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Protein

Eyes absent homolog 1

Gene

Eya1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5. Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis. Has also phosphatase activity with proteins phosphorylated on Ser and Thr residues (in vitro). Required for normal embryonic development of the craniofacial and trunk skeleton, kidneys and ears. Together with SIX1, it plays an important role in hypaxial muscle development; in this it is functionally redundant with EYA2.4 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Cofactori

Mg2+CuratedNote: Binds 1 Mg2+ ion per subunit.Curated

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei327 – 3271NucleophileBy similarity
Metal bindingi327 – 3271MagnesiumBy similarity
Active sitei329 – 3291Proton donorBy similarity
Metal bindingi329 – 3291MagnesiumBy similarity
Metal bindingi555 – 5551MagnesiumBy similarity

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • protein tyrosine phosphatase activity Source: MGI
  • RNA binding Source: MGI

GO - Biological processi

  • anatomical structure development Source: MGI
  • aorta morphogenesis Source: MGI
  • branching involved in ureteric bud morphogenesis Source: MGI
  • cell fate commitment Source: MGI
  • cellular protein localization Source: MGI
  • cochlea morphogenesis Source: MGI
  • double-strand break repair Source: UniProtKB
  • embryonic skeletal system morphogenesis Source: MGI
  • establishment of mitotic spindle orientation Source: MGI
  • establishment or maintenance of apical/basal cell polarity Source: MGI
  • histone dephosphorylation Source: UniProtKB
  • inner ear morphogenesis Source: MGI
  • lung epithelial cell differentiation Source: MGI
  • mesodermal cell fate specification Source: UniProtKB
  • metanephros development Source: MGI
  • middle ear morphogenesis Source: MGI
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  • neuron fate specification Source: MGI
  • organ morphogenesis Source: MGI
  • otic vesicle development Source: MGI
  • otic vesicle morphogenesis Source: MGI
  • outer ear morphogenesis Source: MGI
  • outflow tract morphogenesis Source: MGI
  • pattern specification process Source: MGI
  • pharyngeal system development Source: MGI
  • positive regulation of DNA repair Source: UniProtKB
  • positive regulation of epithelial cell proliferation Source: MGI
  • positive regulation of Notch signaling pathway Source: MGI
  • positive regulation of secondary heart field cardioblast proliferation Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • protein dephosphorylation Source: MGI
  • protein sumoylation Source: UniProtKB
  • regulation of neuron differentiation Source: MGI
  • response to ionizing radiation Source: UniProtKB
  • semicircular canal morphogenesis Source: MGI
  • striated muscle tissue development Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
  • ureteric bud development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Developmental protein, Hydrolase, Protein phosphatase

Keywords - Biological processi

DNA damage, DNA repair, Transcription, Transcription regulation

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

SABIO-RKP97767.

Names & Taxonomyi

Protein namesi
Recommended name:
Eyes absent homolog 1 (EC:3.1.3.16, EC:3.1.3.48)
Gene namesi
Name:Eya1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:109344. Eya1.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Localizes at sites of DNA damage at double-strand breaks (DSBs).By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nucleus Source: UniProtKB
  • protein complex Source: UniProtKB
  • protein-DNA complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

A spontaneous mutation leading to decreased Eya1 expression gives rise to the Eya1-bor phenotype. It is characterized by circling behavior and deafness, due to gross morphological abnormalities of the inner ear, and dysmorphic or missing kidneys. This autosomal recessive trait resembles human branchio-oto-renal (BOR) syndrome.

Disruption phenotypei

Complete perinatal lethality in homozygotes, due to severe craniofacial and skeletal defects, combined with an absence of thymus, kidneys, parotid glands and ears. Mice present multiple skeletal defects in skull, neck, rib and pelvic girdle, but no major defects in muscle development. Otic anomalies involve the inner, middle and outer ears, with malformed auricles and eardrums, malformations of the incus, malleus, and stapes, while the tympanic cavity never formed. Likewise, mice display an absence of inner ear structures. Heterozygotes present milder symptoms with low penetrance, including renal defects, similar to human BOR (branchio-oto-renal) syndrome. Increased apoptosis and loss of renal tubules seen in the developing kidney with increased immunostaining for 'Ser-139' phosphorylated H2AX. Mice lacking both Six1 and Eya1 show defects in kidney development, complete absence of hypaxial muscle, severe reduction in epaxial muscle and a 5-10-fold by volume smaller pituarity than the wild-type gland. Mice lacking both Eya1 and Eya2 display complete embryonic lethality, due to severe defects in muscle development, including the absence of a diaphragm and of ventral hypaxial muscles of the trunk and the complete absence of muscles in forelimbs and hindlimbs, similar to the phenotype of mice lacking both Six1 and Six4. While Six1 is normally expressed in these mice, it does not active transcription from cognate promoter elements, and does not activate transcription of Pax3.4 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi43 – 431K → R: Markedly reduced sumoylation; when associated with R-459. 1 Publication
Mutagenesisi459 – 4591K → R: Markedly reduced sumoylation; when associated with R-43. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 591591Eyes absent homolog 1PRO_0000218644Add
BLAST

Post-translational modificationi

Sumoylated with SUMO1.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

PRIDEiP97767.

PTM databases

PhosphoSiteiP97767.

Expressioni

Tissue specificityi

Extensively expressed in cranial placodes, branchial arches, CNS and developing eye and nose.

Gene expression databases

CleanExiMM_EYA1.
ExpressionAtlasiP97767. baseline and differential.

Interactioni

Subunit structurei

Probably interacts with SIX2, SIX4 and SIX5. Interacts with H2AX in response to DNA damage. Interacts with SIX3; promotes EYA1 translocation to the nucleus.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Rbck1Q9WUB02EBI-1368503,EBI-6141072
SharpinQ91WA64EBI-1368503,EBI-646097
Six1Q622313EBI-1368503,EBI-1368483
Six2Q622323EBI-1368503,EBI-1368736

Protein-protein interaction databases

BioGridi199559. 11 interactions.
IntActiP97767. 4 interactions.
STRINGi10090.ENSMUSP00000126383.

Structurei

3D structure databases

ProteinModelPortaliP97767.
SMRiP97767. Positions 321-591.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG297494.
GeneTreeiENSGT00390000008860.
HOGENOMiHOG000293149.
HOVERGENiHBG002447.
InParanoidiP97767.
OMAiGQPYGIS.
TreeFamiTF319337.

Family and domain databases

InterProiIPR006545. EYA_dom.
IPR028472. EYA_fam.
IPR028471. Eyes_absent_h1.
[Graphical view]
PANTHERiPTHR10190. PTHR10190. 1 hit.
PTHR10190:SF11. PTHR10190:SF11. 1 hit.
TIGRFAMsiTIGR01658. EYA-cons_domain. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P97767-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEMQDLTSPH SRLSGSSESP SGPKLDSSHI NSTSMTPNGT EVKTEPMSSS
60 70 80 90 100
EIASTAADGS LDSFSGSALG SSSFSPRPAH PFSPPQIYPS KSYPHILPTP
110 120 130 140 150
SSQTMAAYGQ TQFTTGMQQA TAYATYPQPG QPYGISSYGA LWAGIKTESG
160 170 180 190 200
LSQSQSPGQT GFLSYGTSFG TPQPGQAPYS YQMQGSSFTT SSGLYSGNNS
210 220 230 240 250
LTNSSGFNSS QQDYPSYPGF GQGQYAQYYN SSPYPAHYMT SSNTSPTTPS
260 270 280 290 300
TNATYQLQEP PSGVTSQAVT DPTAEYSTIH SPSTPIKETD SERLRRGSDG
310 320 330 340 350
KSRGRGRRNN NPSPPPDSDL ERVFIWDLDE TIIVFHSLLT GSYANRYGRD
360 370 380 390 400
PPTSVSLGLR MEEMIFNLAD THLFFNDLEE CDQVHIDDVS SDDNGQDLST
410 420 430 440 450
YNFGTDGFPA AATSANLCLA TGVRGGVDWM RKLAFRYRRV KEIYNTYKNN
460 470 480 490 500
VGGLLGPAKR EAWLQLRAEI EALTDSWLTL ALKALSLIHS RTNCVNILVT
510 520 530 540 550
TTQLIPALAK VLLYGLGIVF PIENIYSATK IGKESCFERI IQRFGRKVVY
560 570 580 590
VVIGDGVEEE QGAKKHAMPF WRVSSHSDLM ALHHALELEY L
Length:591
Mass (Da):64,324
Last modified:October 3, 2012 - v3
Checksum:iD31F71852FBDC76C
GO
Isoform 2 (identifier: P97767-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-41: MEMQDLTSPHSRLSGSSESPSGPKLDSSHINSTSMTPNGTE → MLLFPQVA
     140-144: Missing.

Note: No experimental confirmation available.
Show »
Length:553
Mass (Da):60,425
Checksum:i659F016F829159A6
GO

Sequence cautioni

The sequence AAB48017.1 differs from that shown. Reason: Frameshift at positions 349 and 360. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti117 – 1171M → V in CAA71312 (PubMed:9020840).Curated
Sequence conflicti163 – 1631L → F in CAA71312 (PubMed:9020840).Curated
Sequence conflicti324 – 3252FI → LL in AAB48017 (PubMed:9006082).Curated
Sequence conflicti405 – 4051T → R in AAB48017 (PubMed:9006082).Curated
Sequence conflicti450 – 4501N → K in AAB48017 (PubMed:9006082).Curated
Sequence conflicti505 – 5051I → S in AAB48017 (PubMed:9006082).Curated
Sequence conflicti535 – 5351S → G in CAA71312 (PubMed:9020840).Curated
Sequence conflicti539 – 5391R → G in CAA71312 (PubMed:9020840).Curated
Sequence conflicti548 – 5481V → L in CAA71312 (PubMed:9020840).Curated
Sequence conflicti551 – 5522VV → LL in AAB48017 (PubMed:9006082).Curated
Sequence conflicti559 – 5591E → K in CAA71312 (PubMed:9020840).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4141MEMQD…PNGTE → MLLFPQVA in isoform 2. CuratedVSP_001487Add
BLAST
Alternative sequencei140 – 1445Missing in isoform 2. CuratedVSP_001488

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U61110 mRNA. Translation: AAB48017.1. Frameshift.
Y10263 Genomic DNA. Translation: CAA71312.1.
AC119875 Genomic DNA. No translation available.
AC156988 Genomic DNA. No translation available.
CH466536 Genomic DNA. Translation: EDL14327.1.
AF097544 Genomic DNA. Translation: AAD19355.1.
AJ007995 mRNA. Translation: CAA07818.1.
RefSeqiXP_011236647.1. XM_011238345.1. [P97767-1]
UniGeneiMm.250185.

Genome annotation databases

EnsembliENSMUST00000027066; ENSMUSP00000027066; ENSMUSG00000025932. [P97767-1]
ENSMUST00000190337; ENSMUSP00000141112; ENSMUSG00000025932. [P97767-1]
GeneIDi14048.
UCSCiuc007aiw.1. mouse. [P97767-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U61110 mRNA. Translation: AAB48017.1. Frameshift.
Y10263 Genomic DNA. Translation: CAA71312.1.
AC119875 Genomic DNA. No translation available.
AC156988 Genomic DNA. No translation available.
CH466536 Genomic DNA. Translation: EDL14327.1.
AF097544 Genomic DNA. Translation: AAD19355.1.
AJ007995 mRNA. Translation: CAA07818.1.
RefSeqiXP_011236647.1. XM_011238345.1. [P97767-1]
UniGeneiMm.250185.

3D structure databases

ProteinModelPortaliP97767.
SMRiP97767. Positions 321-591.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199559. 11 interactions.
IntActiP97767. 4 interactions.
STRINGi10090.ENSMUSP00000126383.

PTM databases

PhosphoSiteiP97767.

Proteomic databases

PRIDEiP97767.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000027066; ENSMUSP00000027066; ENSMUSG00000025932. [P97767-1]
ENSMUST00000190337; ENSMUSP00000141112; ENSMUSG00000025932. [P97767-1]
GeneIDi14048.
UCSCiuc007aiw.1. mouse. [P97767-1]

Organism-specific databases

MGIiMGI:109344. Eya1.

Phylogenomic databases

eggNOGiNOG297494.
GeneTreeiENSGT00390000008860.
HOGENOMiHOG000293149.
HOVERGENiHBG002447.
InParanoidiP97767.
OMAiGQPYGIS.
TreeFamiTF319337.

Enzyme and pathway databases

SABIO-RKP97767.

Miscellaneous databases

PROiP97767.
SOURCEiSearch...

Gene expression databases

CleanExiMM_EYA1.
ExpressionAtlasiP97767. baseline and differential.

Family and domain databases

InterProiIPR006545. EYA_dom.
IPR028472. EYA_fam.
IPR028471. Eyes_absent_h1.
[Graphical view]
PANTHERiPTHR10190. PTHR10190. 1 hit.
PTHR10190:SF11. PTHR10190:SF11. 1 hit.
TIGRFAMsiTIGR01658. EYA-cons_domain. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for expression in lens and nasal placode."
    Xu P.-X., Woo I., Her H., Beier D.R., Maas R.L.
    Development 124:219-231(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Embryo.
  2. "A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family."
    Abdelhak S., Kalatzis V., Heilig R., Compain S., Samson D., Vincent C., Weil D., Cruaud C., Sahly I., Leibovici M., Bitner-Glindzicz M., Francis M., Lacombe D., Vigneron J., Charachon R., Boven K., Bedbeder P., van Regemorter N., Weissenbach J., Petit C.
    Nat. Genet. 15:157-164(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
    Strain: CB/20.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "Inner ear and kidney anomalies caused by IAP insertion in an intron of the Eya1 gene in a mouse model of BOR syndrome."
    Johnson K.R., Cook S.A., Erway L.C., Matthews A.N., Sanford L.P., Paradies N.E., Friedman R.A.
    Hum. Mol. Genet. 8:645-653(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 276-321, DISEASE.
    Strain: 129/SvJ.
  6. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 431-549.
    Tissue: Embryo.
  7. "Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya."
    Ohto H., Kamada S., Tago K., Tominaga S., Ozaki H., Sato S., Kawakami K.
    Mol. Cell. Biol. 19:6815-6824(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SIX2; SIX4 AND SIX5, SUBCELLULAR LOCATION.
  8. "Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia."
    Xu P.X., Adams J., Peters H., Brown M.C., Heaney S., Maas R.
    Nat. Genet. 23:113-117(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  9. "Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis."
    Li X., Oghi K.A., Zhang J., Krones A., Bush K.T., Glass C.K., Nigam S.K., Aggarwal A.K., Maas R., Rose D.W., Rosenfeld M.G.
    Nature 426:247-254(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE.
  10. Cited for: CATALYTIC ACTIVITY.
  11. "Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal placode induction."
    Purcell P., Oliver G., Mardon G., Donner A.L., Maas R.L.
    Gene Expr. Patterns 6:110-118(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SIX3.
  12. "SUMO1 haploinsufficiency leads to cleft lip and palate."
    Alkuraya F.S., Saadi I., Lund J.J., Turbe-Doan A., Morton C.C., Maas R.L.
    Science 313:1751-1751(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION, MUTAGENESIS OF LYS-43 AND LYS-459.
  13. "Eya1 and Eya2 proteins are required for hypaxial somitic myogenesis in the mouse embryo."
    Grifone R., Demignon J., Giordani J., Niro C., Souil E., Bertin F., Laclef C., Xu P.X., Maire P.
    Dev. Biol. 302:602-616(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  14. "Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions."
    Cook P.J., Ju B.G., Telese F., Wang X., Glass C.K., Rosenfeld M.G.
    Nature 458:591-596(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH H2AX.

Entry informationi

Entry nameiEYA1_MOUSE
AccessioniPrimary (citable) accession number: P97767
Secondary accession number(s): G5E864, O08818
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 3, 2012
Last modified: July 22, 2015
This is version 128 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.