Q99504 (EYA3_HUMAN) 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

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	573 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, 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.8 Ref.9
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.8 Ref.9
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.9
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.8 KM=72 µM for H2AXS139ph

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	anatomical structure morphogenesis Traceable author statement Ref.1. Source: ProtInc double-strand break repair Inferred from mutant phenotype Ref.9. Source: UniProtKB histone dephosphorylation Inferred from direct assay Ref.9Ref.8. Source: UniProtKB multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of DNA repair Inferred from mutant phenotype Ref.9. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to ionizing radiation Inferred from direct assay Ref.9. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW visual perception Traceable author statement Ref.2. Source: ProtInc
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay Ref.9. Source: UniProtKB transcription factor complex Inferred from electronic annotation. Source: Compara
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine phosphatase activity Inferred from direct assay Ref.9Ref.8. Source: UniProtKB protein tyrosine/serine/threonine phosphatase activity Inferred from electronic annotation. Source: Compara
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 573	573	Eyes absent homolog 3		PRO_0000218648
Sites
	Active site	309	1	Nucleophile Probable
	Active site	311	1	Proton donor By similarity
	Metal binding	309	1	Magnesium
	Metal binding	311	1	Magnesium By similarity
	Metal binding	537	1	Magnesium By similarity
Amino acid modifications
	Modified residue	266	1	Phosphoserine Ref.9
	Modified residue	472	1	Phosphoserine Ref.11
Natural variations
	Alternative sequence	1 – 126	126	Missing in isoform 2.		VSP_001493
Experimental info
	Mutagenesis	266	1	S → A: Fails to form damage-dependent nuclear foci or interact with H2AX. Ref.9
	Mutagenesis	309	1	D → A: Loss of tyrosine phosphatase activity toward H2AX. Ref.9
	Sequence conflict	105	1	Y → D in CAA71311. Ref.1
	Sequence conflict	142	1	H → R in AAB42066. Ref.2
	Sequence conflict	151	1	L → V in AAB42066. Ref.2
	Sequence conflict	253	1	R → K in CAA71311. Ref.1
	Sequence conflict	268	1	T → S in AAB42066. Ref.2
	Sequence conflict	283	1	T → N in CAA71311. Ref.1
	Sequence conflict	290	1	R → K in CAA71311. Ref.1
	Sequence conflict	305	1	V → L in AAB42066. Ref.2
	Sequence conflict	345	1	E → K in CAA71311. Ref.1
	Sequence conflict	357	1	F → S in CAA71311. Ref.1
	Sequence conflict	361	1	E → K in CAA71311. Ref.1
	Sequence conflict	373 – 381	9	SDDNGQDLS → PNDKGQNLN in CAA71311. Ref.1
	Sequence conflict	388	1	D → N in CAA71311. Ref.1
	Sequence conflict	447 – 449	3	RLR → KLK in CAA71311. Ref.1
	Sequence conflict	457	1	D → N in CAA71311. Ref.1
	Sequence conflict	473	1	R → K in CAA71311. Ref.1
	Sequence conflict	480	1	L → P in AAB42066. Ref.2
	Sequence conflict	487	1	V → L in CAA71311. Ref.1
	Sequence conflict	500	1	E → K in CAA71311. Ref.1
	Sequence conflict	524 – 526	3	SRF → TSL in CAA71311. Ref.1
	Sequence conflict	530	1	V → L in CAA71311. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 16, 2009. Version 3. Checksum: 684B961B1E630371	FASTA	573	62,663
	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
	Isoform 2 [UniParc]. Checksum: 129E0A20B4A7BA2F	FASTA	447	48,652
	10 20 30 40 50 60 MKPESGLIQT PSPSQHSVLT CTTGLTTSQP SPAHYSYPIQ ASSTNASLIS TSSTIANIPA 70 80 90 100 110 120 AAVASISNQD YPTYTILGQN QYQACYPSSS FGVTGQTNSD AESTTLAATT YQSEKPSVMA 130 140 150 160 170 180 PAPAAQRLSS GDPSTSPSLS QTTPSKDTDD QSRKNMTSKN RGKRKADATS SQDSELERVF 190 200 210 220 230 240 LWDLDETIII FHSLLTGSYA QKYGKDPTVV IGSGLTMEEM IFEVADTHLF FNDLEECDQV 250 260 270 280 290 300 HVEDVASDDN GQDLSNYSFS TDGFSGSGGS GSHGSSVGVQ GGVDWMRKLA FRYRKVREIY 310 320 330 340 350 360 DKHKSNVGGL LSPQRKEALQ RLRAEIEVLT DSWLGTALKS LLLIQSRKNC VNVLITTTQL 370 380 390 400 410 420 VPALAKVLLY GLGEIFPIEN IYSATKIGKE SCFERIVSRF GKKVTYVVIG DGRDEEIAAK 430 440 QHNMPFWRIT NHGDLVSLHQ ALELDFL

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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]	"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.
[9]	"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.
[10]	"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].
[11]	"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, MASS SPECTROMETRY.

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.
IPI	IPI00015990. IPI00216103.
RefSeq	NP_001981.2. NM_001990.3.
UniGene	Hs.185774.
3D structure databases
ProteinModelPortal	Q99504.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000362978.
PTM databases
PhosphoSite	Q99504.
Polymorphism databases
DMDM	239938901.
Proteomic databases
PaxDb	Q99504.
PRIDE	Q99504.
Protocols and materials databases
DNASU	2140.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000373871; ENSP00000362978; ENSG00000158161. ENST00000436342; ENSP00000405587; ENSG00000158161.
GeneID	2140.
KEGG	hsa:2140.
UCSC	uc001bpi.2. human.
Organism-specific databases
CTD	2140.
GeneCards	GC01M028296.
HGNC	HGNC:3521. EYA3.
HPA	HPA052432.
MIM	601655. gene.
neXtProt	NX_Q99504.
PharmGKB	PA27933.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG297494.
HOGENOM	HOG000293149.
HOVERGEN	HBG002447.
InParanoid	Q99504.
KO	K01104.
OMA	YTILGQS.
OrthoDB	EOG4RXXZZ.
PhylomeDB	Q99504.
Gene expression databases
ArrayExpress	Q99504.
Bgee	Q99504.
CleanEx	HS_EYA3.
Genevestigator	Q99504.
GermOnline	ENSG00000158161. Homo sapiens.
Family and domain databases
InterPro	IPR006545. EYA. [Graphical view]
TIGRFAMs	TIGR01658. EYA-cons_domain. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	2140.
NextBio	8661.
SOURCE	Search...

Entry information

Entry name

EYA3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 113 of the entry and version 3 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.