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Protein

Eyes absent homolog 3

Gene

EYA3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity2 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.2 Publications

Cofactori

Mg2+By similarityNote: Binds 1 Mg2+ ion per subunit.By similarity

Kineticsi

  1. KM=1.8 µM for H2AXY142ph1 Publication
  2. KM=72 µM for H2AXS139ph1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei309NucleophileCurated1
    Metal bindingi309MagnesiumBy similarity1
    Active sitei311Proton donorBy similarity1
    Metal bindingi311Magnesium; via carbonyl oxygenBy similarity1
    Metal bindingi537MagnesiumBy similarity1

    GO - Molecular functioni

    • metal ion binding Source: UniProtKB-KW
    • protein tyrosine phosphatase activity Source: UniProtKB

    GO - Biological processi

    • anatomical structure morphogenesis Source: ProtInc
    • cell differentiation Source: GO_Central
    • double-strand break repair Source: UniProtKB
    • histone dephosphorylation Source: UniProtKB
    • multicellular organism development Source: UniProtKB-KW
    • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central
    • positive regulation of DNA repair Source: UniProtKB
    • regulation of transcription, DNA-templated Source: UniProtKB-KW
    • response to ionizing radiation Source: UniProtKB
    • transcription, DNA-templated Source: UniProtKB-KW
    • visual perception Source: ProtInc

    Keywordsi

    Molecular functionActivator, Chromatin regulator, Developmental protein, Hydrolase, Protein phosphatase
    Biological processDNA damage, DNA repair, Transcription, Transcription regulation
    LigandMagnesium, Metal-binding

    Enzyme and pathway databases

    ReactomeiR-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
    SABIO-RKQ99504
    SIGNORiQ99504

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Eyes absent homolog 3 (EC:3.1.3.482 Publications)
    Gene namesi
    Name:EYA3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000158161.15
    HGNCiHGNC:3521 EYA3
    MIMi601655 gene
    neXtProtiNX_Q99504

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi266S → A: Fails to form damage-dependent nuclear foci or interact with H2AX. 1 Publication1
    Mutagenesisi309D → A: Loss of tyrosine phosphatase activity toward H2AX. 1 Publication1

    Organism-specific databases

    DisGeNETi2140
    OpenTargetsiENSG00000158161
    PharmGKBiPA27933

    Polymorphism and mutation databases

    BioMutaiEYA3
    DMDMi239938901

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002186481 – 573Eyes absent homolog 3Add BLAST573

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1
    Modified residuei262PhosphoserineCombined sources1
    Modified residuei266Phosphoserine1 Publication1
    Modified residuei438PhosphoserineCombined sources1
    Modified residuei472PhosphoserineCombined sources1

    Post-translational modificationi

    Ser-266 phosphorylation is required for localization at sites of DNA damage and directing interaction with H2AX.1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiQ99504
    MaxQBiQ99504
    PaxDbiQ99504
    PeptideAtlasiQ99504
    PRIDEiQ99504
    TopDownProteomicsiQ99504-2 [Q99504-2]

    PTM databases

    DEPODiQ99504
    iPTMnetiQ99504
    PhosphoSitePlusiQ99504

    Expressioni

    Gene expression databases

    BgeeiENSG00000158161
    CleanExiHS_EYA3
    ExpressionAtlasiQ99504 baseline and differential
    GenevisibleiQ99504 HS

    Organism-specific databases

    HPAiHPA052432
    HPA062889

    Interactioni

    Subunit structurei

    Interacts with SIX1 and DACH1, and probably SIX2, SIX4, SIX5.By similarity

    Protein-protein interaction databases

    BioGridi108441, 28 interactors
    DIPiDIP-60448N
    IntActiQ99504, 3 interactors
    STRINGi9606.ENSP00000362978

    Structurei

    3D structure databases

    ProteinModelPortaliQ99504
    SMRiQ99504
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG410IR14 Eukaryota
    ENOG410XQHR LUCA
    GeneTreeiENSGT00390000008860
    HOGENOMiHOG000293149
    HOVERGENiHBG002447
    InParanoidiQ99504
    KOiK17621
    OMAiSQYQACY
    OrthoDBiEOG091G04YD
    PhylomeDBiQ99504
    TreeFamiTF319337

    Family and domain databases

    CDDicd02601 HAD_Eya, 1 hit
    Gene3Di3.40.50.12350, 1 hit
    InterProiView protein in InterPro
    IPR028479 EYA3
    IPR006545 EYA_dom
    IPR038102 EYA_dom_sf
    IPR028472 EYA_fam
    PANTHERiPTHR10190 PTHR10190, 1 hit
    PTHR10190:SF5 PTHR10190:SF5, 1 hit
    TIGRFAMsiTIGR01658 EYA-cons_domain, 1 hit

    Sequences (5)i

    Sequence statusi: Complete.

    This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q99504-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MEEEQDLPEQ PVKKAKMQES GEQTISQVSN PDVSDQKPET SSLASNLPMS
    60 70 80 90 100
    EEIMTCTDYI PRSSNDYTSQ MYSAKPYAHI LSVPVSETAY PGQTQYQTLQ
    110 120 130 140 150
    QTQPYAVYPQ ATQTYGLPPF GALWPGMKPE SGLIQTPSPS QHSVLTCTTG
    160 170 180 190 200
    LTTSQPSPAH YSYPIQASST NASLISTSST IANIPAAAVA SISNQDYPTY
    210 220 230 240 250
    TILGQNQYQA CYPSSSFGVT GQTNSDAEST TLAATTYQSE KPSVMAPAPA
    260 270 280 290 300
    AQRLSSGDPS TSPSLSQTTP SKDTDDQSRK NMTSKNRGKR KADATSSQDS
    310 320 330 340 350
    ELERVFLWDL DETIIIFHSL LTGSYAQKYG KDPTVVIGSG LTMEEMIFEV
    360 370 380 390 400
    ADTHLFFNDL EECDQVHVED VASDDNGQDL SNYSFSTDGF SGSGGSGSHG
    410 420 430 440 450
    SSVGVQGGVD WMRKLAFRYR KVREIYDKHK SNVGGLLSPQ RKEALQRLRA
    460 470 480 490 500
    EIEVLTDSWL GTALKSLLLI QSRKNCVNVL ITTTQLVPAL AKVLLYGLGE
    510 520 530 540 550
    IFPIENIYSA TKIGKESCFE RIVSRFGKKV TYVVIGDGRD EEIAAKQHNM
    560 570
    PFWRITNHGD LVSLHQALEL DFL
    Length:573
    Mass (Da):62,663
    Last modified:June 16, 2009 - v3
    Checksum:i684B961B1E630371
    GO
    Isoform 2 (identifier: Q99504-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-126: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:447
    Mass (Da):48,652
    Checksum:i129E0A20B4A7BA2F
    GO
    Isoform 3 (identifier: Q99504-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         121-166: Missing.
         548-572: HNMPFWRITNHGDLVSLHQALELDF → QLYFLDMEALGCQLEPTALILFIQLSGNLSNYNK

    Note: No experimental confirmation available.
    Show »
    Length:536
    Mass (Da):58,697
    Checksum:i7F502740058138F7
    GO
    Isoform 4 (identifier: Q99504-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-53: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:520
    Mass (Da):56,805
    Checksum:iEE85E9F3F4E00708
    GO
    Isoform 5 (identifier: Q99504-5) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         121-166: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:527
    Mass (Da):57,827
    Checksum:i33DA17379017618E
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti105Y → D in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti142H → R in AAB42066 (PubMed:9049631).Curated1
    Sequence conflicti151L → V in AAB42066 (PubMed:9049631).Curated1
    Sequence conflicti253R → K in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti268T → S in AAB42066 (PubMed:9049631).Curated1
    Sequence conflicti283T → N in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti290R → K in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti305V → L in AAB42066 (PubMed:9049631).Curated1
    Sequence conflicti345E → K in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti357F → S in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti361E → K in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti373 – 381SDDNGQDLS → PNDKGQNLN in CAA71311 (PubMed:9020840).Curated9
    Sequence conflicti388D → N in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti447 – 449RLR → KLK in CAA71311 (PubMed:9020840).Curated3
    Sequence conflicti457D → N in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti473R → K in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti480L → P in AAB42066 (PubMed:9049631).Curated1
    Sequence conflicti487V → L in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti500E → K in CAA71311 (PubMed:9020840).Curated1
    Sequence conflicti524 – 526SRF → TSL in CAA71311 (PubMed:9020840).Curated3
    Sequence conflicti530V → L in CAA71311 (PubMed:9020840).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0014931 – 126Missing in isoform 2. 1 PublicationAdd BLAST126
    Alternative sequenceiVSP_0545301 – 53Missing in isoform 4. 1 PublicationAdd BLAST53
    Alternative sequenceiVSP_054518121 – 166Missing in isoform 3 and isoform 5. 2 PublicationsAdd BLAST46
    Alternative sequenceiVSP_054519548 – 572HNMPF…LELDF → QLYFLDMEALGCQLEPTALI LFIQLSGNLSNYNK in isoform 3. 1 PublicationAdd BLAST25

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Y10262 Genomic DNA Translation: CAA71311.1
    U81602 mRNA Translation: AAB42066.1
    AK289805 mRNA Translation: BAF82494.1
    AK295745 mRNA Translation: BAG58579.1
    AK298129 mRNA Translation: BAG60409.1
    AL137792 Genomic DNA No translation available.
    AL512288 Genomic DNA No translation available.
    CH471059 Genomic DNA Translation: EAX07713.1
    CH471059 Genomic DNA Translation: EAX07714.1
    BC041667 mRNA Translation: AAH41667.1
    AJ007991 mRNA Translation: CAA07814.1
    CCDSiCCDS316.1 [Q99504-1]
    CCDS60050.1 [Q99504-4]
    CCDS60051.1 [Q99504-5]
    CCDS60052.1 [Q99504-3]
    RefSeqiNP_001269489.1, NM_001282560.1 [Q99504-3]
    NP_001269490.1, NM_001282561.1 [Q99504-5]
    NP_001269491.1, NM_001282562.1 [Q99504-4]
    NP_001981.2, NM_001990.3 [Q99504-1]
    UniGeneiHs.185774

    Genome annotation databases

    EnsembliENST00000373863; ENSP00000362970; ENSG00000158161 [Q99504-3]
    ENST00000373871; ENSP00000362978; ENSG00000158161 [Q99504-1]
    ENST00000436342; ENSP00000405587; ENSG00000158161 [Q99504-4]
    ENST00000540618; ENSP00000442558; ENSG00000158161 [Q99504-5]
    GeneIDi2140
    KEGGihsa:2140
    UCSCiuc001bpi.3 human [Q99504-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiEYA3_HUMAN
    AccessioniPrimary (citable) accession number: Q99504
    Secondary accession number(s): A8K190
    , B4DIR7, B4DNZ7, O95463, Q8IVX7, Q99813
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: June 16, 2009
    Last modified: May 23, 2018
    This is version 157 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health