O00167 (EYA2_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	538 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. 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.11
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.11
Cofactor	Binds 1 Mg2+ ion per subunit.
Subunit structure	Interacts with GNAZ and GNAI2. Interacts with DACH2 and SIX1, and probably with SIX2, SIX4 and SIX5. Interacts with CAPN8 By similarity. Ref.9
Subcellular location	Cytoplasm. Nucleus Ref.9 Ref.10.
Tissue specificity	Highest expression in muscle with lower levels in kidney, placenta, pancreas, brain and heart.
Developmental stage	At the begin of fourth week of development detected in cytoplasm of somite cells. Between the sixth and eighth week of development detected in cytoplasm of limb bud cells. Ref.10
Sequence similarities	Belongs to the HAD-like hydrolase superfamily. EYA family.
Biophysicochemical properties	Kinetic parameters: KM=1.9 µM for H2AXY142ph Ref.11 KM=80 µM for H2AXS139ph
Sequence caution	The sequence AAH13882.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	DNA damage DNA repair Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Activator Chromatin regulator Developmental protein Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW apoptotic process Inferred from electronic annotation. Source: Compara histone dephosphorylation Inferred from direct assay Ref.11. Source: UniProtKB mesodermal cell fate specification Traceable author statement Ref.3. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW striated muscle tissue development Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	mitochondrion Inferred from direct assay. Source: HPA nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	magnesium ion binding Inferred from direct assay Ref.11. Source: UniProtKB protein tyrosine phosphatase activity Inferred from direct assay Ref.11. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: O00167-1)

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: O00167-2)

The sequence of this isoform differs from the canonical sequence as follows:
     99-122: Missing.

Isoform 3 (identifier: O00167-3)

The sequence of this isoform differs from the canonical sequence as follows:
     401-479: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 538

538

Eyes absent homolog 2

PRO_0000218646

Sites

Active site

274

1

Nucleophile By similarity

Active site

276

1

Proton donor By similarity

Metal binding

274

1

Magnesium

Metal binding

276

1

Magnesium

Metal binding

502

1

Magnesium

Amino acid modifications

Modified residue

257

1

Phosphoserine By similarity

Natural variations

Alternative sequence

99 – 122

24

Missing in isoform 2.

VSP_001490

Alternative sequence

401 – 479

79

Missing in isoform 3.

VSP_001491

Natural variant

83

1

P → S.
Corresponds to variant rs2275596 [ dbSNP | Ensembl ].

VAR_048964

Natural variant

238

1

T → A.
Corresponds to variant rs866936 [ dbSNP | Ensembl ].

VAR_048965

Experimental info

Sequence conflict

296

1

K → E in AAB42065. Ref.7

Sequence conflict

361

1

G → A in AAP35328. Ref.4

Sequence conflict

361

1

G → A in AAH08803. Ref.6

Sequence conflict

381

1

A → S in AAB42065. Ref.7

Sequence conflict

419

1

A → V in CAA07815. Ref.8

Sequence conflict

525

1

D → N in AAB51120. Ref.1

Secondary structure

1

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538

Helix Strand Turn

Details...

Beta strand

269 – 273

5

Turn

277 – 279

3

Helix

283 – 286

4

Helix

289 – 294

6

Helix

298 – 319

22

Helix

322 – 325

4

Helix

326 – 328

3

Turn

333 – 336

4

Helix

337 – 339

3

Beta strand

350 – 353

4

Helix

376 – 394

19

Helix

398 – 402

5

Helix

406 – 420

15

Turn

421 – 423

3

Helix

424 – 437

14

Beta strand

441 – 449

9

Helix

451 – 460

10

Turn

464 – 466

3

Helix

469 – 471

3

Beta strand

472 – 474

3

Turn

475 – 478

4

Helix

480 – 491

12

Beta strand

495 – 503

9

Helix

504 – 512

9

Beta strand

517 – 519

3

Helix

523 – 535

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 2, 2002. Version 2. Checksum: 3DBFC31D8BE1E85D	FASTA	538	59,232
	10 20 30 40 50 60 MVELVISPSL TVNSDCLDKL KFNRADAAVW TLSDRQGITK SAPLRVSQLF SRSCPRVLPR 70 80 90 100 110 120 QPSTAMAAYG QTQYSAGIQQ ATPYTAYPPP AQAYGIPSYS IKTEDSLNHS PGQSGFLSYG 130 140 150 160 170 180 SSFSTSPTGQ SPYTYQMHGT TGFYQGGNGL GNAAGFGSVH QDYPSYPGFP QSQYPQYYGS 190 200 210 220 230 240 SYNPPYVPAS SICPSPLSTS TYVLQEASHN VPNQSSESLA GEYNTHNGPS TPAKEGDTDR 250 260 270 280 290 300 PHRASDGKLR GRSKRSSDPS PAGDNEIERV FVWDLDETII IFHSLLTGTF ASRYGKDTTT 310 320 330 340 350 360 SVRIGLMMEE MIFNLADTHL FFNDLEDCDQ IHVDDVSSDD NGQDLSTYNF SADGFHSSAP 370 380 390 400 410 420 GANLCLGSGV HGGVDWMRKL AFRYRRVKEM YNTYKNNVGG LIGTPKRETW LQLRAELEAL 430 440 450 460 470 480 TDLWLTHSLK ALNLINSRPN CVNVLVTTTQ LIPALAKVLL YGLGSVFPIE NIYSATKTGK 490 500 510 520 530 ESCFERIMQR FGRKAVYVVI GDGVEEEQGA KKHNMPFWRI SCHADLEALR HALELEYL
	Isoform 2 [UniParc]. Checksum: 970E63DB345E484A	FASTA	514	56,688
	10 20 30 40 50 60 MVELVISPSL TVNSDCLDKL KFNRADAAVW TLSDRQGITK SAPLRVSQLF SRSCPRVLPR 70 80 90 100 110 120 QPSTAMAAYG QTQYSAGIQQ ATPYTAYPPP AQAYGIPSFS TSPTGQSPYT YQMHGTTGFY 130 140 150 160 170 180 QGGNGLGNAA GFGSVHQDYP SYPGFPQSQY PQYYGSSYNP PYVPASSICP SPLSTSTYVL 190 200 210 220 230 240 QEASHNVPNQ SSESLAGEYN THNGPSTPAK EGDTDRPHRA SDGKLRGRSK RSSDPSPAGD 250 260 270 280 290 300 NEIERVFVWD LDETIIIFHS LLTGTFASRY GKDTTTSVRI GLMMEEMIFN LADTHLFFND 310 320 330 340 350 360 LEDCDQIHVD DVSSDDNGQD LSTYNFSADG FHSSAPGANL CLGSGVHGGV DWMRKLAFRY 370 380 390 400 410 420 RRVKEMYNTY KNNVGGLIGT PKRETWLQLR AELEALTDLW LTHSLKALNL INSRPNCVNV 430 440 450 460 470 480 LVTTTQLIPA LAKVLLYGLG SVFPIENIYS ATKTGKESCF ERIMQRFGRK AVYVVIGDGV 490 500 510 EEEQGAKKHN MPFWRISCHA DLEALRHALE LEYL
	Isoform 3 [UniParc]. Checksum: 774885A6F04CA6B2	FASTA	459	50,533
	10 20 30 40 50 60 MVELVISPSL TVNSDCLDKL KFNRADAAVW TLSDRQGITK SAPLRVSQLF SRSCPRVLPR 70 80 90 100 110 120 QPSTAMAAYG QTQYSAGIQQ ATPYTAYPPP AQAYGIPSYS IKTEDSLNHS PGQSGFLSYG 130 140 150 160 170 180 SSFSTSPTGQ SPYTYQMHGT TGFYQGGNGL GNAAGFGSVH QDYPSYPGFP QSQYPQYYGS 190 200 210 220 230 240 SYNPPYVPAS SICPSPLSTS TYVLQEASHN VPNQSSESLA GEYNTHNGPS TPAKEGDTDR 250 260 270 280 290 300 PHRASDGKLR GRSKRSSDPS PAGDNEIERV FVWDLDETII IFHSLLTGTF ASRYGKDTTT 310 320 330 340 350 360 SVRIGLMMEE MIFNLADTHL FFNDLEDCDQ IHVDDVSSDD NGQDLSTYNF SADGFHSSAP 370 380 390 400 410 420 GANLCLGSGV HGGVDWMRKL AFRYRRVKEM YNTYKNNVGG KESCFERIMQ RFGRKAVYVV 430 440 450 IGDGVEEEQG AKKHNMPFWR ISCHADLEAL RHALELEYL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM 1). Tissue: Embryonic brain.
[2]	Erratum Duncan M.K., Kos L., Jenkins N.A., Gilbert D.J., Copeland N.G., Tomarev S.I. Mamm. Genome 8:877-877(1997)
[3]	"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]. Tissue: Embryo.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 2 AND 3). Tissue: Lung.
[7]	"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 295-538. Tissue: Brain.
[8]	"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 378-496. Tissue: Lens epithelium.
[9]	"The alpha subunits of Gz and Gi interact with the eyes absent transcription cofactor Eya2, preventing its interaction with the six class of homeodomain-containing proteins." Fan X., Brass L.F., Poncz M., Spitz F., Maire P., Manning D.R. J. Biol. Chem. 275:32129-32134(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH GNAZ AND GNAI2.
[10]	"Six and Eya expression during human somitogenesis and MyoD gene family activation." Fougerousse F., Durand M., Lopez S., Suel L., Demignon J., Thornton C., Ozaki H., Kawakami K., Barbet P., Beckmann J.S., Maire P. J. Muscle Res. Cell Motil. 23:255-264(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[11]	"Dephosphorylation of the C-terminal tyrosyl residue of the DNA damage-related histone H2A.X is mediated by the protein phosphatase eyes absent." Krishnan N., Jeong D.G., Jung S.-K., Ryu S.E., Xiao A., Allis C.D., Kim S.J., Tonks N.K. J. Biol. Chem. 284:16066-16070(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 268-538 IN COMPLEX WITH MAGNESIUM, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U71207 mRNA. Translation: AAB51120.1.
Y10261 Genomic DNA. Translation: CAA71310.1.
BT006682 mRNA. Translation: AAP35328.1.
AL049540 , AL121776, AL359434, AL022342 Genomic DNA. Translation: CAI23166.1.
AL121776 , AL049540, AL359434, AL022342 Genomic DNA. Translation: CAI42150.1.
AL359434 , AL049540, AL121776, AL022342 Genomic DNA. Translation: CAI40099.1.
BC000289 mRNA. Translation: AAH00289.2.
BC008803 mRNA. Translation: AAH08803.1.
BC013882 mRNA. Translation: AAH13882.2. Different initiation.
U81601 mRNA. Translation: AAB42065.1.
AJ007992 mRNA. Translation: CAA07815.1.

IPI

IPI00216797.
IPI00332969.
IPI00745292.

RefSeq

NP_005235.3. NM_005244.4.
NP_742108.2. NM_172110.3.

UniGene

Hs.472877.
Hs.722040.
Hs.722415.
Hs.722416.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GEB	X-ray	2.40	A/B/C/D	268-538	[»]
3HB0	X-ray	2.50	A/B/C/D	268-538	[»]
3HB1	X-ray	2.51	A/B/C/D	268-538	[»]
4EGC	X-ray	1.99	B	253-538	[»]

ProteinModelPortal

O00167.

ModBase

Search...

Protein-protein interaction databases

IntAct

O00167. 1 interaction.

MINT

MINT-139839.

PTM databases

PhosphoSite

O00167.

Proteomic databases

PaxDb

O00167.

PRIDE

O00167.

Protocols and materials databases

DNASU

2139.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000327619; ENSP00000333640; ENSG00000064655.
ENST00000357410; ENSP00000349986; ENSG00000064655.

GeneID

2139.

KEGG

hsa:2139.

UCSC

uc002xsm.3. human.
uc010ghp.3. human.

Organism-specific databases

CTD

2139.

GeneCards

GC20P045523.

HGNC

HGNC:3520. EYA2.

HPA

HPA027024.

MIM

601654. gene.

neXtProt

NX_O00167.

PharmGKB

PA27932.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG297494.

HOVERGEN

HBG002447.

InParanoid

O00167.

KO

K01104.

OMA

IHSRPNC.

OrthoDB

EOG45B1F9.

PhylomeDB

O00167.

Gene expression databases

ArrayExpress

O00167.

Bgee

O00167.

Genevestigator

O00167.

GermOnline

ENSG00000064655. Homo sapiens.

Family and domain databases

InterPro

IPR006545. EYA.
[Graphical view]

TIGRFAMs

TIGR01658. EYA-cons_domain. 1 hit.

ProtoNet

Search...

Other

ChEMBL

CHEMBL1293275.

EvolutionaryTrace

O00167.

GenomeRNAi

2139.

NextBio

8649.

SOURCE

Search...

Entry information

Entry name

EYA2_HUMAN

Accession

Primary (citable) accession number: O00167
Secondary accession number(s): Q5JSW8 , Q86U84, Q96CV6, Q96H97, Q99503, Q99812, Q9BWF6, Q9H4S3, Q9H4S9, Q9NPZ4, Q9UIX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 2, 2002
Last modified:	May 1, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.