ID EYA1_MOUSE Reviewed; 591 AA. AC P97767; G5E864; O08818; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2012, sequence version 3. DT 02-SEP-2026, entry version 193. DE RecName: Full=Protein phosphatase EYA1 {ECO:0000305}; DE EC=3.1.3.16 {ECO:0000269|PubMed:14628052}; DE EC=3.1.3.48 {ECO:0000269|PubMed:14628052}; DE AltName: Full=Eyes absent homolog 1; GN Name=Eya1; 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] (ISOFORM 1), AND TISSUE SPECIFICITY. 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 [GENOMIC DNA] (ISOFORM 2). RC STRAIN=CB/20; 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 [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 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 [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 276-321, AND DISEASE. RC STRAIN=129/SvJ; RX PubMed=10072433; DOI=10.1093/hmg/8.4.645; RA Johnson K.R., Cook S.A., Erway L.C., Matthews A.N., Sanford L.P., RA Paradies N.E., Friedman R.A.; RT "Inner ear and kidney anomalies caused by IAP insertion in an intron of the RT Eya1 gene in a mouse model of BOR syndrome."; RL Hum. Mol. Genet. 8:645-653(1999). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 431-549. 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 [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 DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=10471511; DOI=10.1038/12722; RA Xu P.X., Adams J., Peters H., Brown M.C., Heaney S., Maas R.; RT "Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of RT organ primordia."; RL Nat. Genet. 23:113-117(1999). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE. RX PubMed=14628042; DOI=10.1038/nature02083; RA Li X., Oghi K.A., Zhang J., Krones A., Bush K.T., Glass C.K., Nigam S.K., RA Aggarwal A.K., Maas R., Rose D.W., Rosenfeld M.G.; RT "Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional RT effects in mammalian organogenesis."; RL Nature 426:247-254(2003). RN [10] RP ERRATUM OF PUBMED:14628042. RA Li X., Oghi K.A., Zhang J., Krones A., Bush K.T., Glass C.K., Nigam S.K., RA Aggarwal A.K., Maas R., Rose D.W., Rosenfeld M.G.; RL Nature 427:265-265(2004). RN [11] 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 [12] RP INTERACTION WITH SIX3. RX PubMed=16024294; DOI=10.1016/j.modgep.2005.04.010; RA Purcell P., Oliver G., Mardon G., Donner A.L., Maas R.L.; RT "Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal RT placode induction."; RL Gene Expr. Patterns 6:110-118(2005). RN [13] RP SUMOYLATION, AND MUTAGENESIS OF LYS-43 AND LYS-459. RX PubMed=16990542; DOI=10.1126/science.1128406; RA Alkuraya F.S., Saadi I., Lund J.J., Turbe-Doan A., Morton C.C., Maas R.L.; RT "SUMO1 haploinsufficiency leads to cleft lip and palate."; RL Science 313:1751-1751(2006). RN [14] 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). RN [15] RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RP H2AX. RX PubMed=19234442; DOI=10.1038/nature07849; RA Cook P.J., Ju B.G., Telese F., Wang X., Glass C.K., Rosenfeld M.G.; RT "Tyrosine dephosphorylation of H2AX modulates apoptosis and survival RT decisions."; RL Nature 458:591-596(2009). 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). Tyrosine phosphatase that dephosphorylates 'Tyr-142' CC of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the CC recruitment of DNA repair complexes containing MDC1. 'Tyr-142' CC phosphorylation of histone H2AX plays a central role in DNA repair and CC acts as a mark that distinguishes between apoptotic and repair CC responses to genotoxic stress (PubMed:19234442). Its function as CC histone phosphatase may contribute to its function in transcription CC regulation during organogenesis (PubMed:14628042). Also has phosphatase CC activity with proteins phosphorylated on Ser and Thr residues (in CC vitro). Required for normal embryonic development of the craniofacial CC and trunk skeleton, kidneys and ears (PubMed:10471511). Together with CC SIX1, it plays an important role in hypaxial muscle development; in CC this it is functionally redundant with EYA2 (PubMed:17098221). CC {ECO:0000269|PubMed:10471511, ECO:0000269|PubMed:10490620, CC ECO:0000269|PubMed:14628042, ECO:0000269|PubMed:17098221, CC ECO:0000269|PubMed:19234442}. CC -!- CATALYTIC ACTIVITY: CC Reaction=O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978; EC=3.1.3.48; CC Evidence={ECO:0000269|PubMed:14628052}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83421; EC=3.1.3.16; CC Evidence={ECO:0000269|PubMed:14628052}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:61977; EC=3.1.3.16; 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 H2AX in response to DNA damage. Interacts with SIX3; promotes EYA1 CC translocation to the nucleus. {ECO:0000269|PubMed:10490620, CC ECO:0000269|PubMed:16024294, ECO:0000269|PubMed:19234442}. CC -!- INTERACTION: CC P97767; Q9WUB0: Rbck1; NbExp=2; IntAct=EBI-1368503, EBI-6141072; CC P97767; Q91WA6: Sharpin; NbExp=4; IntAct=EBI-1368503, EBI-646097; CC P97767; Q62231: Six1; NbExp=3; IntAct=EBI-1368503, EBI-1368483; CC P97767; Q62232: Six2; NbExp=3; IntAct=EBI-1368503, EBI-1368736; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10490620}. Nucleus CC {ECO:0000269|PubMed:10490620, ECO:0000269|PubMed:19234442}. CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). CC {ECO:0000250|UniProtKB:Q99502}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P97767-1; Sequence=Displayed; CC Name=2; CC IsoId=P97767-2; Sequence=VSP_001487, VSP_001488; CC -!- TISSUE SPECIFICITY: Extensively expressed in cranial placodes, CC branchial arches, CNS and developing eye and nose. CC {ECO:0000269|PubMed:9006082}. CC -!- PTM: Sumoylated with SUMO1. {ECO:0000269|PubMed:16990542}. CC -!- DISEASE: Note=A spontaneous mutation leading to decreased Eya1 CC expression gives rise to the Eya1-bor phenotype. It is characterized by CC circling behavior and deafness, due to gross morphological CC abnormalities of the inner ear, and dysmorphic or missing kidneys. This CC autosomal recessive trait resembles human branchio-oto-renal (BOR) CC syndrome. {ECO:0000269|PubMed:10072433}. CC -!- DISRUPTION PHENOTYPE: Complete perinatal lethality in homozygotes, due CC to severe craniofacial and skeletal defects, combined with an absence CC of thymus, kidneys, parotid glands and ears. Mice present multiple CC skeletal defects in skull, neck, rib and pelvic girdle, but no major CC defects in muscle development. Otic anomalies involve the inner, middle CC and outer ears, with malformed auricles and eardrums, malformations of CC the incus, malleus, and stapes, while the tympanic cavity never formed. CC Likewise, mice display an absence of inner ear structures. CC Heterozygotes present milder symptoms with low penetrance, including CC renal defects, similar to human BOR (branchio-oto-renal) syndrome. CC Increased apoptosis and loss of renal tubules seen in the developing CC kidney with increased immunostaining for 'Ser-139' phosphorylated H2AX. CC Mice lacking both Six1 and Eya1 show defects in kidney development, CC complete absence of hypaxial muscle, severe reduction in epaxial muscle CC and a 5-10-fold by volume smaller pituarity than the wild-type gland. CC Mice lacking both Eya1 and Eya2 display complete embryonic lethality, CC due to severe defects in muscle development, including the absence of a CC diaphragm and of ventral hypaxial muscles of the trunk and the complete CC absence of muscles in forelimbs and hindlimbs, similar to the phenotype CC of mice lacking both Six1 and Six4. While Six1 is normally expressed in CC these mice, it does not active transcription from cognate promoter CC elements, and does not activate transcription of Pax3. CC {ECO:0000269|PubMed:10471511, ECO:0000269|PubMed:14628042, CC ECO:0000269|PubMed:17098221, ECO:0000269|PubMed:19234442}. CC -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily. EYA family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB48017.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U61110; AAB48017.1; ALT_FRAME; mRNA. DR EMBL; Y10263; CAA71312.1; -; Genomic_DNA. DR EMBL; AC119875; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC156988; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH466536; EDL14327.1; -; Genomic_DNA. DR EMBL; AF097544; AAD19355.1; -; Genomic_DNA. DR EMBL; AJ007995; CAA07818.1; -; mRNA. DR CCDS; CCDS78545.1; -. [P97767-1] DR RefSeq; NP_001297388.1; NM_001310459.2. [P97767-1] DR RefSeq; XP_017170837.1; XM_017315348.3. [P97767-1] DR AlphaFoldDB; P97767; -. DR SMR; P97767; -. DR BioGRID; 199559; 16. DR CORUM; P97767; -. DR FunCoup; P97767; 1145. DR IntAct; P97767; 5. DR STRING; 10090.ENSMUSP00000027066; -. DR GlyGen; P97767; 1 site. DR iPTMnet; P97767; -. DR PhosphoSitePlus; P97767; -. DR PaxDb; 10090-ENSMUSP00000027066; -. DR ProteomicsDB; 275954; -. [P97767-1] DR ProteomicsDB; 275955; -. [P97767-2] DR Antibodypedia; 25098; 222 antibodies from 31 providers. DR DNASU; 14048; -. DR Ensembl; ENSMUST00000027066.13; ENSMUSP00000027066.7; ENSMUSG00000025932.15. [P97767-1] DR Ensembl; ENSMUST00000190337.7; ENSMUSP00000141112.2; ENSMUSG00000025932.15. [P97767-1] DR GeneID; 14048; -. DR KEGG; mmu:14048; -. DR UCSC; uc007aiw.1; mouse. [P97767-1] DR AGR; MGI:109344; -. DR CTD; 2138; -. DR MGI; MGI:109344; Eya1. DR VEuPathDB; HostDB:ENSMUSG00000025932; -. DR eggNOG; KOG3107; Eukaryota. DR GeneTree; ENSGT00950000182978; -. DR InParanoid; P97767; -. DR OMA; QCASANN; -. DR OrthoDB; 167668at2759; -. DR PhylomeDB; P97767; -. DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks. DR SABIO-RK; P97767; -. DR BioGRID-ORCS; 14048; 2 hits in 102 CRISPR screens. DR PRO; PR:P97767; -. DR Proteomes; UP000000589; Chromosome 1. DR RNAct; P97767; protein. DR Bgee; ENSMUSG00000025932; Expressed in epithelium of cochlear duct and 246 other cell types or tissues. DR ExpressionAtlas; P97767; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0016604; C:nuclear body; ISO:GO_Central. DR GO; GO:0005654; C:nucleoplasm; ISO:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0032993; C:protein-DNA complex; IDA:UniProtKB. DR GO; GO:0140793; F:histone H2AXY142 phosphatase activity; ISS:UniProtKB. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; EXP:UniProtKB. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:MGI. DR GO; GO:0003723; F:RNA binding; IDA:MGI. DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI. DR GO; GO:0035909; P:aorta morphogenesis; IMP:MGI. DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IGI:MGI. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0045165; P:cell fate commitment; IMP:MGI. DR GO; GO:0090103; P:cochlea morphogenesis; IMP:MGI. DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB. DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IMP:MGI. DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI. DR GO; GO:0007501; P:mesodermal cell fate specification; IDA:UniProtKB. DR GO; GO:0001656; P:metanephros development; IMP:MGI. 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; IMP:MGI. DR GO; GO:0048665; P:neuron fate specification; IGI:MGI. DR GO; GO:0071599; P:otic vesicle development; IGI:MGI. DR GO; GO:0071600; P:otic vesicle morphogenesis; IMP:MGI. DR GO; GO:0042473; P:outer ear morphogenesis; IMP:MGI. DR GO; GO:0003151; P:outflow tract morphogenesis; IMP:MGI. DR GO; GO:0007389; P:pattern specification process; IMP:MGI. DR GO; GO:0060037; P:pharyngeal system development; IMP:MGI. DR GO; GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI. DR GO; GO:0072513; P:positive regulation of secondary heart field cardioblast proliferation; IGI:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI. DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI. DR GO; GO:0016925; P:protein sumoylation; IDA:UniProtKB. DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:MGI. DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB. DR GO; GO:0048752; P:semicircular canal morphogenesis; IMP:MGI. DR GO; GO:0014706; P:striated muscle tissue development; IGI:MGI. DR GO; GO:0001657; P:ureteric bud development; IGI:MGI. DR CDD; cd02601; HAD_Eya; 1. DR FunFam; 3.40.50.12350:FF:000001; Eyes absent homolog; 1. DR Gene3D; 3.40.50.12350; -; 1. DR InterPro; IPR028472; EYA. DR InterPro; IPR006545; EYA_dom. DR InterPro; IPR042577; EYA_dom_metazoan. DR InterPro; IPR038102; EYA_dom_sf. DR NCBIfam; TIGR01658; EYA-cons_domain; 1. DR PANTHER; PTHR10190; EYES ABSENT; 1. DR PANTHER; PTHR10190:SF11; EYES ABSENT HOMOLOG 1; 1. DR Pfam; PF00702; Hydrolase; 1. DR SFLD; SFLDG01129; C1.5:_HAD__Beta-PGM__Phosphata; 1. DR SFLD; SFLDS00003; Haloacid_Dehalogenase; 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; Ubl conjugation. FT CHAIN 1..591 FT /note="Protein phosphatase EYA1" FT /id="PRO_0000218644" FT REGION 1..95 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 150..169 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 239..319 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 8..23 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 28..53 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 56..75 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 78..87 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 240..252 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 253..286 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 287..302 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 327 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:O00167" FT ACT_SITE 329 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:O00167" FT BINDING 327 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:O00167" FT BINDING 329 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:O00167" FT BINDING 555 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:O00167" FT VAR_SEQ 1..41 FT /note="MEMQDLTSPHSRLSGSSESPSGPKLDSSHINSTSMTPNGTE -> MLLFPQV FT A (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_001487" FT VAR_SEQ 140..144 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_001488" FT MUTAGEN 43 FT /note="K->R: Markedly reduced sumoylation; when associated FT with R-459." FT /evidence="ECO:0000269|PubMed:16990542" FT MUTAGEN 459 FT /note="K->R: Markedly reduced sumoylation; when associated FT with R-43." FT /evidence="ECO:0000269|PubMed:16990542" FT CONFLICT 117 FT /note="M -> V (in Ref. 2; CAA71312)" FT /evidence="ECO:0000305" FT CONFLICT 163 FT /note="L -> F (in Ref. 2; CAA71312)" FT /evidence="ECO:0000305" FT CONFLICT 324..325 FT /note="FI -> LL (in Ref. 1; AAB48017)" FT /evidence="ECO:0000305" FT CONFLICT 405 FT /note="T -> R (in Ref. 1; AAB48017)" FT /evidence="ECO:0000305" FT CONFLICT 450 FT /note="N -> K (in Ref. 1; AAB48017)" FT /evidence="ECO:0000305" FT CONFLICT 505 FT /note="I -> S (in Ref. 1; AAB48017)" FT /evidence="ECO:0000305" FT CONFLICT 535 FT /note="S -> G (in Ref. 2; CAA71312)" FT /evidence="ECO:0000305" FT CONFLICT 539 FT /note="R -> G (in Ref. 2; CAA71312)" FT /evidence="ECO:0000305" FT CONFLICT 548 FT /note="V -> L (in Ref. 2; CAA71312)" FT /evidence="ECO:0000305" FT CONFLICT 551..552 FT /note="VV -> LL (in Ref. 1; AAB48017)" FT /evidence="ECO:0000305" FT CONFLICT 559 FT /note="E -> K (in Ref. 2; CAA71312)" FT /evidence="ECO:0000305" SQ SEQUENCE 591 AA; 64324 MW; D31F71852FBDC76C CRC64; MEMQDLTSPH SRLSGSSESP SGPKLDSSHI NSTSMTPNGT EVKTEPMSSS EIASTAADGS LDSFSGSALG SSSFSPRPAH PFSPPQIYPS KSYPHILPTP SSQTMAAYGQ TQFTTGMQQA TAYATYPQPG QPYGISSYGA LWAGIKTESG LSQSQSPGQT GFLSYGTSFG TPQPGQAPYS YQMQGSSFTT SSGLYSGNNS LTNSSGFNSS QQDYPSYPGF GQGQYAQYYN SSPYPAHYMT SSNTSPTTPS TNATYQLQEP PSGVTSQAVT DPTAEYSTIH SPSTPIKETD SERLRRGSDG KSRGRGRRNN NPSPPPDSDL ERVFIWDLDE TIIVFHSLLT GSYANRYGRD PPTSVSLGLR MEEMIFNLAD THLFFNDLEE CDQVHIDDVS SDDNGQDLST YNFGTDGFPA AATSANLCLA TGVRGGVDWM RKLAFRYRRV KEIYNTYKNN VGGLLGPAKR EAWLQLRAEI EALTDSWLTL ALKALSLIHS RTNCVNILVT TTQLIPALAK VLLYGLGIVF PIENIYSATK IGKESCFERI IQRFGRKVVY VVIGDGVEEE QGAKKHAMPF WRVSSHSDLM ALHHALELEY L //