EYA3_MOUSE
ID EYA3_MOUSE Reviewed; 510 AA.
AC P97480; G5E8I5; P97768;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Eyes absent homolog 3;
DE EC=3.1.3.48 {ECO:0000269|PubMed:14628042, ECO:0000269|PubMed:14628052, ECO:0000269|PubMed:14628053};
GN Name=Eya3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=9049631; DOI=10.1101/gr.7.2.128;
RA Zimmerman J.E., Bui Q.T., Steingrimsson E., Nagle D.L., Fu W., Genin A.,
RA Spinner N.B., Copeland N.G., Jenkins N.A., Bucan M., Bonini N.M.;
RT "Cloning and characterization of two vertebrate homologs of the Drosophila
RT eyes absent gene.";
RL Genome Res. 7:128-141(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Embryo;
RX PubMed=9006082; DOI=10.1242/dev.124.1.219;
RA Xu P.-X., Woo I., Her H., Beier D.R., Maas R.L.;
RT "Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for
RT expression in lens and nasal placode.";
RL Development 124:219-231(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 350-468.
RC TISSUE=Embryo;
RX PubMed=9887327; DOI=10.1093/hmg/8.1.11;
RA Borsani G., DeGrandi A., Ballabio A., Bulfone A., Bernard L., Banfi S.,
RA Gattuso C., Mariani M., Dixon M., Donnai D., Metcalfe K., Winter R.,
RA Robertson M., Axton R., Brown A., van Heyningen V., Hanson I.;
RT "EYA4, a novel vertebrate gene related to Drosophila eyes absent.";
RL Hum. Mol. Genet. 8:11-23(1999).
RN [6]
RP FUNCTION, INTERACTION WITH SIX2; SIX4 AND SIX5, AND SUBCELLULAR LOCATION.
RX PubMed=10490620; DOI=10.1128/mcb.19.10.6815;
RA Ohto H., Kamada S., Tago K., Tominaga S., Ozaki H., Sato S., Kawakami K.;
RT "Cooperation of six and eya in activation of their target genes through
RT nuclear translocation of Eya.";
RL Mol. Cell. Biol. 19:6815-6824(1999).
RN [7]
RP INTERACTION WITH SIX1; SIX2; SIX4 AND SIX5.
RX PubMed=12215533; DOI=10.1128/mcb.22.19.6759-6766.2002;
RA Ikeda K., Watanabe Y., Ohto H., Kawakami K.;
RT "Molecular interaction and synergistic activation of a promoter by Six,
RT Eya, and Dach proteins mediated through CREB binding protein.";
RL Mol. Cell. Biol. 22:6759-6766(2002).
RN [8]
RP CATALYTIC ACTIVITY, INTERACTION WITH DACH1 AND SIX1, AND MUTAGENESIS OF
RP ASP-246.
RX PubMed=14628042; DOI=10.1038/nature02083;
RA Li X., Oghi K.A., Zhang J., Krones A., Bush K.T., Glass C.K., Nigam S.K.,
RA Aggarwal A.K., Maas R., Rose D.W., Rosenfeld M.G.;
RT "Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional
RT effects in mammalian organogenesis.";
RL Nature 426:247-254(2003).
RN [9]
RP ERRATUM OF PUBMED:14628042.
RA Li X., Oghi K.A., Zhang J., Krones A., Bush K.T., Glass C.K., Nigam S.K.,
RA Aggarwal A.K., Maas R., Rose D.W., Rosenfeld M.G.;
RL Nature 427:265-265(2004).
RN [10]
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-246;
RP ASP-248; THR-250; THR-419; GLY-473; ASP-474 AND GLU-478.
RX PubMed=14628052; DOI=10.1038/nature02093;
RA Rayapureddi J.P., Kattamuri C., Steinmetz B.D., Frankfort B.J.,
RA Ostrin E.J., Mardon G., Hegde R.S.;
RT "Eyes absent represents a class of protein tyrosine phosphatases.";
RL Nature 426:295-298(2003).
RN [11]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-246; THR-420; LYS-449; ASP-474
RP AND GLU-478.
RX PubMed=14628053; DOI=10.1038/nature02097;
RA Tootle T.L., Silver S.J., Davies E.L., Newman V., Latek R.R., Mills I.A.,
RA Selengut J.D., Parlikar B.E., Rebay I.;
RT "The transcription factor Eyes absent is a protein tyrosine phosphatase.";
RL Nature 426:299-302(2003).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Tyrosine phosphatase that specifically dephosphorylates 'Tyr-
CC 142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone
CC H2AX plays a central role in DNA repair and acts as a mark that
CC distinguishes between apoptotic and repair responses to genotoxic
CC stress. Promotes efficient DNA repair by dephosphorylating H2AX,
CC promoting the recruitment of DNA repair complexes containing MDC1 (By
CC similarity). Its function as histone phosphatase probably explains its
CC role in transcription regulation during organogenesis. The phosphatase
CC activity has been shown in vitro. Coactivates SIX1. Seems to coactivate
CC SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in
CC myoblasts by SIX1 is switched to activation through recruitment of EYA3
CC to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase
CC activity. May be involved in development of the eye. May play a role in
CC mediating the induction and differentiation of cranial placodes.
CC {ECO:0000250|UniProtKB:Q99504, ECO:0000269|PubMed:10490620}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48;
CC Evidence={ECO:0000269|PubMed:14628042, ECO:0000269|PubMed:14628052,
CC ECO:0000269|PubMed:14628053};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O00167};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:O00167};
CC -!- SUBUNIT: Interacts with SIX1 and DACH1, and probably SIX2, SIX4 and
CC SIX5. {ECO:0000269|PubMed:10490620, ECO:0000269|PubMed:12215533,
CC ECO:0000269|PubMed:14628042}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10490620}. Nucleus
CC {ECO:0000269|PubMed:10490620, ECO:0000269|PubMed:14628052}.
CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs).
CC {ECO:0000250|UniProtKB:Q99504}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P97480-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P97480-2; Sequence=VSP_001494;
CC -!- TISSUE SPECIFICITY: Expressed in branchial arches, CNS and developing
CC eye.
CC -!- PTM: Ser-203 phosphorylation is required for localization at sites of
CC DNA damage and directing interaction with H2AX. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily. EYA family.
CC {ECO:0000305}.
CC -!- CAUTION: According to PubMed:14628042 also shows serine/threonine
CC protein phosphatase activity. {ECO:0000305}.
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DR EMBL; U81604; AAB42068.1; -; mRNA.
DR EMBL; U61112; AAB48019.1; -; mRNA.
DR EMBL; AL627130; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466552; EDL30095.1; -; Genomic_DNA.
DR EMBL; AJ007996; CAA07819.1; -; mRNA.
DR CCDS; CCDS18730.1; -. [P97480-1]
DR CCDS; CCDS18731.1; -. [P97480-2]
DR RefSeq; NP_034296.2; NM_010166.3. [P97480-1]
DR AlphaFoldDB; P97480; -.
DR SMR; P97480; -.
DR BioGRID; 199561; 4.
DR IntAct; P97480; 4.
DR MINT; P97480; -.
DR STRING; 10090.ENSMUSP00000080425; -.
DR ChEMBL; CHEMBL4296244; -.
DR iPTMnet; P97480; -.
DR PhosphoSitePlus; P97480; -.
DR EPD; P97480; -.
DR MaxQB; P97480; -.
DR PaxDb; P97480; -.
DR PeptideAtlas; P97480; -.
DR PRIDE; P97480; -.
DR ProteomicsDB; 275707; -. [P97480-1]
DR ProteomicsDB; 275708; -. [P97480-2]
DR Antibodypedia; 16480; 166 antibodies from 27 providers.
DR DNASU; 14050; -.
DR Ensembl; ENSMUST00000020197; ENSMUSP00000020197; ENSMUSG00000028886. [P97480-2]
DR Ensembl; ENSMUST00000079157; ENSMUSP00000078157; ENSMUSG00000028886. [P97480-1]
DR Ensembl; ENSMUST00000180250; ENSMUSP00000136812; ENSMUSG00000028886. [P97480-2]
DR GeneID; 14050; -.
DR KEGG; mmu:14050; -.
DR UCSC; uc008vbo.2; mouse. [P97480-1]
DR UCSC; uc008vbq.2; mouse. [P97480-2]
DR CTD; 2140; -.
DR MGI; MGI:109339; Eya3.
DR VEuPathDB; HostDB:ENSMUSG00000028886; -.
DR eggNOG; KOG3107; Eukaryota.
DR GeneTree; ENSGT00950000182978; -.
DR HOGENOM; CLU_021184_2_0_1; -.
DR InParanoid; P97480; -.
DR OrthoDB; 1030296at2759; -.
DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR SABIO-RK; P97480; -.
DR BioGRID-ORCS; 14050; 1 hit in 109 CRISPR screens.
DR ChiTaRS; Eya3; mouse.
DR PRO; PR:P97480; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P97480; protein.
DR Bgee; ENSMUSG00000028886; Expressed in undifferentiated genital tubercle and 264 other tissues.
DR ExpressionAtlas; P97480; baseline and differential.
DR Genevisible; P97480; MM.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IPI:MGI.
DR GO; GO:0003682; F:chromatin binding; IGI:MGI.
DR GO; GO:0140793; F:histone tyrosine phosphatase activity (H2-Y142 specific); ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:MGI.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IDA:MGI.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IBA:GO_Central.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR CDD; cd02601; HAD_Eya; 1.
DR Gene3D; 3.40.50.12350; -; 1.
DR InterPro; IPR028479; EYA3.
DR InterPro; IPR006545; EYA_dom.
DR InterPro; IPR042577; EYA_dom_metazoan.
DR InterPro; IPR038102; EYA_dom_sf.
DR InterPro; IPR028472; EYA_fam.
DR PANTHER; PTHR10190; PTHR10190; 2.
DR PANTHER; PTHR10190:SF5; PTHR10190:SF5; 2.
DR TIGRFAMs; TIGR01658; EYA-cons_domain; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Chromatin regulator; Cytoplasm;
KW Developmental protein; DNA damage; DNA repair; Hydrolase; Magnesium;
KW Metal-binding; Nucleus; Phosphoprotein; Protein phosphatase;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..510
FT /note="Eyes absent homolog 3"
FT /id="PRO_0000218649"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 175..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..209
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 210..233
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 246
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT ACT_SITE 248
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT BINDING 246
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT BINDING 248
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT BINDING 474
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99504"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99504"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99504"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99504"
FT VAR_SEQ 1..105
FT /note="MQEPREQTLSQVNNPDASDEKPETSSLASNLSMSEEIMTCTDYIPRSSNDYT
FT SQMYSAKPYAHILSVPVSETTYPGQTQYQTLQQSQPYAVYPQATQTYGLPPFA -> MI
FT IPHKCILQT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9006082"
FT /id="VSP_001494"
FT MUTAGEN 246
FT /note="D->A: Abolishes phosphatase activity and abolishes
FT coactivation of the SIX1-DACH1 complex."
FT /evidence="ECO:0000269|PubMed:14628042,
FT ECO:0000269|PubMed:14628052, ECO:0000269|PubMed:14628053"
FT MUTAGEN 246
FT /note="D->N: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:14628042,
FT ECO:0000269|PubMed:14628052, ECO:0000269|PubMed:14628053"
FT MUTAGEN 248
FT /note="D->N: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:14628052"
FT MUTAGEN 250
FT /note="T->A: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:14628052"
FT MUTAGEN 419
FT /note="T->A: Diminishes phosphatase activity by 24-fold."
FT /evidence="ECO:0000269|PubMed:14628052"
FT MUTAGEN 420
FT /note="T->A: Diminishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:14628053"
FT MUTAGEN 449
FT /note="K->Q: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:14628053"
FT MUTAGEN 473
FT /note="G->A: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:14628052"
FT MUTAGEN 474
FT /note="D->N: Diminishes phosphatase activity by 70%."
FT /evidence="ECO:0000269|PubMed:14628052,
FT ECO:0000269|PubMed:14628053"
FT MUTAGEN 478
FT /note="E->Q: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:14628052,
FT ECO:0000269|PubMed:14628053"
FT CONFLICT 200
FT /note="P -> L (in Ref. 2; AAB48019)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="V -> A (in Ref. 1; AAB42068)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 510 AA; 55973 MW; E82CC71DD1FD05F5 CRC64;
MQEPREQTLS QVNNPDASDE KPETSSLASN LSMSEEIMTC TDYIPRSSND YTSQMYSAKP
YAHILSVPVS ETTYPGQTQY QTLQQSQPYA VYPQATQTYG LPPFASSTNA SLIPTSSAIA
NIPAAAVASI SNQDYPTYTI LGQNQYQACY PSSSFGVTGQ TNSDAETTTL AATTYQTEKP
SAMVPAPATQ RLPSDSSASP PLSQTTPNKD ADDQARKNMT VKNRGKRKAD ASSSQDSELE
RVFLWDLDET IIIFHSLLTG SYAQKYGKDP TVVIGSGLTM EEMIFEVADT HLFFNDLEEC
DQVHVEDVAS DDNGQDLSNY SFSTDGFSGS GGSGSHGSSV GVQGGVDWMR KLAFRYRKVR
EIYDKHKSNV GGLLSPQRKE ALQRLRAEIE VLTDSWLGTA LKSLLLIQSR KNCANVLITT
TQLVPALAKV LLYGLGEIFP IENIYSATKI GKESCFERIV SRFGKKVTYV VIGDGRDEEI
AAKQHNMPFW RITNHGDLVS LHQALELDFL
