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P97480 (EYA3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Eyes absent homolog 3

EC=3.1.3.48
Gene names
Name:Eya3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length510 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.8 Ref.10 Ref.11

Cofactor

Binds 1 Mg2+ ion per subunit Probable.

Subunit structure

Interacts with SIX1 and DACH1, and probably SIX2, SIX4 and SIX5. Ref.6 Ref.7 Ref.8

Subcellular location

Cytoplasm. Nucleus. Note: Localizes at sites of DNA damage at double-strand breaks (DSBs) By similarity. Ref.6 Ref.10

Tissue specificity

Expressed in branchial arches, CNS and developing eye.

Post-translational modification

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

Sequence similarities

Belongs to the HAD-like hydrolase superfamily. EYA family.

Caution

According to Ref.8 also shows serine/threonine protein phosphatase activity.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandMagnesium
Metal-binding
   Molecular functionActivator
Chromatin regulator
Developmental protein
Hydrolase
Protein phosphatase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdouble-strand break repair

Inferred from sequence or structural similarity. Source: UniProtKB

histone dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

peptidyl-tyrosine dephosphorylation

Inferred from direct assay Ref.10. Source: GOC

positive regulation of DNA repair

Inferred from sequence or structural similarity. Source: UniProtKB

protein dephosphorylation

Inferred from direct assay Ref.10. Source: MGI

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

response to ionizing radiation

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

transcription factor complex

Inferred from physical interaction PubMed 19008232. Source: MGI

   Molecular_functionchromatin binding

Inferred from genetic interaction PubMed 19008232. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein tyrosine phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein tyrosine/serine/threonine phosphatase activity

Inferred from direct assay Ref.8. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P97480-1)

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.
Isoform 2 (identifier: P97480-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: MQEPREQTLS...TQTYGLPPFA → MIIPHKCILQT
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 510510Eyes absent homolog 3
PRO_0000218649

Sites

Active site2461Nucleophile By similarity
Active site2481Proton donor By similarity
Metal binding2461Magnesium By similarity
Metal binding2481Magnesium By similarity
Metal binding4741Magnesium By similarity

Amino acid modifications

Modified residue2031Phosphoserine By similarity
Modified residue4091Phosphoserine By similarity

Natural variations

Alternative sequence1 – 105105MQEPR…LPPFA → MIIPHKCILQT in isoform 2.
VSP_001494

Experimental info

Mutagenesis2461D → A: Abolishes phosphatase activity and abolishes coactivation of the SIX1-DACH1 complex. Ref.8 Ref.10 Ref.11
Mutagenesis2461D → N: Abolishes phosphatase activity. Ref.8 Ref.10 Ref.11
Mutagenesis2481D → N: Abolishes phosphatase activity. Ref.10
Mutagenesis2501T → A: Abolishes phosphatase activity. Ref.10
Mutagenesis4191T → A: Diminishes phosphatase activity by 24-fold. Ref.10
Mutagenesis4201T → A: Diminishes phosphatase activity. Ref.11
Mutagenesis4491K → Q: Abolishes phosphatase activity. Ref.11
Mutagenesis4731G → A: Abolishes phosphatase activity. Ref.10
Mutagenesis4741D → N: Diminishes phosphatase activity by 70%. Ref.10 Ref.11
Mutagenesis4781E → Q: Abolishes phosphatase activity. Ref.10 Ref.11
Sequence conflict2001P → L in AAB48019. Ref.2
Sequence conflict2721V → A in AAB42068. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 3, 2012. Version 2.
Checksum: E82CC71DD1FD05F5

FASTA51055,973
        10         20         30         40         50         60 
MQEPREQTLS QVNNPDASDE KPETSSLASN LSMSEEIMTC TDYIPRSSND YTSQMYSAKP 

        70         80         90        100        110        120 
YAHILSVPVS ETTYPGQTQY QTLQQSQPYA VYPQATQTYG LPPFASSTNA SLIPTSSAIA 

       130        140        150        160        170        180 
NIPAAAVASI SNQDYPTYTI LGQNQYQACY PSSSFGVTGQ TNSDAETTTL AATTYQTEKP 

       190        200        210        220        230        240 
SAMVPAPATQ RLPSDSSASP PLSQTTPNKD ADDQARKNMT VKNRGKRKAD ASSSQDSELE 

       250        260        270        280        290        300 
RVFLWDLDET IIIFHSLLTG SYAQKYGKDP TVVIGSGLTM EEMIFEVADT HLFFNDLEEC 

       310        320        330        340        350        360 
DQVHVEDVAS DDNGQDLSNY SFSTDGFSGS GGSGSHGSSV GVQGGVDWMR KLAFRYRKVR 

       370        380        390        400        410        420 
EIYDKHKSNV GGLLSPQRKE ALQRLRAEIE VLTDSWLGTA LKSLLLIQSR KNCANVLITT 

       430        440        450        460        470        480 
TQLVPALAKV LLYGLGEIFP IENIYSATKI GKESCFERIV SRFGKKVTYV VIGDGRDEEI 

       490        500        510 
AAKQHNMPFW RITNHGDLVS LHQALELDFL 

« Hide

Isoform 2 [UniParc].

Checksum: A19B88372DA2A767
Show »

FASTA41645,518

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"EYA4, a novel vertebrate gene related to Drosophila eyes absent."
Borsani G., DeGrandi A., Ballabio A., Bulfone A., Bernard L., Banfi S., Gattuso C., Mariani M., Dixon M., Donnai D., Metcalfe K., Winter R., Robertson M., Axton R., Brown A., van Heyningen V., Hanson I.
Hum. Mol. Genet. 8:11-23(1999) [PubMed] [Europe PMC] [Abstract]
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]Erratum
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 427:265-265(2004)
[10]"Eyes absent represents a class of protein tyrosine phosphatases."
Rayapureddi J.P., Kattamuri C., Steinmetz B.D., Frankfort B.J., Ostrin E.J., Mardon G., Hegde R.S.
Nature 426:295-298(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-246; ASP-248; THR-250; THR-419; GLY-473; ASP-474 AND GLU-478.
[11]"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.
[12]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_034296.2. NM_010166.3.
UniGeneMm.227733.

3D structure databases

ProteinModelPortalP97480.
SMRP97480. Positions 237-510.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199561. 4 interactions.
IntActP97480. 2 interactions.

PTM databases

PhosphoSiteP97480.

Proteomic databases

PaxDbP97480.
PRIDEP97480.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020197; ENSMUSP00000020197; ENSMUSG00000028886. [P97480-2]
ENSMUST00000079157; ENSMUSP00000078157; ENSMUSG00000028886. [P97480-1]
ENSMUST00000180250; ENSMUSP00000136812; ENSMUSG00000028886. [P97480-2]
GeneID14050.
KEGGmmu:14050.
UCSCuc008vbo.1. mouse.

Organism-specific databases

CTD2140.
MGIMGI:109339. Eya3.

Phylogenomic databases

eggNOGNOG297494.
GeneTreeENSGT00390000008860.
HOGENOMHOG000293149.
HOVERGENHBG002447.
InParanoidP97480.
KOK17621.

Enzyme and pathway databases

SABIO-RKP97480.

Gene expression databases

ArrayExpressP97480.
CleanExMM_EYA3.
GenevestigatorP97480.

Family and domain databases

InterProIPR028479. EYA3.
IPR006545. EYA_dom.
IPR028472. EYA_fam.
[Graphical view]
PANTHERPTHR10190. PTHR10190. 1 hit.
PTHR10190:SF5. PTHR10190:SF5. 1 hit.
TIGRFAMsTIGR01658. EYA-cons_domain. 1 hit.
ProtoNetSearch...

Other

ChiTaRSEYA3. mouse.
NextBio284996.
PROP97480.
SOURCESearch...

Entry information

Entry nameEYA3_MOUSE
AccessionPrimary (citable) accession number: P97480
Secondary accession number(s): G5E8I5, P97768
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 3, 2012
Last modified: April 16, 2014
This is version 115 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot