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O08575

- EYA2_MOUSE

UniProt

O08575 - EYA2_MOUSE

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Protein

Eyes absent homolog 2

Gene

Eya2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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

Mg2+Note: Binds 1 Mg(2+) 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 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. peptidyl-tyrosine dephosphorylation Source: GOC
  7. protein dephosphorylation Source: MGI
  8. regulation of transcription, DNA-templated Source: UniProtKB-KW
  9. striated muscle tissue development Source: MGI
  10. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

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. centrosome Source: Ensembl
  2. cytoplasm Source: MGI
  3. mitochondrion Source: GOC
  4. nucleus Source: MGI
Complete GO annotation...

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

BgeeiO08575.
CleanExiMM_EYA2.
ExpressionAtlasiO08575. baseline and differential.
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.
InParanoidiO08575.
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

        10         20         30         40         50
MLEVVTSPSL ATSSDWSEHG AAVGTLSDRE GIAKSAALSV PQLFVKSHPR
60 70 80 90 100
VPPGQSSTAM AAYGQTQYST GIQQAPPYTA YPTPAQAYGI PPYSIKTEDS
110 120 130 140 150
LNHSPSQSGF LSYGPSFSTA PAGQSPYTYP VHSTAGLYQG ANGLTNTAGF
160 170 180 190 200
GSVHQDYPSY PSFSQNQYPQ YFSPSYNPPY VPASSLCSSP LSTSTYVLQE
210 220 230 240 250
APHNVPSQSS ESLAGDYNTH NGPSTPAKEG DTERPHRASD GKLRGRSKRN
260 270 280 290 300
SDPSPAGDNE IERVFVWDLD ETIIIFHSLL TGTFASRYGK DTTTSVRIGL
310 320 330 340 350
MMEEMIFNLA DTHLFFNDLE DCDQIHVDDV SSDDNGQDLS TYNFSTDGFH
360 370 380 390 400
STAPGASLCL GTGVHGGVDW MRKLAFRYRR VKEMYNTYRN NVGGLIGAPK
410 420 430 440 450
RETWLQLRAE LEALTDLWLT HSLKALNLIN SRPNCVNVLV TTTQLIPALA
460 470 480 490 500
KVLLYGLGSV FPIENIYSAT KTGKESCFER IMQRFGRKAV YIVIGDGVEE
510 520 530
EQGAKKHNMP FWRISCHADL EALRHALELE YL
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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 O08575.
KOi K17620.
OMAi IHSRPNC.
OrthoDBi EOG7DNNTZ.
TreeFami TF319337.

Miscellaneous databases

NextBioi 284992.
PROi O08575.
SOURCEi Search...

Gene expression databases

Bgeei O08575.
CleanExi MM_EYA2.
ExpressionAtlasi O08575. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 121 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