TISIDB

Summary
Symbol	EPHA3
Name	EPH receptor A3
Aliases	HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location	3p11.2
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	EPHA3
Name	EPH receptor A3
Aliases	HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location	3p11.2
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

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Literatures describing the relation between EPHA3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27922598	Pre-B Acute Lymphoblastic Leukemia	Essential for immunotherapy	We 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
Symbol	EPHA3
Name	EPH receptor A3
Aliases	HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location	3p11.2
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

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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
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	EPHA3
Name	EPH receptor A3
Aliases	HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location	3p11.2
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-1.394	0.0268
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-2.472	0.0107
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.627	0.522
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.901	0.125
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.879	0.631
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.93	0.683
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.049	0.118
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.005	0.997
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	2.338	0.0546
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.796	0.416
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	1.72	0.181
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.402	0.039

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	14.8	2.7	12.1	0.0439
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	14.8	3.4	11.4	0.0746
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	19	11.8	7.2	0.672
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	25	0	25	0.473
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	18.2	-2.8	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	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	11.1	-8.5	0.299
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	7.7	-7.7	0.371
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	14.3	-8.1	0.586
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	EPHA3
Name	EPH receptor A3
Aliases	HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location	3p11.2
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 [ TOP ]

Summary
Symbol	EPHA3
Name	EPH receptor A3
Aliases	HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location	3p11.2
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	EPHA3
Name	EPH receptor A3
Aliases	HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location	3p11.2
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	EPHA3
Name	EPH receptor A3
Aliases	HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location	3p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of EPHA3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	EPHA3
Name	EPH receptor A3
Aliases	HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location	3p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between EPHA3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	EPHA3
Name	EPH receptor A3
Aliases	HEK; HEK4; ETK1; EK4; EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human em ......
Chromosomal Location	3p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting EPHA3 collected from DrugBank database.

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

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