O08575 (EYA2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eyes absent homolog 2
EC=3.1.3.48

Gene names

Name:	Eya2
Synonyms:	Eab1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	532 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 By similarity. Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1. Seems to coactivate SIX2, SIX4 and SIX5. Together with SIX1 and DACH2 seem to be involved in myogenesis. May be involved in development of the eye. Interaction with GNAZ and GNAI2 prevents nuclear translocation and transcriptional activity. Ref.7
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.8
Cofactor	Binds 1 Mg2+ ion per subunit.
Subunit structure	Interacts with SIX1, and probably with SIX2, SIX4 and SIX5. Interacts with GNAZ, GNAI2 and DACH2 By similarity. Interacts with CAPN8. Ref.5 Ref.7 Ref.9
Subcellular location	Cytoplasm. Nucleus Ref.7.
Tissue specificity	Extensively expressed in cranial placodes, branchial arches, CNS and developing eye and nose. Low expression in lung with little or no expression in skin, liver, intestine and kidney. Predominantly expressed in the upper one-third of the oxyntic mucosa and in most regions of the pyloric mucosa. Ref.9
Sequence similarities	Belongs to the HAD-like hydrolase superfamily. EYA family.

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
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW apoptotic process Inferred from direct assay PubMed 11700312. Source: MGI histone dephosphorylation Inferred from sequence or structural similarity. Source: UniProtKB multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW striated muscle tissue development Inferred from genetic interaction PubMed 17098221. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay PubMed 11700312. Source: MGI mitochondrion Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay PubMed 11700312. Source: MGI
Molecular_function	magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB protein tyrosine phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Sharpin	Q91WA6	2	EBI-986503,EBI-646097

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O08575-1)

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: O08575-2)

The sequence of this isoform differs from the canonical sequence as follows:
     114-142: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 532	532	Eyes absent homolog 2		PRO_0000218647
Sites
	Active site	268	1	Nucleophile By similarity
	Active site	270	1	Proton donor By similarity
	Metal binding	268	1	Magnesium By similarity
	Metal binding	270	1	Magnesium By similarity
	Metal binding	496	1	Magnesium By similarity
Amino acid modifications
	Modified residue	251	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	114 – 142	29	Missing in isoform 2.		VSP_001492

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 9A29BC6BB77DF880	FASTA	532	58,246
	10 20 30 40 50 60 MLEVVTSPSL ATSSDWSEHG AAVGTLSDRE GIAKSAALSV PQLFVKSHPR VPPGQSSTAM 70 80 90 100 110 120 AAYGQTQYST GIQQAPPYTA YPTPAQAYGI PPYSIKTEDS LNHSPSQSGF LSYGPSFSTA 130 140 150 160 170 180 PAGQSPYTYP VHSTAGLYQG ANGLTNTAGF GSVHQDYPSY PSFSQNQYPQ YFSPSYNPPY 190 200 210 220 230 240 VPASSLCSSP LSTSTYVLQE APHNVPSQSS ESLAGDYNTH NGPSTPAKEG DTERPHRASD 250 260 270 280 290 300 GKLRGRSKRN SDPSPAGDNE IERVFVWDLD ETIIIFHSLL TGTFASRYGK DTTTSVRIGL 310 320 330 340 350 360 MMEEMIFNLA DTHLFFNDLE DCDQIHVDDV SSDDNGQDLS TYNFSTDGFH STAPGASLCL 370 380 390 400 410 420 GTGVHGGVDW MRKLAFRYRR VKEMYNTYRN NVGGLIGAPK RETWLQLRAE LEALTDLWLT 430 440 450 460 470 480 HSLKALNLIN SRPNCVNVLV TTTQLIPALA KVLLYGLGSV FPIENIYSAT KTGKESCFER 490 500 510 520 530 IMQRFGRKAV YIVIGDGVEE EQGAKKHNMP FWRISCHADL EALRHALELE YL
	Isoform 2 [UniParc]. Checksum: F12F8FD4B0291F16	FASTA	503	55,337
	10 20 30 40 50 60 MLEVVTSPSL ATSSDWSEHG AAVGTLSDRE GIAKSAALSV PQLFVKSHPR VPPGQSSTAM 70 80 90 100 110 120 AAYGQTQYST GIQQAPPYTA YPTPAQAYGI PPYSIKTEDS LNHSPSQSGF LSYGLTNTAG 130 140 150 160 170 180 FGSVHQDYPS YPSFSQNQYP QYFSPSYNPP YVPASSLCSS PLSTSTYVLQ EAPHNVPSQS 190 200 210 220 230 240 SESLAGDYNT HNGPSTPAKE GDTERPHRAS DGKLRGRSKR NSDPSPAGDN EIERVFVWDL 250 260 270 280 290 300 DETIIIFHSL LTGTFASRYG KDTTTSVRIG LMMEEMIFNL ADTHLFFNDL EDCDQIHVDD 310 320 330 340 350 360 VSSDDNGQDL STYNFSTDGF HSTAPGASLC LGTGVHGGVD WMRKLAFRYR RVKEMYNTYR 370 380 390 400 410 420 NNVGGLIGAP KRETWLQLRA ELEALTDLWL THSLKALNLI NSRPNCVNVL VTTTQLIPAL 430 440 450 460 470 480 AKVLLYGLGS VFPIENIYSA TKTGKESCFE RIMQRFGRKA VYIVIGDGVE EEQGAKKHNM 490 500 PFWRISCHAD LEALRHALEL EYL

References

	« Hide 'large scale' referencesShow '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]. Tissue: Embryo.
[2]	"Eyes absent: a gene family found in several metazoan phyla." Duncan M.K., Kos L., Jenkins N.A., Gilbert D.J., Copeland N.G., Tomarev S.I. Mamm. Genome 8:479-485(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Embryo.
[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. , 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]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Mammary gland.
[5]	"Identification of transcriptional targets for Six5: implication for the pathogenesis of myotonic dystrophy type 1." Sato S., Nakamura M., Cho D.H., Tapscott S.J., Ozaki H., Kawakami K. Hum. Mol. Genet. 11:1045-1058(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SIX1.
[6]	"Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene." Zimmerman J.E., Bui Q.T., Steingrimsson E., Nagle D.L., Fu W., Genin A., Spinner N.B., Copeland N.G., Jenkins N.A., Bucan M., Bonini N.M. Genome Res. 7:128-141(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 60-532. 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]	"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.
[9]	"Stomach-specific calpain, nCL-2, localizes in mucus cells and proteolyzes the beta-subunit of coatomer complex, beta-COP." Hata S., Koyama S., Kawahara H., Doi N., Maeda T., Toyama-Sorimachi N., Abe K., Suzuki K., Sorimachi H. J. Biol. Chem. 281:11214-11224(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CAPN8, TISSUE SPECIFICITY.
[10]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-251, MASS SPECTROMETRY. Tissue: Melanoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U71208 mRNA. Translation: AAB51121.1. U61111 mRNA. Translation: AAB48018.1. Sequence problems. AL591712 Genomic DNA. Translation: CAM14837.1. BC003755 mRNA. Translation: AAH03755.1. U81603 mRNA. Translation: AAB42067.1.
IPI	IPI00230691. IPI00409303.
RefSeq	NP_001258891.1. NM_001271962.1. NP_001258892.1. NM_001271963.1. NP_034295.1. NM_010165.3.
UniGene	Mm.282719.
3D structure databases
ProteinModelPortal	O08575.
SMR	O08575. Positions 262-532.
ModBase	Search...
Protein-protein interaction databases
IntAct	O08575. 3 interactions.
PTM databases
PhosphoSite	O08575.
Proteomic databases
PRIDE	O08575.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000063433; ENSMUSP00000066244; ENSMUSG00000017897. ENSMUST00000088132; ENSMUSP00000085455; ENSMUSG00000017897.
GeneID	14049.
KEGG	mmu:14049.
UCSC	uc008nxw.1. mouse.
Organism-specific databases
CTD	2139.
MGI	MGI:109341. Eya2.
Phylogenomic databases
eggNOG	NOG297494.
GeneTree	ENSGT00390000008860.
HOVERGEN	HBG002447.
InParanoid	A2A5S4.
KO	K01104.
OMA	IHSRPNC.
OrthoDB	EOG45B1F9.
Gene expression databases
ArrayExpress	O08575.
Bgee	O08575.
CleanEx	MM_EYA2.
Genevestigator	O08575.
GermOnline	ENSMUSG00000017897. Mus musculus.
Family and domain databases
InterPro	IPR006545. EYA. [Graphical view]
TIGRFAMs	TIGR01658. EYA-cons_domain. 1 hit.
ProtoNet	Search...
Other
NextBio	284992.
SOURCE	Search...

Entry information

Entry name

EYA2_MOUSE

Accession

Primary (citable) accession number: O08575
Secondary accession number(s): A2A5S4, P97925

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 1, 1997
Last modified:	May 29, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program