Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P97767 (EYA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Eyes absent homolog 1

EC=3.1.3.16
EC=3.1.3.48
Gene names
Name:Eya1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length591 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.8 Ref.9 Ref.14

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.9 Ref.11

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate. Ref.9 Ref.11

Cofactor

Binds 1 Mg2+ ion per subunit Probable.

Subunit structure

Probably interacts with SIX2, SIX4 and SIX5. Interacts with H2AX in response to DNA damage. Ref.7 Ref.14

Subcellular location

Cytoplasm. Nucleus. Note: Localizes at sites of DNA damage at double-strand breaks (DSBs) By similarity. Ref.7 Ref.14

Tissue specificity

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

Post-translational modification

Sumoylated with SUMO1. Ref.12

Involvement in disease

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. Ref.5

Disruption phenotype

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. Ref.8 Ref.9 Ref.13 Ref.14

Sequence similarities

Belongs to the HAD-like hydrolase superfamily. EYA family.

Sequence caution

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

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandMagnesium
Metal-binding
   Molecular functionActivator
Chromatin regulator
Developmental protein
Hydrolase
Protein phosphatase
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanatomical structure development

Inferred from genetic interaction PubMed 16530750. Source: MGI

aorta morphogenesis

Inferred from mutant phenotype PubMed 21364285. Source: MGI

branching involved in ureteric bud morphogenesis

Inferred from genetic interaction PubMed 12783782. Source: MGI

cell fate commitment

Inferred from mutant phenotype PubMed 15817220PubMed 16018995. Source: MGI

cellular protein localization

Inferred from mutant phenotype PubMed 21385765. Source: MGI

cochlea morphogenesis

Inferred from mutant phenotype Ref.5. Source: MGI

double-strand break repair

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic skeletal system morphogenesis

Inferred from mutant phenotype Ref.8. Source: MGI

establishment of mitotic spindle orientation

Inferred from mutant phenotype PubMed 21385765. Source: MGI

establishment or maintenance of apical/basal cell polarity

Inferred from mutant phenotype PubMed 21385765. Source: MGI

histone dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

inner ear morphogenesis

Inferred from mutant phenotype Ref.8PubMed 15817220. Source: MGI

lung epithelial cell differentiation

Inferred from genetic interaction PubMed 21385765. Source: MGI

mesodermal cell fate specification

Inferred from direct assay PubMed 17785448. Source: UniProtKB

metanephros development

Inferred from mutant phenotype Ref.5PubMed 16018995. Source: MGI

middle ear morphogenesis

Inferred from mutant phenotype Ref.8. Source: MGI

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from mutant phenotype PubMed 15817220. Source: MGI

neuron fate specification

Inferred from genetic interaction PubMed 22513373. Source: MGI

organ morphogenesis

Inferred from mutant phenotype PubMed 12070080. Source: MGI

otic vesicle development

Inferred from genetic interaction PubMed 22513373. Source: MGI

otic vesicle morphogenesis

Inferred from mutant phenotype PubMed 16916509. Source: MGI

outer ear morphogenesis

Inferred from mutant phenotype Ref.8. Source: MGI

outflow tract morphogenesis

Inferred from mutant phenotype PubMed 21364285. Source: MGI

pattern specification process

Inferred from mutant phenotype PubMed 16916509. Source: MGI

pharyngeal system development

Inferred from mutant phenotype PubMed 21364285. Source: MGI

positive regulation of DNA repair

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of Notch signaling pathway

Inferred from mutant phenotype PubMed 21385765. Source: MGI

positive regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 16916509. Source: MGI

positive regulation of secondary heart field cardioblast proliferation

Inferred from genetic interaction PubMed 21364285. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 21364285PubMed 22513373. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 17785448. Source: UniProtKB

protein dephosphorylation

Inferred from direct assay Ref.11. Source: MGI

protein sumoylation

Inferred from direct assay Ref.12. Source: UniProtKB

regulation of neuron differentiation

Inferred from mutant phenotype PubMed 15496442. Source: MGI

response to ionizing radiation

Inferred from sequence or structural similarity. Source: UniProtKB

semicircular canal morphogenesis

Inferred from mutant phenotype Ref.5. Source: MGI

striated muscle tissue development

Inferred from genetic interaction Ref.13. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

ureteric bud development

Inferred from genetic interaction PubMed 16018995. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 16024294. Source: MGI

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

protein complex

Inferred from direct assay PubMed 17785448. Source: UniProtKB

protein-DNA complex

Inferred from direct assay PubMed 17785448. Source: UniProtKB

   Molecular_functionRNA binding

Inferred from direct assay PubMed 21936910. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 11734542PubMed 15141091PubMed 20956555. Source: IntAct

protein tyrosine phosphatase activity

Inferred from direct assay Ref.11PubMed 21385765. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P97767-1)

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.
Isoform 2 (identifier: P97767-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-41: MEMQDLTSPHSRLSGSSESPSGPKLDSSHINSTSMTPNGTE → MLLFPQVA
     140-144: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 591591Eyes absent homolog 1
PRO_0000218644

Sites

Active site3271Nucleophile By similarity
Active site3291Proton donor By similarity
Metal binding3271Magnesium By similarity
Metal binding3291Magnesium By similarity
Metal binding5551Magnesium By similarity

Natural variations

Alternative sequence1 – 4141MEMQD…PNGTE → MLLFPQVA in isoform 2.
VSP_001487
Alternative sequence140 – 1445Missing in isoform 2.
VSP_001488

Experimental info

Mutagenesis431K → R: Markedly reduced sumoylation; when associated with R-459. Ref.12
Mutagenesis4591K → R: Markedly reduced sumoylation; when associated with R-43. Ref.12
Sequence conflict1171M → V in CAA71312. Ref.2
Sequence conflict1631L → F in CAA71312. Ref.2
Sequence conflict324 – 3252FI → LL in AAB48017. Ref.1
Sequence conflict4051T → R in AAB48017. Ref.1
Sequence conflict4501N → K in AAB48017. Ref.1
Sequence conflict5051I → S in AAB48017. Ref.1
Sequence conflict5351S → G in CAA71312. Ref.2
Sequence conflict5391R → G in CAA71312. Ref.2
Sequence conflict5481V → L in CAA71312. Ref.2
Sequence conflict551 – 5522VV → LL in AAB48017. Ref.1
Sequence conflict5591E → K in CAA71312. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 3, 2012. Version 3.
Checksum: D31F71852FBDC76C

FASTA59164,324
        10         20         30         40         50         60 
MEMQDLTSPH SRLSGSSESP SGPKLDSSHI NSTSMTPNGT EVKTEPMSSS EIASTAADGS 

        70         80         90        100        110        120 
LDSFSGSALG SSSFSPRPAH PFSPPQIYPS KSYPHILPTP SSQTMAAYGQ TQFTTGMQQA 

       130        140        150        160        170        180 
TAYATYPQPG QPYGISSYGA LWAGIKTESG LSQSQSPGQT GFLSYGTSFG TPQPGQAPYS 

       190        200        210        220        230        240 
YQMQGSSFTT SSGLYSGNNS LTNSSGFNSS QQDYPSYPGF GQGQYAQYYN SSPYPAHYMT 

       250        260        270        280        290        300 
SSNTSPTTPS TNATYQLQEP PSGVTSQAVT DPTAEYSTIH SPSTPIKETD SERLRRGSDG 

       310        320        330        340        350        360 
KSRGRGRRNN NPSPPPDSDL ERVFIWDLDE TIIVFHSLLT GSYANRYGRD PPTSVSLGLR 

       370        380        390        400        410        420 
MEEMIFNLAD THLFFNDLEE CDQVHIDDVS SDDNGQDLST YNFGTDGFPA AATSANLCLA 

       430        440        450        460        470        480 
TGVRGGVDWM RKLAFRYRRV KEIYNTYKNN VGGLLGPAKR EAWLQLRAEI EALTDSWLTL 

       490        500        510        520        530        540 
ALKALSLIHS RTNCVNILVT TTQLIPALAK VLLYGLGIVF PIENIYSATK IGKESCFERI 

       550        560        570        580        590 
IQRFGRKVVY VVIGDGVEEE QGAKKHAMPF WRVSSHSDLM ALHHALELEY L 

« Hide

Isoform 2 [UniParc].

Checksum: 659F016F829159A6
Show »

FASTA55360,425

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"EYA4, a novel vertebrate gene related to Drosophila eyes absent."
Borsani G., DeGrandi A., Ballabio A., Bulfone A., Bernard L., Banfi S., Gattuso C., Mariani M., Dixon M., Donnai D., Metcalfe K., Winter R., Robertson M., Axton R., Brown A., van Heyningen V., Hanson I.
Hum. Mol. Genet. 8:11-23(1999) [PubMed] [Europe PMC] [Abstract]
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]Erratum
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 427:265-265(2004)
[11]"Eyes absent represents a class of protein tyrosine phosphatases."
Rayapureddi J.P., Kattamuri C., Steinmetz B.D., Frankfort B.J., Ostrin E.J., Mardon G., Hegde R.S.
Nature 426:295-298(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY.
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqXP_006495511.1. XM_006495448.1. [P97767-1]
UniGeneMm.250185.

3D structure databases

ProteinModelPortalP97767.
SMRP97767. Positions 321-591.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP97767. 4 interactions.

PTM databases

PhosphoSiteP97767.

Proteomic databases

PRIDEP97767.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000027066; ENSMUSP00000027066; ENSMUSG00000025932. [P97767-1]
GeneID14048.
KEGGmmu:14048.
UCSCuc007aiw.1. mouse.

Organism-specific databases

CTD2138.
MGIMGI:109344. Eya1.

Phylogenomic databases

eggNOGNOG297494.
GeneTreeENSGT00390000008860.
HOGENOMHOG000293149.
HOVERGENHBG002447.
InParanoidP97767.
KOK15616.
OMAGQPYGIS.
TreeFamTF319337.

Enzyme and pathway databases

SABIO-RKP97767.

Gene expression databases

ArrayExpressP97767.
CleanExMM_EYA1.
GenevestigatorP97767.

Family and domain databases

InterProIPR006545. EYA_dom.
IPR028472. EYA_fam.
IPR028471. Eyes_absent_h1.
[Graphical view]
PANTHERPTHR10190. PTHR10190. 1 hit.
PTHR10190:SF11. PTHR10190:SF11. 1 hit.
TIGRFAMsTIGR01658. EYA-cons_domain. 1 hit.
ProtoNetSearch...

Other

PROP97767.
SOURCESearch...

Entry information

Entry nameEYA1_MOUSE
AccessionPrimary (citable) accession number: P97767
Secondary accession number(s): G5E864, O08818
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 3, 2012
Last modified: June 11, 2014
This is version 120 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot