EYA2_MOUSE
ID EYA2_MOUSE Reviewed; 532 AA.
AC O08575; A2A5S4; P97925;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Eyes absent homolog 2;
DE EC=3.1.3.48 {ECO:0000269|PubMed:14628052};
GN Name=Eya2; Synonyms=Eab1;
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].
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
RX PubMed=9195991; DOI=10.1007/s003359900480;
RA Duncan M.K., Kos L., Jenkins N.A., Gilbert D.J., Copeland N.G.,
RA Tomarev S.I.;
RT "Eyes absent: a gene family found in several metazoan phyla.";
RL Mamm. Genome 8:479-485(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 MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH SIX1.
RX PubMed=11978764; DOI=10.1093/hmg/11.9.1045;
RA Sato S., Nakamura M., Cho D.H., Tapscott S.J., Ozaki H., Kawakami K.;
RT "Identification of transcriptional targets for Six5: implication for the
RT pathogenesis of myotonic dystrophy type 1.";
RL Hum. Mol. Genet. 11:1045-1058(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 60-532.
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 [7]
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 [8]
RP CATALYTIC ACTIVITY.
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 [9]
RP INTERACTION WITH CAPN8, AND TISSUE SPECIFICITY.
RX PubMed=16476741; DOI=10.1074/jbc.m509244200;
RA Hata S., Koyama S., Kawahara H., Doi N., Maeda T., Toyama-Sorimachi N.,
RA Abe K., Suzuki K., Sorimachi H.;
RT "Stomach-specific calpain, nCL-2, localizes in mucus cells and proteolyzes
RT the beta-subunit of coatomer complex, beta-COP.";
RL J. Biol. Chem. 281:11214-11224(2006).
RN [10]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17098221; DOI=10.1016/j.ydbio.2006.08.059;
RA Grifone R., Demignon J., Giordani J., Niro C., Souil E., Bertin F.,
RA Laclef C., Xu P.X., Maire P.;
RT "Eya1 and Eya2 proteins are required for hypaxial somitic myogenesis in the
RT mouse embryo.";
RL Dev. Biol. 302:602-616(2007).
CC -!- FUNCTION: Functions both as protein phosphatase and as transcriptional
CC coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5
CC (PubMed:10490620, PubMed:17098221). Tyrosine phosphatase that
CC dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes
CC efficient DNA repair via the recruitment of DNA repair complexes
CC containing MDC1. 'Tyr-142' phosphorylation of histone H2AX plays a
CC central role in DNA repair and acts as a mark that distinguishes
CC between apoptotic and repair responses to genotoxic stress. Its
CC function as histone phosphatase may contribute to its function in
CC transcription regulation during organogenesis (By similarity). Plays an
CC important role in hypaxial muscle development together with SIX1 and
CC DACH2; in this it is functionally redundant with EYA1 (By similarity).
CC {ECO:0000250|UniProtKB:O00167, ECO:0000269|PubMed:10490620,
CC ECO:0000269|PubMed:17098221}.
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:14628052};
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: Probably interacts with SIX2, SIX4 and SIX5. Interacts with
CC DACH2. Interacts with GNAZ and GNAI2; this retains EYA2 in the
CC cytoplasm and prevents its translocation into the nucleus and
CC transcriptional activity (By similarity). Interacts with SIX1.
CC Interacts with CAPN8. {ECO:0000250, ECO:0000269|PubMed:10490620,
CC ECO:0000269|PubMed:11978764, ECO:0000269|PubMed:16476741}.
CC -!- INTERACTION:
CC O08575; Q91WA6: Sharpin; NbExp=2; IntAct=EBI-986503, EBI-646097;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10490620}. Nucleus
CC {ECO:0000269|PubMed:10490620}. Note=Retained in the cytoplasm via
CC interaction with GNAZ and GNAI2 (By similarity). Interaction with SIX1,
CC SIX2, SIX4 or SIX5 is required for translocation to the nucleus.
CC {ECO:0000250|UniProtKB:O00167}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O08575-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O08575-2; Sequence=VSP_001492;
CC -!- TISSUE SPECIFICITY: Extensively expressed in cranial placodes,
CC branchial arches, CNS and developing eye and nose. Low expression in
CC lung with little or no expression in skin, liver, intestine and kidney.
CC Predominantly expressed in the upper one-third of the oxyntic mucosa
CC and in most regions of the pyloric mucosa.
CC {ECO:0000269|PubMed:16476741}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. In contrast, mice lacking
CC both Eya1 and Eya2 display complete embryonic lethality, due to severe
CC defects in muscle development, including the absence of the diaphragm,
CC the absence of ventral hypaxial muscles of the trunk and muscles in
CC forelimbs and hindlimbs, similar to the phenotype of mice lacking both
CC Six1 and Six4. While Six1 is normally expressed in these mice, it does
CC not activate transcription from cognate promoter elements, and does not
CC activate transcription of Pax3. {ECO:0000269|PubMed:17098221}.
CC -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily. EYA family.
CC {ECO:0000305}.
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DR EMBL; U71208; AAB51121.1; -; mRNA.
DR EMBL; U61111; AAB48018.1; ALT_SEQ; mRNA.
DR EMBL; AL591712; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003755; AAH03755.1; -; mRNA.
DR EMBL; U81603; AAB42067.1; -; mRNA.
DR CCDS; CCDS17084.1; -. [O08575-1]
DR RefSeq; NP_001258891.1; NM_001271962.1. [O08575-1]
DR RefSeq; NP_001258892.1; NM_001271963.1. [O08575-1]
DR RefSeq; NP_034295.1; NM_010165.3. [O08575-1]
DR AlphaFoldDB; O08575; -.
DR SMR; O08575; -.
DR BioGRID; 199560; 1.
DR IntAct; O08575; 3.
DR STRING; 10090.ENSMUSP00000066244; -.
DR iPTMnet; O08575; -.
DR PhosphoSitePlus; O08575; -.
DR PaxDb; O08575; -.
DR PeptideAtlas; O08575; -.
DR PRIDE; O08575; -.
DR ProteomicsDB; 275807; -. [O08575-1]
DR ProteomicsDB; 275808; -. [O08575-2]
DR Antibodypedia; 13258; 277 antibodies from 29 providers.
DR DNASU; 14049; -.
DR Ensembl; ENSMUST00000063433; ENSMUSP00000066244; ENSMUSG00000017897. [O08575-1]
DR Ensembl; ENSMUST00000088132; ENSMUSP00000085455; ENSMUSG00000017897. [O08575-1]
DR GeneID; 14049; -.
DR KEGG; mmu:14049; -.
DR UCSC; uc008nxw.2; mouse. [O08575-1]
DR CTD; 2139; -.
DR MGI; MGI:109341; Eya2.
DR VEuPathDB; HostDB:ENSMUSG00000017897; -.
DR eggNOG; KOG3107; Eukaryota.
DR GeneTree; ENSGT00950000182978; -.
DR HOGENOM; CLU_021184_2_0_1; -.
DR InParanoid; O08575; -.
DR OMA; HTQGYSV; -.
DR PhylomeDB; O08575; -.
DR TreeFam; TF319337; -.
DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR BioGRID-ORCS; 14049; 2 hits in 109 CRISPR screens.
DR ChiTaRS; Eya2; mouse.
DR PRO; PR:O08575; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O08575; protein.
DR Bgee; ENSMUSG00000017897; Expressed in olfactory placode and 129 other tissues.
DR Genevisible; O08575; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0140793; F:histone tyrosine phosphatase activity (H2-Y142 specific); ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine 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:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IDA:MGI.
DR GO; GO:0097345; P:mitochondrial outer membrane permeabilization; IDA:MGI.
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; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI.
DR GO; GO:0014706; P:striated muscle tissue development; IGI:MGI.
DR CDD; cd02601; HAD_Eya; 1.
DR Gene3D; 3.40.50.12350; -; 1.
DR InterPro; IPR028473; EYA2.
DR InterPro; IPR006545; EYA_dom.
DR InterPro; IPR042577; EYA_dom_metazoan.
DR InterPro; IPR038102; EYA_dom_sf.
DR InterPro; IPR028472; EYA_fam.
DR InterPro; IPR036412; HAD-like_sf.
DR PANTHER; PTHR10190; PTHR10190; 1.
DR PANTHER; PTHR10190:SF7; PTHR10190:SF7; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
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; Protein phosphatase; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..532
FT /note="Eyes absent homolog 2"
FT /id="PRO_0000218647"
FT REGION 202..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 202..226
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..256
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 268
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT ACT_SITE 270
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT BINDING 268
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT BINDING 270
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT BINDING 496
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT VAR_SEQ 114..142
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_001492"
SQ SEQUENCE 532 AA; 58246 MW; 9A29BC6BB77DF880 CRC64;
MLEVVTSPSL ATSSDWSEHG AAVGTLSDRE GIAKSAALSV PQLFVKSHPR VPPGQSSTAM
AAYGQTQYST GIQQAPPYTA YPTPAQAYGI PPYSIKTEDS LNHSPSQSGF LSYGPSFSTA
PAGQSPYTYP VHSTAGLYQG ANGLTNTAGF GSVHQDYPSY PSFSQNQYPQ YFSPSYNPPY
VPASSLCSSP LSTSTYVLQE APHNVPSQSS ESLAGDYNTH NGPSTPAKEG DTERPHRASD
GKLRGRSKRN SDPSPAGDNE IERVFVWDLD ETIIIFHSLL TGTFASRYGK DTTTSVRIGL
MMEEMIFNLA DTHLFFNDLE DCDQIHVDDV SSDDNGQDLS TYNFSTDGFH STAPGASLCL
GTGVHGGVDW MRKLAFRYRR VKEMYNTYRN NVGGLIGAPK RETWLQLRAE LEALTDLWLT
HSLKALNLIN SRPNCVNVLV TTTQLIPALA KVLLYGLGSV FPIENIYSAT KTGKESCFER
IMQRFGRKAV YIVIGDGVEE EQGAKKHNMP FWRISCHADL EALRHALELE YL
