Eya2

Functionⁱ

Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5 (PubMed:10490620, PubMed:17098221). 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 (By similarity). Plays an important role in hypaxial muscle development together with SIX1 and DACH2; in this it is functionally redundant with EYA1 (By similarity).By similarity2 Publications

Catalytic activityⁱ

Protein tyrosine phosphate + H₂O = protein tyrosine + phosphate.1 Publication

Cofactorⁱ

Mg²⁺By similarityNote: Binds 1 Mg²⁺ ion per subunit.By similarity

Sites

Feature key	Position(s)	DescriptionActions	Length
Active siteⁱ	268	NucleophileBy similarity	1
Metal bindingⁱ	268	MagnesiumBy similarity	1
Active siteⁱ	270	Proton donorBy similarity	1
Metal bindingⁱ	270	Magnesium; via carbonyl oxygenBy similarity	1
Metal bindingⁱ	496	MagnesiumBy similarity	1

GO - Molecular functionⁱ

magnesium ion binding Source: UniProtKB
protein tyrosine phosphatase activity
Source: MGI
Inferred from direct assayⁱ
- 14628052
transcription factor binding Source: MGI

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cell differentiation Source: GO_Central
DNA repair Source: UniProtKB-KW
extrinsic apoptotic signaling pathway in absence of ligand
Source: MGI
Inferred from direct assayⁱ
- 11700312
histone dephosphorylation Source: UniProtKB
mitochondrial outer membrane permeabilization
Source: MGI
Inferred from direct assayⁱ
- 11700312
multicellular organism development Source: UniProtKB-KW
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central
positive regulation of DNA repair Source: GO_Central
protein dephosphorylation
Source: MGI
Inferred from direct assayⁱ
- 14628052
regulation of transcription, DNA-templated Source: UniProtKB-KW
striated muscle tissue development
Source: MGI
Inferred from genetic interactionⁱ
- 17098221
transcription, DNA-templated Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Activator, Chromatin regulator, Developmental protein, Hydrolase, Protein phosphatase
Biological process	DNA damage, DNA repair, Transcription, Transcription regulation
Ligand	Magnesium, Metal-binding

Enzyme and pathway databases

Reactomeⁱ	R-MMU-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks

Reactomeⁱ

R-MMU-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Eyes absent homolog 2 (EC:3.1.3.481 Publication)
Gene namesⁱ	Name:Eya2 Synonyms:Eab1
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 2

Organism-specific databases

MGIⁱ	MGI:109341 Eya2

Keywords - Cellular componentⁱ

Cytoplasm, Nucleus

Pathology & Biotechⁱ

Disruption phenotypeⁱ

No visible phenotype. In contrast, mice lacking both Eya1 and Eya2 display complete embryonic lethality, due to severe defects in muscle development, including the absence of the diaphragm, the absence of ventral hypaxial muscles of the trunk and 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 activate transcription from cognate promoter elements, and does not activate transcription of Pax3.1 Publication

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000218647	1 – 532	Eyes absent homolog 2Add BLAST		532

Proteomic databases

PaxDbⁱ	O08575
PeptideAtlas More...PeptideAtlasⁱ	O08575
PRIDEⁱ	O08575

PTM databases

iPTMnetⁱ	O08575
PhosphoSitePlusⁱ	O08575

Expressionⁱ

Tissue specificityⁱ

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.1 Publication

Gene expression databases

Bgeeⁱ	ENSMUSG00000017897 Expressed in 110 organ(s), highest expression level in stomach
CleanExⁱ	MM_EYA2
Genevisibleⁱ	O08575 MM

Interactionⁱ

Subunit structureⁱ

Probably interacts with SIX2, SIX4 and SIX5. Interacts with DACH2. Interacts with GNAZ and GNAI2; this retains EYA2 in the cytoplasm and prevents its translocation into the nucleus and transcriptional activity (By similarity). Interacts with SIX1. Interacts with CAPN8.By similarity3 Publications

Binary interactionsⁱ

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

With

Entry

#Exp.

IntAct

Notes

Sharpin

Q91WA6

2

EBI-986503,EBI-646097

GO - Molecular functionⁱ

transcription factor binding Source: MGI

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	199560, 1 interactor
IntActⁱ	O08575, 3 interactors
STRINGⁱ	10090.ENSMUSP00000066244

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	O08575
SMRⁱ	O08575
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the HAD-like hydrolase superfamily. EYA family.Curated

Phylogenomic databases

eggNOGⁱ	KOG3107 Eukaryota ENOG410XT12 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000008860
HOVERGENⁱ	HBG002447
InParanoidⁱ	O08575
KEGG Orthology (KO) More...KOⁱ	K17620
OMAⁱ	SADGFHS
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G04YD
TreeFamⁱ	TF319337

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd02601 HAD_Eya, 1 hit
Gene3Dⁱ	3.40.50.12350, 1 hit
InterProⁱ	View protein in InterPro IPR028473 EYA2 IPR006545 EYA_dom IPR038102 EYA_dom_sf IPR028472 EYA_fam IPR036412 HAD-like_sf
PANTHERⁱ	PTHR10190 PTHR10190, 1 hit PTHR10190:SF7 PTHR10190:SF7, 1 hit
SUPFAMⁱ	SSF56784 SSF56784, 1 hit
TIGRFAMsⁱ	TIGR01658 EYA-cons_domain, 1 hit

Sequences (2)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

Isoform 1 (identifier: O08575-1) [UniParc]FASTA Add 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

        10         20         30         40         50
MLEVVTSPSL ATSSDWSEHG AAVGTLSDRE GIAKSAALSV PQLFVKSHPR 
        60         70         80         90        100
VPPGQSSTAM AAYGQTQYST GIQQAPPYTA YPTPAQAYGI PPYSIKTEDS 
       110        120        130        140        150
LNHSPSQSGF LSYGPSFSTA PAGQSPYTYP VHSTAGLYQG ANGLTNTAGF 
       160        170        180        190        200
GSVHQDYPSY PSFSQNQYPQ YFSPSYNPPY VPASSLCSSP LSTSTYVLQE 
       210        220        230        240        250
APHNVPSQSS ESLAGDYNTH NGPSTPAKEG DTERPHRASD GKLRGRSKRN 
       260        270        280        290        300
SDPSPAGDNE IERVFVWDLD ETIIIFHSLL TGTFASRYGK DTTTSVRIGL 
       310        320        330        340        350
MMEEMIFNLA DTHLFFNDLE DCDQIHVDDV SSDDNGQDLS TYNFSTDGFH 
       360        370        380        390        400
STAPGASLCL GTGVHGGVDW MRKLAFRYRR VKEMYNTYRN NVGGLIGAPK 
       410        420        430        440        450
RETWLQLRAE LEALTDLWLT HSLKALNLIN SRPNCVNVLV TTTQLIPALA 
       460        470        480        490        500
KVLLYGLGSV FPIENIYSAT KTGKESCFER IMQRFGRKAV YIVIGDGVEE 
       510        520        530 
EQGAKKHNMP FWRISCHADL EALRHALELE YL

Length:532

Mass (Da):58,246

Last modified:July 1, 1997 - v1

Checksum:ⁱ9A29BC6BB77DF880

GO

Isoform 2 (identifier: O08575-2) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MLEVVTSPSL ATSSDWSEHG AAVGTLSDRE GIAKSAALSV PQLFVKSHPR 
        60         70         80         90        100
VPPGQSSTAM AAYGQTQYST GIQQAPPYTA YPTPAQAYGI PPYSIKTEDS 
       110        120        130        140        150
LNHSPSQSGF LSYGLTNTAG FGSVHQDYPS YPSFSQNQYP QYFSPSYNPP 
       160        170        180        190        200
YVPASSLCSS PLSTSTYVLQ EAPHNVPSQS SESLAGDYNT HNGPSTPAKE 
       210        220        230        240        250
GDTERPHRAS DGKLRGRSKR NSDPSPAGDN EIERVFVWDL DETIIIFHSL 
       260        270        280        290        300
LTGTFASRYG KDTTTSVRIG LMMEEMIFNL ADTHLFFNDL EDCDQIHVDD 
       310        320        330        340        350
VSSDDNGQDL STYNFSTDGF HSTAPGASLC LGTGVHGGVD WMRKLAFRYR 
       360        370        380        390        400
RVKEMYNTYR NNVGGLIGAP KRETWLQLRA ELEALTDLWL THSLKALNLI 
       410        420        430        440        450
NSRPNCVNVL VTTTQLIPAL AKVLLYGLGS VFPIENIYSA TKTGKESCFE 
       460        470        480        490        500
RIMQRFGRKA VYIVIGDGVE EEQGAKKHNM PFWRISCHAD LEALRHALEL 

EYL

Show »

Length:503

Mass (Da):55,337

Checksum:ⁱF12F8FD4B0291F16

GO

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_001492	114 – 142	Missing in isoform 2. CuratedAdd BLAST		29

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U71208 mRNA Translation: AAB51121.1 U61111 mRNA Translation: AAB48018.1 Sequence problems. AL591712 Genomic DNA No translation available. BC003755 mRNA Translation: AAH03755.1 U81603 mRNA Translation: AAB42067.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS17084.1 [O08575-1]
NCBI Reference Sequences More...RefSeqⁱ	NP_001258891.1, NM_001271962.1 [O08575-1] NP_001258892.1, NM_001271963.1 [O08575-1] NP_034295.1, NM_010165.3 [O08575-1]
UniGeneⁱ	Mm.282719

Genome annotation databases

Ensemblⁱ	ENSMUST00000063433; ENSMUSP00000066244; ENSMUSG00000017897 [O08575-1] ENSMUST00000088132; ENSMUSP00000085455; ENSMUSG00000017897 [O08575-1]
GeneIDⁱ	14049
KEGGⁱ	mmu:14049
UCSC genome browser More...UCSCⁱ	uc008nxw.2 mouse [O08575-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
O08575	Eyes absent homolog (Fragment)		MOUSE		614	UniRef100_O08575
UPI0003D704F3		MOUSE		473

Protein	Similar proteins		Species	Score	Length	Source
O08575	Eyes absent homolog (Fragment)		MOUSE		614	UniRef90_O08575
Eyes absent homolog		MESAU		538
Eyes absent homolog		RAT		531
UPI0004546A91		CRIGR		538
UPI0004ED16A0		NANGA		538
+8

Protein	Similar proteins		Species	Score	Length	Source
O08575	Isoform 2 of Eyes absent homolog 1		MOUSE		553	UniRef50_P97767-2
Eyes absent homolog 4		HUMAN		639
Eyes absent homolog 4 (Fragment)		TAKRU		119
Eyes absent homolog		MONDO		678
Eyes absent homolog		MACFA		591
+1589
O08575-2	Eyes absent homolog		Florida manatee		503	UniRef50_O08575-2
Eyes absent homolog		ALLSI		513
Eyes absent homolog		CAMFR		625
UPI0004ED4B25		NANGA		499
UPI000653AC5B		MUSPF		510
+4

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U71208 mRNA Translation: AAB51121.1 U61111 mRNA Translation: AAB48018.1 Sequence problems. AL591712 Genomic DNA No translation available. BC003755 mRNA Translation: AAH03755.1 U81603 mRNA Translation: AAB42067.1
CCDSⁱ	CCDS17084.1 [O08575-1]
RefSeqⁱ	NP_001258891.1, NM_001271962.1 [O08575-1] NP_001258892.1, NM_001271963.1 [O08575-1] NP_034295.1, NM_010165.3 [O08575-1]
UniGeneⁱ	Mm.282719

3D structure databases

ProteinModelPortalⁱ	O08575
SMRⁱ	O08575
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	199560, 1 interactor
IntActⁱ	O08575, 3 interactors
STRINGⁱ	10090.ENSMUSP00000066244

PTM databases

iPTMnetⁱ	O08575
PhosphoSitePlusⁱ	O08575

Proteomic databases

PaxDbⁱ	O08575
PeptideAtlasⁱ	O08575
PRIDEⁱ	O08575

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000063433; ENSMUSP00000066244; ENSMUSG00000017897 [O08575-1] ENSMUST00000088132; ENSMUSP00000085455; ENSMUSG00000017897 [O08575-1]
GeneIDⁱ	14049
KEGGⁱ	mmu:14049
UCSCⁱ	uc008nxw.2 mouse [O08575-1]

Organism-specific databases

CTDⁱ	2139
MGIⁱ	MGI:109341 Eya2

Phylogenomic databases

eggNOGⁱ	KOG3107 Eukaryota ENOG410XT12 LUCA
GeneTreeⁱ	ENSGT00390000008860
HOVERGENⁱ	HBG002447
InParanoidⁱ	O08575
KOⁱ	K17620
OMAⁱ	SADGFHS
OrthoDBⁱ	EOG091G04YD
TreeFamⁱ	TF319337

Enzyme and pathway databases

Reactomeⁱ	R-MMU-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks

Reactomeⁱ

R-MMU-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:O08575
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000017897 Expressed in 110 organ(s), highest expression level in stomach
CleanExⁱ	MM_EYA2
Genevisibleⁱ	O08575 MM

Family and domain databases

CDDⁱ	cd02601 HAD_Eya, 1 hit
Gene3Dⁱ	3.40.50.12350, 1 hit
InterProⁱ	View protein in InterPro IPR028473 EYA2 IPR006545 EYA_dom IPR038102 EYA_dom_sf IPR028472 EYA_fam IPR036412 HAD-like_sf
PANTHERⁱ	PTHR10190 PTHR10190, 1 hit PTHR10190:SF7 PTHR10190:SF7, 1 hit
SUPFAMⁱ	SSF56784 SSF56784, 1 hit
TIGRFAMsⁱ	TIGR01658 EYA-cons_domain, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	EYA2_MOUSE
Accessionⁱ	O08575Primary (citable) accession number: O08575 Secondary accession number(s): A2A5S4, P97925
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
	Last sequence update:	July 1, 1997
	Last modified:	September 12, 2018
	This is version 150 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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UniProtKB - O08575 (EYA2_MOUSE)

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Eyes absent homolog 2

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

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GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

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Mitochondrion

Nucleus

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Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

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Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

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Protocols and materials databases

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<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ