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Protein

Eyes absent homolog 2

Gene

EYA2

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

Functioni

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).4 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.1 Publication

Cofactori

Mg2+1 PublicationNote: Binds 1 Mg2+ ion per subunit.1 Publication

Kineticsi

  1. KM=1.9 µM for H2AXY142ph1 Publication
  2. KM=80 µM for H2AXS139ph1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei274Nucleophile1 Publication1
    Metal bindingi274Magnesium1 Publication1
    Active sitei276Proton donor1 Publication1
    Metal bindingi276Magnesium; via carbonyl oxygen1 Publication1
    Metal bindingi502Magnesium1 Publication1

    GO - Molecular functioni

    GO - Biological processi

    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

    BRENDAi3.1.3.48 2681
    ReactomeiR-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
    SABIO-RKiO00167

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Eyes absent homolog 2 (EC:3.1.3.481 Publication)
    Gene namesi
    Name:EYA2
    Synonyms:EAB1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 20

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000064655.18
    HGNCiHGNC:3520 EYA2
    MIMi601654 gene
    neXtProtiNX_O00167

    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
    Mutagenesisi516P → R: Strongly reduces SIX1 binding. 1 Publication1
    Mutagenesisi532A → R: Abolishes interaction with SIX1. 1 Publication1

    Organism-specific databases

    DisGeNETi2139
    OpenTargetsiENSG00000064655
    PharmGKBiPA27932

    Chemistry databases

    ChEMBLiCHEMBL1293275

    Polymorphism and mutation databases

    BioMutaiEYA2

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002186461 – 538Eyes absent homolog 2Add BLAST538

    Proteomic databases

    PaxDbiO00167
    PeptideAtlasiO00167
    PRIDEiO00167
    ProteomicsDBi47756
    47757 [O00167-2]
    47758 [O00167-3]

    PTM databases

    DEPODiO00167
    iPTMnetiO00167
    PhosphoSitePlusiO00167

    Expressioni

    Tissue specificityi

    Highest expression in muscle with lower levels in kidney, placenta, pancreas, brain and heart.1 Publication

    Developmental stagei

    At the begin of fourth week of development detected in cytoplasm of somite cells. Between the sixth and eighth week of development detected in cytoplasm of limb bud cells.1 Publication

    Gene expression databases

    BgeeiENSG00000064655 Expressed in 147 organ(s), highest expression level in nasal cavity epithelium
    ExpressionAtlasiO00167 baseline and differential
    GenevisibleiO00167 HS

    Organism-specific databases

    HPAiHPA027024
    HPA059291

    Interactioni

    Subunit structurei

    Interacts with DACH2 and SIX1, and probably with SIX2, SIX4 and SIX5. Interacts with CAPN8 (By similarity). Interacts with GNAZ and GNAI2; this precludes interaction with SIX1.By similarity5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    SIX1Q154753EBI-16038245,EBI-743675

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi108440, 83 interactors
    DIPiDIP-40707N
    IntActiO00167, 35 interactors
    MINTiO00167
    STRINGi9606.ENSP00000333640

    Structurei

    Secondary structure

    1538
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliO00167
    SMRiO00167
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO00167

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG3107 Eukaryota
    ENOG410XT12 LUCA
    GeneTreeiENSGT00390000008860
    HOVERGENiHBG002447
    InParanoidiO00167
    KOiK17620
    OMAiIYQGANG
    OrthoDBiEOG091G04YD
    PhylomeDBiO00167
    TreeFamiTF319337

    Family and domain databases

    CDDicd02601 HAD_Eya, 1 hit
    Gene3Di3.40.50.12350, 1 hit
    InterProiView protein in InterPro
    IPR028473 EYA2
    IPR006545 EYA_dom
    IPR038102 EYA_dom_sf
    IPR028472 EYA_fam
    IPR036412 HAD-like_sf
    PANTHERiPTHR10190 PTHR10190, 1 hit
    PTHR10190:SF7 PTHR10190:SF7, 1 hit
    SUPFAMiSSF56784 SSF56784, 1 hit
    TIGRFAMsiTIGR01658 EYA-cons_domain, 1 hit

    Sequences (3+)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket
    Note: Experimental confirmation may be lacking for some isoforms.

    This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: O00167-1) [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
    MVELVISPSL TVNSDCLDKL KFNRADAAVW TLSDRQGITK SAPLRVSQLF
    60 70 80 90 100
    SRSCPRVLPR QPSTAMAAYG QTQYSAGIQQ ATPYTAYPPP AQAYGIPSYS
    110 120 130 140 150
    IKTEDSLNHS PGQSGFLSYG SSFSTSPTGQ SPYTYQMHGT TGFYQGGNGL
    160 170 180 190 200
    GNAAGFGSVH QDYPSYPGFP QSQYPQYYGS SYNPPYVPAS SICPSPLSTS
    210 220 230 240 250
    TYVLQEASHN VPNQSSESLA GEYNTHNGPS TPAKEGDTDR PHRASDGKLR
    260 270 280 290 300
    GRSKRSSDPS PAGDNEIERV FVWDLDETII IFHSLLTGTF ASRYGKDTTT
    310 320 330 340 350
    SVRIGLMMEE MIFNLADTHL FFNDLEDCDQ IHVDDVSSDD NGQDLSTYNF
    360 370 380 390 400
    SADGFHSSAP GANLCLGSGV HGGVDWMRKL AFRYRRVKEM YNTYKNNVGG
    410 420 430 440 450
    LIGTPKRETW LQLRAELEAL TDLWLTHSLK ALNLINSRPN CVNVLVTTTQ
    460 470 480 490 500
    LIPALAKVLL YGLGSVFPIE NIYSATKTGK ESCFERIMQR FGRKAVYVVI
    510 520 530
    GDGVEEEQGA KKHNMPFWRI SCHADLEALR HALELEYL
    Length:538
    Mass (Da):59,232
    Last modified:May 2, 2002 - v2
    Checksum:i3DBFC31D8BE1E85D
    GO
    Isoform 2 (identifier: O00167-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         99-122: Missing.

    Show »
    Length:514
    Mass (Da):56,688
    Checksum:i970E63DB345E484A
    GO
    Isoform 3 (identifier: O00167-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         401-479: Missing.

    Show »
    Length:459
    Mass (Da):50,533
    Checksum:i774885A6F04CA6B2
    GO

    Computationally mapped potential isoform sequencesi

    There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    E7ETN2E7ETN2_HUMAN
    Eyes absent homolog
    EYA2
    508Annotation score:
    B1AKW3B1AKW3_HUMAN
    Eyes absent homolog
    EYA2
    197Annotation score:

    Sequence cautioni

    The sequence AAH13882 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti296K → E in AAB42065 (PubMed:9049631).Curated1
    Sequence conflicti361G → A in AAP35328 (Ref. 3) Curated1
    Sequence conflicti361G → A in AAH08803 (PubMed:15489334).Curated1
    Sequence conflicti381A → S in AAB42065 (PubMed:9049631).Curated1
    Sequence conflicti419A → V in CAA07815 (PubMed:9887327).Curated1
    Sequence conflicti525D → N in AAB51120 (PubMed:9195991).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_04896483P → S. Corresponds to variant dbSNP:rs2275596Ensembl.1
    Natural variantiVAR_048965238T → A. Corresponds to variant dbSNP:rs866936Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_00149099 – 122Missing in isoform 2. 2 PublicationsAdd BLAST24
    Alternative sequenceiVSP_001491401 – 479Missing in isoform 3. 1 PublicationAdd BLAST79

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U71207 mRNA Translation: AAB51120.1
    Y10261 Genomic DNA Translation: CAA71310.1
    BT006682 mRNA Translation: AAP35328.1
    AL049540
    , AL121776, AL359434, AL022342 Genomic DNA Translation: CAI23166.1
    BC000289 mRNA Translation: AAH00289.2
    BC008803 mRNA Translation: AAH08803.1
    BC013882 mRNA Translation: AAH13882.2 Different initiation.
    U81601 mRNA Translation: AAB42065.1
    AJ007992 mRNA Translation: CAA07815.1
    CCDSiCCDS13403.1 [O00167-1]
    CCDS54471.1 [O00167-3]
    RefSeqiNP_005235.3, NM_005244.4 [O00167-1]
    NP_742108.2, NM_172110.3 [O00167-3]
    UniGeneiHs.472877
    Hs.722040
    Hs.722415
    Hs.722416

    Genome annotation databases

    EnsembliENST00000327619; ENSP00000333640; ENSG00000064655 [O00167-1]
    ENST00000357410; ENSP00000349986; ENSG00000064655 [O00167-3]
    ENST00000497062; ENSP00000417105; ENSG00000064655 [O00167-2]
    GeneIDi2139
    KEGGihsa:2139
    UCSCiuc002xsm.3 human [O00167-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U71207 mRNA Translation: AAB51120.1
    Y10261 Genomic DNA Translation: CAA71310.1
    BT006682 mRNA Translation: AAP35328.1
    AL049540
    , AL121776, AL359434, AL022342 Genomic DNA Translation: CAI23166.1
    BC000289 mRNA Translation: AAH00289.2
    BC008803 mRNA Translation: AAH08803.1
    BC013882 mRNA Translation: AAH13882.2 Different initiation.
    U81601 mRNA Translation: AAB42065.1
    AJ007992 mRNA Translation: CAA07815.1
    CCDSiCCDS13403.1 [O00167-1]
    CCDS54471.1 [O00167-3]
    RefSeqiNP_005235.3, NM_005244.4 [O00167-1]
    NP_742108.2, NM_172110.3 [O00167-3]
    UniGeneiHs.472877
    Hs.722040
    Hs.722415
    Hs.722416

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3GEBX-ray2.40A/B/C/D268-538[»]
    3HB0X-ray2.50A/B/C/D268-538[»]
    3HB1X-ray2.51A/B/C/D268-538[»]
    4EGCX-ray1.99B253-538[»]
    ProteinModelPortaliO00167
    SMRiO00167
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108440, 83 interactors
    DIPiDIP-40707N
    IntActiO00167, 35 interactors
    MINTiO00167
    STRINGi9606.ENSP00000333640

    Chemistry databases

    ChEMBLiCHEMBL1293275

    PTM databases

    DEPODiO00167
    iPTMnetiO00167
    PhosphoSitePlusiO00167

    Polymorphism and mutation databases

    BioMutaiEYA2

    Proteomic databases

    PaxDbiO00167
    PeptideAtlasiO00167
    PRIDEiO00167
    ProteomicsDBi47756
    47757 [O00167-2]
    47758 [O00167-3]

    Protocols and materials databases

    DNASUi2139
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000327619; ENSP00000333640; ENSG00000064655 [O00167-1]
    ENST00000357410; ENSP00000349986; ENSG00000064655 [O00167-3]
    ENST00000497062; ENSP00000417105; ENSG00000064655 [O00167-2]
    GeneIDi2139
    KEGGihsa:2139
    UCSCiuc002xsm.3 human [O00167-1]

    Organism-specific databases

    CTDi2139
    DisGeNETi2139
    EuPathDBiHostDB:ENSG00000064655.18
    GeneCardsiEYA2
    HGNCiHGNC:3520 EYA2
    HPAiHPA027024
    HPA059291
    MIMi601654 gene
    neXtProtiNX_O00167
    OpenTargetsiENSG00000064655
    PharmGKBiPA27932
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3107 Eukaryota
    ENOG410XT12 LUCA
    GeneTreeiENSGT00390000008860
    HOVERGENiHBG002447
    InParanoidiO00167
    KOiK17620
    OMAiIYQGANG
    OrthoDBiEOG091G04YD
    PhylomeDBiO00167
    TreeFamiTF319337

    Enzyme and pathway databases

    BRENDAi3.1.3.48 2681
    ReactomeiR-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
    SABIO-RKiO00167

    Miscellaneous databases

    ChiTaRSiEYA2 human
    EvolutionaryTraceiO00167
    GeneWikiiEYA2
    GenomeRNAii2139
    PROiPR:O00167
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000064655 Expressed in 147 organ(s), highest expression level in nasal cavity epithelium
    ExpressionAtlasiO00167 baseline and differential
    GenevisibleiO00167 HS

    Family and domain databases

    CDDicd02601 HAD_Eya, 1 hit
    Gene3Di3.40.50.12350, 1 hit
    InterProiView protein in InterPro
    IPR028473 EYA2
    IPR006545 EYA_dom
    IPR038102 EYA_dom_sf
    IPR028472 EYA_fam
    IPR036412 HAD-like_sf
    PANTHERiPTHR10190 PTHR10190, 1 hit
    PTHR10190:SF7 PTHR10190:SF7, 1 hit
    SUPFAMiSSF56784 SSF56784, 1 hit
    TIGRFAMsiTIGR01658 EYA-cons_domain, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiEYA2_HUMAN
    AccessioniPrimary (citable) accession number: O00167
    Secondary accession number(s): Q5JSW8
    , Q86U84, Q96CV6, Q96H97, Q99503, Q99812, Q9BWF6, Q9H4S3, Q9H4S9, Q9NPZ4, Q9UIX7
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: May 2, 2002
    Last modified: November 7, 2018
    This is version 176 of the entry and version 2 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Human chromosome 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
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