Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Eyes absent homolog 2

Gene

EYA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

    • magnesium ion binding Source: UniProtKB
    • protein tyrosine phosphatase activity Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Activator, Chromatin regulator, Developmental protein, Hydrolase, Protein phosphatase

    Keywords - Biological processi

    DNA damage, DNA repair, Transcription, Transcription regulation

    Keywords - Ligandi

    Magnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciZFISH:HS00812-MONOMER.
    BRENDAi3.1.3.48. 2681.
    ReactomeiR-HSA-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
    SABIO-RKO00167.

    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

    HGNCiHGNC:3520. EYA2.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    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.

    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.
    ExpressionAtlasiO00167. baseline and differential.
    GenevisibleiO00167. HS.

    Organism-specific databases

    HPAiHPA027024.

    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
    SIX1Q154752EBI-750211,EBI-743675

    Protein-protein interaction databases

    BioGridi108440. 9 interactors.
    DIPiDIP-40707N.
    IntActiO00167. 4 interactors.
    MINTiMINT-139839.
    STRINGi9606.ENSP00000333640.

    Structurei

    Secondary structure

    1538
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi269 – 273Combined sources5
    Turni277 – 279Combined sources3
    Helixi283 – 287Combined sources5
    Helixi289 – 294Combined sources6
    Helixi298 – 319Combined sources22
    Helixi322 – 325Combined sources4
    Helixi326 – 328Combined sources3
    Turni333 – 336Combined sources4
    Helixi337 – 339Combined sources3
    Helixi350 – 352Combined sources3
    Helixi374 – 394Combined sources21
    Helixi398 – 402Combined sources5
    Helixi406 – 420Combined sources15
    Turni421 – 423Combined sources3
    Helixi424 – 436Combined sources13
    Beta strandi441 – 449Combined sources9
    Helixi451 – 460Combined sources10
    Turni464 – 466Combined sources3
    Helixi469 – 471Combined sources3
    Beta strandi472 – 474Combined sources3
    Turni476 – 478Combined sources3
    Helixi480 – 491Combined sources12
    Beta strandi493 – 503Combined sources11
    Helixi504 – 512Combined sources9
    Beta strandi517 – 519Combined sources3
    Helixi523 – 534Combined sources12

    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...

    Miscellaneous databases

    EvolutionaryTraceiO00167.

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG3107. Eukaryota.
    ENOG410XT12. LUCA.
    GeneTreeiENSGT00390000008860.
    HOVERGENiHBG002447.
    InParanoidiO00167.
    KOiK17620.
    OMAiIHSRPNC.
    OrthoDBiEOG091G04YD.
    PhylomeDBiO00167.
    TreeFamiTF319337.

    Family and domain databases

    Gene3Di3.40.50.1000. 2 hits.
    InterProiIPR028473. EYA2.
    IPR006545. EYA_dom.
    IPR028472. EYA_fam.
    IPR023214. HAD-like_dom.
    [Graphical view]
    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.
    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

    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 rs2275596dbSNPEnsembl.1
    Natural variantiVAR_048965238T → A.Corresponds to variant rs866936dbSNPEnsembl.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.
    AL121776
    , AL049540, AL359434, AL022342 Genomic DNA. Translation: CAI42150.1.
    AL359434
    , AL049540, AL121776, AL022342 Genomic DNA. Translation: CAI40099.1.
    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

    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.
    AL121776
    , AL049540, AL359434, AL022342 Genomic DNA. Translation: CAI42150.1.
    AL359434
    , AL049540, AL121776, AL022342 Genomic DNA. Translation: CAI40099.1.
    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. 9 interactors.
    DIPiDIP-40707N.
    IntActiO00167. 4 interactors.
    MINTiMINT-139839.
    STRINGi9606.ENSP00000333640.

    Chemistry databases

    ChEMBLiCHEMBL1293275.

    PTM databases

    DEPODiO00167.
    iPTMnetiO00167.
    PhosphoSitePlusiO00167.

    Polymorphism and mutation databases

    BioMutaiEYA2.

    Proteomic databases

    PaxDbiO00167.
    PeptideAtlasiO00167.
    PRIDEiO00167.

    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.
    GeneCardsiEYA2.
    HGNCiHGNC:3520. EYA2.
    HPAiHPA027024.
    MIMi601654. gene.
    neXtProtiNX_O00167.
    OpenTargetsiENSG00000064655.
    PharmGKBiPA27932.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3107. Eukaryota.
    ENOG410XT12. LUCA.
    GeneTreeiENSGT00390000008860.
    HOVERGENiHBG002447.
    InParanoidiO00167.
    KOiK17620.
    OMAiIHSRPNC.
    OrthoDBiEOG091G04YD.
    PhylomeDBiO00167.
    TreeFamiTF319337.

    Enzyme and pathway databases

    BioCyciZFISH:HS00812-MONOMER.
    BRENDAi3.1.3.48. 2681.
    ReactomeiR-HSA-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
    SABIO-RKO00167.

    Miscellaneous databases

    EvolutionaryTraceiO00167.
    GeneWikiiEYA2.
    GenomeRNAii2139.
    PROiO00167.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000064655.
    ExpressionAtlasiO00167. baseline and differential.
    GenevisibleiO00167. HS.

    Family and domain databases

    Gene3Di3.40.50.1000. 2 hits.
    InterProiIPR028473. EYA2.
    IPR006545. EYA_dom.
    IPR028472. EYA_fam.
    IPR023214. HAD-like_dom.
    [Graphical view]
    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 historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: May 2, 2002
    Last modified: November 30, 2016
    This is version 159 of the entry and version 2 of the sequence. [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. Human chromosome 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.