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Protein

Eyes absent homolog 4

Gene

EYA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.By similarity

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei375NucleophileBy similarity1
Metal bindingi375MagnesiumBy similarity1
Active sitei377Proton donorBy similarity1
Metal bindingi377Magnesium; via carbonyl oxygenBy similarity1
Metal bindingi603MagnesiumBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Developmental protein, Hydrolase, Protein phosphatase

Keywords - Biological processi

DNA damage, DNA repair, Transcription, Transcription regulation

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS03559-MONOMER.
ReactomeiR-HSA-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 4 (EC:3.1.3.48By similarity)
Gene namesi
Name:EYA4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:3522. EYA4.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal dominant, 10 (DFNA10)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:601316
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074570171G → R in DFNA10. 1 Publication1
Natural variantiVAR_074571548T → R in DFNA10. 1 Publication1
Cardiomyopathy, dilated 1J (CMD1J)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:605362

Keywords - Diseasei

Cardiomyopathy, Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

DisGeNETi2070.
MalaCardsiEYA4.
MIMi601316. phenotype.
605362. phenotype.
OpenTargetsiENSG00000112319.
Orphaneti90635. Autosomal dominant non-syndromic sensorineural deafness type DFNA.
217622. Sensorineural deafness with dilated cardiomyopathy.
PharmGKBiPA27934.

Polymorphism and mutation databases

BioMutaiEYA4.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002186511 – 639Eyes absent homolog 4Add BLAST639

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei361PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiO95677.
PaxDbiO95677.
PeptideAtlasiO95677.
PRIDEiO95677.

PTM databases

DEPODiO95677.
iPTMnetiO95677.
PhosphoSitePlusiO95677.

Expressioni

Tissue specificityi

Highly expressed in heart and skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000112319.
CleanExiHS_EYA4.
ExpressionAtlasiO95677. baseline and differential.
GenevisibleiO95677. HS.

Organism-specific databases

HPAiHPA004805.
HPA038771.
HPA038772.

Interactioni

Subunit structurei

Interacts with SIX3; translocates EYA4 from the cytoplasm to the nucleus and promotes activation of their target genes.1 Publication

Protein-protein interaction databases

BioGridi108382. 4 interactors.
IntActiO95677. 1 interactor.
STRINGi9606.ENSP00000347294.

Structurei

3D structure databases

ProteinModelPortaliO95677.
SMRiO95677.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3107. Eukaryota.
ENOG410XT12. LUCA.
GeneTreeiENSGT00390000008860.
HOGENOMiHOG000293149.
HOVERGENiHBG002447.
InParanoidiO95677.
KOiK17622.
PhylomeDBiO95677.
TreeFamiTF319337.

Family and domain databases

Gene3Di3.40.50.1000. 2 hits.
InterProiIPR028478. EYA4.
IPR006545. EYA_dom.
IPR028472. EYA_fam.
IPR023214. HAD-like_dom.
[Graphical view]
PANTHERiPTHR10190. PTHR10190. 2 hits.
PTHR10190:SF17. PTHR10190:SF17. 2 hits.
TIGRFAMsiTIGR01658. EYA-cons_domain. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95677-1) [UniParc]FASTAAdd 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
MEDSQDLNEQ SVKKTCTESD VSQSQNSRSM EMQDLASPHT LVGGGDTPGS
60 70 80 90 100
SKLEKSNLSS TSVTTNGTGG ENMTVLNTAD WLLSCNTPSS ATMSLLAVKT
110 120 130 140 150
EPLNSSETTA TTGDGALDTF TGSVITSSGY SPRSAHQYSP QLYPSKPYPH
160 170 180 190 200
ILSTPAAQTM SAYAGQTQYS GMQQPAVYTA YSQTGQPYSL PTYDLGVMLP
210 220 230 240 250
AIKTESGLSQ TQSPLQSGCL SYSPGFSTPQ PGQTPYSYQM PGSSFAPSST
260 270 280 290 300
IYANNSVSNS TNFSGSQQDY PSYTAFGQNQ YAQYYSASTY GAYMTSNNTA
310 320 330 340 350
DGTPSSTSTY QLQESLPGLT NQPGEFDTMQ SPSTPIKDLD ERTCRSSGSK
360 370 380 390 400
SRGRGRKNNP SPPPDSDLER VFVWDLDETI IVFHSLLTGS YAQKYGKDPP
410 420 430 440 450
MAVTLGLRME EMIFNLADTH LFFNDLEECD QVHIDDVSSD DNGQDLSTYS
460 470 480 490 500
FATDGFHAAA SSANLCLPTG VRGGVDWMRK LAFRYRRVKE LYNTYKNNVG
510 520 530 540 550
GLLGPAKRDA WLQLRAEIEG LTDSWLTNAL KSLSIISTRS NCINVLVTTT
560 570 580 590 600
QLIPALAKVL LYSLGGAFPI ENIYSATKIG KESCFERIMQ RFGRKVVYVV
610 620 630
IGDGVEEEQA AKKHNMPFWR ISSHSDLLAL HQALELEYL
Length:639
Mass (Da):69,505
Last modified:July 19, 2005 - v2
Checksum:iCC59A8FB1527A0EC
GO
Isoform 2 (identifier: O95677-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     70-92: Missing.
     93-93: M → V

Show »
Length:616
Mass (Da):67,065
Checksum:i61BC97D2981AC16E
GO
Isoform 3 (identifier: O95677-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:452
Mass (Da):48,735
Checksum:iCE4391D2A264B937
GO
Isoform 4 (identifier: O95677-4) [UniParc]FASTAAdd to basket

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

Show »
Length:639
Mass (Da):69,417
Checksum:i514B81F45BD98DA2
GO
Isoform 5 (identifier: O95677-5) [UniParc]FASTAAdd to basket

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

Show »
Length:585
Mass (Da):63,911
Checksum:iF11418BAC8175189
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti177V → A in BAH13593 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036248152L → R in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_074570171G → R in DFNA10. 1 Publication1
Natural variantiVAR_022932277G → S.1 PublicationCorresponds to variant rs9493627dbSNPEnsembl.1
Natural variantiVAR_036249301D → N in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs779172192dbSNPEnsembl.1
Natural variantiVAR_074571548T → R in DFNA10. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04216070 – 123Missing in isoform 5. 1 PublicationAdd BLAST54
Alternative sequenceiVSP_00149570 – 92Missing in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_00149693M → V in isoform 2. 1 Publication1
Alternative sequenceiVSP_001497447 – 452STYSFA → RCKRRG in isoform 3. Curated6
Alternative sequenceiVSP_001498453 – 639Missing in isoform 3. CuratedAdd BLAST187
Alternative sequenceiVSP_001499589 – 613MQRFG…QAAKK → VSRFGTNITYVVIGDGRDEE HAANQ in isoform 4 and isoform 5. 1 PublicationAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS43506.1. [O95677-2]
CCDS5165.1. [O95677-1]
CCDS5166.1. [O95677-4]
CCDS75523.1. [O95677-5]
RefSeqiNP_001287941.1. NM_001301012.1. [O95677-5]
NP_001287942.1. NM_001301013.1.
NP_004091.3. NM_004100.4. [O95677-1]
NP_742101.2. NM_172103.3. [O95677-2]
NP_742103.1. NM_172105.3. [O95677-4]
UniGeneiHs.596680.

Genome annotation databases

EnsembliENST00000355167; ENSP00000347294; ENSG00000112319. [O95677-4]
ENST00000355286; ENSP00000347434; ENSG00000112319. [O95677-2]
ENST00000367895; ENSP00000356870; ENSG00000112319. [O95677-1]
ENST00000431403; ENSP00000404558; ENSG00000112319. [O95677-4]
ENST00000452339; ENSP00000395916; ENSG00000112319. [O95677-5]
GeneIDi2070.
KEGGihsa:2070.
UCSCiuc003qec.5. human. [O95677-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS43506.1. [O95677-2]
CCDS5165.1. [O95677-1]
CCDS5166.1. [O95677-4]
CCDS75523.1. [O95677-5]
RefSeqiNP_001287941.1. NM_001301012.1. [O95677-5]
NP_001287942.1. NM_001301013.1.
NP_004091.3. NM_004100.4. [O95677-1]
NP_742101.2. NM_172103.3. [O95677-2]
NP_742103.1. NM_172105.3. [O95677-4]
UniGeneiHs.596680.

3D structure databases

ProteinModelPortaliO95677.
SMRiO95677.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108382. 4 interactors.
IntActiO95677. 1 interactor.
STRINGi9606.ENSP00000347294.

PTM databases

DEPODiO95677.
iPTMnetiO95677.
PhosphoSitePlusiO95677.

Polymorphism and mutation databases

BioMutaiEYA4.

Proteomic databases

MaxQBiO95677.
PaxDbiO95677.
PeptideAtlasiO95677.
PRIDEiO95677.

Protocols and materials databases

DNASUi2070.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355167; ENSP00000347294; ENSG00000112319. [O95677-4]
ENST00000355286; ENSP00000347434; ENSG00000112319. [O95677-2]
ENST00000367895; ENSP00000356870; ENSG00000112319. [O95677-1]
ENST00000431403; ENSP00000404558; ENSG00000112319. [O95677-4]
ENST00000452339; ENSP00000395916; ENSG00000112319. [O95677-5]
GeneIDi2070.
KEGGihsa:2070.
UCSCiuc003qec.5. human. [O95677-1]

Organism-specific databases

CTDi2070.
DisGeNETi2070.
GeneCardsiEYA4.
GeneReviewsiEYA4.
HGNCiHGNC:3522. EYA4.
HPAiHPA004805.
HPA038771.
HPA038772.
MalaCardsiEYA4.
MIMi601316. phenotype.
603550. gene.
605362. phenotype.
neXtProtiNX_O95677.
OpenTargetsiENSG00000112319.
Orphaneti90635. Autosomal dominant non-syndromic sensorineural deafness type DFNA.
217622. Sensorineural deafness with dilated cardiomyopathy.
PharmGKBiPA27934.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3107. Eukaryota.
ENOG410XT12. LUCA.
GeneTreeiENSGT00390000008860.
HOGENOMiHOG000293149.
HOVERGENiHBG002447.
InParanoidiO95677.
KOiK17622.
PhylomeDBiO95677.
TreeFamiTF319337.

Enzyme and pathway databases

BioCyciZFISH:HS03559-MONOMER.
ReactomeiR-HSA-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.

Miscellaneous databases

GeneWikiiEYA4.
GenomeRNAii2070.
PROiO95677.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112319.
CleanExiHS_EYA4.
ExpressionAtlasiO95677. baseline and differential.
GenevisibleiO95677. HS.

Family and domain databases

Gene3Di3.40.50.1000. 2 hits.
InterProiIPR028478. EYA4.
IPR006545. EYA_dom.
IPR028472. EYA_fam.
IPR023214. HAD-like_dom.
[Graphical view]
PANTHERiPTHR10190. PTHR10190. 2 hits.
PTHR10190:SF17. PTHR10190:SF17. 2 hits.
TIGRFAMsiTIGR01658. EYA-cons_domain. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiEYA4_HUMAN
AccessioniPrimary (citable) accession number: O95677
Secondary accession number(s): B7Z7F7
, O95464, O95679, Q8IW39, Q9NTR7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 19, 2005
Last modified: November 30, 2016
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.