Reviewed, UniProtKB/Swiss-Prot P97767 (EYA1_MOUSE)

Names and origin

Protein names

Recommended name:
    Eyes absent homolog 1
    EC=3.1.3.48

Gene names

Name:

Eya1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	591 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.6 Ref.8
Cofactor	Binds 1 Mg2+ ion per subunit Probable.
Subunit structure	Probably interacts with SIX2, SIX4 and SIX5. Ref.5
Subcellular location	Cytoplasm. Nucleus. Note: Localizes at sites of DNA damage at double-strand breaks (DSBs) By similarity. Ref.5
Tissue specificity	Extensively expressed in cranial placodes, branchial arches, CNS and developing eye and nose.
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.
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 process	DNA damage DNA repair Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Magnesium Metal-binding
Molecular function	Activator Chromatin regulator Developmental protein Hydrolase Protein phosphatase
Gene Ontology (GO)
Biological process	branching involved in ureteric bud morphogenesis Inferred from genetic interaction. Source: MGI cell fate commitment Inferred from mutant phenotype. Source: MGI double-strand break repair Inferred from sequence or structural similarity. Source: UniProtKB embryonic skeletal system morphogenesis Inferred from mutant phenotype. Source: MGI histone dephosphorylation Inferred from sequence or structural similarity. Source: UniProtKB inner ear morphogenesis Inferred from mutant phenotype. Source: MGI middle ear morphogenesis Inferred from mutant phenotype. Source: MGI negative regulation of apoptosis Inferred from mutant phenotype. Source: MGI outer ear morphogenesis Inferred from mutant phenotype. Source: MGI pattern specification process Inferred from genetic interaction. Source: MGI positive regulation of DNA repair Inferred from sequence or structural similarity. Source: UniProtKB regulation of neuron differentiation Inferred from mutant phenotype. Source: MGI regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to ionizing radiation Inferred from sequence or structural similarity. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: MGI nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein tyrosine phosphatase activity Ref.8 Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Six1	Q62231	2	EBI-1368503,EBI-1368483
Six2	Q62232	2	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
	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	LL → FI in CAA71312. Ref.2
	Sequence conflict	405	1	R → T in CAA71312. Ref.2
	Sequence conflict	450	1	K → N Ref.2
	Sequence conflict	450	1	K → N Ref.4
	Sequence conflict	505	1	S → I Ref.2
	Sequence conflict	505	1	S → I Ref.4
	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	LL → VV in CAA71312. Ref.2
	Sequence conflict	559	1	E → K in CAA71312. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 6, 2007. Version 2. Checksum: F70E48EF77009142	FASTA	591	64,361
	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 ERVLLWDLDE TIIVFHSLLT GSYANRYGRD PPTSVSLGLR 370 380 390 400 410 420 MEEMIFNLAD THLFFNDLEE CDQVHIDDVS SDDNGQDLST YNFGRDGFPA AATSANLCLA 430 440 450 460 470 480 TGVRGGVDWM RKLAFRYRRV KEIYNTYKNK VGGLLGPAKR EAWLQLRAEI EALTDSWLTL 490 500 510 520 530 540 ALKALSLIHS RTNCVNILVT TTQLSPALAK VLLYGLGIVF PIENIYSATK IGKESCFERI 550 560 570 580 590 IQRFGRKVVY LLIGDGVEEE QGAKKHAMPF WRVSSHSDLM ALHHALELEY L
	Isoform 2. Checksum: 418E3805DA2C0F88	FASTA	553	60,462
	10 20 30 40 50 60 MLLFPQVAVK TEPMSSSEIA STAADGSLDS FSGSALGSSS FSPRPAHPFS PPQIYPSKSY 70 80 90 100 110 120 PHILPTPSSQ TMAAYGQTQF TTGMQQATAY ATYPQPGQPY GISSYGIKTE SGLSQSQSPG 130 140 150 160 170 180 QTGFLSYGTS FGTPQPGQAP YSYQMQGSSF TTSSGLYSGN NSLTNSSGFN SSQQDYPSYP 190 200 210 220 230 240 GFGQGQYAQY YNSSPYPAHY MTSSNTSPTT PSTNATYQLQ EPPSGVTSQA VTDPTAEYST 250 260 270 280 290 300 IHSPSTPIKE TDSERLRRGS DGKSRGRGRR NNNPSPPPDS DLERVLLWDL DETIIVFHSL 310 320 330 340 350 360 LTGSYANRYG RDPPTSVSLG LRMEEMIFNL ADTHLFFNDL EECDQVHIDD VSSDDNGQDL 370 380 390 400 410 420 STYNFGRDGF PAAATSANLC LATGVRGGVD WMRKLAFRYR RVKEIYNTYK NKVGGLLGPA 430 440 450 460 470 480 KREAWLQLRA EIEALTDSWL TLALKALSLI HSRTNCVNIL VTTTQLSPAL AKVLLYGLGI 490 500 510 520 530 540 VFPIENIYSA TKIGKESCFE RIIQRFGRKV VYLLIGDGVE EEQGAKKHAM PFWRVSSHSD 550 LMALHHALEL EYL

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: 9006082] [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: 9020840] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2). Strain: CB/20.
[3]	"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: 10072433] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 276-321, DISRUPTION PHENOTYPE. Strain: 129/SvJ.
[4]	"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: 9887327] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 431-549. Tissue: Embryo.
[5]	"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: 10490620] [Abstract] Cited for: FUNCTION, INTERACTION WITH SIX2; SIX4 AND SIX5, SUBCELLULAR LOCATION.
[6]	"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: 14628042] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE.
[7]	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)
[8]	"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: 14628052] [Abstract] Cited for: CATALYTIC ACTIVITY.
[9]	"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: 19234442] [Abstract] Cited for: DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U61110 mRNA. Translation: AAB48017.1. Frameshift. Y10263 Genomic DNA. Translation: CAA71312.1. AF097544 Genomic DNA. Translation: AAD19355.1. AJ007995 mRNA. Translation: CAA07818.1.
IPI	IPI00274663. IPI00621402.
UniGene	Mm.250185
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P97767. 2 interactions.
Genome annotation databases
Ensembl	ENSMUSG00000025932. Mus musculus. [Contig view]
Organism-specific databases
MGI	MGI:109344. Eya1.
Phylogenomic databases
HOGENOM	P97767.
HOVERGEN	P97767.
Enzyme and pathway databases
BRENDA	3.1.3.48. 244.
Gene expression databases
ArrayExpress	P97767.
Bgee	P97767.
CleanEx	MM_EYA1.
GermOnline	ENSMUSG00000025932. Mus musculus.
Family and domain databases
InterPro	IPR005834. Dehalogen-like_hydro. IPR006545. EYA. [Graphical view]
Pfam	PF00702. Hydrolase. 1 hit. [Graphical view]
TIGRFAMs	TIGR01658. EYA-cons_domain. 1 hit.
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

EYA1_MOUSE

Accession

Primary (citable) accession number: P97767
Secondary accession number(s): O08818

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	February 6, 2007
Last modified:	June 16, 2009
This is version 74 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)