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O08575 (EYA2_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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Eyes absent homolog 2

EC=3.1.3.48
Gene names
Name:Eya2
Synonyms:Eab1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length532 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.10

Catalytic activity

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

Cofactor

Binds 1 Mg2+ ion per subunit.

Subunit structure

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. Ref.5 Ref.7 Ref.9

Subcellular location

Cytoplasm. Nucleus. 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. Ref.7

Tissue specificity

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. Ref.9

Disruption phenotype

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. Ref.10

Sequence similarities

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

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
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Inferred from electronic annotation. Source: UniProtKB-KW

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from direct assay PubMed 11700312. Source: MGI

histone dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial outer membrane permeabilization

Inferred from direct assay PubMed 11700312. Source: MGI

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

protein dephosphorylation

Inferred from direct assay Ref.8. Source: MGI

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

striated muscle tissue development

Inferred from genetic interaction Ref.10. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11700312. Source: MGI

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 11700312. Source: MGI

   Molecular_functionmagnesium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein tyrosine phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SharpinQ91WA62EBI-986503,EBI-646097

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O08575-1)

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: O08575-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 532532Eyes absent homolog 2
PRO_0000218647

Sites

Active site2681Nucleophile By similarity
Active site2701Proton donor By similarity
Metal binding2681Magnesium By similarity
Metal binding2701Magnesium; via carbonyl oxygen By similarity
Metal binding4961Magnesium By similarity

Natural variations

Alternative sequence114 – 14229Missing in isoform 2.
VSP_001492

Sequences

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

Last modified July 1, 1997. Version 1.
Checksum: 9A29BC6BB77DF880

FASTA53258,246
        10         20         30         40         50         60 
MLEVVTSPSL ATSSDWSEHG AAVGTLSDRE GIAKSAALSV PQLFVKSHPR VPPGQSSTAM 

        70         80         90        100        110        120 
AAYGQTQYST GIQQAPPYTA YPTPAQAYGI PPYSIKTEDS LNHSPSQSGF LSYGPSFSTA 

       130        140        150        160        170        180 
PAGQSPYTYP VHSTAGLYQG ANGLTNTAGF GSVHQDYPSY PSFSQNQYPQ YFSPSYNPPY 

       190        200        210        220        230        240 
VPASSLCSSP LSTSTYVLQE APHNVPSQSS ESLAGDYNTH NGPSTPAKEG DTERPHRASD 

       250        260        270        280        290        300 
GKLRGRSKRN SDPSPAGDNE IERVFVWDLD ETIIIFHSLL TGTFASRYGK DTTTSVRIGL 

       310        320        330        340        350        360 
MMEEMIFNLA DTHLFFNDLE DCDQIHVDDV SSDDNGQDLS TYNFSTDGFH STAPGASLCL 

       370        380        390        400        410        420 
GTGVHGGVDW MRKLAFRYRR VKEMYNTYRN NVGGLIGAPK RETWLQLRAE LEALTDLWLT 

       430        440        450        460        470        480 
HSLKALNLIN SRPNCVNVLV TTTQLIPALA KVLLYGLGSV FPIENIYSAT KTGKESCFER 

       490        500        510        520        530 
IMQRFGRKAV YIVIGDGVEE EQGAKKHNMP FWRISCHADL EALRHALELE YL 

« Hide

Isoform 2 [UniParc].

Checksum: F12F8FD4B0291F16
Show »

FASTA50355,337

References

« Hide 'large scale' references
[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]"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]"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]"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.
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001258891.1. NM_001271962.1.
NP_001258892.1. NM_001271963.1.
NP_034295.1. NM_010165.3.
UniGeneMm.282719.

3D structure databases

ProteinModelPortalO08575.
SMRO08575. Positions 262-532.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199560. 1 interaction.
IntActO08575. 3 interactions.

PTM databases

PhosphoSiteO08575.

Proteomic databases

PRIDEO08575.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000063433; ENSMUSP00000066244; ENSMUSG00000017897. [O08575-1]
ENSMUST00000088132; ENSMUSP00000085455; ENSMUSG00000017897. [O08575-1]
GeneID14049.
KEGGmmu:14049.
UCSCuc008nxw.1. mouse. [O08575-1]

Organism-specific databases

CTD2139.
MGIMGI:109341. Eya2.

Phylogenomic databases

eggNOGNOG297494.
GeneTreeENSGT00390000008860.
HOVERGENHBG002447.
InParanoidA2A5S4.
KOK17620.
OMAIHSRPNC.
OrthoDBEOG7DNNTZ.
TreeFamTF319337.

Gene expression databases

ArrayExpressO08575.
BgeeO08575.
CleanExMM_EYA2.
GenevestigatorO08575.

Family and domain databases

InterProIPR028473. EYA2.
IPR006545. EYA_dom.
IPR028472. EYA_fam.
IPR023214. HAD-like_dom.
[Graphical view]
PANTHERPTHR10190. PTHR10190. 1 hit.
PTHR10190:SF7. PTHR10190:SF7. 1 hit.
SUPFAMSSF56784. SSF56784. 1 hit.
TIGRFAMsTIGR01658. EYA-cons_domain. 1 hit.
ProtoNetSearch...

Other

NextBio284992.
PROO08575.
SOURCESearch...

Entry information

Entry nameEYA2_MOUSE
AccessionPrimary (citable) accession number: O08575
Secondary accession number(s): A2A5S4, P97925
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 115 of the entry and version 1 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