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P97480

- EYA3_MOUSE

UniProt

P97480 - EYA3_MOUSE

Protein

Eyes absent homolog 3

Gene

Eya3

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 2 (03 Oct 2012)
      Previous versions | rss
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    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 By similarity. Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. The phosphatase activity has been shown in vitro. Coactivates SIX1. 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. May be involved in development of the eye. May play a role in mediating the induction and differentiation of cranial placodes.By similarity1 Publication

    Catalytic activityi

    Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.3 Publications

    Cofactori

    Binds 1 Mg2+ ion per subunit.Curated

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei246 – 2461NucleophileBy similarity
    Metal bindingi246 – 2461MagnesiumBy similarity
    Active sitei248 – 2481Proton donorBy similarity
    Metal bindingi248 – 2481MagnesiumBy similarity
    Metal bindingi474 – 4741MagnesiumBy similarity

    GO - Molecular functioni

    1. chromatin binding Source: MGI
    2. metal ion binding Source: UniProtKB-KW
    3. protein binding Source: UniProtKB
    4. protein tyrosine/serine/threonine phosphatase activity Source: MGI
    5. protein tyrosine phosphatase activity Source: UniProtKB

    GO - Biological processi

    1. double-strand break repair Source: UniProtKB
    2. histone dephosphorylation Source: UniProtKB
    3. multicellular organismal development Source: UniProtKB-KW
    4. peptidyl-tyrosine dephosphorylation Source: GOC
    5. positive regulation of DNA repair Source: UniProtKB
    6. protein dephosphorylation Source: MGI
    7. regulation of transcription, DNA-templated Source: UniProtKB-KW
    8. response to ionizing radiation Source: UniProtKB
    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

    Enzyme and pathway databases

    SABIO-RKP97480.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Eyes absent homolog 3 (EC:3.1.3.48)
    Gene namesi
    Name:Eya3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 4

    Organism-specific databases

    MGIiMGI:109339. Eya3.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Localizes at sites of DNA damage at double-strand breaks (DSBs).By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB
    3. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi246 – 2461D → A: Abolishes phosphatase activity and abolishes coactivation of the SIX1-DACH1 complex. 3 Publications
    Mutagenesisi246 – 2461D → N: Abolishes phosphatase activity. 3 Publications
    Mutagenesisi248 – 2481D → N: Abolishes phosphatase activity. 1 Publication
    Mutagenesisi250 – 2501T → A: Abolishes phosphatase activity. 1 Publication
    Mutagenesisi419 – 4191T → A: Diminishes phosphatase activity by 24-fold. 1 Publication
    Mutagenesisi420 – 4201T → A: Diminishes phosphatase activity. 1 Publication
    Mutagenesisi449 – 4491K → Q: Abolishes phosphatase activity. 1 Publication
    Mutagenesisi473 – 4731G → A: Abolishes phosphatase activity. 1 Publication
    Mutagenesisi474 – 4741D → N: Diminishes phosphatase activity by 70%. 2 Publications
    Mutagenesisi478 – 4781E → Q: Abolishes phosphatase activity. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 510510Eyes absent homolog 3PRO_0000218649Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei203 – 2031PhosphoserineBy similarity
    Modified residuei409 – 4091PhosphoserineBy similarity

    Post-translational modificationi

    Ser-203 phosphorylation is required for localization at sites of DNA damage and directing interaction with H2AX.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP97480.
    PRIDEiP97480.

    PTM databases

    PhosphoSiteiP97480.

    Expressioni

    Tissue specificityi

    Expressed in branchial arches, CNS and developing eye.

    Gene expression databases

    ArrayExpressiP97480.
    CleanExiMM_EYA3.
    GenevestigatoriP97480.

    Interactioni

    Subunit structurei

    Interacts with SIX1 and DACH1, and probably SIX2, SIX4 and SIX5.3 Publications

    Protein-protein interaction databases

    BioGridi199561. 4 interactions.
    IntActiP97480. 2 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP97480.
    SMRiP97480. Positions 237-510.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG297494.
    GeneTreeiENSGT00390000008860.
    HOGENOMiHOG000293149.
    HOVERGENiHBG002447.
    InParanoidiP97480.
    KOiK17621.

    Family and domain databases

    InterProiIPR028479. EYA3.
    IPR006545. EYA_dom.
    IPR028472. EYA_fam.
    [Graphical view]
    PANTHERiPTHR10190. PTHR10190. 1 hit.
    PTHR10190:SF5. PTHR10190:SF5. 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: P97480-1) [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

    MQEPREQTLS QVNNPDASDE KPETSSLASN LSMSEEIMTC TDYIPRSSND    50
    YTSQMYSAKP YAHILSVPVS ETTYPGQTQY QTLQQSQPYA VYPQATQTYG 100
    LPPFASSTNA SLIPTSSAIA NIPAAAVASI SNQDYPTYTI LGQNQYQACY 150
    PSSSFGVTGQ TNSDAETTTL AATTYQTEKP SAMVPAPATQ RLPSDSSASP 200
    PLSQTTPNKD ADDQARKNMT VKNRGKRKAD ASSSQDSELE RVFLWDLDET 250
    IIIFHSLLTG SYAQKYGKDP TVVIGSGLTM EEMIFEVADT HLFFNDLEEC 300
    DQVHVEDVAS DDNGQDLSNY SFSTDGFSGS GGSGSHGSSV GVQGGVDWMR 350
    KLAFRYRKVR EIYDKHKSNV GGLLSPQRKE ALQRLRAEIE VLTDSWLGTA 400
    LKSLLLIQSR KNCANVLITT TQLVPALAKV LLYGLGEIFP IENIYSATKI 450
    GKESCFERIV SRFGKKVTYV VIGDGRDEEI AAKQHNMPFW RITNHGDLVS 500
    LHQALELDFL 510
    Length:510
    Mass (Da):55,973
    Last modified:October 3, 2012 - v2
    Checksum:iE82CC71DD1FD05F5
    GO
    Isoform 2 (identifier: P97480-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-105: MQEPREQTLS...TQTYGLPPFA → MIIPHKCILQT

    Note: No experimental confirmation available.

    Show »
    Length:416
    Mass (Da):45,518
    Checksum:iA19B88372DA2A767
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti200 – 2001P → L in AAB48019. (PubMed:9006082)Curated
    Sequence conflicti272 – 2721V → A in AAB42068. (PubMed:9049631)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 105105MQEPR…LPPFA → MIIPHKCILQT in isoform 2. 1 PublicationVSP_001494Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U81604 mRNA. Translation: AAB42068.1.
    U61112 mRNA. Translation: AAB48019.1.
    AL627130 Genomic DNA. No translation available.
    CH466552 Genomic DNA. Translation: EDL30095.1.
    AJ007996 mRNA. Translation: CAA07819.1.
    CCDSiCCDS18730.1. [P97480-1]
    CCDS18731.1. [P97480-2]
    RefSeqiNP_034296.2. NM_010166.3. [P97480-1]
    UniGeneiMm.227733.

    Genome annotation databases

    EnsembliENSMUST00000020197; ENSMUSP00000020197; ENSMUSG00000028886. [P97480-2]
    ENSMUST00000079157; ENSMUSP00000078157; ENSMUSG00000028886. [P97480-1]
    ENSMUST00000180250; ENSMUSP00000136812; ENSMUSG00000028886. [P97480-2]
    GeneIDi14050.
    KEGGimmu:14050.
    UCSCiuc008vbo.1. mouse.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U81604 mRNA. Translation: AAB42068.1 .
    U61112 mRNA. Translation: AAB48019.1 .
    AL627130 Genomic DNA. No translation available.
    CH466552 Genomic DNA. Translation: EDL30095.1 .
    AJ007996 mRNA. Translation: CAA07819.1 .
    CCDSi CCDS18730.1. [P97480-1 ]
    CCDS18731.1. [P97480-2 ]
    RefSeqi NP_034296.2. NM_010166.3. [P97480-1 ]
    UniGenei Mm.227733.

    3D structure databases

    ProteinModelPortali P97480.
    SMRi P97480. Positions 237-510.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 199561. 4 interactions.
    IntActi P97480. 2 interactions.

    PTM databases

    PhosphoSitei P97480.

    Proteomic databases

    PaxDbi P97480.
    PRIDEi P97480.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000020197 ; ENSMUSP00000020197 ; ENSMUSG00000028886 . [P97480-2 ]
    ENSMUST00000079157 ; ENSMUSP00000078157 ; ENSMUSG00000028886 . [P97480-1 ]
    ENSMUST00000180250 ; ENSMUSP00000136812 ; ENSMUSG00000028886 . [P97480-2 ]
    GeneIDi 14050.
    KEGGi mmu:14050.
    UCSCi uc008vbo.1. mouse.

    Organism-specific databases

    CTDi 2140.
    MGIi MGI:109339. Eya3.

    Phylogenomic databases

    eggNOGi NOG297494.
    GeneTreei ENSGT00390000008860.
    HOGENOMi HOG000293149.
    HOVERGENi HBG002447.
    InParanoidi P97480.
    KOi K17621.

    Enzyme and pathway databases

    SABIO-RK P97480.

    Miscellaneous databases

    ChiTaRSi EYA3. mouse.
    NextBioi 284996.
    PROi P97480.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P97480.
    CleanExi MM_EYA3.
    Genevestigatori P97480.

    Family and domain databases

    InterProi IPR028479. EYA3.
    IPR006545. EYA_dom.
    IPR028472. EYA_fam.
    [Graphical view ]
    PANTHERi PTHR10190. PTHR10190. 1 hit.
    PTHR10190:SF5. PTHR10190:SF5. 1 hit.
    TIGRFAMsi TIGR01658. EYA-cons_domain. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "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] (ISOFORM 1).
      Tissue: Embryo.
    2. "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] (ISOFORM 2).
      Tissue: Embryo.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 350-468.
      Tissue: Embryo.
    6. "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.
    7. "Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein."
      Ikeda K., Watanabe Y., Ohto H., Kawakami K.
      Mol. Cell. Biol. 22:6759-6766(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SIX1; SIX2; SIX4 AND SIX5.
    8. "Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis."
      Li X., Oghi K.A., Zhang J., Krones A., Bush K.T., Glass C.K., Nigam S.K., Aggarwal A.K., Maas R., Rose D.W., Rosenfeld M.G.
      Nature 426:247-254(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, INTERACTION WITH DACH1 AND SIX1, MUTAGENESIS OF ASP-246.
    9. Cited for: CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-246; ASP-248; THR-250; THR-419; GLY-473; ASP-474 AND GLU-478.
    10. "The transcription factor Eyes absent is a protein tyrosine phosphatase."
      Tootle T.L., Silver S.J., Davies E.L., Newman V., Latek R.R., Mills I.A., Selengut J.D., Parlikar B.E., Rebay I.
      Nature 426:299-302(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-246; THR-420; LYS-449; ASP-474 AND GLU-478.
    11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.

    Entry informationi

    Entry nameiEYA3_MOUSE
    AccessioniPrimary (citable) accession number: P97480
    Secondary accession number(s): G5E8I5, P97768
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: October 3, 2012
    Last modified: October 1, 2014
    This is version 119 of the entry and version 2 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