TISIDB

Summary
Symbol	EYA2
Name	EYA transcriptional coactivator and phosphatase 2
Aliases	EAB1; eyes absent (Drosophila) homolog 2; eyes absent homolog 2 (Drosophila); Eyes absent homolog 2
Chromosomal Location	20q13.1
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	Cytoplasm Nucleus Note=Retained in the cytoplasm via interaction with GNAZ and GNAI2 (PubMed:10906137). Interaction with SIX1, SIX2, SIX4 or SIX5 is required for translocation to the nucleus (PubMed:10906137, PubMed:12500905).
Domain	-
Function	Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5 (PubMed:12500905, PubMed:23435380). Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress (PubMed:19351884). Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis. Plays an important role in hypaxial muscle development together with SIX1 and DACH2; in this it is functionally redundant with EYA1 (PubMed:12500905).

> Gene Ontology [ TOP ]
Biological Process	GO:0001704 formation of primary germ layer GO:0001707 mesoderm formation GO:0001708 cell fate specification GO:0001710 mesodermal cell fate commitment GO:0006282 regulation of DNA repair GO:0006470 protein dephosphorylation GO:0006839 mitochondrial transport GO:0007006 mitochondrial membrane organization GO:0007369 gastrulation GO:0007498 mesoderm development GO:0007501 mesodermal cell fate specification GO:0008637 apoptotic mitochondrial changes GO:0014706 striated muscle tissue development GO:0016311 dephosphorylation GO:0016570 histone modification GO:0016576 histone dephosphorylation GO:0035335 peptidyl-tyrosine dephosphorylation GO:0035794 positive regulation of mitochondrial membrane permeability GO:0038034 signal transduction in absence of ligand GO:0045165 cell fate commitment GO:0045739 positive regulation of DNA repair GO:0046902 regulation of mitochondrial membrane permeability GO:0048332 mesoderm morphogenesis GO:0048333 mesodermal cell differentiation GO:0051052 regulation of DNA metabolic process GO:0051054 positive regulation of DNA metabolic process GO:0060537 muscle tissue development GO:0060795 cell fate commitment involved in formation of primary germ layer GO:0090559 regulation of membrane permeability GO:0097191 extrinsic apoptotic signaling pathway GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand GO:0097345 mitochondrial outer membrane permeabilization GO:1901099 negative regulation of signal transduction in absence of ligand GO:1902108 regulation of mitochondrial membrane permeability involved in apoptotic process GO:1902110 positive regulation of mitochondrial membrane permeability involved in apoptotic process GO:1902686 mitochondrial outer membrane permeabilization involved in programmed cell death GO:2001020 regulation of response to DNA damage stimulus GO:2001022 positive regulation of response to DNA damage stimulus GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001236 regulation of extrinsic apoptotic signaling pathway GO:2001237 negative regulation of extrinsic apoptotic signaling pathway GO:2001239 regulation of extrinsic apoptotic signaling pathway in absence of ligand GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
Molecular Function	GO:0000287 magnesium ion binding GO:0004721 phosphoprotein phosphatase activity GO:0004725 protein tyrosine phosphatase activity GO:0016791 phosphatase activity GO:0042578 phosphoric ester hydrolase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-5693606: DNA Double Strand Break Response R-HSA-5693532: DNA Double-Strand Break Repair R-HSA-73894: DNA Repair R-HSA-5693565: Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks

Summary
Symbol	EYA2
Name	EYA transcriptional coactivator and phosphatase 2
Aliases	EAB1; eyes absent (Drosophila) homolog 2; eyes absent homolog 2 (Drosophila); Eyes absent homolog 2
Chromosomal Location	20q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between EYA2 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	EYA2
Name	EYA transcriptional coactivator and phosphatase 2
Aliases	EAB1; eyes absent (Drosophila) homolog 2; eyes absent homolog 2 (Drosophila); Eyes absent homolog 2
Chromosomal Location	20q13.1
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 EYA2 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	EYA2
Name	EYA transcriptional coactivator and phosphatase 2
Aliases	EAB1; eyes absent (Drosophila) homolog 2; eyes absent homolog 2 (Drosophila); Eyes absent homolog 2
Chromosomal Location	20q13.1
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 EYA2 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	0.413	0.153
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.042	0.94
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.689	0.103
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.648	0.255
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.917	0.558
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.311	0.875
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.14	0.789
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.507	0.518
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.347	0.686
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.354	0.578
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	0.932	0.264
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.076	0.76

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of EYA2 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	28.6	0	28.6	0.0318
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	50	0	50	0.0392
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	14.8	4.1	10.7	0.0828
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	5.1	9.7	0.199
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	11.8	-7	0.577
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	18.2	-18.2	0.199
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	5.3	3.7	1.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	7.7	1.4	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
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	EYA2
Name	EYA transcriptional coactivator and phosphatase 2
Aliases	EAB1; eyes absent (Drosophila) homolog 2; eyes absent homolog 2 (Drosophila); Eyes absent homolog 2
Chromosomal Location	20q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of EYA2. 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	EYA2
Name	EYA transcriptional coactivator and phosphatase 2
Aliases	EAB1; eyes absent (Drosophila) homolog 2; eyes absent homolog 2 (Drosophila); Eyes absent homolog 2
Chromosomal Location	20q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of EYA2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by EYA2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	EYA2
Name	EYA transcriptional coactivator and phosphatase 2
Aliases	EAB1; eyes absent (Drosophila) homolog 2; eyes absent homolog 2 (Drosophila); Eyes absent homolog 2
Chromosomal Location	20q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of EYA2. 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	EYA2
Name	EYA transcriptional coactivator and phosphatase 2
Aliases	EAB1; eyes absent (Drosophila) homolog 2; eyes absent homolog 2 (Drosophila); Eyes absent homolog 2
Chromosomal Location	20q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of EYA2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	EYA2
Name	EYA transcriptional coactivator and phosphatase 2
Aliases	EAB1; eyes absent (Drosophila) homolog 2; eyes absent homolog 2 (Drosophila); Eyes absent homolog 2
Chromosomal Location	20q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between EYA2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	EYA2
Name	EYA transcriptional coactivator and phosphatase 2
Aliases	EAB1; eyes absent (Drosophila) homolog 2; eyes absent homolog 2 (Drosophila); Eyes absent homolog 2
Chromosomal Location	20q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting EYA2 collected from DrugBank database.

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

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