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Q99504 (EYA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Eyes absent homolog 3

EC=3.1.3.48
Gene names
Name:EYA3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length573 AA.
Sequence statusComplete.
Protein existenceEvidence 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, and 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 By similarity. May be involved in development of the eye. Ref.9 Ref.10

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.9 Ref.10

Cofactor

Binds 1 Mg2+ ion per subunit By similarity.

Subunit structure

Interacts with SIX1 and DACH1, and probably SIX2, SIX4, SIX5 By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus. Note: Localizes at sites of DNA damage at double-strand breaks (DSBs). With decreasing efficiency, translocalized to the nucleus by SIX2 and SIX5, and SIX4, respectively By similarity. Ref.10

Post-translational modification

Ser-266 phosphorylation is required for localization at sites of DNA damage and directing interaction with H2AX.

Sequence similarities

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

Biophysicochemical properties

Kinetic parameters:

KM=1.8 µM for H2AXY142ph Ref.9

KM=72 µM for H2AXS139ph

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandMagnesium
Metal-binding
   Molecular functionActivator
Chromatin regulator
Developmental protein
Hydrolase
Protein phosphatase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanatomical structure morphogenesis

Traceable author statement Ref.1. Source: ProtInc

double-strand break repair

Inferred from mutant phenotype Ref.10. Source: UniProtKB

histone dephosphorylation

Inferred from direct assay Ref.10Ref.9. Source: UniProtKB

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

peptidyl-tyrosine dephosphorylation

Inferred from direct assay Ref.10Ref.9. Source: GOC

positive regulation of DNA repair

Inferred from mutant phenotype Ref.10. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

response to ionizing radiation

Inferred from direct assay Ref.10. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

visual perception

Traceable author statement Ref.2. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay Ref.10. Source: UniProtKB

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionchromatin binding

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein tyrosine phosphatase activity

Inferred from direct assay Ref.10Ref.9. Source: UniProtKB

protein tyrosine/serine/threonine phosphatase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99504-1)

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: Q99504-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-126: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 573573Eyes absent homolog 3
PRO_0000218648

Sites

Active site3091Nucleophile Probable
Active site3111Proton donor By similarity
Metal binding3091Magnesium
Metal binding3111Magnesium By similarity
Metal binding5371Magnesium By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.8
Modified residue2661Phosphoserine Ref.10
Modified residue4721Phosphoserine Ref.12

Natural variations

Alternative sequence1 – 126126Missing in isoform 2.
VSP_001493

Experimental info

Mutagenesis2661S → A: Fails to form damage-dependent nuclear foci or interact with H2AX. Ref.10
Mutagenesis3091D → A: Loss of tyrosine phosphatase activity toward H2AX. Ref.10
Sequence conflict1051Y → D in CAA71311. Ref.1
Sequence conflict1421H → R in AAB42066. Ref.2
Sequence conflict1511L → V in AAB42066. Ref.2
Sequence conflict2531R → K in CAA71311. Ref.1
Sequence conflict2681T → S in AAB42066. Ref.2
Sequence conflict2831T → N in CAA71311. Ref.1
Sequence conflict2901R → K in CAA71311. Ref.1
Sequence conflict3051V → L in AAB42066. Ref.2
Sequence conflict3451E → K in CAA71311. Ref.1
Sequence conflict3571F → S in CAA71311. Ref.1
Sequence conflict3611E → K in CAA71311. Ref.1
Sequence conflict373 – 3819SDDNGQDLS → PNDKGQNLN in CAA71311. Ref.1
Sequence conflict3881D → N in CAA71311. Ref.1
Sequence conflict447 – 4493RLR → KLK in CAA71311. Ref.1
Sequence conflict4571D → N in CAA71311. Ref.1
Sequence conflict4731R → K in CAA71311. Ref.1
Sequence conflict4801L → P in AAB42066. Ref.2
Sequence conflict4871V → L in CAA71311. Ref.1
Sequence conflict5001E → K in CAA71311. Ref.1
Sequence conflict524 – 5263SRF → TSL in CAA71311. Ref.1
Sequence conflict5301V → L in CAA71311. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 16, 2009. Version 3.
Checksum: 684B961B1E630371

FASTA57362,663
        10         20         30         40         50         60 
MEEEQDLPEQ PVKKAKMQES GEQTISQVSN PDVSDQKPET SSLASNLPMS EEIMTCTDYI 

        70         80         90        100        110        120 
PRSSNDYTSQ MYSAKPYAHI LSVPVSETAY PGQTQYQTLQ QTQPYAVYPQ ATQTYGLPPF 

       130        140        150        160        170        180 
GALWPGMKPE SGLIQTPSPS QHSVLTCTTG LTTSQPSPAH YSYPIQASST NASLISTSST 

       190        200        210        220        230        240 
IANIPAAAVA SISNQDYPTY TILGQNQYQA CYPSSSFGVT GQTNSDAEST TLAATTYQSE 

       250        260        270        280        290        300 
KPSVMAPAPA AQRLSSGDPS TSPSLSQTTP SKDTDDQSRK NMTSKNRGKR KADATSSQDS 

       310        320        330        340        350        360 
ELERVFLWDL DETIIIFHSL LTGSYAQKYG KDPTVVIGSG LTMEEMIFEV ADTHLFFNDL 

       370        380        390        400        410        420 
EECDQVHVED VASDDNGQDL SNYSFSTDGF SGSGGSGSHG SSVGVQGGVD WMRKLAFRYR 

       430        440        450        460        470        480 
KVREIYDKHK SNVGGLLSPQ RKEALQRLRA EIEVLTDSWL GTALKSLLLI QSRKNCVNVL 

       490        500        510        520        530        540 
ITTTQLVPAL AKVLLYGLGE IFPIENIYSA TKIGKESCFE RIVSRFGKKV TYVVIGDGRD 

       550        560        570 
EEIAAKQHNM PFWRITNHGD LVSLHQALEL DFL 

« Hide

Isoform 2 [UniParc].

Checksum: 129E0A20B4A7BA2F
Show »

FASTA44748,652

References

« Hide 'large scale' references
[1]"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] (ISOFORM 1).
Tissue: Embryo.
[2]"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 2).
Tissue: Retina.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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 413-531.
[7]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"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: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[10]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-266, MUTAGENESIS OF SER-266 AND ASP-309.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-472, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y10262 Genomic DNA. Translation: CAA71311.1.
U81602 mRNA. Translation: AAB42066.1.
AK289805 mRNA. Translation: BAF82494.1.
AL512288, AL137792 Genomic DNA. Translation: CAI14297.1.
CH471059 Genomic DNA. Translation: EAX07713.1.
AJ007991 mRNA. Translation: CAA07814.1.
RefSeqNP_001981.2. NM_001990.3.
UniGeneHs.185774.

3D structure databases

ProteinModelPortalQ99504.
SMRQ99504. Positions 300-573.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108441. 3 interactions.
DIPDIP-60448N.
STRING9606.ENSP00000362978.

PTM databases

PhosphoSiteQ99504.

Polymorphism databases

DMDM239938901.

Proteomic databases

PaxDbQ99504.
PRIDEQ99504.

Protocols and materials databases

DNASU2140.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373871; ENSP00000362978; ENSG00000158161. [Q99504-1]
ENST00000436342; ENSP00000405587; ENSG00000158161. [Q99504-2]
GeneID2140.
KEGGhsa:2140.
UCSCuc001bpi.2. human. [Q99504-1]

Organism-specific databases

CTD2140.
GeneCardsGC01M028296.
HGNCHGNC:3521. EYA3.
HPAHPA052432.
MIM601655. gene.
neXtProtNX_Q99504.
PharmGKBPA27933.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG297494.
HOGENOMHOG000293149.
HOVERGENHBG002447.
InParanoidQ99504.
KOK17621.
OMAYTILGQS.
OrthoDBEOG7DNNTZ.
PhylomeDBQ99504.
TreeFamTF319337.

Enzyme and pathway databases

SABIO-RKQ99504.

Gene expression databases

ArrayExpressQ99504.
BgeeQ99504.
CleanExHS_EYA3.
GenevestigatorQ99504.

Family and domain databases

InterProIPR028479. EYA3.
IPR006545. EYA_dom.
IPR028472. EYA_fam.
[Graphical view]
PANTHERPTHR10190. PTHR10190. 1 hit.
PTHR10190:SF5. PTHR10190:SF5. 1 hit.
TIGRFAMsTIGR01658. EYA-cons_domain. 1 hit.
ProtoNetSearch...

Other

GenomeRNAi2140.
NextBio8661.
PROQ99504.
SOURCESearch...

Entry information

Entry nameEYA3_HUMAN
AccessionPrimary (citable) accession number: Q99504
Secondary accession number(s): A8K190, O95463, Q99813
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 16, 2009
Last modified: April 16, 2014
This is version 121 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM