SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P97767

- EYA1_MOUSE

UniProt

P97767 - EYA1_MOUSE

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein
Eyes absent homolog 1
Gene
Eya1
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.2 Publications
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.2 Publications

Cofactori

Binds 1 Mg2+ ion per subunit Inferred.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei327 – 3271Nucleophile By similarity
Metal bindingi327 – 3271Magnesium By similarity
Active sitei329 – 3291Proton donor By similarity
Metal bindingi329 – 3291Magnesium By similarity
Metal bindingi555 – 5551Magnesium By similarity

GO - Molecular functioni

  1. RNA binding Source: MGI
  2. metal ion binding Source: UniProtKB-KW
  3. protein binding Source: IntAct
  4. protein tyrosine phosphatase activity Source: MGI
Complete GO annotation...

GO - Biological processi

  1. anatomical structure development Source: MGI
  2. aorta morphogenesis Source: MGI
  3. branching involved in ureteric bud morphogenesis Source: MGI
  4. cell fate commitment Source: MGI
  5. cellular protein localization Source: MGI
  6. cochlea morphogenesis Source: MGI
  7. double-strand break repair Source: UniProtKB
  8. embryonic skeletal system morphogenesis Source: MGI
  9. establishment of mitotic spindle orientation Source: MGI
  10. establishment or maintenance of apical/basal cell polarity Source: MGI
  11. histone dephosphorylation Source: UniProtKB
  12. inner ear morphogenesis Source: MGI
  13. lung epithelial cell differentiation Source: MGI
  14. mesodermal cell fate specification Source: UniProtKB
  15. metanephros development Source: MGI
  16. middle ear morphogenesis Source: MGI
  17. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  18. neuron fate specification Source: MGI
  19. organ morphogenesis Source: MGI
  20. otic vesicle development Source: MGI
  21. otic vesicle morphogenesis Source: MGI
  22. outer ear morphogenesis Source: MGI
  23. outflow tract morphogenesis Source: MGI
  24. pattern specification process Source: MGI
  25. pharyngeal system development Source: MGI
  26. positive regulation of DNA repair Source: UniProtKB
  27. positive regulation of Notch signaling pathway Source: MGI
  28. positive regulation of epithelial cell proliferation Source: MGI
  29. positive regulation of secondary heart field cardioblast proliferation Source: MGI
  30. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  31. positive regulation of transcription, DNA-templated Source: UniProtKB
  32. protein dephosphorylation Source: MGI
  33. protein sumoylation Source: UniProtKB
  34. regulation of neuron differentiation Source: MGI
  35. response to ionizing radiation Source: UniProtKB
  36. semicircular canal morphogenesis Source: MGI
  37. striated muscle tissue development Source: MGI
  38. transcription, DNA-templated Source: UniProtKB-KW
  39. 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: 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.2 Publications

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. nucleus Source: UniProtKB
  3. protein complex Source: UniProtKB
  4. 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.1 Publication

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 1
PRO_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

ArrayExpressiP97767.
CleanExiMM_EYA1.
GenevestigatoriP97767.

Interactioni

Subunit structurei

Probably interacts with SIX2, SIX4 and SIX5. Interacts with H2AX in response to DNA damage.2 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

IntActiP97767. 4 interactions.

Structurei

3D structure databases

ProteinModelPortaliP97767.
SMRiP97767. Positions 321-591.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG297494.
GeneTreeiENSGT00390000008860.
HOGENOMiHOG000293149.
HOVERGENiHBG002447.
InParanoidiP97767.
KOiK15616.
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. Align

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

MEMQDLTSPH SRLSGSSESP SGPKLDSSHI NSTSMTPNGT EVKTEPMSSS    50
EIASTAADGS LDSFSGSALG SSSFSPRPAH PFSPPQIYPS KSYPHILPTP 100
SSQTMAAYGQ TQFTTGMQQA TAYATYPQPG QPYGISSYGA LWAGIKTESG 150
LSQSQSPGQT GFLSYGTSFG TPQPGQAPYS YQMQGSSFTT SSGLYSGNNS 200
LTNSSGFNSS QQDYPSYPGF GQGQYAQYYN SSPYPAHYMT SSNTSPTTPS 250
TNATYQLQEP PSGVTSQAVT DPTAEYSTIH SPSTPIKETD SERLRRGSDG 300
KSRGRGRRNN NPSPPPDSDL ERVFIWDLDE TIIVFHSLLT GSYANRYGRD 350
PPTSVSLGLR MEEMIFNLAD THLFFNDLEE CDQVHIDDVS SDDNGQDLST 400
YNFGTDGFPA AATSANLCLA TGVRGGVDWM RKLAFRYRRV KEIYNTYKNN 450
VGGLLGPAKR EAWLQLRAEI EALTDSWLTL ALKALSLIHS RTNCVNILVT 500
TTQLIPALAK VLLYGLGIVF PIENIYSATK IGKESCFERI IQRFGRKVVY 550
VVIGDGVEEE QGAKKHAMPF WRVSSHSDLM ALHHALELEY L 591
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.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4141MEMQD…PNGTE → MLLFPQVA in isoform 2.
VSP_001487Add
BLAST
Alternative sequencei140 – 1445Missing in isoform 2.
VSP_001488

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti117 – 1171M → V in CAA71312. 1 Publication
Sequence conflicti163 – 1631L → F in CAA71312. 1 Publication
Sequence conflicti324 – 3252FI → LL in AAB48017. 1 Publication
Sequence conflicti405 – 4051T → R in AAB48017. 1 Publication
Sequence conflicti450 – 4501N → K in AAB48017. 1 Publication
Sequence conflicti505 – 5051I → S in AAB48017. 1 Publication
Sequence conflicti535 – 5351S → G in CAA71312. 1 Publication
Sequence conflicti539 – 5391R → G in CAA71312. 1 Publication
Sequence conflicti548 – 5481V → L in CAA71312. 1 Publication
Sequence conflicti551 – 5522VV → LL in AAB48017. 1 Publication
Sequence conflicti559 – 5591E → K in CAA71312. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_006495511.1. XM_006495448.1. [P97767-1]
UniGeneiMm.250185.

Genome annotation databases

EnsembliENSMUST00000027066; ENSMUSP00000027066; ENSMUSG00000025932. [P97767-1]
GeneIDi14048.
KEGGimmu:14048.
UCSCiuc007aiw.1. mouse.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
RefSeqi XP_006495511.1. XM_006495448.1. [P97767-1 ]
UniGenei Mm.250185.

3D structure databases

ProteinModelPortali P97767.
SMRi P97767. Positions 321-591.
ModBasei Search...

Protein-protein interaction databases

IntActi P97767. 4 interactions.

PTM databases

PhosphoSitei P97767.

Proteomic databases

PRIDEi P97767.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000027066 ; ENSMUSP00000027066 ; ENSMUSG00000025932 . [P97767-1 ]
GeneIDi 14048.
KEGGi mmu:14048.
UCSCi uc007aiw.1. mouse.

Organism-specific databases

CTDi 2138.
MGIi MGI:109344. Eya1.

Phylogenomic databases

eggNOGi NOG297494.
GeneTreei ENSGT00390000008860.
HOGENOMi HOG000293149.
HOVERGENi HBG002447.
InParanoidi P97767.
KOi K15616.
OMAi GQPYGIS.
TreeFami TF319337.

Enzyme and pathway databases

SABIO-RK P97767.

Miscellaneous databases

PROi P97767.
SOURCEi Search...

Gene expression databases

ArrayExpressi P97767.
CleanExi MM_EYA1.
Genevestigatori P97767.

Family and domain databases

InterProi IPR006545. EYA_dom.
IPR028472. EYA_fam.
IPR028471. Eyes_absent_h1.
[Graphical view ]
PANTHERi PTHR10190. PTHR10190. 1 hit.
PTHR10190:SF11. PTHR10190:SF11. 1 hit.
TIGRFAMsi TIGR01658. EYA-cons_domain. 1 hit.
ProtoNeti Search...

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. "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.
  12. "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.
  13. "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: June 11, 2014
This is version 120 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