EYA2_HUMAN
ID EYA2_HUMAN Reviewed; 538 AA.
AC O00167; Q5JSW8; Q86U84; Q96CV6; Q96H97; Q99503; Q99812; Q9BWF6; Q9H4S3;
AC Q9H4S9; Q9NPZ4; Q9UIX7;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Eyes absent homolog 2;
DE EC=3.1.3.48 {ECO:0000269|PubMed:19351884};
GN Name=EYA2; Synonyms=EAB1;
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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Embryonic brain;
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 [2]
RP ERRATUM OF PUBMED:9195991.
RA Duncan M.K., Kos L., Jenkins N.A., Gilbert D.J., Copeland N.G.,
RA Tomarev S.I.;
RL Mamm. Genome 8:877-877(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Embryo;
RX PubMed=9020840; DOI=10.1038/ng0297-157;
RA Abdelhak S., Kalatzis V., Heilig R., Compain S., Samson D., Vincent C.,
RA Weil D., Cruaud C., Sahly I., Leibovici M., Bitner-Glindzicz M.,
RA Francis M., Lacombe D., Vigneron J., Charachon R., Boven K., Bedbeder P.,
RA van Regemorter N., Weissenbach J., Petit C.;
RT "A human homologue of the Drosophila eyes absent gene underlies branchio-
RT oto-renal (BOR) syndrome and identifies a novel gene family.";
RL Nat. Genet. 15:157-164(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Lung;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 295-538.
RC TISSUE=Brain;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 378-496.
RC TISSUE=Lens epithelium;
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 [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH GNAZ AND GNAI2.
RX PubMed=10906137; DOI=10.1074/jbc.m004577200;
RA Fan X., Brass L.F., Poncz M., Spitz F., Maire P., Manning D.R.;
RT "The alpha subunits of Gz and Gi interact with the eyes absent
RT transcription cofactor Eya2, preventing its interaction with the six class
RT of homeodomain-containing proteins.";
RL J. Biol. Chem. 275:32129-32134(2000).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=12500905; DOI=10.1023/a:1020990825644;
RA Fougerousse F., Durand M., Lopez S., Suel L., Demignon J., Thornton C.,
RA Ozaki H., Kawakami K., Barbet P., Beckmann J.S., Maire P.;
RT "Six and Eya expression during human somitogenesis and MyoD gene family
RT activation.";
RL J. Muscle Res. Cell Motil. 23:255-264(2002).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SIX1.
RX PubMed=19497856; DOI=10.1074/jbc.m109.016832;
RA Patrick A.N., Schiemann B.J., Yang K., Zhao R., Ford H.L.;
RT "Biochemical and functional characterization of six SIX1 Branchio-oto-renal
RT syndrome mutations.";
RL J. Biol. Chem. 284:20781-20790(2009).
RN [12]
RP FUNCTION.
RX PubMed=21706047; DOI=10.1038/onc.2011.259;
RA Farabaugh S.M., Micalizzi D.S., Jedlicka P., Zhao R., Ford H.L.;
RT "Eya2 is required to mediate the pro-metastatic functions of Six1 via the
RT induction of TGF-beta signaling, epithelial-mesenchymal transition, and
RT cancer stem cell properties.";
RL Oncogene 31:552-562(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 268-538 IN COMPLEX WITH
RP MAGNESIUM, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19351884; DOI=10.1074/jbc.c900032200;
RA Krishnan N., Jeong D.G., Jung S.-K., Ryu S.E., Xiao A., Allis C.D.,
RA Kim S.J., Tonks N.K.;
RT "Dephosphorylation of the C-terminal tyrosyl residue of the DNA damage-
RT related histone H2A.X is mediated by the protein phosphatase eyes absent.";
RL J. Biol. Chem. 284:16066-16070(2009).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 268-538 IN COMPLEX WITH MAGNESIUM
RP IONS AND TRANSITION STATE ANALOGS, COFACTOR, AND ACTIVE SITE.
RX PubMed=19858093; DOI=10.1096/fj.09-143891;
RA Jung S.K., Jeong D.G., Chung S.J., Kim J.H., Park B.C., Tonks N.K.,
RA Ryu S.E., Kim S.J.;
RT "Crystal structure of ED-Eya2: insight into dual roles as a protein
RT tyrosine phosphatase and a transcription factor.";
RL FASEB J. 24:560-569(2010).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 253-538 IN COMPLEX WITH SIX1,
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF PRO-516 AND ALA-532.
RX PubMed=23435380; DOI=10.1038/nsmb.2505;
RA Patrick A.N., Cabrera J.H., Smith A.L., Chen X.S., Ford H.L., Zhao R.;
RT "Structure-function analyses of the human SIX1-EYA2 complex reveal insights
RT into metastasis and BOR syndrome.";
RL Nat. Struct. Mol. Biol. 20:447-453(2013).
CC -!- FUNCTION: Functions both as protein phosphatase and as transcriptional
CC coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5
CC (PubMed:12500905, PubMed:23435380). 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
CC (PubMed:19351884). Its function as histone phosphatase may contribute
CC to its function in transcription regulation during organogenesis. Plays
CC an important role in hypaxial muscle development together with SIX1 and
CC DACH2; in this it is functionally redundant with EYA1
CC (PubMed:12500905). {ECO:0000269|PubMed:12500905,
CC ECO:0000269|PubMed:19351884, ECO:0000269|PubMed:21706047,
CC ECO:0000269|PubMed:23435380}.
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:19351884};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:19858093};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:19858093};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.9 uM for H2AXY142ph {ECO:0000269|PubMed:19351884};
CC KM=80 uM for H2AXS139ph {ECO:0000269|PubMed:19351884};
CC -!- SUBUNIT: Interacts with DACH2 and SIX1, and probably with SIX2, SIX4
CC and SIX5. Interacts with CAPN8 (By similarity). Interacts with GNAZ and
CC GNAI2; this precludes interaction with SIX1. {ECO:0000250,
CC ECO:0000269|PubMed:10906137, ECO:0000269|PubMed:19351884,
CC ECO:0000269|PubMed:19497856, ECO:0000269|PubMed:19858093,
CC ECO:0000269|PubMed:23435380}.
CC -!- INTERACTION:
CC O00167; Q15475: SIX1; NbExp=4; IntAct=EBI-750211, EBI-743675;
CC O00167-1; Q15475: SIX1; NbExp=3; IntAct=EBI-16038245, EBI-743675;
CC O00167-2; O95817: BAG3; NbExp=4; IntAct=EBI-12807776, EBI-747185;
CC O00167-2; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-12807776, EBI-744545;
CC O00167-2; Q07002: CDK18; NbExp=3; IntAct=EBI-12807776, EBI-746238;
CC O00167-2; Q86UW9: DTX2; NbExp=3; IntAct=EBI-12807776, EBI-740376;
CC O00167-2; Q9H596: DUSP21; NbExp=3; IntAct=EBI-12807776, EBI-7357329;
CC O00167-2; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-12807776, EBI-744099;
CC O00167-2; Q7L5A3: FAM214B; NbExp=3; IntAct=EBI-12807776, EBI-745689;
CC O00167-2; O14964: HGS; NbExp=3; IntAct=EBI-12807776, EBI-740220;
CC O00167-2; Q8NA54: IQUB; NbExp=3; IntAct=EBI-12807776, EBI-10220600;
CC O00167-2; P56470: LGALS4; NbExp=3; IntAct=EBI-12807776, EBI-720805;
CC O00167-2; Q71SY5: MED25; NbExp=3; IntAct=EBI-12807776, EBI-394558;
CC O00167-2; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-12807776, EBI-11022007;
CC O00167-2; P55771: PAX9; NbExp=3; IntAct=EBI-12807776, EBI-12111000;
CC O00167-2; Q13526: PIN1; NbExp=3; IntAct=EBI-12807776, EBI-714158;
CC O00167-2; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-12807776, EBI-1389308;
CC O00167-2; P48378: RFX2; NbExp=3; IntAct=EBI-12807776, EBI-746731;
CC O00167-2; Q15475: SIX1; NbExp=3; IntAct=EBI-12807776, EBI-743675;
CC O00167-2; P09234: SNRPC; NbExp=3; IntAct=EBI-12807776, EBI-766589;
CC O00167-2; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-12807776, EBI-742688;
CC O00167-2; P51687: SUOX; NbExp=3; IntAct=EBI-12807776, EBI-3921347;
CC O00167-2; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-12807776, EBI-750487;
CC O00167-2; Q96M29: TEKT5; NbExp=3; IntAct=EBI-12807776, EBI-10239812;
CC O00167-2; Q92734: TFG; NbExp=3; IntAct=EBI-12807776, EBI-357061;
CC O00167-2; Q08117-2: TLE5; NbExp=3; IntAct=EBI-12807776, EBI-11741437;
CC O00167-2; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-12807776, EBI-3650647;
CC O00167-2; O75865-2: TRAPPC6A; NbExp=3; IntAct=EBI-12807776, EBI-8451480;
CC O00167-2; Q96PN8: TSSK3; NbExp=3; IntAct=EBI-12807776, EBI-3918381;
CC O00167-2; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-12807776, EBI-2559305;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10906137,
CC ECO:0000269|PubMed:12500905}. Nucleus {ECO:0000269|PubMed:10906137,
CC ECO:0000269|PubMed:12500905, ECO:0000269|PubMed:19497856}.
CC Note=Retained in the cytoplasm via interaction with GNAZ and GNAI2
CC (PubMed:10906137). Interaction with SIX1, SIX2, SIX4 or SIX5 is
CC required for translocation to the nucleus (PubMed:10906137,
CC PubMed:12500905). {ECO:0000269|PubMed:10906137,
CC ECO:0000269|PubMed:12500905}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1;
CC IsoId=O00167-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00167-2; Sequence=VSP_001490;
CC Name=3;
CC IsoId=O00167-3; Sequence=VSP_001491;
CC -!- TISSUE SPECIFICITY: Highest expression in muscle with lower levels in
CC kidney, placenta, pancreas, brain and heart.
CC {ECO:0000269|PubMed:9195991}.
CC -!- DEVELOPMENTAL STAGE: At the begin of fourth week of development
CC detected in cytoplasm of somite cells. Between the sixth and eighth
CC week of development detected in cytoplasm of limb bud cells.
CC {ECO:0000269|PubMed:12500905}.
CC -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily. EYA family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH13882.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U71207; AAB51120.1; -; mRNA.
DR EMBL; Y10261; CAA71310.1; -; Genomic_DNA.
DR EMBL; BT006682; AAP35328.1; -; mRNA.
DR EMBL; AL049540; CAI23166.1; -; Genomic_DNA.
DR EMBL; AL121776; CAI23166.1; JOINED; Genomic_DNA.
DR EMBL; AL359434; CAI23166.1; JOINED; Genomic_DNA.
DR EMBL; AL022342; CAI23166.1; JOINED; Genomic_DNA.
DR EMBL; BC000289; AAH00289.2; -; mRNA.
DR EMBL; BC008803; AAH08803.1; -; mRNA.
DR EMBL; BC013882; AAH13882.2; ALT_INIT; mRNA.
DR EMBL; U81601; AAB42065.1; -; mRNA.
DR EMBL; AJ007992; CAA07815.1; -; mRNA.
DR CCDS; CCDS13403.1; -. [O00167-1]
DR CCDS; CCDS54471.1; -. [O00167-3]
DR RefSeq; NP_005235.3; NM_005244.4. [O00167-1]
DR RefSeq; NP_742108.2; NM_172110.3. [O00167-3]
DR PDB; 3GEB; X-ray; 2.40 A; A/B/C/D=268-538.
DR PDB; 3HB0; X-ray; 2.50 A; A/B/C/D=268-538.
DR PDB; 3HB1; X-ray; 2.51 A; A/B/C/D=268-538.
DR PDB; 4EGC; X-ray; 1.99 A; B=253-538.
DR PDB; 5ZMA; X-ray; 3.17 A; A/B/C=253-538.
DR PDB; 7F8G; X-ray; 3.49 A; A/B=253-538.
DR PDB; 7F8H; X-ray; 3.30 A; A/B/C=253-538.
DR PDBsum; 3GEB; -.
DR PDBsum; 3HB0; -.
DR PDBsum; 3HB1; -.
DR PDBsum; 4EGC; -.
DR PDBsum; 5ZMA; -.
DR PDBsum; 7F8G; -.
DR PDBsum; 7F8H; -.
DR AlphaFoldDB; O00167; -.
DR SMR; O00167; -.
DR BioGRID; 108440; 122.
DR DIP; DIP-40707N; -.
DR IntAct; O00167; 72.
DR MINT; O00167; -.
DR STRING; 9606.ENSP00000333640; -.
DR ChEMBL; CHEMBL1293275; -.
DR DEPOD; EYA2; -.
DR iPTMnet; O00167; -.
DR PhosphoSitePlus; O00167; -.
DR BioMuta; EYA2; -.
DR jPOST; O00167; -.
DR MassIVE; O00167; -.
DR PaxDb; O00167; -.
DR PeptideAtlas; O00167; -.
DR PRIDE; O00167; -.
DR ProteomicsDB; 47756; -. [O00167-1]
DR ProteomicsDB; 47757; -. [O00167-2]
DR ProteomicsDB; 47758; -. [O00167-3]
DR Antibodypedia; 13258; 277 antibodies from 29 providers.
DR DNASU; 2139; -.
DR Ensembl; ENST00000327619.10; ENSP00000333640.5; ENSG00000064655.19. [O00167-1]
DR Ensembl; ENST00000357410.7; ENSP00000349986.3; ENSG00000064655.19. [O00167-3]
DR Ensembl; ENST00000497062.6; ENSP00000417105.3; ENSG00000064655.19. [O00167-2]
DR GeneID; 2139; -.
DR KEGG; hsa:2139; -.
DR MANE-Select; ENST00000327619.10; ENSP00000333640.5; NM_005244.5; NP_005235.3.
DR UCSC; uc002xsm.3; human. [O00167-1]
DR CTD; 2139; -.
DR DisGeNET; 2139; -.
DR GeneCards; EYA2; -.
DR HGNC; HGNC:3520; EYA2.
DR HPA; ENSG00000064655; Tissue enhanced (cervix).
DR MIM; 601654; gene.
DR neXtProt; NX_O00167; -.
DR OpenTargets; ENSG00000064655; -.
DR PharmGKB; PA27932; -.
DR VEuPathDB; HostDB:ENSG00000064655; -.
DR eggNOG; KOG3107; Eukaryota.
DR GeneTree; ENSGT00950000182978; -.
DR HOGENOM; CLU_021184_2_0_1; -.
DR InParanoid; O00167; -.
DR OMA; HTQGYSV; -.
DR OrthoDB; 1030296at2759; -.
DR PhylomeDB; O00167; -.
DR TreeFam; TF319337; -.
DR BRENDA; 3.1.3.48; 2681.
DR PathwayCommons; O00167; -.
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR SABIO-RK; O00167; -.
DR SignaLink; O00167; -.
DR BioGRID-ORCS; 2139; 14 hits in 1075 CRISPR screens.
DR ChiTaRS; EYA2; human.
DR EvolutionaryTrace; O00167; -.
DR GeneWiki; EYA2; -.
DR GenomeRNAi; 2139; -.
DR Pharos; O00167; Tbio.
DR PRO; PR:O00167; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; O00167; protein.
DR Bgee; ENSG00000064655; Expressed in olfactory segment of nasal mucosa and 130 other tissues.
DR ExpressionAtlas; O00167; baseline and differential.
DR Genevisible; O00167; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0140793; F:histone tyrosine phosphatase activity (H2-Y142 specific); IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
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:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0007501; P:mesodermal cell fate specification; TAS:ProtInc.
DR GO; GO:0097345; P:mitochondrial outer membrane permeabilization; 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:0006470; P:protein dephosphorylation; IEA:Ensembl.
DR GO; GO:0014706; P:striated muscle tissue development; IEA:Ensembl.
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 3D-structure; Activator; Alternative splicing; Chromatin regulator;
KW Cytoplasm; Developmental protein; DNA damage; DNA repair; Hydrolase;
KW Magnesium; Metal-binding; Nucleus; Protein phosphatase; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..538
FT /note="Eyes absent homolog 2"
FT /id="PRO_0000218646"
FT REGION 209..263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 209..232
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 233..262
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 274
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:19858093"
FT ACT_SITE 276
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:19858093"
FT BINDING 274
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:19351884"
FT BINDING 276
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:19351884"
FT BINDING 502
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:19351884"
FT VAR_SEQ 99..122
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_001490"
FT VAR_SEQ 401..479
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_001491"
FT VARIANT 83
FT /note="P -> S (in dbSNP:rs2275596)"
FT /id="VAR_048964"
FT VARIANT 238
FT /note="T -> A (in dbSNP:rs866936)"
FT /id="VAR_048965"
FT MUTAGEN 516
FT /note="P->R: Strongly reduces SIX1 binding."
FT /evidence="ECO:0000269|PubMed:23435380"
FT MUTAGEN 532
FT /note="A->R: Abolishes interaction with SIX1."
FT /evidence="ECO:0000269|PubMed:23435380"
FT CONFLICT 296
FT /note="K -> E (in Ref. 7; AAB42065)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="G -> A (in Ref. 4; AAP35328 and 6; AAH08803)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="A -> S (in Ref. 7; AAB42065)"
FT /evidence="ECO:0000305"
FT CONFLICT 419
FT /note="A -> V (in Ref. 8; CAA07815)"
FT /evidence="ECO:0000305"
FT CONFLICT 525
FT /note="D -> N (in Ref. 1; AAB51120)"
FT /evidence="ECO:0000305"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:4EGC"
FT TURN 277..279
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 283..287
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 289..294
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 298..319
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 322..325
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 326..328
FT /evidence="ECO:0007829|PDB:3HB0"
FT TURN 333..336
FT /evidence="ECO:0007829|PDB:3GEB"
FT HELIX 337..339
FT /evidence="ECO:0007829|PDB:3GEB"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 374..394
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 398..402
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 406..420
FT /evidence="ECO:0007829|PDB:4EGC"
FT TURN 421..423
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 424..436
FT /evidence="ECO:0007829|PDB:4EGC"
FT STRAND 441..449
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 451..460
FT /evidence="ECO:0007829|PDB:4EGC"
FT TURN 464..466
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 469..471
FT /evidence="ECO:0007829|PDB:4EGC"
FT STRAND 472..474
FT /evidence="ECO:0007829|PDB:4EGC"
FT TURN 476..478
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 480..491
FT /evidence="ECO:0007829|PDB:4EGC"
FT STRAND 493..503
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 504..512
FT /evidence="ECO:0007829|PDB:4EGC"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 523..534
FT /evidence="ECO:0007829|PDB:4EGC"
SQ SEQUENCE 538 AA; 59232 MW; 3DBFC31D8BE1E85D CRC64;
MVELVISPSL TVNSDCLDKL KFNRADAAVW TLSDRQGITK SAPLRVSQLF SRSCPRVLPR
QPSTAMAAYG QTQYSAGIQQ ATPYTAYPPP AQAYGIPSYS IKTEDSLNHS PGQSGFLSYG
SSFSTSPTGQ SPYTYQMHGT TGFYQGGNGL GNAAGFGSVH QDYPSYPGFP QSQYPQYYGS
SYNPPYVPAS SICPSPLSTS TYVLQEASHN VPNQSSESLA GEYNTHNGPS TPAKEGDTDR
PHRASDGKLR GRSKRSSDPS PAGDNEIERV FVWDLDETII IFHSLLTGTF ASRYGKDTTT
SVRIGLMMEE MIFNLADTHL FFNDLEDCDQ IHVDDVSSDD NGQDLSTYNF SADGFHSSAP
GANLCLGSGV HGGVDWMRKL AFRYRRVKEM YNTYKNNVGG LIGTPKRETW LQLRAELEAL
TDLWLTHSLK ALNLINSRPN CVNVLVTTTQ LIPALAKVLL YGLGSVFPIE NIYSATKTGK
ESCFERIMQR FGRKAVYVVI GDGVEEEQGA KKHNMPFWRI SCHADLEALR HALELEYL
