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Protein

Eyes absent homolog 3

Gene

Eya3

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

Functioni

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.By similarity1 Publication

Caution

According to PubMed:14628042 also shows serine/threonine protein phosphatase activity.Curated

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.3 Publications

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei246NucleophileBy similarity1
Metal bindingi246MagnesiumBy similarity1
Active sitei248Proton donorBy similarity1
Metal bindingi248Magnesium; via carbonyl oxygenBy similarity1
Metal bindingi474MagnesiumBy similarity1

GO - Molecular functioni

  • chromatin binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • protein tyrosine/serine/threonine phosphatase activity Source: MGI
  • protein tyrosine phosphatase activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionActivator, Chromatin regulator, Developmental protein, Hydrolase, Protein phosphatase
Biological processDNA damage, DNA repair, Transcription, Transcription regulation
LigandMagnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
SABIO-RKiP97480

Names & Taxonomyi

Protein namesi
Recommended name:
Eyes absent homolog 3 (EC:3.1.3.483 Publications)
Gene namesi
Name:Eya3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:109339 Eya3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi246D → A: Abolishes phosphatase activity and abolishes coactivation of the SIX1-DACH1 complex. 3 Publications1
Mutagenesisi246D → N: Abolishes phosphatase activity. 3 Publications1
Mutagenesisi248D → N: Abolishes phosphatase activity. 1 Publication1
Mutagenesisi250T → A: Abolishes phosphatase activity. 1 Publication1
Mutagenesisi419T → A: Diminishes phosphatase activity by 24-fold. 1 Publication1
Mutagenesisi420T → A: Diminishes phosphatase activity. 1 Publication1
Mutagenesisi449K → Q: Abolishes phosphatase activity. 1 Publication1
Mutagenesisi473G → A: Abolishes phosphatase activity. 1 Publication1
Mutagenesisi474D → N: Diminishes phosphatase activity by 70%. 2 Publications1
Mutagenesisi478E → Q: Abolishes phosphatase activity. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002186491 – 510Eyes absent homolog 3Add BLAST510

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei199PhosphoserineBy similarity1
Modified residuei203PhosphoserineBy similarity1
Modified residuei375PhosphoserineBy similarity1
Modified residuei409PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP97480
MaxQBiP97480
PaxDbiP97480
PeptideAtlasiP97480
PRIDEiP97480

PTM databases

iPTMnetiP97480
PhosphoSitePlusiP97480

Expressioni

Tissue specificityi

Expressed in branchial arches, CNS and developing eye.

Gene expression databases

BgeeiENSMUSG00000028886 Expressed in 284 organ(s), highest expression level in mesenteric lymph node
CleanExiMM_EYA3
ExpressionAtlasiP97480 baseline and differential
GenevisibleiP97480 MM

Interactioni

Subunit structurei

Interacts with SIX1 and DACH1, and probably SIX2, SIX4 and SIX5.3 Publications

Protein-protein interaction databases

BioGridi199561, 4 interactors
IntActiP97480, 2 interactors
MINTiP97480
STRINGi10090.ENSMUSP00000080425

Structurei

3D structure databases

ProteinModelPortaliP97480
SMRiP97480
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3107 Eukaryota
ENOG410XT12 LUCA
GeneTreeiENSGT00390000008860
HOGENOMiHOG000293149
HOVERGENiHBG002447
InParanoidiP97480
KOiK17621

Family and domain databases

CDDicd02601 HAD_Eya, 1 hit
Gene3Di3.40.50.12350, 1 hit
InterProiView protein in InterPro
IPR028479 EYA3
IPR006545 EYA_dom
IPR038102 EYA_dom_sf
IPR028472 EYA_fam
PANTHERiPTHR10190 PTHR10190, 2 hits
PTHR10190:SF5 PTHR10190:SF5, 2 hits
TIGRFAMsiTIGR01658 EYA-cons_domain, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P97480-1) [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
MQEPREQTLS QVNNPDASDE KPETSSLASN LSMSEEIMTC TDYIPRSSND
60 70 80 90 100
YTSQMYSAKP YAHILSVPVS ETTYPGQTQY QTLQQSQPYA VYPQATQTYG
110 120 130 140 150
LPPFASSTNA SLIPTSSAIA NIPAAAVASI SNQDYPTYTI LGQNQYQACY
160 170 180 190 200
PSSSFGVTGQ TNSDAETTTL AATTYQTEKP SAMVPAPATQ RLPSDSSASP
210 220 230 240 250
PLSQTTPNKD ADDQARKNMT VKNRGKRKAD ASSSQDSELE RVFLWDLDET
260 270 280 290 300
IIIFHSLLTG SYAQKYGKDP TVVIGSGLTM EEMIFEVADT HLFFNDLEEC
310 320 330 340 350
DQVHVEDVAS DDNGQDLSNY SFSTDGFSGS GGSGSHGSSV GVQGGVDWMR
360 370 380 390 400
KLAFRYRKVR EIYDKHKSNV GGLLSPQRKE ALQRLRAEIE VLTDSWLGTA
410 420 430 440 450
LKSLLLIQSR KNCANVLITT TQLVPALAKV LLYGLGEIFP IENIYSATKI
460 470 480 490 500
GKESCFERIV SRFGKKVTYV VIGDGRDEEI AAKQHNMPFW RITNHGDLVS
510
LHQALELDFL
Length:510
Mass (Da):55,973
Last modified:October 3, 2012 - v2
Checksum:iE82CC71DD1FD05F5
GO
Isoform 2 (identifier: P97480-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: MQEPREQTLS...TQTYGLPPFA → MIIPHKCILQT

Note: No experimental confirmation available.
Show »
Length:416
Mass (Da):45,518
Checksum:iA19B88372DA2A767
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q6P4T3Q6P4T3_MOUSE
Eyes absent homolog
Eya3
526Annotation score:
A2A953A2A953_MOUSE
Eyes absent homolog
Eya3
302Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti200P → L in AAB48019 (PubMed:9006082).Curated1
Sequence conflicti272V → A in AAB42068 (PubMed:9049631).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0014941 – 105MQEPR…LPPFA → MIIPHKCILQT in isoform 2. 1 PublicationAdd BLAST105

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS18730.1 [P97480-1]
CCDS18731.1 [P97480-2]
RefSeqiNP_034296.2, NM_010166.3 [P97480-1]
UniGeneiMm.227733

Genome annotation databases

EnsembliENSMUST00000020197; ENSMUSP00000020197; ENSMUSG00000028886 [P97480-2]
ENSMUST00000079157; ENSMUSP00000078157; ENSMUSG00000028886 [P97480-1]
ENSMUST00000180250; ENSMUSP00000136812; ENSMUSG00000028886 [P97480-2]
GeneIDi14050
KEGGimmu:14050
UCSCiuc008vbo.2 mouse [P97480-1]
uc008vbq.2 mouse [P97480-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS18730.1 [P97480-1]
CCDS18731.1 [P97480-2]
RefSeqiNP_034296.2, NM_010166.3 [P97480-1]
UniGeneiMm.227733

3D structure databases

ProteinModelPortaliP97480
SMRiP97480
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199561, 4 interactors
IntActiP97480, 2 interactors
MINTiP97480
STRINGi10090.ENSMUSP00000080425

PTM databases

iPTMnetiP97480
PhosphoSitePlusiP97480

Proteomic databases

EPDiP97480
MaxQBiP97480
PaxDbiP97480
PeptideAtlasiP97480
PRIDEiP97480

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020197; ENSMUSP00000020197; ENSMUSG00000028886 [P97480-2]
ENSMUST00000079157; ENSMUSP00000078157; ENSMUSG00000028886 [P97480-1]
ENSMUST00000180250; ENSMUSP00000136812; ENSMUSG00000028886 [P97480-2]
GeneIDi14050
KEGGimmu:14050
UCSCiuc008vbo.2 mouse [P97480-1]
uc008vbq.2 mouse [P97480-2]

Organism-specific databases

CTDi2140
MGIiMGI:109339 Eya3

Phylogenomic databases

eggNOGiKOG3107 Eukaryota
ENOG410XT12 LUCA
GeneTreeiENSGT00390000008860
HOGENOMiHOG000293149
HOVERGENiHBG002447
InParanoidiP97480
KOiK17621

Enzyme and pathway databases

ReactomeiR-MMU-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
SABIO-RKiP97480

Miscellaneous databases

ChiTaRSiEya3 mouse
PROiPR:P97480
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028886 Expressed in 284 organ(s), highest expression level in mesenteric lymph node
CleanExiMM_EYA3
ExpressionAtlasiP97480 baseline and differential
GenevisibleiP97480 MM

Family and domain databases

CDDicd02601 HAD_Eya, 1 hit
Gene3Di3.40.50.12350, 1 hit
InterProiView protein in InterPro
IPR028479 EYA3
IPR006545 EYA_dom
IPR038102 EYA_dom_sf
IPR028472 EYA_fam
PANTHERiPTHR10190 PTHR10190, 2 hits
PTHR10190:SF5 PTHR10190:SF5, 2 hits
TIGRFAMsiTIGR01658 EYA-cons_domain, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiEYA3_MOUSE
AccessioniPrimary (citable) accession number: P97480
Secondary accession number(s): G5E8I5, P97768
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 3, 2012
Last modified: September 12, 2018
This is version 148 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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