P97767 (EYA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 108.
History...
Clusters with 
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Eyes absent homolog 1 EC=3.1.3.48 | ||
| Gene names |
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| Organism | Mus musculus (Mouse) [Reference proteome] | ||
| Taxonomic identifier | 10090 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus |
Protein attributes
| Sequence length | 591 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). '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. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1. Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Seems to coactivate SIX2, SIX4 and SIX5. May be involved in development of the eye. May play a role in mediating the induction and differentiation of cranial placodes. Ref.7 Ref.8 |
| Catalytic activity | Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.8 Ref.10 |
| Cofactor | Binds 1 Mg2+ ion per subunit Probable. |
| Subunit structure | Probably interacts with SIX2, SIX4 and SIX5. Ref.7 |
| Subcellular location | Cytoplasm. Nucleus. Note: Localizes at sites of DNA damage at double-strand breaks (DSBs) By similarity. Ref.7 |
| Tissue specificity | Extensively expressed in cranial placodes, branchial arches, CNS and developing eye and nose. |
| Post-translational modification | Sumoylated with SUMO1. Ref.11 |
| Disruption phenotype | Increased apoptosis and loss of renal tubules seen in the developing kidney with increased immunostaining for 'Se-139' phosphorylated H2AX. Mice show the Eya1-bor mutation, an autosomal recessive disorder which resembles human branchio-oto-renal (BOR) syndrome. The condition is characterized by gross morphological abnormalities of the inner ear and dysmorphic or missing kidneys. 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. Ref.5 Ref.8 Ref.12 |
| 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
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Rbck1 | Q9WUB0 | 2 | EBI-1368503,EBI-6141072 | |
| Sharpin | Q91WA6 | 4 | EBI-1368503,EBI-646097 | |
| Six1 | Q62231 | 3 | EBI-1368503,EBI-1368483 | |
| Six2 | Q62232 | 3 | EBI-1368503,EBI-1368736 |
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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 591 | 591 | Eyes absent homolog 1 | PRO_0000218644 | |||||
Sites | |||||||||
| Active site | 327 | 1 | Nucleophile By similarity | ||||||
| Active site | 329 | 1 | Proton donor By similarity | ||||||
| Metal binding | 327 | 1 | Magnesium By similarity | ||||||
| Metal binding | 329 | 1 | Magnesium By similarity | ||||||
| Metal binding | 555 | 1 | Magnesium By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 41 | 41 | MEMQD…PNGTE → MLLFPQVA in isoform 2. | VSP_001487 | |||||
| Alternative sequence | 140 – 144 | 5 | Missing in isoform 2. | VSP_001488 | |||||
Experimental info | |||||||||
| Mutagenesis | 43 | 1 | K → R: Markedly reduced sumoylation; when associated with R-459. Ref.11 | ||||||
| Mutagenesis | 459 | 1 | K → R: Markedly reduced sumoylation; when associated with R-43. Ref.11 | ||||||
| Sequence conflict | 117 | 1 | M → V in CAA71312. Ref.2 | ||||||
| Sequence conflict | 163 | 1 | L → F in CAA71312. Ref.2 | ||||||
| Sequence conflict | 324 – 325 | 2 | FI → LL in AAB48017. Ref.1 | ||||||
| Sequence conflict | 405 | 1 | T → R in AAB48017. Ref.1 | ||||||
| Sequence conflict | 450 | 1 | N → K in AAB48017. Ref.1 | ||||||
| Sequence conflict | 505 | 1 | I → S in AAB48017. Ref.1 | ||||||
| Sequence conflict | 535 | 1 | S → G in CAA71312. Ref.2 | ||||||
| Sequence conflict | 539 | 1 | R → G in CAA71312. Ref.2 | ||||||
| Sequence conflict | 548 | 1 | V → L in CAA71312. Ref.2 | ||||||
| Sequence conflict | 551 – 552 | 2 | VV → LL in AAB48017. Ref.1 | ||||||
| Sequence conflict | 559 | 1 | E → K in CAA71312. Ref.2 | ||||||
Sequences
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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.  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, DISRUPTION PHENOTYPE. 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] | "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. |
| [9] | 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) |
| [10] | "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. |
| [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] | "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. |
| + | 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. |
| IPI | IPI00274663. IPI00621402. |
| UniGene | Mm.250185. |
3D structure databases | |
| ProteinModelPortal | P97767. |
| SMR | P97767. Positions 321-591. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P97767. 4 interactions. |
PTM databases | |
| PhosphoSite | P97767. |
Proteomic databases | |
| PRIDE | P97767. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENSMUST00000027066; ENSMUSP00000027066; ENSMUSG00000025932. |
Organism-specific databases | |
| MGI | MGI:109344. Eya1. |
Phylogenomic databases | |
| eggNOG | NOG297494. |
| GeneTree | ENSGT00390000008860. |
| HOGENOM | HOG000293149. |
| HOVERGEN | HBG002447. |
| InParanoid | P97767. |
| OMA | GQPYGIS. |
| OrthoDB | EOG4XH000. |
Enzyme and pathway databases | |
| SABIO-RK | P97767. |
Gene expression databases | |
| CleanEx | MM_EYA1. |
| Genevestigator | P97767. |
| GermOnline | ENSMUSG00000025932. Mus musculus. |
Family and domain databases | |
| InterPro | IPR006545. EYA. [Graphical view] |
| TIGRFAMs | TIGR01658. EYA-cons_domain. 1 hit. |
| ProtoNet | Search... |
Other | |
| SOURCE | Search... |
Entry information
| Entry name | EYA1_MOUSE | ||||||||
| Accession | Primary (citable) accession number: P97767 Secondary accession number(s): G5E864, O08818 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |