ID   EYA4_MOUSE              Reviewed;         616 AA.
AC   Q9Z191; Q0VAV8;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   24-JAN-2024, entry version 141.
DE   RecName: Full=Eyes absent homolog 4;
DE            EC=3.1.3.48 {ECO:0000250|UniProtKB:Q99502};
GN   Name=Eya4;
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], AND TISSUE SPECIFICITY.
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   [2]
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
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. Its
CC       function as histone phosphatase probably explains its role in
CC       transcription regulation during organogenesis. May be involved in
CC       development of the eye (By similarity). {ECO:0000250|UniProtKB:Q99502}.
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:0000250|UniProtKB:Q99502};
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 SIX3; translocates EYA4 from the cytoplasm to
CC       the nucleus and promotes activation of their target genes.
CC       {ECO:0000250|UniProtKB:O95677}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q99502}. Nucleus
CC       {ECO:0000250|UniProtKB:Q99502}.
CC   -!- TISSUE SPECIFICITY: In the embryo, expressed mainly in the craniofacial
CC       mesenchyme, dermamyotome and limb. {ECO:0000269|PubMed:9887327}.
CC   -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily. EYA family.
CC       {ECO:0000305}.
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DR   EMBL; Y17115; CAA76637.1; -; mRNA.
DR   EMBL; AJ007997; CAA07820.1; -; mRNA.
DR   EMBL; CH466540; EDL04766.1; -; Genomic_DNA.
DR   EMBL; BC120899; AAI20900.1; -; mRNA.
DR   CCDS; CCDS83687.1; -.
DR   RefSeq; NP_001334301.1; NM_001347372.1.
DR   RefSeq; XP_006512586.1; XM_006512523.3.
DR   RefSeq; XP_006512587.1; XM_006512524.3.
DR   AlphaFoldDB; Q9Z191; -.
DR   SMR; Q9Z191; -.
DR   BioGRID; 199562; 1.
DR   MINT; Q9Z191; -.
DR   STRING; 10090.ENSMUSP00000090335; -.
DR   GlyGen; Q9Z191; 8 sites, 1 O-linked glycan (8 sites).
DR   iPTMnet; Q9Z191; -.
DR   PhosphoSitePlus; Q9Z191; -.
DR   MaxQB; Q9Z191; -.
DR   PaxDb; 10090-ENSMUSP00000090335; -.
DR   PeptideAtlas; Q9Z191; -.
DR   ProteomicsDB; 275562; -.
DR   Pumba; Q9Z191; -.
DR   Antibodypedia; 32953; 268 antibodies from 31 providers.
DR   DNASU; 14051; -.
DR   Ensembl; ENSMUST00000220299.2; ENSMUSP00000151287.2; ENSMUSG00000010461.17.
DR   GeneID; 14051; -.
DR   KEGG; mmu:14051; -.
DR   UCSC; uc007epu.1; mouse.
DR   AGR; MGI:1337104; -.
DR   CTD; 2070; -.
DR   MGI; MGI:1337104; Eya4.
DR   VEuPathDB; HostDB:ENSMUSG00000010461; -.
DR   eggNOG; KOG3107; Eukaryota.
DR   GeneTree; ENSGT00950000182978; -.
DR   InParanoid; Q9Z191; -.
DR   OrthoDB; 452222at2759; -.
DR   PhylomeDB; Q9Z191; -.
DR   Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR   BioGRID-ORCS; 14051; 2 hits in 112 CRISPR screens.
DR   ChiTaRS; Eya4; mouse.
DR   PRO; PR:Q9Z191; -.
DR   Proteomes; UP000000589; Chromosome 10.
DR   RNAct; Q9Z191; Protein.
DR   Bgee; ENSMUSG00000010461; Expressed in epithelium of cochlear duct and 196 other cell types or tissues.
DR   ExpressionAtlas; Q9Z191; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central.
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:0042474; P:middle ear morphogenesis; IMP: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:0007605; P:sensory perception of sound; IMP:MGI.
DR   CDD; cd02601; HAD_Eya; 1.
DR   Gene3D; 3.40.50.12350; -; 1.
DR   InterPro; IPR006545; EYA_dom.
DR   InterPro; IPR042577; EYA_dom_metazoan.
DR   InterPro; IPR038102; EYA_dom_sf.
DR   InterPro; IPR028472; EYA_fam.
DR   NCBIfam; TIGR01658; EYA-cons_domain; 1.
DR   PANTHER; PTHR10190; EYES ABSENT; 1.
DR   PANTHER; PTHR10190:SF17; EYES ABSENT HOMOLOG 4; 1.
DR   Pfam; PF00702; Hydrolase; 1.
DR   SFLD; SFLDG01129; C1.5:_HAD__Beta-PGM__Phosphata; 1.
DR   SFLD; SFLDS00003; Haloacid_Dehalogenase; 1.
DR   Genevisible; Q9Z191; MM.
PE   2: Evidence at transcript level;
KW   Acetylation; Activator; Chromatin regulator; Cytoplasm;
KW   Developmental protein; DNA damage; DNA repair; Hydrolase; Isopeptide bond;
KW   Magnesium; Metal-binding; Nucleus; Phosphoprotein; Protein phosphatase;
KW   Reference proteome; Transcription; Transcription regulation;
KW   Ubl conjugation.
FT   CHAIN           1..616
FT                   /note="Eyes absent homolog 4"
FT                   /id="PRO_0000218652"
FT   REGION          1..66
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          186..211
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          277..345
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        49..66
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        277..314
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        352
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:O00167"
FT   ACT_SITE        354
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:O00167"
FT   BINDING         352
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:O00167"
FT   BINDING         354
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:O00167"
FT   BINDING         580
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:O00167"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:O95677"
FT   MOD_RES         338
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O95677"
FT   CROSSLNK        14
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:O95677"
FT   CROSSLNK        52
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:O95677"
FT   CONFLICT        337
FT                   /note="P -> L (in Ref. 1; CAA76637)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   616 AA;  66875 MW;  AC4B7E891AB7A6F3 CRC64;
     MEDTQDLNEQ SVKKTCPEAD VSEPQNSRSM EMQDLASPHA LVGGSDTPGS SKLDKSGLSS
     TSVTTNGTGV SLLAVKTEPL HSSESTTTTG DGALDTFTGS VITSSGYSPR SAQQYSPQLY
     PSKPYPHILS TPAAQTMSAY AGQTQYSGMQ QPAVYTAYSQ TGQPYSLPAY DLGVMLPAIK
     TESGLSQTQS PLQSGCLSYS PGFSTPQPGQ TPYSYQMPGS SFAPSSTIYA NNSVSNSTNF
     SSSQQDYPSY TAFGQNQYAQ YYSASTYGAY MTSNNTADGT SSSTSTYQLQ ESLQGLTSQP
     GEFDTVQSPS TPIKDLDDRT CRSSGSKSRG RGRKNNPSPP PDSDLERVFV WDLDETIIVF
     HSLLTGSYAQ KYGKDPPMAV TLGLRMEEMI FNLADTHLFF NDLEECDQVH IDDVSSDDNG
     QDLSTYSFAT DGFHAAASSA NLCLPTGVRG GVDWMRKLAF RYRRVKELYN TYKNNVGGLL
     GPAKRDAWLQ LRAEIEGLTD SWLTNALKSL SIISTRSNCV NVLVTTTQLI PALAKVLLYS
     LGGAFPIENI YSATKIGKES CFERIVSRFG TNITYVVIGD GRDEEHAANQ HNMPFWRISS
     HSDLLALHQA LELEYL
//