This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator and have a role during development. It can act as a mediator of chemoresistance and cell survival in Ewing sarcoma cells, where this gene is up-regulated via a micro-RNA that binds to the 3' UTR of the transcript. A similar protein in mice acts as a... See more...

Aliases for EYA3 Gene

Aliases for EYA3 Gene

  • EYA Transcriptional Coactivator And Phosphatase 3 2 3 5
  • Eyes Absent Homolog 3 3 4
  • EC 3.1.3.48 4 51
  • Eyes Absent (Drosophila) Homolog 3 2
  • Eyes Absent Homolog 3 (Drosophila) 2
  • Eyes Absent 3 3
  • DKFZp686C132 2
  • EYA3 5

External Ids for EYA3 Gene

Previous GeneCards Identifiers for EYA3 Gene

  • GC01P027044
  • GC01M027311
  • GC01M027533
  • GC01M027905
  • GC01M027901
  • GC01M027981
  • GC01M028170
  • GC01M028296
  • GC01M026556

Summaries for EYA3 Gene

Entrez Gene Summary for EYA3 Gene

  • This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator and have a role during development. It can act as a mediator of chemoresistance and cell survival in Ewing sarcoma cells, where this gene is up-regulated via a micro-RNA that binds to the 3' UTR of the transcript. A similar protein in mice acts as a transcriptional activator. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2013]

GeneCards Summary for EYA3 Gene

EYA3 (EYA Transcriptional Coactivator And Phosphatase 3) is a Protein Coding gene. Diseases associated with EYA3 include Ewing Sarcoma and Cardiomyopathy, Dilated, 1J. Among its related pathways are DNA Double Strand Break Response and DNA Double-Strand Break Repair. Gene Ontology (GO) annotations related to this gene include chromatin binding and protein tyrosine/serine/threonine phosphatase activity. An important paralog of this gene is EYA4.

UniProtKB/Swiss-Prot Summary for EYA3 Gene

  • Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). '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. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 (PubMed:19234442, PubMed:19351884). Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1, and seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity (By similarity). May be involved in development of the eye.

Additional gene information for EYA3 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for EYA3 Gene

Genomics for EYA3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for EYA3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J028086 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 647.5 +0.4 370 3.4 ARHGAP35 SP1 CREB1 GATAD2A PRDM10 ZNF629 TFE3 ZNF512 LEF1 IKZF1 EYA3 GMEB1 YTHDF2 ACTG1P20 RCC1 TRNAU1AP FAM76A SNHG12 ENSG00000231344 XKR8
GH01J028171 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 616.8 -85.6 -85639 6.2 ARHGAP35 SP1 PRDM10 ZNF512 LEF1 IKZF1 RCOR2 POLR2A BACH1 JUND PTAFR EYA3 GMEB1 SNHG12 TRNAU1AP ACTG1P20 YTHDF2 PHACTR4 NPM1P39 SNORA73B
GH01J028881 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 57 -796.8 -796763 7.1 RNF2 ARHGAP35 SP1 HNRNPL CREB1 GATAD2A CTCF ATF7 TEAD4 PRDM10 EPB41 ENSG00000233427 SRSF4 GMEB1 TRNAU1AP SNHG12 YTHDF2 EYA3 PHACTR4 TMEM200B
GH01J028090 Enhancer 0.2 FANTOM5 605.8 -1.8 -1764 0.1 EYA3 PTAFR FGR THEMIS2 STX12 SESN2 MED18 XKR8 lnc-EYA3-2
GH01J027596 Promoter/Enhancer 2.3 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 38 +484.0 483980 15.4 SP1 HNRNPL GATAD2A CTCF TEAD4 PRDM10 ZNF629 SIX5 LEF1 SOX13 AHDC1 lnc-AHDC1-1 ARID1A ACTG1P20 TRNAU1AP GPN2 NPM1P39 ENSG00000231344 EYA3 PHACTR4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around EYA3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for EYA3

Top Transcription factor binding sites by QIAGEN in the EYA3 gene promoter:
  • AML1a
  • HOXA9
  • HOXA9B
  • Ik-2
  • Meis-1
  • Meis-1a
  • MyoD
  • NF-E2
  • Sox9
  • TGIF

Genomic Locations for EYA3 Gene

Genomic Locations for EYA3 Gene
chr1:27,970,344-28,088,671
(GRCh38/hg38)
Size:
118,328 bases
Orientation:
Minus strand
chr1:28,296,855-28,415,207
(GRCh37/hg19)
Size:
118,353 bases
Orientation:
Minus strand

Genomic View for EYA3 Gene

Genes around EYA3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EYA3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EYA3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EYA3 Gene

Proteins for EYA3 Gene

  • Protein details for EYA3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99504-EYA3_HUMAN
    Recommended name:
    Eyes absent homolog 3
    Protein Accession:
    Q99504
    Secondary Accessions:
    • A8K190
    • B4DIR7
    • B4DNZ7
    • O95463
    • Q8IVX7
    • Q99813

    Protein attributes for EYA3 Gene

    Size:
    573 amino acids
    Molecular mass:
    62663 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with SIX1 and DACH1, and probably SIX2, SIX4, SIX5.

    Alternative splice isoforms for EYA3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EYA3 Gene

Selected DME Specific Peptides for EYA3 Gene

Q99504:
  • WDLDETII
  • GGVDWMRKLAFRYR
  • GKESCFERI
  • PALAKVLL
  • FPIENIYSATK
  • SDDNGQDLS

Post-translational modifications for EYA3 Gene

  • Ser-266 phosphorylation is required for localization at sites of DNA damage and directing interaction with H2AX.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for EYA3 Gene

Gene Families for EYA3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for EYA3 Gene

Suggested Antigen Peptide Sequences for EYA3 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ50734, highly similar to Eyes absent homolog 3 (EC 3.1.3.48) (B4DIR7_HUMAN)
  • cDNA FLJ60747, highly similar to Eyes absent homolog 3 (EC 3.1.3.48) (B4DNZ7_HUMAN)
  • Eyes absent homolog 3 (EYA3_HUMAN)
  • HCG1640928, isoform CRA_c (Q0P685_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99504

UniProtKB/Swiss-Prot:

EYA3_HUMAN :
  • Belongs to the HAD-like hydrolase superfamily. EYA family.
Family:
  • Belongs to the HAD-like hydrolase superfamily. EYA family.
genes like me logo Genes that share domains with EYA3: view

Function for EYA3 Gene

Molecular function for EYA3 Gene

UniProtKB/Swiss-Prot Function:
Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). '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. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 (PubMed:19234442, PubMed:19351884). Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1, and seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity (By similarity). May be involved in development of the eye.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:19351884};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=1.8 uM for H2AXY142ph {ECO:0000269|PubMed:19351884}; KM=72 uM for H2AXS139ph {ECO:0000269|PubMed:19351884};
GENATLAS Biochemistry:
Drosophila eyes absent gene (eya) homolog 3,Dres67,mouse homolog undetectable in embryo (E10,5;E12,5;E17,5)

Enzyme Numbers (IUBMB) for EYA3 Gene

Phenotypes From GWAS Catalog for EYA3 Gene

Gene Ontology (GO) - Molecular Function for EYA3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004721 phosphoprotein phosphatase activity IEA --
GO:0004725 protein tyrosine phosphatase activity IBA,IDA 19234442
GO:0005515 protein binding IPI 19234442
GO:0016787 hydrolase activity IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with EYA3: view
genes like me logo Genes that share phenotypes with EYA3: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EYA3

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for EYA3 Gene

Localization for EYA3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EYA3 Gene

Cytoplasm. Nucleus. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs) (PubMed:19234442). With decreasing efficiency, translocalized to the nucleus by SIX2 and SIX5, and SIX4, respectively (By similarity). {ECO:0000250 UniProtKB:P97480, ECO:0000269 PubMed:19234442}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for EYA3 gene
Compartment Confidence
nucleus 5
cytoskeleton 4
cytosol 2
plasma membrane 1
extracellular 1
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for EYA3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,IDA 19234442
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IEA --
GO:0005737 cytoplasm IEA --
GO:0005813 centrosome IDA --
genes like me logo Genes that share ontologies with EYA3: view

Pathways & Interactions for EYA3 Gene

genes like me logo Genes that share pathways with EYA3: view

SIGNOR curated interactions for EYA3 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for EYA3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006281 DNA repair IEA --
GO:0006302 double-strand break repair IMP 19234442
GO:0006325 chromatin organization IEA --
GO:0006470 protein dephosphorylation IEA --
GO:0006974 cellular response to DNA damage stimulus IEA --
genes like me logo Genes that share ontologies with EYA3: view

Drugs & Compounds for EYA3 Gene

(3) Drugs for EYA3 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Magnesium Approved, Experimental, Investigational Pharma 0
Phosphoric acid Approved Pharma 0
Water Approved Pharma 0

(1) Additional Compounds for EYA3 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Phosphate
  • [po(OH)3]
  • Acide phosphorique
  • Acidum phosphoricum
  • H3PO4
  • Orthophosphoric acid
14066-19-4, 14265-44-2
genes like me logo Genes that share compounds with EYA3: view

Transcripts for EYA3 Gene

mRNA/cDNA for EYA3 Gene

5 REFSEQ mRNAs :
16 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EYA3

Alternative Splicing Database (ASD) splice patterns (SP) for EYA3 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b ^ 18 ^ 19 ^ 20
SP1:
SP2: - - -
SP3: - - -

Relevant External Links for EYA3 Gene

GeneLoc Exon Structure for
EYA3

Expression for EYA3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for EYA3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for EYA3 Gene

This gene is overexpressed in Prostate (26.0), Testis (10.4), and Fetal ovary (7.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for EYA3 Gene



Protein tissue co-expression partners for EYA3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for EYA3

SOURCE GeneReport for Unigene cluster for EYA3 Gene:

Hs.185774

Evidence on tissue expression from TISSUES for EYA3 Gene

  • Nervous system(4.7)
  • Eye(4.3)
  • Kidney(2.3)
  • Thyroid gland(2.2)
genes like me logo Genes that share expression patterns with EYA3: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for EYA3 Gene

Orthologs for EYA3 Gene

This gene was present in the common ancestor of animals.

Orthologs for EYA3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia EYA3 30 31
  • 99.81 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia EYA3 30 31
  • 94.65 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia EYA3 30 31
  • 94.07 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia EYA3 31
  • 93 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Eya3 30 17 31
  • 91.19 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Eya3 30
  • 90.33 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia EYA3 31
  • 76 (a)
OneToOne
Chicken
(Gallus gallus)
Aves EYA3 30 31
  • 81.06 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia EYA3 31
  • 82 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia eya3 30
  • 71.02 (n)
Str.6428 30
Zebrafish
(Danio rerio)
Actinopterygii eya3 30 31
  • 59.56 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta eya 31 32
  • 30 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea eya-1 31
  • 23 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.8681 31
  • 55 (a)
OneToMany
Species where no ortholog for EYA3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for EYA3 Gene

ENSEMBL:
Gene Tree for EYA3 (if available)
TreeFam:
Gene Tree for EYA3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for EYA3: view image

Paralogs for EYA3 Gene

Paralogs for EYA3 Gene

(4) SIMAP similar genes for EYA3 Gene using alignment to 6 proteins:

  • EYA3_HUMAN
  • B1APR7_HUMAN
  • B4DIR7_HUMAN
  • B4DNZ7_HUMAN
  • Q0P685_HUMAN
  • Q8IVX7_HUMAN
genes like me logo Genes that share paralogs with EYA3: view

Variants for EYA3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for EYA3 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
736351 Benign: not provided 28,000,058(-) C/T INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for EYA3 Gene

Structural Variations from Database of Genomic Variants (DGV) for EYA3 Gene

Variant ID Type Subtype PubMed ID
esv2255639 CNV deletion 18987734
esv2641492 CNV deletion 19546169
nsv1122316 CNV deletion 24896259
nsv947420 CNV duplication 23825009
nsv998557 CNV gain 25217958

Variation tolerance for EYA3 Gene

Residual Variation Intolerance Score: 21.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.97; 19.93% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for EYA3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
EYA3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EYA3 Gene

Disorders for EYA3 Gene

MalaCards: The human disease database

(10) MalaCards diseases for EYA3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
ewing sarcoma
  • es
cardiomyopathy, dilated, 1j
  • cmd1j
syndromic microphthalmia
  • microphthalmia, syndromic
branchiootorenal syndrome 1
  • bor1
malignant peripheral nerve sheath tumor
  • neurofibrosarcoma
- elite association - COSMIC cancer census association via MalaCards
Search EYA3 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with EYA3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for EYA3 Gene

Publications for EYA3 Gene

  1. A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. (PMID: 9020840) Abdelhak S … Petit C (Nature genetics 1997) 2 3 4 23
  2. Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. (PMID: 19234442) Cook PJ … Rosenfeld MG (Nature 2009) 3 4
  3. Dephosphorylation of the C-terminal tyrosyl residue of the DNA damage-related histone H2A.X is mediated by the protein phosphatase eyes absent. (PMID: 19351884) Krishnan N … Tonks NK (The Journal of biological chemistry 2009) 3 4
  4. EYA4, a novel vertebrate gene related to Drosophila eyes absent. (PMID: 9887327) Borsani G … Hanson I (Human molecular genetics 1999) 3 4
  5. Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene. (PMID: 9049631) Zimmerman JE … Bonini NM (Genome research 1997) 3 4

Products for EYA3 Gene

Sources for EYA3 Gene