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P97480

- EYA3_MOUSE

UniProt

P97480 - EYA3_MOUSE

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Protein
Eyes absent homolog 3
Gene
Eya3
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - 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.1 Publication

Catalytic activityi

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

Cofactori

Binds 1 Mg2+ ion per subunit Inferred.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei246 – 2461Nucleophile By similarity
Metal bindingi246 – 2461Magnesium By similarity
Active sitei248 – 2481Proton donor By similarity
Metal bindingi248 – 2481Magnesium By similarity
Metal bindingi474 – 4741Magnesium By similarity

GO - Molecular functioni

  1. chromatin binding Source: MGI
  2. metal ion binding Source: UniProtKB-KW
  3. protein binding Source: UniProtKB
  4. protein tyrosine phosphatase activity Source: UniProtKB
  5. protein tyrosine/serine/threonine phosphatase activity Source: MGI

GO - Biological processi

  1. double-strand break repair Source: UniProtKB
  2. histone dephosphorylation Source: UniProtKB
  3. multicellular organismal development Source: UniProtKB-KW
  4. peptidyl-tyrosine dephosphorylation Source: GOC
  5. positive regulation of DNA repair Source: UniProtKB
  6. protein dephosphorylation Source: MGI
  7. regulation of transcription, DNA-templated Source: UniProtKB-KW
  8. response to ionizing radiation Source: UniProtKB
  9. 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

Enzyme and pathway databases

SABIO-RKP97480.

Names & Taxonomyi

Protein namesi
Recommended name:
Eyes absent homolog 3 (EC:3.1.3.48)
Gene namesi
Name:Eya3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:109339. Eya3.

Subcellular locationi

Cytoplasm. Nucleus
Note: Localizes at sites of DNA damage at double-strand breaks (DSBs) By similarity.2 Publications

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. nucleus Source: UniProtKB
  3. transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi246 – 2461D → A: Abolishes phosphatase activity and abolishes coactivation of the SIX1-DACH1 complex. 3 Publications
Mutagenesisi246 – 2461D → N: Abolishes phosphatase activity. 3 Publications
Mutagenesisi248 – 2481D → N: Abolishes phosphatase activity. 1 Publication
Mutagenesisi250 – 2501T → A: Abolishes phosphatase activity. 1 Publication
Mutagenesisi419 – 4191T → A: Diminishes phosphatase activity by 24-fold. 1 Publication
Mutagenesisi420 – 4201T → A: Diminishes phosphatase activity. 1 Publication
Mutagenesisi449 – 4491K → Q: Abolishes phosphatase activity. 1 Publication
Mutagenesisi473 – 4731G → A: Abolishes phosphatase activity. 1 Publication
Mutagenesisi474 – 4741D → N: Diminishes phosphatase activity by 70%. 2 Publications
Mutagenesisi478 – 4781E → Q: Abolishes phosphatase activity. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 510510Eyes absent homolog 3
PRO_0000218649Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei203 – 2031Phosphoserine By similarity
Modified residuei409 – 4091Phosphoserine By similarity

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

PaxDbiP97480.
PRIDEiP97480.

PTM databases

PhosphoSiteiP97480.

Expressioni

Tissue specificityi

Expressed in branchial arches, CNS and developing eye.

Gene expression databases

ArrayExpressiP97480.
CleanExiMM_EYA3.
GenevestigatoriP97480.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi199561. 4 interactions.
IntActiP97480. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliP97480.
SMRiP97480. Positions 237-510.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG297494.
GeneTreeiENSGT00390000008860.
HOGENOMiHOG000293149.
HOVERGENiHBG002447.
InParanoidiP97480.
KOiK17621.

Family and domain databases

InterProiIPR028479. EYA3.
IPR006545. EYA_dom.
IPR028472. EYA_fam.
[Graphical view]
PANTHERiPTHR10190. PTHR10190. 1 hit.
PTHR10190:SF5. PTHR10190:SF5. 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: 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

MQEPREQTLS QVNNPDASDE KPETSSLASN LSMSEEIMTC TDYIPRSSND    50
YTSQMYSAKP YAHILSVPVS ETTYPGQTQY QTLQQSQPYA VYPQATQTYG 100
LPPFASSTNA SLIPTSSAIA NIPAAAVASI SNQDYPTYTI LGQNQYQACY 150
PSSSFGVTGQ TNSDAETTTL AATTYQTEKP SAMVPAPATQ RLPSDSSASP 200
PLSQTTPNKD ADDQARKNMT VKNRGKRKAD ASSSQDSELE RVFLWDLDET 250
IIIFHSLLTG SYAQKYGKDP TVVIGSGLTM EEMIFEVADT HLFFNDLEEC 300
DQVHVEDVAS DDNGQDLSNY SFSTDGFSGS GGSGSHGSSV GVQGGVDWMR 350
KLAFRYRKVR EIYDKHKSNV GGLLSPQRKE ALQRLRAEIE VLTDSWLGTA 400
LKSLLLIQSR KNCANVLITT TQLVPALAKV LLYGLGEIFP IENIYSATKI 450
GKESCFERIV SRFGKKVTYV VIGDGRDEEI AAKQHNMPFW RITNHGDLVS 500
LHQALELDFL 510
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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 105105MQEPR…LPPFA → MIIPHKCILQT in isoform 2.
VSP_001494Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti200 – 2001P → L in AAB48019. 1 Publication
Sequence conflicti272 – 2721V → A in AAB42068. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.1. mouse.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS18730.1. [P97480-1 ]
CCDS18731.1. [P97480-2 ]
RefSeqi NP_034296.2. NM_010166.3. [P97480-1 ]
UniGenei Mm.227733.

3D structure databases

ProteinModelPortali P97480.
SMRi P97480. Positions 237-510.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 199561. 4 interactions.
IntActi P97480. 2 interactions.

PTM databases

PhosphoSitei P97480.

Proteomic databases

PaxDbi P97480.
PRIDEi P97480.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000020197 ; ENSMUSP00000020197 ; ENSMUSG00000028886 . [P97480-2 ]
ENSMUST00000079157 ; ENSMUSP00000078157 ; ENSMUSG00000028886 . [P97480-1 ]
ENSMUST00000180250 ; ENSMUSP00000136812 ; ENSMUSG00000028886 . [P97480-2 ]
GeneIDi 14050.
KEGGi mmu:14050.
UCSCi uc008vbo.1. mouse.

Organism-specific databases

CTDi 2140.
MGIi MGI:109339. Eya3.

Phylogenomic databases

eggNOGi NOG297494.
GeneTreei ENSGT00390000008860.
HOGENOMi HOG000293149.
HOVERGENi HBG002447.
InParanoidi P97480.
KOi K17621.

Enzyme and pathway databases

SABIO-RK P97480.

Miscellaneous databases

ChiTaRSi EYA3. mouse.
NextBioi 284996.
PROi P97480.
SOURCEi Search...

Gene expression databases

ArrayExpressi P97480.
CleanExi MM_EYA3.
Genevestigatori P97480.

Family and domain databases

InterProi IPR028479. EYA3.
IPR006545. EYA_dom.
IPR028472. EYA_fam.
[Graphical view ]
PANTHERi PTHR10190. PTHR10190. 1 hit.
PTHR10190:SF5. PTHR10190:SF5. 1 hit.
TIGRFAMsi TIGR01658. EYA-cons_domain. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. Cited for: CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-246; ASP-248; THR-250; THR-419; GLY-473; ASP-474 AND GLU-478.
  10. "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.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiEYA3_MOUSE
AccessioniPrimary (citable) accession number: P97480
Secondary accession number(s): G5E8I5, P97768
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 3, 2012
Last modified: July 9, 2014
This is version 118 of the entry and version 2 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

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