P97480 (EYA3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eyes absent homolog 3
EC=3.1.3.48

Gene names

Name:

Eya3

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	510 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. The phosphatase activity has been shown in vitro. Coactivates SIX1. Seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity. May be involved in development of the eye. May play a role in mediating the induction and differentiation of cranial placodes. Ref.6
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.8 Ref.10 Ref.11
Cofactor	Binds 1 Mg2+ ion per subunit Probable.
Subunit structure	Interacts with SIX1 and DACH1, and probably SIX2, SIX4 and SIX5. Ref.6 Ref.7 Ref.8
Subcellular location	Cytoplasm. Nucleus. Note: Localizes at sites of DNA damage at double-strand breaks (DSBs) By similarity. Ref.6 Ref.10
Tissue specificity	Expressed in branchial arches, CNS and developing eye.
Post-translational modification	Ser-203 phosphorylation is required for localization at sites of DNA damage and directing interaction with H2AX By similarity.
Sequence similarities	Belongs to the HAD-like hydrolase superfamily. EYA family.
Caution	According to Ref.8 also shows serine/threonine protein phosphatase activity.

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	double-strand break repair Inferred from sequence or structural similarity. Source: UniProtKB histone dephosphorylation Inferred from sequence or structural similarity. Source: UniProtKB multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of DNA repair Inferred from sequence or structural similarity. Source: UniProtKB 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, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell transcription factor complex Inferred from physical interaction PubMed 19008232. Source: MGI
Molecular_function	chromatin binding Inferred from genetic interaction PubMed 19008232. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB protein tyrosine/serine/threonine phosphatase activity Inferred from direct assay Ref.8. Source: MGI
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P97480-1)

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: P97480-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: MQEPREQTLS...TQTYGLPPFA → MIIPHKCILQT

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 510	510	Eyes absent homolog 3		PRO_0000218649
Sites
	Active site	246	1	Nucleophile By similarity
	Active site	248	1	Proton donor By similarity
	Metal binding	246	1	Magnesium By similarity
	Metal binding	248	1	Magnesium By similarity
	Metal binding	474	1	Magnesium By similarity
Amino acid modifications
	Modified residue	203	1	Phosphoserine Ref.12
	Modified residue	409	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 105	105	MQEPR…LPPFA → MIIPHKCILQT in isoform 2.		VSP_001494
Experimental info
	Mutagenesis	246	1	D → A: Abolishes phosphatase activity and abolishes coactivation of the SIX1-DACH1 complex. Ref.8 Ref.10 Ref.11
	Mutagenesis	246	1	D → N: Abolishes phosphatase activity. Ref.8 Ref.10 Ref.11
	Mutagenesis	248	1	D → N: Abolishes phosphatase activity. Ref.10
	Mutagenesis	250	1	T → A: Abolishes phosphatase activity. Ref.10
	Mutagenesis	419	1	T → A: Diminishes phosphatase activity by 24-fold. Ref.10
	Mutagenesis	420	1	T → A: Diminishes phosphatase activity. Ref.11
	Mutagenesis	449	1	K → Q: Abolishes phosphatase activity. Ref.11
	Mutagenesis	473	1	G → A: Abolishes phosphatase activity. Ref.10
	Mutagenesis	474	1	D → N: Diminishes phosphatase activity by 70%. Ref.10 Ref.11
	Mutagenesis	478	1	E → Q: Abolishes phosphatase activity. Ref.10 Ref.11
	Sequence conflict	200	1	P → L in AAB48019. Ref.2
	Sequence conflict	272	1	V → A in AAB42068. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 3, 2012. Version 2. Checksum: E82CC71DD1FD05F5	FASTA	510	55,973
	10 20 30 40 50 60 MQEPREQTLS QVNNPDASDE KPETSSLASN LSMSEEIMTC TDYIPRSSND YTSQMYSAKP 70 80 90 100 110 120 YAHILSVPVS ETTYPGQTQY QTLQQSQPYA VYPQATQTYG LPPFASSTNA SLIPTSSAIA 130 140 150 160 170 180 NIPAAAVASI SNQDYPTYTI LGQNQYQACY PSSSFGVTGQ TNSDAETTTL AATTYQTEKP 190 200 210 220 230 240 SAMVPAPATQ RLPSDSSASP PLSQTTPNKD ADDQARKNMT VKNRGKRKAD ASSSQDSELE 250 260 270 280 290 300 RVFLWDLDET IIIFHSLLTG SYAQKYGKDP TVVIGSGLTM EEMIFEVADT HLFFNDLEEC 310 320 330 340 350 360 DQVHVEDVAS DDNGQDLSNY SFSTDGFSGS GGSGSHGSSV GVQGGVDWMR KLAFRYRKVR 370 380 390 400 410 420 EIYDKHKSNV GGLLSPQRKE ALQRLRAEIE VLTDSWLGTA LKSLLLIQSR KNCANVLITT 430 440 450 460 470 480 TQLVPALAKV LLYGLGEIFP IENIYSATKI GKESCFERIV SRFGKKVTYV VIGDGRDEEI 490 500 510 AAKQHNMPFW RITNHGDLVS LHQALELDFL
	Isoform 2 [UniParc]. Checksum: A19B88372DA2A767	FASTA	416	45,518
	10 20 30 40 50 60 MIIPHKCILQ TSSTNASLIP TSSAIANIPA AAVASISNQD YPTYTILGQN QYQACYPSSS 70 80 90 100 110 120 FGVTGQTNSD AETTTLAATT YQTEKPSAMV PAPATQRLPS DSSASPPLSQ TTPNKDADDQ 130 140 150 160 170 180 ARKNMTVKNR GKRKADASSS QDSELERVFL WDLDETIIIF HSLLTGSYAQ KYGKDPTVVI 190 200 210 220 230 240 GSGLTMEEMI FEVADTHLFF NDLEECDQVH VEDVASDDNG QDLSNYSFST DGFSGSGGSG 250 260 270 280 290 300 SHGSSVGVQG GVDWMRKLAF RYRKVREIYD KHKSNVGGLL SPQRKEALQR LRAEIEVLTD 310 320 330 340 350 360 SWLGTALKSL LLIQSRKNCA NVLITTTQLV PALAKVLLYG LGEIFPIENI YSATKIGKES 370 380 390 400 410 CFERIVSRFG KKVTYVVIGD GRDEEIAAKQ HNMPFWRITN HGDLVSLHQA LELDFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM 1). Tissue: Embryo.
[2]	"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 2). 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]	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]	"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 350-468. Tissue: Embryo.
[6]	"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.
[7]	"Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein." Ikeda K., Watanabe Y., Ohto H., Kawakami K. Mol. Cell. Biol. 22:6759-6766(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SIX1; SIX2; SIX4 AND SIX5.
[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: CATALYTIC ACTIVITY, INTERACTION WITH DACH1 AND SIX1, MUTAGENESIS OF ASP-246.
[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, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-246; ASP-248; THR-250; THR-419; GLY-473; ASP-474 AND GLU-478.
[11]	"The transcription factor Eyes absent is a protein tyrosine phosphatase." Tootle T.L., Silver S.J., Davies E.L., Newman V., Latek R.R., Mills I.A., Selengut J.D., Parlikar B.E., Rebay I. Nature 426:299-302(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-246; THR-420; LYS-449; ASP-474 AND GLU-478.
[12]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U81604 mRNA. Translation: AAB42068.1. U61112 mRNA. Translation: AAB48019.1. AL627130 Genomic DNA. No translation available. CH466552 Genomic DNA. Translation: EDL30095.1. AJ007996 mRNA. Translation: CAA07819.1.
IPI	IPI00227775. IPI00411085.
RefSeq	NP_034296.2. NM_010166.2. NP_997592.1. NM_210071.1. NP_997596.1. NM_211357.1.
UniGene	Mm.227733.
3D structure databases
ProteinModelPortal	P97480.
SMR	P97480. Positions 237-510.
ModBase	Search...
Protein-protein interaction databases
IntAct	P97480. 2 interactions.
PTM databases
PhosphoSite	P97480.
Proteomic databases
PaxDb	P97480.
PRIDE	P97480.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000020197; ENSMUSP00000020197; ENSMUSG00000028886. ENSMUST00000079157; ENSMUSP00000078157; ENSMUSG00000028886. ENSMUST00000180250; ENSMUSP00000136812; ENSMUSG00000028886.
GeneID	14050.
KEGG	mmu:14050.
Organism-specific databases
CTD	2140.
MGI	MGI:109339. Eya3.
Phylogenomic databases
eggNOG	NOG297494.
GeneTree	ENSGT00390000008860.
HOGENOM	HOG000293149.
HOVERGEN	HBG002447.
InParanoid	P97480.
KO	K01104.
OrthoDB	EOG4RXXZZ.
Enzyme and pathway databases
SABIO-RK	P97480.
Gene expression databases
CleanEx	MM_EYA3.
Genevestigator	P97480.
GermOnline	ENSMUSG00000028886. Mus musculus.
Family and domain databases
InterPro	IPR006545. EYA. [Graphical view]
TIGRFAMs	TIGR01658. EYA-cons_domain. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	EYA3. mouse.
NextBio	284996.
SOURCE	Search...

Entry information

Entry name

EYA3_MOUSE

Accession

Primary (citable) accession number: P97480
Secondary accession number(s): G5E8I5, P97768

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	October 3, 2012
Last modified:	May 1, 2013
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program