Browse HBEGF

Summary
SymbolHBEGF
Nameheparin-binding EGF-like growth factor
Aliases Diphtheria toxin receptor (heparin-binding EGF-like growth factor); heparin-binding epidermal growth factor; ......
Chromosomal Location5q23
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 Heparin-binding EGF-like growth factor: Secreted, extracellular space. Note=Mature HB-EGF is released into the extracellular space and probably binds to a receptor.; SUBCELLULAR LOCATION: Proheparin-binding EGF-like growth factor: Cell membrane; Single-pass type I membrane protein.
Domain PF00008 EGF-like domain
Function

Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4. Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor.

> Gene Ontology
 
Biological Process GO:0001558 regulation of cell growth
GO:0001667 ameboidal-type cell migration
GO:0002011 morphogenesis of an epithelial sheet
GO:0003013 circulatory system process
GO:0003015 heart process
GO:0006644 phospholipid metabolic process
GO:0006650 glycerophospholipid metabolic process
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007517 muscle organ development
GO:0008015 blood circulation
GO:0008016 regulation of heart contraction
GO:0009100 glycoprotein metabolic process
GO:0009101 glycoprotein biosynthetic process
GO:0010559 regulation of glycoprotein biosynthetic process
GO:0010561 negative regulation of glycoprotein biosynthetic process
GO:0010631 epithelial cell migration
GO:0010632 regulation of epithelial cell migration
GO:0010634 positive regulation of epithelial cell migration
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0014066 regulation of phosphatidylinositol 3-kinase signaling
GO:0016049 cell growth
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0030258 lipid modification
GO:0030307 positive regulation of cell growth
GO:0030335 positive regulation of cell migration
GO:0033002 muscle cell proliferation
GO:0035313 wound healing, spreading of epidermal cells
GO:0038127 ERBB signaling pathway
GO:0038128 ERBB2 signaling pathway
GO:0040017 positive regulation of locomotion
GO:0043491 protein kinase B signaling
GO:0044057 regulation of system process
GO:0044319 wound healing, spreading of cells
GO:0045927 positive regulation of growth
GO:0046486 glycerolipid metabolic process
GO:0046488 phosphatidylinositol metabolic process
GO:0046834 lipid phosphorylation
GO:0046854 phosphatidylinositol phosphorylation
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048017 inositol lipid-mediated signaling
GO:0048659 smooth muscle cell proliferation
GO:0048660 regulation of smooth muscle cell proliferation
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0051272 positive regulation of cellular component movement
GO:0051541 elastin metabolic process
GO:0051542 elastin biosynthetic process
GO:0051543 regulation of elastin biosynthetic process
GO:0051545 negative regulation of elastin biosynthetic process
GO:0051546 keratinocyte migration
GO:0051547 regulation of keratinocyte migration
GO:0051549 positive regulation of keratinocyte migration
GO:0051896 regulation of protein kinase B signaling
GO:0051897 positive regulation of protein kinase B signaling
GO:0060047 heart contraction
GO:0060326 cell chemotaxis
GO:0061041 regulation of wound healing
GO:0090130 tissue migration
GO:0090132 epithelium migration
GO:0090303 positive regulation of wound healing
GO:0090504 epiboly
GO:0090505 epiboly involved in wound healing
GO:1903018 regulation of glycoprotein metabolic process
GO:1903019 negative regulation of glycoprotein metabolic process
GO:1903034 regulation of response to wounding
GO:1903036 positive regulation of response to wounding
GO:1903522 regulation of blood circulation
GO:2000147 positive regulation of cell motility
Molecular Function GO:0004713 protein tyrosine kinase activity
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0005154 epidermal growth factor receptor binding
GO:0005539 glycosaminoglycan binding
GO:0008083 growth factor activity
GO:0008201 heparin binding
GO:0035004 phosphatidylinositol 3-kinase activity
GO:0046934 phosphatidylinositol-4,5-bisphosphate 3-kinase activity
GO:0052813 phosphatidylinositol bisphosphate kinase activity
GO:0070851 growth factor receptor binding
GO:1901681 sulfur compound binding
Cellular Component GO:0030135 coated vesicle
GO:0030136 clathrin-coated vesicle
GO:0030139 endocytic vesicle
GO:0030659 cytoplasmic vesicle membrane
GO:0030662 coated vesicle membrane
GO:0030665 clathrin-coated vesicle membrane
GO:0030666 endocytic vesicle membrane
GO:0030669 clathrin-coated endocytic vesicle membrane
GO:0045334 clathrin-coated endocytic vesicle
> KEGG and Reactome Pathway
 
KEGG hsa04012 ErbB signaling pathway
hsa04912 GnRH signaling pathway
hsa04915 Estrogen signaling pathway
Reactome R-HSA-170984: ARMS-mediated activation
R-HSA-1280218: Adaptive Immune System
R-HSA-422475: Axon guidance
R-HSA-2219530: Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-8863795: Downregulation of ERBB2 signaling
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-2179392: EGFR Transactivation by Gastrin
R-HSA-8847993: ERBB2 Activates PTK6 Signaling
R-HSA-6785631: ERBB2 Regulates Cell Motility
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-170968: Frs2-mediated activation
R-HSA-180292: GAB1 signalosome
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-1963640: GRB2 events in ERBB2 signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-5683057: MAPK family signaling cascades
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-375165: NCAM signaling for neurite out-growth
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-199418: Negative regulation of the PI3K/AKT network
R-HSA-1251985: Nuclear signaling by ERBB4
R-HSA-1963642: PI3K events in ERBB2 signaling
R-HSA-1250342: PI3K events in ERBB4 signaling
R-HSA-2219528: PI3K/AKT Signaling in Cancer
R-HSA-198203: PI3K/AKT activation
R-HSA-6811558: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-8857538: PTK6 promotes HIF1A stabilization
R-HSA-169893: Prolonged ERK activation events
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-1250196: SHC1 events in ERBB2 signaling
R-HSA-1250347: SHC1 events in ERBB4 signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-1227986: Signaling by ERBB2
R-HSA-1236394: Signaling by ERBB4
R-HSA-372790: Signaling by GPCR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-186797: Signaling by PDGF
R-HSA-8848021: Signaling by PTK6
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
R-HSA-187706: Signalling to p38 via RIT and RIN
R-HSA-5339562: Uptake and actions of bacterial toxins
R-HSA-5336415: Uptake and function of diphtheria toxin
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation
Summary
SymbolHBEGF
Nameheparin-binding EGF-like growth factor
Aliases Diphtheria toxin receptor (heparin-binding EGF-like growth factor); heparin-binding epidermal growth factor; ......
Chromosomal Location5q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between HBEGF 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 HBEGF and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
24346967Lung CarcinomaInhibit immunityThe combination of HB-EGF (heparin-binding EGF-like growth factor) and CXCL5 (CXCL5/epithelial neutrophil-activating peptide-78) produced a strong synergistic effect on cancer proliferation, epithelial-mesenchymal transition, migration and invasion.
Summary
SymbolHBEGF
Nameheparin-binding EGF-like growth factor
Aliases Diphtheria toxin receptor (heparin-binding EGF-like growth factor); heparin-binding epidermal growth factor; ......
Chromosomal Location5q23
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 HBEGF 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
SymbolHBEGF
Nameheparin-binding EGF-like growth factor
Aliases Diphtheria toxin receptor (heparin-binding EGF-like growth factor); heparin-binding epidermal growth factor; ......
Chromosomal Location5q23
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 HBEGF in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.2660.582
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.530.743
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0610.955
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.7060.176
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.9420.544
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.4040.841
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0680.862
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.4830.675
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.4430.713
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.3660.727
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.8670.554
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.4980.00523
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of HBEGF 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)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) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
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
SymbolHBEGF
Nameheparin-binding EGF-like growth factor
Aliases Diphtheria toxin receptor (heparin-binding EGF-like growth factor); heparin-binding epidermal growth factor; ......
Chromosomal Location5q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HBEGF. 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
SymbolHBEGF
Nameheparin-binding EGF-like growth factor
Aliases Diphtheria toxin receptor (heparin-binding EGF-like growth factor); heparin-binding epidermal growth factor; ......
Chromosomal Location5q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HBEGF. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HBEGF.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolHBEGF
Nameheparin-binding EGF-like growth factor
Aliases Diphtheria toxin receptor (heparin-binding EGF-like growth factor); heparin-binding epidermal growth factor; ......
Chromosomal Location5q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HBEGF. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolHBEGF
Nameheparin-binding EGF-like growth factor
Aliases Diphtheria toxin receptor (heparin-binding EGF-like growth factor); heparin-binding epidermal growth factor; ......
Chromosomal Location5q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of HBEGF expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolHBEGF
Nameheparin-binding EGF-like growth factor
Aliases Diphtheria toxin receptor (heparin-binding EGF-like growth factor); heparin-binding epidermal growth factor; ......
Chromosomal Location5q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between HBEGF and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolHBEGF
Nameheparin-binding EGF-like growth factor
Aliases Diphtheria toxin receptor (heparin-binding EGF-like growth factor); heparin-binding epidermal growth factor; ......
Chromosomal Location5q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting HBEGF collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.