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O95677 (EYA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Eyes absent homolog 4

EC=3.1.3.48
Gene names
Name:EYA4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length639 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. May be involved in development of the eye By similarity.

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Cofactor

Binds 1 Mg2+ ion per subunit By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Tissue specificity

Highly expressed in heart and skeletal muscle. Ref.6

Involvement in disease

Deafness, autosomal dominant, 10 (DFNA10) [MIM:601316]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Cardiomyopathy, dilated 1J (CMD1J) [MIM:605362]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD1J is characterized by the association of sensorineural hearing loss and dilated cardiomyopathy in the absence of other anomalies.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

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

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCardiomyopathy
Deafness
Non-syndromic deafness
   LigandMagnesium
Metal-binding
   Molecular functionActivator
Chromatin regulator
Developmental protein
Hydrolase
Protein phosphatase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Inferred from electronic annotation. Source: UniProtKB-KW

anatomical structure morphogenesis

Traceable author statement Ref.1. Source: ProtInc

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

inner ear development

Inferred from electronic annotation. Source: Ensembl

middle ear morphogenesis

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

visual perception

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein tyrosine phosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95677-1)

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: O95677-2)

The sequence of this isoform differs from the canonical sequence as follows:
     70-92: Missing.
     93-93: M → V
Isoform 3 (identifier: O95677-3)

The sequence of this isoform differs from the canonical sequence as follows:
     447-452: STYSFA → RCKRRG
     453-639: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 4 (identifier: O95677-4)

The sequence of this isoform differs from the canonical sequence as follows:
     589-613: MQRFGRKVVYVVIGDGVEEEQAAKK → VSRFGTNITYVVIGDGRDEEHAANQ
Isoform 5 (identifier: O95677-5)

The sequence of this isoform differs from the canonical sequence as follows:
     70-123: Missing.
     589-613: MQRFGRKVVYVVIGDGVEEEQAAKK → VSRFGTNITYVVIGDGRDEEHAANQ

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 639639Eyes absent homolog 4
PRO_0000218651

Sites

Active site3751Nucleophile By similarity
Active site3771Proton donor By similarity
Metal binding3751Magnesium By similarity
Metal binding3771Magnesium By similarity
Metal binding6031Magnesium By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.8
Modified residue3611Phosphoserine Ref.7

Natural variations

Alternative sequence70 – 12354Missing in isoform 5.
VSP_042160
Alternative sequence70 – 9223Missing in isoform 2.
VSP_001495
Alternative sequence931M → V in isoform 2.
VSP_001496
Alternative sequence447 – 4526STYSFA → RCKRRG in isoform 3.
VSP_001497
Alternative sequence453 – 639187Missing in isoform 3.
VSP_001498
Alternative sequence589 – 61325MQRFG…QAAKK → VSRFGTNITYVVIGDGRDEE HAANQ in isoform 4 and isoform 5.
VSP_001499
Natural variant1521L → R in a colorectal cancer sample; somatic mutation. Ref.9
VAR_036248
Natural variant2771G → S. Ref.1
Corresponds to variant rs9493627 [ dbSNP | Ensembl ].
VAR_022932
Natural variant3011D → N in a colorectal cancer sample; somatic mutation. Ref.9
VAR_036249

Experimental info

Sequence conflict1771V → A in BAH13593. Ref.2

Sequences

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

Last modified July 19, 2005. Version 2.
Checksum: CC59A8FB1527A0EC

FASTA63969,505
        10         20         30         40         50         60 
MEDSQDLNEQ SVKKTCTESD VSQSQNSRSM EMQDLASPHT LVGGGDTPGS SKLEKSNLSS 

        70         80         90        100        110        120 
TSVTTNGTGG ENMTVLNTAD WLLSCNTPSS ATMSLLAVKT EPLNSSETTA TTGDGALDTF 

       130        140        150        160        170        180 
TGSVITSSGY SPRSAHQYSP QLYPSKPYPH ILSTPAAQTM SAYAGQTQYS GMQQPAVYTA 

       190        200        210        220        230        240 
YSQTGQPYSL PTYDLGVMLP AIKTESGLSQ TQSPLQSGCL SYSPGFSTPQ PGQTPYSYQM 

       250        260        270        280        290        300 
PGSSFAPSST IYANNSVSNS TNFSGSQQDY PSYTAFGQNQ YAQYYSASTY GAYMTSNNTA 

       310        320        330        340        350        360 
DGTPSSTSTY QLQESLPGLT NQPGEFDTMQ SPSTPIKDLD ERTCRSSGSK SRGRGRKNNP 

       370        380        390        400        410        420 
SPPPDSDLER VFVWDLDETI IVFHSLLTGS YAQKYGKDPP MAVTLGLRME EMIFNLADTH 

       430        440        450        460        470        480 
LFFNDLEECD QVHIDDVSSD DNGQDLSTYS FATDGFHAAA SSANLCLPTG VRGGVDWMRK 

       490        500        510        520        530        540 
LAFRYRRVKE LYNTYKNNVG GLLGPAKRDA WLQLRAEIEG LTDSWLTNAL KSLSIISTRS 

       550        560        570        580        590        600 
NCINVLVTTT QLIPALAKVL LYSLGGAFPI ENIYSATKIG KESCFERIMQ RFGRKVVYVV 

       610        620        630 
IGDGVEEEQA AKKHNMPFWR ISSHSDLLAL HQALELEYL 

« Hide

Isoform 2 [UniParc].

Checksum: 61BC97D2981AC16E
Show »

FASTA61667,065
Isoform 3 [UniParc].

Checksum: CE4391D2A264B937
Show »

FASTA45248,735
Isoform 4 [UniParc].

Checksum: 514B81F45BD98DA2
Show »

FASTA63969,417
Isoform 5 [UniParc].

Checksum: F11418BAC8175189
Show »

FASTA58563,911

References

« Hide 'large scale' references
[1]"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 [GENOMIC DNA / MRNA], VARIANT SER-277, ALTERNATIVE SPLICING.
Tissue: Lens epithelium and Skeletal muscle.
[2]"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] (ISOFORM 5).
Tissue: Testis.
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORM 2).
Tissue: Brain.
[5]"Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus."
Wayne S., Robertson N.G., DeClau F., Chen N., Verhoeven K., Prasad S., Tranebjaerg L., Morton C.C., Ryan A.F., Van Camp G., Smith R.J.H.
Hum. Mol. Genet. 10:195-200(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN DFNA10.
[6]"Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss."
Schoenberger J., Wang L., Shin J.T., Kim S.D., Depreux F.F.S., Zhu H., Zon L., Pizard A., Kim J.B., Macrae C.A., Mungall A.J., Seidman J.G., Seidman C.E.
Nat. Genet. 37:418-422(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CMD1J, TISSUE SPECIFICITY.
[7]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[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]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-152 AND ASN-301.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y17114 mRNA. Translation: CAA76636.1.
Y17847 Genomic DNA. Translation: CAA76891.1.
AJ007993 mRNA. Translation: CAA07816.1.
AJ007994 mRNA. Translation: CAA07817.1.
AK301950 mRNA. Translation: BAH13593.1.
AL121959, AL024497, AL450270 Genomic DNA. Translation: CAB92069.2.
AL024497, AL121959, AL450270 Genomic DNA. Translation: CAI42524.1.
AL450270, AL024497, AL121959 Genomic DNA. Translation: CAI41272.1.
BC041063 mRNA. Translation: AAH41063.1.
RefSeqNP_004091.3. NM_004100.4.
NP_742101.2. NM_172103.3.
NP_742103.1. NM_172105.3.
UniGeneHs.596680.

3D structure databases

ProteinModelPortalO95677.
SMRO95677. Positions 369-639.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000347294.

PTM databases

PhosphoSiteO95677.

Proteomic databases

PaxDbO95677.
PRIDEO95677.

Protocols and materials databases

DNASU2070.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000355167; ENSP00000347294; ENSG00000112319. [O95677-4]
ENST00000355286; ENSP00000347434; ENSG00000112319. [O95677-2]
ENST00000367895; ENSP00000356870; ENSG00000112319. [O95677-1]
ENST00000431403; ENSP00000404558; ENSG00000112319. [O95677-4]
ENST00000452339; ENSP00000395916; ENSG00000112319. [O95677-5]
GeneID2070.
KEGGhsa:2070.
UCSCuc003qec.4. human. [O95677-1]
uc003qed.4. human. [O95677-4]
uc003qee.4. human. [O95677-2]
uc011ecq.2. human. [O95677-5]

Organism-specific databases

CTD2070.
GeneCardsGC06P133563.
HGNCHGNC:3522. EYA4.
HPAHPA004805.
HPA038771.
HPA038772.
MIM601316. phenotype.
603550. gene.
605362. phenotype.
neXtProtNX_O95677.
Orphanet90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
217622. Sensorineural deafness with dilated cardiomyopathy.
PharmGKBPA27934.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG297494.
HOGENOMHOG000293149.
HOVERGENHBG002447.
KOK17622.
OrthoDBEOG7DNNTZ.
PhylomeDBO95677.
TreeFamTF319337.

Gene expression databases

ArrayExpressO95677.
BgeeO95677.
CleanExHS_EYA4.
GenevestigatorO95677.

Family and domain databases

InterProIPR028478. EYA4.
IPR006545. EYA_dom.
IPR028472. EYA_fam.
[Graphical view]
PANTHERPTHR10190. PTHR10190. 1 hit.
PTHR10190:SF9. PTHR10190:SF9. 1 hit.
TIGRFAMsTIGR01658. EYA-cons_domain. 1 hit.
ProtoNetSearch...

Other

GeneWikiEYA4.
GenomeRNAi2070.
NextBio8417.
PROO95677.
SOURCESearch...

Entry information

Entry nameEYA4_HUMAN
AccessionPrimary (citable) accession number: O95677
Secondary accession number(s): B7Z7F7 expand/collapse secondary AC list , O95464, O95679, Q8IW39, Q9NTR7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 19, 2005
Last modified: April 16, 2014
This is version 127 of the entry and version 2 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM