Browse EPHA3

Summary
SymbolEPHA3
NameEPH receptor A3
Aliases HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location3p11.2
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 Isoform 1: Cell membrane Single-pass type I membrane protein ; SUBCELLULAR LOCATION: Isoform 2: Secreted
Domain PF14575 Ephrin type-A receptor 2 transmembrane domain
PF01404 Ephrin receptor ligand binding domain
PF07699 Putative ephrin-receptor like
PF00041 Fibronectin type III domain
PF07714 Protein tyrosine kinase
PF07647 SAM domain (Sterile alpha motif)
Function

Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development.

> Gene Ontology
 
Biological Process GO:0000226 microtubule cytoskeleton organization
GO:0001101 response to acid chemical
GO:0001837 epithelial to mesenchymal transition
GO:0001952 regulation of cell-matrix adhesion
GO:0007044 cell-substrate junction assembly
GO:0007045 cell-substrate adherens junction assembly
GO:0007160 cell-matrix adhesion
GO:0007413 axonal fasciculation
GO:0008037 cell recognition
GO:0008038 neuron recognition
GO:0010717 regulation of epithelial to mesenchymal transition
GO:0010720 positive regulation of cell development
GO:0010810 regulation of cell-substrate adhesion
GO:0010975 regulation of neuron projection development
GO:0010976 positive regulation of neuron projection development
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0031346 positive regulation of cell projection organization
GO:0031589 cell-substrate adhesion
GO:0032526 response to retinoic acid
GO:0032886 regulation of microtubule-based process
GO:0032956 regulation of actin cytoskeleton organization
GO:0032970 regulation of actin filament-based process
GO:0034329 cell junction assembly
GO:0034330 cell junction organization
GO:0034332 adherens junction organization
GO:0034333 adherens junction assembly
GO:0045216 cell-cell junction organization
GO:0045666 positive regulation of neuron differentiation
GO:0048013 ephrin receptor signaling pathway
GO:0048041 focal adhesion assembly
GO:0048762 mesenchymal cell differentiation
GO:0050769 positive regulation of neurogenesis
GO:0051493 regulation of cytoskeleton organization
GO:0051893 regulation of focal adhesion assembly
GO:0051962 positive regulation of nervous system development
GO:0060485 mesenchyme development
GO:0061564 axon development
GO:0070507 regulation of microtubule cytoskeleton organization
GO:0071229 cellular response to acid chemical
GO:0071300 cellular response to retinoic acid
GO:0071396 cellular response to lipid
GO:0090109 regulation of cell-substrate junction assembly
GO:0097155 fasciculation of sensory neuron axon
GO:0097156 fasciculation of motor neuron axon
GO:1901888 regulation of cell junction assembly
GO:1903391 regulation of adherens junction organization
Molecular Function GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005003 ephrin receptor activity
GO:0005004 GPI-linked ephrin receptor activity
GO:0019199 transmembrane receptor protein kinase activity
Cellular Component GO:0005769 early endosome
> KEGG and Reactome Pathway
 
KEGG hsa04360 Axon guidance
Reactome R-HSA-422475: Axon guidance
R-HSA-1266738: Developmental Biology
R-HSA-2682334: EPH-Ephrin signaling
R-HSA-3928665: EPH-ephrin mediated repulsion of cells
R-HSA-3928663: EPHA-mediated growth cone collapse
Summary
SymbolEPHA3
NameEPH receptor A3
Aliases HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location3p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between EPHA3 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 EPHA3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27922598Pre-B Acute Lymphoblastic LeukemiaEssential for immunotherapyWe use two models of human pre-B-ALL to examine EphA3 function. No antitumor effect in the xenografts with no EphA3 expression providing evidence that EphA3 is a functional therapeutic target in pre-B-ALL.
Summary
SymbolEPHA3
NameEPH receptor A3
Aliases HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location3p11.2
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 EPHA3 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
SymbolEPHA3
NameEPH receptor A3
Aliases HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location3p11.2
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 EPHA3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-1.3940.0268
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-2.4720.0107
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.6270.522
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.9010.125
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.8790.631
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.930.683
729033130MelanomaallAnti-PD-1 (nivolumab) 26231.0490.118
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0050.997
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11122.3380.0546
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.7960.416
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.720.181
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.4020.039
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of EPHA3 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) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277314.82.712.10.0439
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275914.83.411.40.0746
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21171911.87.20.672
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86250250.473
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.418.2-2.81
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.611.1-8.50.299
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221307.7-7.70.371
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.214.3-8.10.586
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
SymbolEPHA3
NameEPH receptor A3
Aliases HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location3p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of EPHA3. 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
SymbolEPHA3
NameEPH receptor A3
Aliases HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location3p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of EPHA3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by EPHA3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolEPHA3
NameEPH receptor A3
Aliases HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location3p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of EPHA3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolEPHA3
NameEPH receptor A3
Aliases HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location3p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of EPHA3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolEPHA3
NameEPH receptor A3
Aliases HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location3p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between EPHA3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolEPHA3
NameEPH receptor A3
Aliases HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location3p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting EPHA3 collected from DrugBank database.
> Drugs from DrugBank database
 

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