TISIDB

Summary
Symbol	EPHA8
Name	EPH receptor A8
Aliases	Hek3; EEK; EK3; EPH- and ELK-related kinase; EPH- and ELK-related tyrosine kinase; EPH-like kinase 3; tyrosi ......
Chromosomal Location	1p36.12
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 Cell projection Early endosome membrane Note=Undergoes clathrin-mediated endocytosis upon EFNA5-binding and is targeted to early endosomes.
Domain	PF14575 Ephrin type-A receptor 2 transmembrane domain PF01404 Ephrin receptor ligand binding domain PF00041 Fibronectin type III domain PF07714 Protein tyrosine kinase PF00536 SAM domain (Sterile alpha motif)
Function	Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A 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. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system plays also a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0006644 phospholipid metabolic process GO:0006929 substrate-dependent cell migration GO:0007409 axonogenesis GO:0007411 axon guidance GO:0016322 neuron remodeling GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0019216 regulation of lipid metabolic process GO:0021700 developmental maturation GO:0032354 response to follicle-stimulating hormone GO:0033627 cell adhesion mediated by integrin GO:0033628 regulation of cell adhesion mediated by integrin GO:0033674 positive regulation of kinase activity GO:0034698 response to gonadotropin GO:0042551 neuron maturation GO:0043410 positive regulation of MAPK cascade GO:0043550 regulation of lipid kinase activity GO:0043551 regulation of phosphatidylinositol 3-kinase activity GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity GO:0045834 positive regulation of lipid metabolic process GO:0046777 protein autophosphorylation GO:0048013 ephrin receptor signaling pathway GO:0048469 cell maturation GO:0048667 cell morphogenesis involved in neuron differentiation GO:0061564 axon development GO:0071371 cellular response to gonadotropin stimulus GO:0071372 cellular response to follicle-stimulating hormone stimulus GO:0090218 positive regulation of lipid kinase activity GO:0097485 neuron projection guidance GO:1903725 regulation of phospholipid metabolic process GO:1903727 positive regulation of phospholipid metabolic process
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 GO:0010008 endosome membrane GO:0031901 early endosome membrane GO:0044440 endosomal part

> 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	EPHA8
Name	EPH receptor A8
Aliases	Hek3; EEK; EK3; EPH- and ELK-related kinase; EPH- and ELK-related tyrosine kinase; EPH-like kinase 3; tyrosi ......
Chromosomal Location	1p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between EPHA8 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	EPHA8
Name	EPH receptor A8
Aliases	Hek3; EEK; EK3; EPH- and ELK-related kinase; EPH- and ELK-related tyrosine kinase; EPH-like kinase 3; tyrosi ......
Chromosomal Location	1p36.12
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 EPHA8 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	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	EPHA8
Name	EPH receptor A8
Aliases	Hek3; EEK; EK3; EPH- and ELK-related kinase; EPH- and ELK-related tyrosine kinase; EPH-like kinase 3; tyrosi ......
Chromosomal Location	1p36.12
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 EPHA8 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	-0.365	0.219
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.954	0.118
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.051	0.902
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.587	0.441
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.912	0.104
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.069	0.397
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.423	0.0841
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	2.275	0.16
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.302	0.849
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.239	0.624
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	-0.239	0.736
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.441	0.0121

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of EPHA8 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	21.4	0	21.4	0.081
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	20	0	20	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	25	0	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	5.5	-1.8	1
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	3.7	6.8	-3.1	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	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	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
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	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	10.5	3.7	6.8	0.393
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	18.2	0	18.2	0.274
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
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	EPHA8
Name	EPH receptor A8
Aliases	Hek3; EEK; EK3; EPH- and ELK-related kinase; EPH- and ELK-related tyrosine kinase; EPH-like kinase 3; tyrosi ......
Chromosomal Location	1p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of EPHA8. 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	EPHA8
Name	EPH receptor A8
Aliases	Hek3; EEK; EK3; EPH- and ELK-related kinase; EPH- and ELK-related tyrosine kinase; EPH-like kinase 3; tyrosi ......
Chromosomal Location	1p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of EPHA8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by EPHA8. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	EPHA8
Name	EPH receptor A8
Aliases	Hek3; EEK; EK3; EPH- and ELK-related kinase; EPH- and ELK-related tyrosine kinase; EPH-like kinase 3; tyrosi ......
Chromosomal Location	1p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of EPHA8. 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	EPHA8
Name	EPH receptor A8
Aliases	Hek3; EEK; EK3; EPH- and ELK-related kinase; EPH- and ELK-related tyrosine kinase; EPH-like kinase 3; tyrosi ......
Chromosomal Location	1p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of EPHA8 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	EPHA8
Name	EPH receptor A8
Aliases	Hek3; EEK; EK3; EPH- and ELK-related kinase; EPH- and ELK-related tyrosine kinase; EPH-like kinase 3; tyrosi ......
Chromosomal Location	1p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between EPHA8 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	EPHA8
Name	EPH receptor A8
Aliases	Hek3; EEK; EK3; EPH- and ELK-related kinase; EPH- and ELK-related tyrosine kinase; EPH-like kinase 3; tyrosi ......
Chromosomal Location	1p36.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting EPHA8 collected from DrugBank database.

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

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