EYA4_HUMAN
ID EYA4_HUMAN Reviewed; 639 AA.
AC O95677; B7Z7F7; O95464; O95679; Q8IW39; Q9NTR7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Eyes absent homolog 4;
DE EC=3.1.3.48 {ECO:0000250|UniProtKB:Q99502};
GN Name=EYA4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT SER-277, AND ALTERNATIVE
RP SPLICING.
RC TISSUE=Lens epithelium, and Skeletal muscle;
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 MRNA] (ISOFORM 5).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 INVOLVEMENT IN DFNA10.
RX PubMed=11159937; DOI=10.1093/hmg/10.3.195;
RA Wayne S., Robertson N.G., DeClau F., Chen N., Verhoeven K., Prasad S.,
RA Tranebjaerg L., Morton C.C., Ryan A.F., Van Camp G., Smith R.J.H.;
RT "Mutations in the transcriptional activator EYA4 cause late-onset deafness
RT at the DFNA10 locus.";
RL Hum. Mol. Genet. 10:195-200(2001).
RN [6]
RP INVOLVEMENT IN CMD1J, AND TISSUE SPECIFICITY.
RX PubMed=15735644; DOI=10.1038/ng1527;
RA Schoenberger J., Wang L., Shin J.T., Kim S.D., Depreux F.F.S., Zhu H.,
RA Zon L., Pizard A., Kim J.B., Macrae C.A., Mungall A.J., Seidman J.G.,
RA Seidman C.E.;
RT "Mutation in the transcriptional coactivator EYA4 causes dilated
RT cardiomyopathy and sensorineural hearing loss.";
RL Nat. Genet. 37:418-422(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP INTERACTION WITH SIX3.
RX PubMed=19606496; DOI=10.1002/humu.21094;
RA Abe Y., Oka A., Mizuguchi M., Igarashi T., Ishikawa S., Aburatani H.,
RA Yokoyama S., Asahara H., Nagao K., Yamada M., Miyashita T.;
RT "EYA4, deleted in a case with middle interhemispheric variant of
RT holoprosencephaly, interacts with SIX3 both physically and functionally.";
RL Hum. Mutat. 30:E946-E955(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-14 AND LYS-52, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [12]
RP VARIANTS [LARGE SCALE ANALYSIS] ARG-152 AND ASN-301.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [13]
RP VARIANT DFNA10 288-SER--LEU-639 DEL.
RX PubMed=22938506; DOI=10.1186/1750-1172-7-60;
RA Baek J.I., Oh S.K., Kim D.B., Choi S.Y., Kim U.K., Lee K.Y., Lee S.H.;
RT "Targeted massive parallel sequencing: the effective detection of novel
RT causative mutations associated with hearing loss in small families.";
RL Orphanet J. Rare Dis. 7:60-60(2012).
RN [14]
RP VARIANT DFNA10 ARG-548.
RX PubMed=25809937; DOI=10.1038/jhg.2015.19;
RA Sun Y., Zhang Z., Cheng J., Lu Y., Yang C.L., Luo Y.Y., Yang G., Yang H.,
RA Zhu L., Zhou J., Yao H.Q.;
RT "A novel mutation of EYA4 in a large Chinese family with autosomal dominant
RT middle-frequency sensorineural hearing loss by targeted exome sequencing.";
RL J. Hum. Genet. 60:299-304(2015).
RN [15]
RP VARIANT DFNA10 ARG-171.
RX PubMed=25961296; DOI=10.1371/journal.pone.0126602;
RA Liu F., Hu J., Xia W., Hao L., Ma J., Ma D., Ma Z.;
RT "Exome sequencing identifies a mutation in EYA4 as a novel cause of
RT autosomal dominant non-syndromic hearing loss.";
RL PLoS ONE 10:E0126602-E0126602(2015).
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:0000269|PubMed:19606496}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q99502}. Nucleus
CC {ECO:0000250|UniProtKB:Q99502}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=O95677-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95677-2; Sequence=VSP_001495, VSP_001496;
CC Name=3;
CC IsoId=O95677-3; Sequence=VSP_001497, VSP_001498;
CC Name=4;
CC IsoId=O95677-4; Sequence=VSP_001499;
CC Name=5;
CC IsoId=O95677-5; Sequence=VSP_042160, VSP_001499;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart and skeletal muscle.
CC {ECO:0000269|PubMed:15735644}.
CC -!- DISEASE: Deafness, autosomal dominant, 10 (DFNA10) [MIM:601316]: A form
CC of non-syndromic sensorineural hearing loss. Sensorineural deafness
CC results from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. {ECO:0000269|PubMed:11159937, ECO:0000269|PubMed:22938506,
CC ECO:0000269|PubMed:25809937, ECO:0000269|PubMed:25961296}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cardiomyopathy, dilated 1J (CMD1J) [MIM:605362]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. CMD1J is characterized by the association of
CC sensorineural hearing loss and dilated cardiomyopathy in the absence of
CC other anomalies. {ECO:0000269|PubMed:15735644}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily. EYA family.
CC {ECO:0000305}.
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DR EMBL; Y17114; CAA76636.1; -; mRNA.
DR EMBL; Y17847; CAA76891.1; -; Genomic_DNA.
DR EMBL; AJ007993; CAA07816.1; -; mRNA.
DR EMBL; AJ007994; CAA07817.1; -; mRNA.
DR EMBL; AK301950; BAH13593.1; -; mRNA.
DR EMBL; AL024497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121959; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL450270; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC041063; AAH41063.1; -; mRNA.
DR CCDS; CCDS43506.1; -. [O95677-2]
DR CCDS; CCDS5165.1; -. [O95677-1]
DR CCDS; CCDS5166.1; -. [O95677-4]
DR CCDS; CCDS75523.1; -. [O95677-5]
DR RefSeq; NP_001287941.1; NM_001301012.1. [O95677-5]
DR RefSeq; NP_001287942.1; NM_001301013.1.
DR RefSeq; NP_004091.3; NM_004100.4. [O95677-1]
DR RefSeq; NP_742101.2; NM_172103.3. [O95677-2]
DR RefSeq; NP_742103.1; NM_172105.3. [O95677-4]
DR AlphaFoldDB; O95677; -.
DR SMR; O95677; -.
DR BioGRID; 108382; 84.
DR IntAct; O95677; 15.
DR MINT; O95677; -.
DR STRING; 9606.ENSP00000432770; -.
DR DEPOD; EYA4; -.
DR GlyGen; O95677; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95677; -.
DR PhosphoSitePlus; O95677; -.
DR BioMuta; EYA4; -.
DR jPOST; O95677; -.
DR MassIVE; O95677; -.
DR MaxQB; O95677; -.
DR PaxDb; O95677; -.
DR PeptideAtlas; O95677; -.
DR PRIDE; O95677; -.
DR ProteomicsDB; 50990; -. [O95677-1]
DR ProteomicsDB; 50991; -. [O95677-2]
DR ProteomicsDB; 50992; -. [O95677-3]
DR ProteomicsDB; 50993; -. [O95677-4]
DR ProteomicsDB; 50994; -. [O95677-5]
DR Antibodypedia; 32953; 238 antibodies from 31 providers.
DR DNASU; 2070; -.
DR Ensembl; ENST00000355286.12; ENSP00000347434.7; ENSG00000112319.20. [O95677-1]
DR Ensembl; ENST00000431403.3; ENSP00000404558.3; ENSG00000112319.20. [O95677-2]
DR Ensembl; ENST00000452339.6; ENSP00000395916.2; ENSG00000112319.20. [O95677-5]
DR GeneID; 2070; -.
DR KEGG; hsa:2070; -.
DR MANE-Select; ENST00000355286.12; ENSP00000347434.7; NM_004100.5; NP_004091.3.
DR UCSC; uc003qec.5; human. [O95677-1]
DR CTD; 2070; -.
DR DisGeNET; 2070; -.
DR GeneCards; EYA4; -.
DR GeneReviews; EYA4; -.
DR HGNC; HGNC:3522; EYA4.
DR HPA; ENSG00000112319; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; EYA4; -.
DR MIM; 601316; phenotype.
DR MIM; 603550; gene.
DR MIM; 605362; phenotype.
DR neXtProt; NX_O95677; -.
DR OpenTargets; ENSG00000112319; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR Orphanet; 217622; Sensorineural deafness with dilated cardiomyopathy.
DR PharmGKB; PA27934; -.
DR VEuPathDB; HostDB:ENSG00000112319; -.
DR eggNOG; KOG3107; Eukaryota.
DR GeneTree; ENSGT00950000182978; -.
DR HOGENOM; CLU_021184_2_1_1; -.
DR InParanoid; O95677; -.
DR OMA; MSAYGGQ; -.
DR OrthoDB; 1030296at2759; -.
DR PhylomeDB; O95677; -.
DR TreeFam; TF319337; -.
DR PathwayCommons; O95677; -.
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR SignaLink; O95677; -.
DR BioGRID-ORCS; 2070; 11 hits in 1075 CRISPR screens.
DR ChiTaRS; EYA4; human.
DR GeneWiki; EYA4; -.
DR GenomeRNAi; 2070; -.
DR Pharos; O95677; Tbio.
DR PRO; PR:O95677; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O95677; protein.
DR Bgee; ENSG00000112319; Expressed in biceps brachii and 147 other tissues.
DR ExpressionAtlas; O95677; baseline and differential.
DR Genevisible; O95677; HS.
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:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
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:0048839; P:inner ear development; IEA:Ensembl.
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; IEA:InterPro.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
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 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Cardiomyopathy;
KW Chromatin regulator; Cytoplasm; Deafness; Developmental protein;
KW Disease variant; DNA damage; DNA repair; Hydrolase; Isopeptide bond;
KW Magnesium; Metal-binding; Non-syndromic deafness; Nucleus; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..639
FT /note="Eyes absent homolog 4"
FT /id="PRO_0000218651"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 210..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 300..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..72
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..337
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 375
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT ACT_SITE 377
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT BINDING 375
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT BINDING 377
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O00167"
FT BINDING 603
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:0007744|PubMed:19413330"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 14
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 52
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 70..123
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042160"
FT VAR_SEQ 70..92
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_001495"
FT VAR_SEQ 93
FT /note="M -> V (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_001496"
FT VAR_SEQ 447..452
FT /note="STYSFA -> RCKRRG (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_001497"
FT VAR_SEQ 453..639
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_001498"
FT VAR_SEQ 589..613
FT /note="MQRFGRKVVYVVIGDGVEEEQAAKK -> VSRFGTNITYVVIGDGRDEEHAA
FT NQ (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_001499"
FT VARIANT 152
FT /note="L -> R (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036248"
FT VARIANT 171
FT /note="G -> R (in DFNA10; dbSNP:rs1471362858)"
FT /evidence="ECO:0000269|PubMed:25961296"
FT /id="VAR_074570"
FT VARIANT 277
FT /note="G -> S (in dbSNP:rs9493627)"
FT /evidence="ECO:0000269|PubMed:9887327"
FT /id="VAR_022932"
FT VARIANT 288..639
FT /note="Missing (in DFNA10)"
FT /evidence="ECO:0000269|PubMed:22938506"
FT /id="VAR_079872"
FT VARIANT 301
FT /note="D -> N (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs779172192)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036249"
FT VARIANT 548
FT /note="T -> R (in DFNA10)"
FT /evidence="ECO:0000269|PubMed:25809937"
FT /id="VAR_074571"
FT CONFLICT 177
FT /note="V -> A (in Ref. 2; BAH13593)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 639 AA; 69505 MW; CC59A8FB1527A0EC CRC64;
MEDSQDLNEQ SVKKTCTESD VSQSQNSRSM EMQDLASPHT LVGGGDTPGS SKLEKSNLSS
TSVTTNGTGG ENMTVLNTAD WLLSCNTPSS ATMSLLAVKT EPLNSSETTA TTGDGALDTF
TGSVITSSGY SPRSAHQYSP QLYPSKPYPH ILSTPAAQTM SAYAGQTQYS GMQQPAVYTA
YSQTGQPYSL PTYDLGVMLP AIKTESGLSQ TQSPLQSGCL SYSPGFSTPQ PGQTPYSYQM
PGSSFAPSST IYANNSVSNS TNFSGSQQDY PSYTAFGQNQ YAQYYSASTY GAYMTSNNTA
DGTPSSTSTY QLQESLPGLT NQPGEFDTMQ SPSTPIKDLD ERTCRSSGSK SRGRGRKNNP
SPPPDSDLER VFVWDLDETI IVFHSLLTGS YAQKYGKDPP MAVTLGLRME EMIFNLADTH
LFFNDLEECD QVHIDDVSSD DNGQDLSTYS FATDGFHAAA SSANLCLPTG VRGGVDWMRK
LAFRYRRVKE LYNTYKNNVG GLLGPAKRDA WLQLRAEIEG LTDSWLTNAL KSLSIISTRS
NCINVLVTTT QLIPALAKVL LYSLGGAFPI ENIYSATKIG KESCFERIMQ RFGRKVVYVV
IGDGVEEEQA AKKHNMPFWR ISSHSDLLAL HQALELEYL
