PubMed:17728344).

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0001569 patterning of blood vessels
GO:0001654 eye development
GO:0001667 ameboidal-type cell migration
GO:0001763 morphogenesis of a branching structure
GO:0001935 endothelial cell proliferation
GO:0001936 regulation of endothelial cell proliferation
GO:0001937 negative regulation of endothelial cell proliferation
GO:0001974 blood vessel remodeling
GO:0002011 morphogenesis of an epithelial sheet
GO:0002040 sprouting angiogenesis
GO:0002042 cell migration involved in sprouting angiogenesis
GO:0002043 blood vessel endothelial cell proliferation involved in sprouting angiogenesis
GO:0002521 leukocyte differentiation
GO:0003002 regionalization
GO:0003007 heart morphogenesis
GO:0003013 circulatory system process
GO:0003158 endothelium development
GO:0003159 morphogenesis of an endothelium
GO:0003205 cardiac chamber development
GO:0003206 cardiac chamber morphogenesis
GO:0003208 cardiac ventricle morphogenesis
GO:0003209 cardiac atrium morphogenesis
GO:0003222 ventricular trabecula myocardium morphogenesis
GO:0003229 ventricular cardiac muscle tissue development
GO:0003230 cardiac atrium development
GO:0003231 cardiac ventricle development
GO:0003344 pericardium morphogenesis
GO:0003407 neural retina development
GO:0007159 leukocyte cell-cell adhesion
GO:0007219 Notch signaling pathway
GO:0007220 Notch receptor processing
GO:0007389 pattern specification process
GO:0007423 sensory organ development
GO:0007507 heart development
GO:0007517 muscle organ development
GO:0007601 visual perception
GO:0008015 blood circulation
GO:0008593 regulation of Notch signaling pathway
GO:0009953 dorsal/ventral pattern formation
GO:0010594 regulation of endothelial cell migration
GO:0010596 negative regulation of endothelial cell migration
GO:0010631 epithelial cell migration
GO:0010632 regulation of epithelial cell migration
GO:0010633 negative regulation of epithelial cell migration
GO:0014706 striated muscle tissue development
GO:0016525 negative regulation of angiogenesis
GO:0021510 spinal cord development
GO:0021511 spinal cord patterning
GO:0021513 spinal cord dorsal/ventral patterning
GO:0021514 ventral spinal cord interneuron differentiation
GO:0021515 cell differentiation in spinal cord
GO:0021517 ventral spinal cord development
GO:0021953 central nervous system neuron differentiation
GO:0030098 lymphocyte differentiation
GO:0030217 T cell differentiation
GO:0030336 negative regulation of cell migration
GO:0035239 tube morphogenesis
GO:0035904 aorta development
GO:0035907 dorsal aorta development
GO:0035909 aorta morphogenesis
GO:0035912 dorsal aorta morphogenesis
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0040013 negative regulation of locomotion
GO:0042110 T cell activation
GO:0043010 camera-type eye development
GO:0043534 blood vessel endothelial cell migration
GO:0043535 regulation of blood vessel endothelial cell migration
GO:0043537 negative regulation of blood vessel endothelial cell migration
GO:0043542 endothelial cell migration
GO:0044344 cellular response to fibroblast growth factor stimulus
GO:0045165 cell fate commitment
GO:0045746 negative regulation of Notch signaling pathway
GO:0045747 positive regulation of Notch signaling pathway
GO:0045765 regulation of angiogenesis
GO:0048514 blood vessel morphogenesis
GO:0048644 muscle organ morphogenesis
GO:0048663 neuron fate commitment
GO:0048738 cardiac muscle tissue development
GO:0048754 branching morphogenesis of an epithelial tube
GO:0048771 tissue remodeling
GO:0048844 artery morphogenesis
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050680 negative regulation of epithelial cell proliferation
GO:0050953 sensory perception of light stimulus
GO:0051271 negative regulation of cellular component movement
GO:0055008 cardiac muscle tissue morphogenesis
GO:0055010 ventricular cardiac muscle tissue morphogenesis
GO:0060039 pericardium development
GO:0060041 retina development in camera-type eye
GO:0060415 muscle tissue morphogenesis
GO:0060537 muscle tissue development
GO:0060562 epithelial tube morphogenesis
GO:0060579 ventral spinal cord interneuron fate commitment
GO:0060581 cell fate commitment involved in pattern specification
GO:0060840 artery development
GO:0061074 regulation of neural retina development
GO:0061138 morphogenesis of a branching epithelium
GO:0061154 endothelial tube morphogenesis
GO:0061311 cell surface receptor signaling pathway involved in heart development
GO:0061314 Notch signaling involved in heart development
GO:0061351 neural precursor cell proliferation
GO:0061383 trabecula morphogenesis
GO:0061384 heart trabecula morphogenesis
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0071593 lymphocyte aggregation
GO:0071774 response to fibroblast growth factor
GO:0072554 blood vessel lumenization
GO:0090049 regulation of cell migration involved in sprouting angiogenesis
GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis
GO:0090130 tissue migration
GO:0090132 epithelium migration
GO:1901342 regulation of vasculature development
GO:1901343 negative regulation of vasculature development
GO:1902866 regulation of retina development in camera-type eye
GO:1903587 regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis
GO:1903588 negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis
GO:1903670 regulation of sprouting angiogenesis
GO:1903671 negative regulation of sprouting angiogenesis
GO:2000146 negative regulation of cell motility
GO:2000177 regulation of neural precursor cell proliferation
GO:2000179 positive regulation of neural precursor cell proliferation
GO:2000181 negative regulation of blood vessel morphogenesis
Molecular Function GO:0005112 Notch binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04330 Notch signaling pathway
Reactome R-HSA-2122948: Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-2691232: Constitutive Signaling by NOTCH1 HD Domain Mutants
R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2660826: Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-2979096: NOTCH2 Activation and Transmission of Signal to the Nucleus
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-1980143: Signaling by NOTCH1
R-HSA-2691230: Signaling by NOTCH1 HD Domain Mutants in Cancer
R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603: Signaling by NOTCH1 in Cancer
R-HSA-2660825: Signaling by NOTCH1 t(7;9)(NOTCH1
R-HSA-1980145: Signaling by NOTCH2
R-HSA-1980148: Signaling by NOTCH3
R-HSA-1980150: Signaling by NOTCH4
Summary
SymbolDLL4
Namedelta-like 4 (Drosophila)
Aliases delta-like 4 homolog (Drosophila); hdelta2; delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 prot ......
Chromosomal Location15q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between DLL4 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 DLL4 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
21825014Lung CarcinomaPromote immunityHere, we report a novel mechanism of escape from T-cell immunity that is caused by reduction in levels of the Delta family Notch ligands DLL1 and DLL4 in hematopoietic microenvironments. An important mediator of this effect was an elevation in the levels of circulating VEGF. Selective activation of the DLL1-Notch signaling pathway in bone marrow precursors enhanced T-cell activation and inhibited tumor growth.
Summary
SymbolDLL4
Namedelta-like 4 (Drosophila)
Aliases delta-like 4 homolog (Drosophila); hdelta2; delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 prot ......
Chromosomal Location15q14
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 DLL4 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
SymbolDLL4
Namedelta-like 4 (Drosophila)
Aliases delta-like 4 homolog (Drosophila); hdelta2; delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 prot ......
Chromosomal Location15q14
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 DLL4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.5520.0641
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.520.546
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.5810.431
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1150.777
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.6260.661
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.5330.776
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2030.536
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.080.925
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3380.719
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.5190.699
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.6810.334
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1860.0835
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of DLL4 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) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.33.71.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
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
SymbolDLL4
Namedelta-like 4 (Drosophila)
Aliases delta-like 4 homolog (Drosophila); hdelta2; delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 prot ......
Chromosomal Location15q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DLL4. 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
SymbolDLL4
Namedelta-like 4 (Drosophila)
Aliases delta-like 4 homolog (Drosophila); hdelta2; delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 prot ......
Chromosomal Location15q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DLL4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DLL4.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolDLL4
Namedelta-like 4 (Drosophila)
Aliases delta-like 4 homolog (Drosophila); hdelta2; delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 prot ......
Chromosomal Location15q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DLL4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolDLL4
Namedelta-like 4 (Drosophila)
Aliases delta-like 4 homolog (Drosophila); hdelta2; delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 prot ......
Chromosomal Location15q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of DLL4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolDLL4
Namedelta-like 4 (Drosophila)
Aliases delta-like 4 homolog (Drosophila); hdelta2; delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 prot ......
Chromosomal Location15q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between DLL4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolDLL4
Namedelta-like 4 (Drosophila)
Aliases delta-like 4 homolog (Drosophila); hdelta2; delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 prot ......
Chromosomal Location15q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting DLL4 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.