EYA4_MOUSE
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 03-AUG-2022, entry version 134.
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 iPTMnet; Q9Z191; -.
DR PhosphoSitePlus; Q9Z191; -.
DR MaxQB; Q9Z191; -.
DR PaxDb; Q9Z191; -.
DR PeptideAtlas; Q9Z191; -.
DR PRIDE; Q9Z191; -.
DR ProteomicsDB; 275562; -.
DR Antibodypedia; 32953; 238 antibodies from 31 providers.
DR DNASU; 14051; -.
DR Ensembl; ENSMUST00000220299; ENSMUSP00000151287; ENSMUSG00000010461.
DR GeneID; 14051; -.
DR KEGG; mmu:14051; -.
DR UCSC; uc007epu.1; mouse.
DR CTD; 2070; -.
DR MGI; MGI:1337104; Eya4.
DR VEuPathDB; HostDB:ENSMUSG00000010461; -.
DR eggNOG; KOG3107; Eukaryota.
DR GeneTree; ENSGT00950000182978; -.
DR InParanoid; Q9Z191; -.
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 106 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 195 other tissues.
DR ExpressionAtlas; Q9Z191; baseline and differential.
DR Genevisible; Q9Z191; MM.
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; IPR028478; EYA4.
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; 1.
DR PANTHER; PTHR10190:SF17; PTHR10190:SF17; 1.
DR TIGRFAMs; TIGR01658; EYA-cons_domain; 1.
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
