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O08575

- EYA2_MOUSE

UniProt

O08575 - EYA2_MOUSE

Protein

Eyes absent homolog 2

Gene

Eya2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Jul 1997)
      Previous versions | rss
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    Functioni

    Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5. 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. Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis By similarity. Plays an important role in hypaxial muscle development together with SIX1 and DACH2; in this it is functionally redundant with EYA1.By similarity2 Publications

    Catalytic activityi

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

    Cofactori

    Binds 1 Mg2+ ion per subunit.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei268 – 2681NucleophileBy similarity
    Metal bindingi268 – 2681MagnesiumBy similarity
    Active sitei270 – 2701Proton donorBy similarity
    Metal bindingi270 – 2701Magnesium; via carbonyl oxygenBy similarity
    Metal bindingi496 – 4961MagnesiumBy similarity

    GO - Molecular functioni

    1. magnesium ion binding Source: UniProtKB
    2. protein binding Source: IntAct
    3. protein tyrosine phosphatase activity Source: UniProtKB

    GO - Biological processi

    1. DNA repair Source: UniProtKB-KW
    2. extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
    3. histone dephosphorylation Source: UniProtKB
    4. mitochondrial outer membrane permeabilization Source: MGI
    5. multicellular organismal development Source: UniProtKB-KW
    6. protein dephosphorylation Source: MGI
    7. regulation of transcription, DNA-templated Source: UniProtKB-KW
    8. striated muscle tissue development Source: MGI
    9. transcription, DNA-templated Source: UniProtKB-KW

    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

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Eyes absent homolog 2 (EC:3.1.3.48)
    Gene namesi
    Name:Eya2
    Synonyms:Eab1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:109341. Eya2.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 Publication
    Note: Retained in the cytoplasm via interaction with GNAZ and GNAI2 By similarity. Interaction with SIX1, SIX2, SIX4 or SIX5 is required for translocation to the nucleus.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. mitochondrion Source: Ensembl
    3. nucleus Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    No visible phenotype. In contrast, mice lacking both Eya1 and Eya2 display complete embryonic lethality, due to severe defects in muscle development, including the absence of the diaphragm, the absence of ventral hypaxial muscles of the trunk and muscles in forelimbs and hindlimbs, similar to the phenotype of mice lacking both Six1 and Six4. While Six1 is normally expressed in these mice, it does not activate transcription from cognate promoter elements, and does not activate transcription of Pax3.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 532532Eyes absent homolog 2PRO_0000218647Add
    BLAST

    Proteomic databases

    PRIDEiO08575.

    PTM databases

    PhosphoSiteiO08575.

    Expressioni

    Tissue specificityi

    Extensively expressed in cranial placodes, branchial arches, CNS and developing eye and nose. Low expression in lung with little or no expression in skin, liver, intestine and kidney. Predominantly expressed in the upper one-third of the oxyntic mucosa and in most regions of the pyloric mucosa.1 Publication

    Gene expression databases

    ArrayExpressiO08575.
    BgeeiO08575.
    CleanExiMM_EYA2.
    GenevestigatoriO08575.

    Interactioni

    Subunit structurei

    Probably interacts with SIX2, SIX4 and SIX5. Interacts with DACH2. Interacts with GNAZ and GNAI2; this retains EYA2 in the cytoplasm and prevents its translocation into the nucleus and transcriptional activity By similarity. Interacts with SIX1. Interacts with CAPN8.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    SharpinQ91WA62EBI-986503,EBI-646097

    Protein-protein interaction databases

    BioGridi199560. 1 interaction.
    IntActiO08575. 3 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliO08575.
    SMRiO08575. Positions 262-532.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG297494.
    GeneTreeiENSGT00390000008860.
    HOVERGENiHBG002447.
    InParanoidiA2A5S4.
    KOiK17620.
    OMAiIHSRPNC.
    OrthoDBiEOG7DNNTZ.
    TreeFamiTF319337.

    Family and domain databases

    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 (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O08575-1) [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

    MLEVVTSPSL ATSSDWSEHG AAVGTLSDRE GIAKSAALSV PQLFVKSHPR    50
    VPPGQSSTAM AAYGQTQYST GIQQAPPYTA YPTPAQAYGI PPYSIKTEDS 100
    LNHSPSQSGF LSYGPSFSTA PAGQSPYTYP VHSTAGLYQG ANGLTNTAGF 150
    GSVHQDYPSY PSFSQNQYPQ YFSPSYNPPY VPASSLCSSP LSTSTYVLQE 200
    APHNVPSQSS ESLAGDYNTH NGPSTPAKEG DTERPHRASD GKLRGRSKRN 250
    SDPSPAGDNE IERVFVWDLD ETIIIFHSLL TGTFASRYGK DTTTSVRIGL 300
    MMEEMIFNLA DTHLFFNDLE DCDQIHVDDV SSDDNGQDLS TYNFSTDGFH 350
    STAPGASLCL GTGVHGGVDW MRKLAFRYRR VKEMYNTYRN NVGGLIGAPK 400
    RETWLQLRAE LEALTDLWLT HSLKALNLIN SRPNCVNVLV TTTQLIPALA 450
    KVLLYGLGSV FPIENIYSAT KTGKESCFER IMQRFGRKAV YIVIGDGVEE 500
    EQGAKKHNMP FWRISCHADL EALRHALELE YL 532
    Length:532
    Mass (Da):58,246
    Last modified:July 1, 1997 - v1
    Checksum:i9A29BC6BB77DF880
    GO
    Isoform 2 (identifier: O08575-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         114-142: Missing.

    Show »
    Length:503
    Mass (Da):55,337
    Checksum:iF12F8FD4B0291F16
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei114 – 14229Missing in isoform 2. CuratedVSP_001492Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U71208 mRNA. Translation: AAB51121.1.
    U61111 mRNA. Translation: AAB48018.1. Sequence problems.
    AL591712 Genomic DNA. Translation: CAM14837.1.
    BC003755 mRNA. Translation: AAH03755.1.
    U81603 mRNA. Translation: AAB42067.1.
    CCDSiCCDS17084.1. [O08575-1]
    RefSeqiNP_001258891.1. NM_001271962.1. [O08575-1]
    NP_001258892.1. NM_001271963.1. [O08575-1]
    NP_034295.1. NM_010165.3. [O08575-1]
    UniGeneiMm.282719.

    Genome annotation databases

    EnsembliENSMUST00000063433; ENSMUSP00000066244; ENSMUSG00000017897. [O08575-1]
    ENSMUST00000088132; ENSMUSP00000085455; ENSMUSG00000017897. [O08575-1]
    GeneIDi14049.
    KEGGimmu:14049.
    UCSCiuc008nxw.1. mouse. [O08575-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U71208 mRNA. Translation: AAB51121.1 .
    U61111 mRNA. Translation: AAB48018.1 . Sequence problems.
    AL591712 Genomic DNA. Translation: CAM14837.1 .
    BC003755 mRNA. Translation: AAH03755.1 .
    U81603 mRNA. Translation: AAB42067.1 .
    CCDSi CCDS17084.1. [O08575-1 ]
    RefSeqi NP_001258891.1. NM_001271962.1. [O08575-1 ]
    NP_001258892.1. NM_001271963.1. [O08575-1 ]
    NP_034295.1. NM_010165.3. [O08575-1 ]
    UniGenei Mm.282719.

    3D structure databases

    ProteinModelPortali O08575.
    SMRi O08575. Positions 262-532.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 199560. 1 interaction.
    IntActi O08575. 3 interactions.

    PTM databases

    PhosphoSitei O08575.

    Proteomic databases

    PRIDEi O08575.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000063433 ; ENSMUSP00000066244 ; ENSMUSG00000017897 . [O08575-1 ]
    ENSMUST00000088132 ; ENSMUSP00000085455 ; ENSMUSG00000017897 . [O08575-1 ]
    GeneIDi 14049.
    KEGGi mmu:14049.
    UCSCi uc008nxw.1. mouse. [O08575-1 ]

    Organism-specific databases

    CTDi 2139.
    MGIi MGI:109341. Eya2.

    Phylogenomic databases

    eggNOGi NOG297494.
    GeneTreei ENSGT00390000008860.
    HOVERGENi HBG002447.
    InParanoidi A2A5S4.
    KOi K17620.
    OMAi IHSRPNC.
    OrthoDBi EOG7DNNTZ.
    TreeFami TF319337.

    Miscellaneous databases

    NextBioi 284992.
    PROi O08575.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O08575.
    Bgeei O08575.
    CleanExi MM_EYA2.
    Genevestigatori O08575.

    Family and domain databases

    InterProi IPR028473. EYA2.
    IPR006545. EYA_dom.
    IPR028472. EYA_fam.
    IPR023214. HAD-like_dom.
    [Graphical view ]
    PANTHERi PTHR10190. PTHR10190. 1 hit.
    PTHR10190:SF7. PTHR10190:SF7. 1 hit.
    SUPFAMi SSF56784. SSF56784. 1 hit.
    TIGRFAMsi TIGR01658. EYA-cons_domain. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for expression in lens and nasal placode."
      Xu P.-X., Woo I., Her H., Beier D.R., Maas R.L.
      Development 124:219-231(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Embryo.
    2. "Eyes absent: a gene family found in several metazoan phyla."
      Duncan M.K., Kos L., Jenkins N.A., Gilbert D.J., Copeland N.G., Tomarev S.I.
      Mamm. Genome 8:479-485(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Embryo.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Strain: C57BL/6J.
      Tissue: Mammary gland.
    5. "Identification of transcriptional targets for Six5: implication for the pathogenesis of myotonic dystrophy type 1."
      Sato S., Nakamura M., Cho D.H., Tapscott S.J., Ozaki H., Kawakami K.
      Hum. Mol. Genet. 11:1045-1058(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SIX1.
    6. "Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene."
      Zimmerman J.E., Bui Q.T., Steingrimsson E., Nagle D.L., Fu W., Genin A., Spinner N.B., Copeland N.G., Jenkins N.A., Bucan M., Bonini N.M.
      Genome Res. 7:128-141(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 60-532.
      Tissue: Embryo.
    7. "Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya."
      Ohto H., Kamada S., Tago K., Tominaga S., Ozaki H., Sato S., Kawakami K.
      Mol. Cell. Biol. 19:6815-6824(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH SIX2; SIX4 AND SIX5, SUBCELLULAR LOCATION.
    8. Cited for: CATALYTIC ACTIVITY.
    9. "Stomach-specific calpain, nCL-2, localizes in mucus cells and proteolyzes the beta-subunit of coatomer complex, beta-COP."
      Hata S., Koyama S., Kawahara H., Doi N., Maeda T., Toyama-Sorimachi N., Abe K., Suzuki K., Sorimachi H.
      J. Biol. Chem. 281:11214-11224(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CAPN8, TISSUE SPECIFICITY.
    10. "Eya1 and Eya2 proteins are required for hypaxial somitic myogenesis in the mouse embryo."
      Grifone R., Demignon J., Giordani J., Niro C., Souil E., Bertin F., Laclef C., Xu P.X., Maire P.
      Dev. Biol. 302:602-616(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.

    Entry informationi

    Entry nameiEYA2_MOUSE
    AccessioniPrimary (citable) accession number: O08575
    Secondary accession number(s): A2A5S4, P97925
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: July 1, 1997
    Last modified: October 1, 2014
    This is version 119 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3