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P97767

- EYA1_MOUSE

UniProt

P97767 - EYA1_MOUSE

Protein

Eyes absent homolog 1

Gene

Eya1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 3 (03 Oct 2012)
      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. Has also phosphatase activity with proteins phosphorylated on Ser and Thr residues (in vitro). Required for normal embryonic development of the craniofacial and trunk skeleton, kidneys and ears. Together with SIX1, it plays an important role in hypaxial muscle development; in this it is functionally redundant with EYA2.4 Publications

    Catalytic activityi

    Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
    [a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

    Cofactori

    Binds 1 Mg2+ ion per subunit.Curated

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei327 – 3271NucleophileBy similarity
    Metal bindingi327 – 3271MagnesiumBy similarity
    Active sitei329 – 3291Proton donorBy similarity
    Metal bindingi329 – 3291MagnesiumBy similarity
    Metal bindingi555 – 5551MagnesiumBy similarity

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. protein binding Source: IntAct
    3. protein tyrosine phosphatase activity Source: MGI
    4. RNA binding Source: MGI

    GO - Biological processi

    1. anatomical structure development Source: MGI
    2. aorta morphogenesis Source: MGI
    3. branching involved in ureteric bud morphogenesis Source: MGI
    4. cell fate commitment Source: MGI
    5. cellular protein localization Source: MGI
    6. cochlea morphogenesis Source: MGI
    7. double-strand break repair Source: UniProtKB
    8. embryonic skeletal system morphogenesis Source: MGI
    9. establishment of mitotic spindle orientation Source: MGI
    10. establishment or maintenance of apical/basal cell polarity Source: MGI
    11. histone dephosphorylation Source: UniProtKB
    12. inner ear morphogenesis Source: MGI
    13. lung epithelial cell differentiation Source: MGI
    14. mesodermal cell fate specification Source: UniProtKB
    15. metanephros development Source: MGI
    16. middle ear morphogenesis Source: MGI
    17. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
    18. neuron fate specification Source: MGI
    19. organ morphogenesis Source: MGI
    20. otic vesicle development Source: MGI
    21. otic vesicle morphogenesis Source: MGI
    22. outer ear morphogenesis Source: MGI
    23. outflow tract morphogenesis Source: MGI
    24. pattern specification process Source: MGI
    25. pharyngeal system development Source: MGI
    26. positive regulation of DNA repair Source: UniProtKB
    27. positive regulation of epithelial cell proliferation Source: MGI
    28. positive regulation of Notch signaling pathway Source: MGI
    29. positive regulation of secondary heart field cardioblast proliferation Source: MGI
    30. positive regulation of transcription, DNA-templated Source: UniProtKB
    31. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    32. protein dephosphorylation Source: MGI
    33. protein sumoylation Source: UniProtKB
    34. regulation of neuron differentiation Source: MGI
    35. response to ionizing radiation Source: UniProtKB
    36. semicircular canal morphogenesis Source: MGI
    37. striated muscle tissue development Source: MGI
    38. transcription, DNA-templated Source: UniProtKB-KW
    39. ureteric bud development Source: MGI

    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-RKP97767.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Eyes absent homolog 1 (EC:3.1.3.16, EC:3.1.3.48)
    Gene namesi
    Name:Eya1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 1

    Organism-specific databases

    MGIiMGI:109344. Eya1.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. nucleus Source: UniProtKB
    3. protein complex Source: UniProtKB
    4. protein-DNA complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    A spontaneous mutation leading to decreased Eya1 expression gives rise to the Eya1-bor phenotype. It is characterized by circling behavior and deafness, due to gross morphological abnormalities of the inner ear, and dysmorphic or missing kidneys. This autosomal recessive trait resembles human branchio-oto-renal (BOR) syndrome.1 Publication

    Disruption phenotypei

    Complete perinatal lethality in homozygotes, due to severe craniofacial and skeletal defects, combined with an absence of thymus, kidneys, parotid glands and ears. Mice present multiple skeletal defects in skull, neck, rib and pelvic girdle, but no major defects in muscle development. Otic anomalies involve the inner, middle and outer ears, with malformed auricles and eardrums, malformations of the incus, malleus, and stapes, while the tympanic cavity never formed. Likewise, mice display an absence of inner ear structures. Heterozygotes present milder symptoms with low penetrance, including renal defects, similar to human BOR (branchio-oto-renal) syndrome. Increased apoptosis and loss of renal tubules seen in the developing kidney with increased immunostaining for 'Ser-139' phosphorylated H2AX. Mice lacking both Six1 and Eya1 show defects in kidney development, complete absence of hypaxial muscle, severe reduction in epaxial muscle and a 5-10-fold by volume smaller pituarity than the wild-type gland. Mice lacking both Eya1 and Eya2 display complete embryonic lethality, due to severe defects in muscle development, including the absence of a diaphragm and of ventral hypaxial muscles of the trunk and the complete absence of 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 active transcription from cognate promoter elements, and does not activate transcription of Pax3.4 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi43 – 431K → R: Markedly reduced sumoylation; when associated with R-459. 1 Publication
    Mutagenesisi459 – 4591K → R: Markedly reduced sumoylation; when associated with R-43. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 591591Eyes absent homolog 1PRO_0000218644Add
    BLAST

    Post-translational modificationi

    Sumoylated with SUMO1.1 Publication

    Keywords - PTMi

    Ubl conjugation

    Proteomic databases

    PRIDEiP97767.

    PTM databases

    PhosphoSiteiP97767.

    Expressioni

    Tissue specificityi

    Extensively expressed in cranial placodes, branchial arches, CNS and developing eye and nose.

    Gene expression databases

    ArrayExpressiP97767.
    CleanExiMM_EYA1.
    GenevestigatoriP97767.

    Interactioni

    Subunit structurei

    Probably interacts with SIX2, SIX4 and SIX5. Interacts with H2AX in response to DNA damage.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Rbck1Q9WUB02EBI-1368503,EBI-6141072
    SharpinQ91WA64EBI-1368503,EBI-646097
    Six1Q622313EBI-1368503,EBI-1368483
    Six2Q622323EBI-1368503,EBI-1368736

    Protein-protein interaction databases

    IntActiP97767. 4 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP97767.
    SMRiP97767. Positions 321-591.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG297494.
    GeneTreeiENSGT00390000008860.
    HOGENOMiHOG000293149.
    HOVERGENiHBG002447.
    InParanoidiP97767.
    KOiK15616.
    OMAiGQPYGIS.
    TreeFamiTF319337.

    Family and domain databases

    InterProiIPR006545. EYA_dom.
    IPR028472. EYA_fam.
    IPR028471. Eyes_absent_h1.
    [Graphical view]
    PANTHERiPTHR10190. PTHR10190. 1 hit.
    PTHR10190:SF11. PTHR10190:SF11. 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: P97767-1) [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

    MEMQDLTSPH SRLSGSSESP SGPKLDSSHI NSTSMTPNGT EVKTEPMSSS    50
    EIASTAADGS LDSFSGSALG SSSFSPRPAH PFSPPQIYPS KSYPHILPTP 100
    SSQTMAAYGQ TQFTTGMQQA TAYATYPQPG QPYGISSYGA LWAGIKTESG 150
    LSQSQSPGQT GFLSYGTSFG TPQPGQAPYS YQMQGSSFTT SSGLYSGNNS 200
    LTNSSGFNSS QQDYPSYPGF GQGQYAQYYN SSPYPAHYMT SSNTSPTTPS 250
    TNATYQLQEP PSGVTSQAVT DPTAEYSTIH SPSTPIKETD SERLRRGSDG 300
    KSRGRGRRNN NPSPPPDSDL ERVFIWDLDE TIIVFHSLLT GSYANRYGRD 350
    PPTSVSLGLR MEEMIFNLAD THLFFNDLEE CDQVHIDDVS SDDNGQDLST 400
    YNFGTDGFPA AATSANLCLA TGVRGGVDWM RKLAFRYRRV KEIYNTYKNN 450
    VGGLLGPAKR EAWLQLRAEI EALTDSWLTL ALKALSLIHS RTNCVNILVT 500
    TTQLIPALAK VLLYGLGIVF PIENIYSATK IGKESCFERI IQRFGRKVVY 550
    VVIGDGVEEE QGAKKHAMPF WRVSSHSDLM ALHHALELEY L 591
    Length:591
    Mass (Da):64,324
    Last modified:October 3, 2012 - v3
    Checksum:iD31F71852FBDC76C
    GO
    Isoform 2 (identifier: P97767-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-41: MEMQDLTSPHSRLSGSSESPSGPKLDSSHINSTSMTPNGTE → MLLFPQVA
         140-144: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:553
    Mass (Da):60,425
    Checksum:i659F016F829159A6
    GO

    Sequence cautioni

    The sequence AAB48017.1 differs from that shown. Reason: Frameshift at positions 349 and 360.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti117 – 1171M → V in CAA71312. (PubMed:9020840)Curated
    Sequence conflicti163 – 1631L → F in CAA71312. (PubMed:9020840)Curated
    Sequence conflicti324 – 3252FI → LL in AAB48017. (PubMed:9006082)Curated
    Sequence conflicti405 – 4051T → R in AAB48017. (PubMed:9006082)Curated
    Sequence conflicti450 – 4501N → K in AAB48017. (PubMed:9006082)Curated
    Sequence conflicti505 – 5051I → S in AAB48017. (PubMed:9006082)Curated
    Sequence conflicti535 – 5351S → G in CAA71312. (PubMed:9020840)Curated
    Sequence conflicti539 – 5391R → G in CAA71312. (PubMed:9020840)Curated
    Sequence conflicti548 – 5481V → L in CAA71312. (PubMed:9020840)Curated
    Sequence conflicti551 – 5522VV → LL in AAB48017. (PubMed:9006082)Curated
    Sequence conflicti559 – 5591E → K in CAA71312. (PubMed:9020840)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 4141MEMQD…PNGTE → MLLFPQVA in isoform 2. CuratedVSP_001487Add
    BLAST
    Alternative sequencei140 – 1445Missing in isoform 2. CuratedVSP_001488

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U61110 mRNA. Translation: AAB48017.1. Frameshift.
    Y10263 Genomic DNA. Translation: CAA71312.1.
    AC119875 Genomic DNA. No translation available.
    AC156988 Genomic DNA. No translation available.
    CH466536 Genomic DNA. Translation: EDL14327.1.
    AF097544 Genomic DNA. Translation: AAD19355.1.
    AJ007995 mRNA. Translation: CAA07818.1.
    RefSeqiXP_006495511.1. XM_006495448.1. [P97767-1]
    UniGeneiMm.250185.

    Genome annotation databases

    EnsembliENSMUST00000027066; ENSMUSP00000027066; ENSMUSG00000025932. [P97767-1]
    GeneIDi14048.
    KEGGimmu:14048.
    UCSCiuc007aiw.1. mouse.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U61110 mRNA. Translation: AAB48017.1 . Frameshift.
    Y10263 Genomic DNA. Translation: CAA71312.1 .
    AC119875 Genomic DNA. No translation available.
    AC156988 Genomic DNA. No translation available.
    CH466536 Genomic DNA. Translation: EDL14327.1 .
    AF097544 Genomic DNA. Translation: AAD19355.1 .
    AJ007995 mRNA. Translation: CAA07818.1 .
    RefSeqi XP_006495511.1. XM_006495448.1. [P97767-1 ]
    UniGenei Mm.250185.

    3D structure databases

    ProteinModelPortali P97767.
    SMRi P97767. Positions 321-591.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P97767. 4 interactions.

    PTM databases

    PhosphoSitei P97767.

    Proteomic databases

    PRIDEi P97767.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000027066 ; ENSMUSP00000027066 ; ENSMUSG00000025932 . [P97767-1 ]
    GeneIDi 14048.
    KEGGi mmu:14048.
    UCSCi uc007aiw.1. mouse.

    Organism-specific databases

    CTDi 2138.
    MGIi MGI:109344. Eya1.

    Phylogenomic databases

    eggNOGi NOG297494.
    GeneTreei ENSGT00390000008860.
    HOGENOMi HOG000293149.
    HOVERGENi HBG002447.
    InParanoidi P97767.
    KOi K15616.
    OMAi GQPYGIS.
    TreeFami TF319337.

    Enzyme and pathway databases

    SABIO-RK P97767.

    Miscellaneous databases

    PROi P97767.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P97767.
    CleanExi MM_EYA1.
    Genevestigatori P97767.

    Family and domain databases

    InterProi IPR006545. EYA_dom.
    IPR028472. EYA_fam.
    IPR028471. Eyes_absent_h1.
    [Graphical view ]
    PANTHERi PTHR10190. PTHR10190. 1 hit.
    PTHR10190:SF11. PTHR10190:SF11. 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] (ISOFORM 1).
      Tissue: Embryo.
    2. "A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family."
      Abdelhak S., Kalatzis V., Heilig R., Compain S., Samson D., Vincent C., Weil D., Cruaud C., Sahly I., Leibovici M., Bitner-Glindzicz M., Francis M., Lacombe D., Vigneron J., Charachon R., Boven K., Bedbeder P., van Regemorter N., Weissenbach J., Petit C.
      Nat. Genet. 15:157-164(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
      Strain: CB/20.
    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. "Inner ear and kidney anomalies caused by IAP insertion in an intron of the Eya1 gene in a mouse model of BOR syndrome."
      Johnson K.R., Cook S.A., Erway L.C., Matthews A.N., Sanford L.P., Paradies N.E., Friedman R.A.
      Hum. Mol. Genet. 8:645-653(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 276-321, DISEASE.
      Strain: 129/SvJ.
    6. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 431-549.
      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. "Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia."
      Xu P.X., Adams J., Peters H., Brown M.C., Heaney S., Maas R.
      Nat. Genet. 23:113-117(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    9. "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: FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE.
    10. Cited for: CATALYTIC ACTIVITY.
    11. "SUMO1 haploinsufficiency leads to cleft lip and palate."
      Alkuraya F.S., Saadi I., Lund J.J., Turbe-Doan A., Morton C.C., Maas R.L.
      Science 313:1751-1751(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUMOYLATION, MUTAGENESIS OF LYS-43 AND LYS-459.
    12. "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.
    13. "Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions."
      Cook P.J., Ju B.G., Telese F., Wang X., Glass C.K., Rosenfeld M.G.
      Nature 458:591-596(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH H2AX.

    Entry informationi

    Entry nameiEYA1_MOUSE
    AccessioniPrimary (citable) accession number: P97767
    Secondary accession number(s): G5E864, O08818
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: October 3, 2012
    Last modified: October 1, 2014
    This is version 121 of the entry and version 3 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