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Protein

Eyes absent homolog 2

Gene

Eya2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 (PubMed:10490620, PubMed:17098221). 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 similarity).By similarity2 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.1 Publication

Cofactori

Mg2+By similarityNote: Binds 1 Mg2+ ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei268NucleophileBy similarity1
Metal bindingi268MagnesiumBy similarity1
Active sitei270Proton donorBy similarity1
Metal bindingi270Magnesium; via carbonyl oxygenBy similarity1
Metal bindingi496MagnesiumBy similarity1

GO - Molecular functioni

GO - Biological processi

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

Enzyme and pathway databases

ReactomeiR-MMU-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.

Names & Taxonomyi

Protein namesi
Recommended name:
Eyes absent homolog 2 (EC:3.1.3.481 Publication)
Gene namesi
Name:Eya2
Synonyms:Eab1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: 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

  • cytoplasm Source: MGI
  • mitochondrion Source: GOC
  • 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)DescriptionActionsGraphical viewLength
ChainiPRO_00002186471 – 532Eyes absent homolog 2Add BLAST532

Proteomic databases

PaxDbiO08575.
PeptideAtlasiO08575.
PRIDEiO08575.

PTM databases

iPTMnetiO08575.
PhosphoSitePlusiO08575.

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

BgeeiENSMUSG00000017897.
CleanExiMM_EYA2.
GenevisibleiO08575. MM.

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 interactor.
IntActiO08575. 3 interactors.
STRINGi10090.ENSMUSP00000066244.

Structurei

3D structure databases

ProteinModelPortaliO08575.
SMRiO08575.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3107. Eukaryota.
ENOG410XT12. LUCA.
GeneTreeiENSGT00390000008860.
HOVERGENiHBG002447.
InParanoidiO08575.
KOiK17620.
OMAiIHSRPNC.
OrthoDBiEOG091G04YD.
TreeFamiTF319337.

Family and domain databases

Gene3Di3.40.50.1000. 2 hits.
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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001492114 – 142Missing in isoform 2. CuratedAdd BLAST29

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.2. 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.
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.

3D structure databases

ProteinModelPortaliO08575.
SMRiO08575.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199560. 1 interactor.
IntActiO08575. 3 interactors.
STRINGi10090.ENSMUSP00000066244.

PTM databases

iPTMnetiO08575.
PhosphoSitePlusiO08575.

Proteomic databases

PaxDbiO08575.
PeptideAtlasiO08575.
PRIDEiO08575.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000063433; ENSMUSP00000066244; ENSMUSG00000017897. [O08575-1]
ENSMUST00000088132; ENSMUSP00000085455; ENSMUSG00000017897. [O08575-1]
GeneIDi14049.
KEGGimmu:14049.
UCSCiuc008nxw.2. mouse. [O08575-1]

Organism-specific databases

CTDi2139.
MGIiMGI:109341. Eya2.

Phylogenomic databases

eggNOGiKOG3107. Eukaryota.
ENOG410XT12. LUCA.
GeneTreeiENSGT00390000008860.
HOVERGENiHBG002447.
InParanoidiO08575.
KOiK17620.
OMAiIHSRPNC.
OrthoDBiEOG091G04YD.
TreeFamiTF319337.

Enzyme and pathway databases

ReactomeiR-MMU-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.

Miscellaneous databases

PROiO08575.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000017897.
CleanExiMM_EYA2.
GenevisibleiO08575. MM.

Family and domain databases

Gene3Di3.40.50.1000. 2 hits.
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.
ProtoNetiSearch...

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 30, 2016
This is version 136 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.