EYA4

Protein identityUniProt · HPA

UniProt accession

O95677

Gene

EYA4

Ensembl

ENSG00000112319

Chromosome

6

Canonical length

639 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator through its protein phosphatase activity, and it may be important for eye development, and for continued function of the mature organ of Corti. Mutations in this gene are associated with postlingual, progressive, autosomal dominant hearing loss at the deafness, autosomal dominant non-syndromic sensorineural 10 locus. The encoded protein is also a putative oncogene that mediates DNA repair, apoptosis, and innate immunity following DNA damage, cellular damage, and viral attack. Defects in this gene are also associated with dilated cardiomyopathy 1J. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

Canonical amino-acid sequenceUniProt

639 residues, UniProt reviewed canonical sequence.

>O95677|EYA4
     1  MEDSQDLNEQ SVKKTCTESD VSQSQNSRSM EMQDLASPHT LVGGGDTPGS SKLEKSNLSS
    61  TSVTTNGTGG ENMTVLNTAD WLLSCNTPSS ATMSLLAVKT EPLNSSETTA TTGDGALDTF
   121  TGSVITSSGY SPRSAHQYSP QLYPSKPYPH ILSTPAAQTM SAYAGQTQYS GMQQPAVYTA
   181  YSQTGQPYSL PTYDLGVMLP AIKTESGLSQ TQSPLQSGCL SYSPGFSTPQ PGQTPYSYQM
   241  PGSSFAPSST IYANNSVSNS TNFSGSQQDY PSYTAFGQNQ YAQYYSASTY GAYMTSNNTA
   301  DGTPSSTSTY QLQESLPGLT NQPGEFDTMQ SPSTPIKDLD ERTCRSSGSK SRGRGRKNNP
   361  SPPPDSDLER VFVWDLDETI IVFHSLLTGS YAQKYGKDPP MAVTLGLRME EMIFNLADTH
   421  LFFNDLEECD QVHIDDVSSD DNGQDLSTYS FATDGFHAAA SSANLCLPTG VRGGVDWMRK
   481  LAFRYRRVKE LYNTYKNNVG GLLGPAKRDA WLQLRAEIEG LTDSWLTNAL KSLSIISTRS
   541  NCINVLVTTT QLIPALAKVL LYSLGGAFPI ENIYSATKIG KESCFERIMQ RFGRKVVYVV
   601  IGDGVEEEQA AKKHNMPFWR ISSHSDLLAL HQALELEYL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against EYA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.53

Highest tissue expression

29 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about EYA4.

Disease | AllUniProt

Conditions EYA4 is implicated in, by any mechanism.

• Deafness, autosomal dominant, 10 (DFNA10) MIM:601316
• Cardiomyopathy, dilated, 1J (CMD1J) MIM:605362

Disease | GeneticClinVar

87 pathogenic / likely-pathogenic of 1,228 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dilated cardiomyopathy 1J
• Autosomal dominant nonsyndromic hearing loss 10
• Cardiovascular phenotype
• Rare genetic deafness
• EYA4-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.45

gnomAD pLI

0.05

gnomAD missense Z

1.12

DepMap mean gene effect

0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• anatomical structure morphogenesis
• cell differentiation
• chromatin organization
• DNA repair
• inner ear development
• negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• positive regulation of DNA repair
• visual perception

Molecular functions

• metal ion binding
• protein tyrosine phosphatase activity

Cellular components

• cytoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• EYA domain
• Protein phosphatase EYA
• EYA domain superfamily
• EYA domain, metazoan
• haloacid dehalogenase-like hydrolase

KeywordsUniProt

• Acetylation
• Activator
• Cardiomyopathy
• Chromatin regulator
• Cytoplasm
• Deafness
• Developmental protein
• DNA damage
• DNA repair
• Hydrolase
• Isopeptide bond
• Magnesium
• Metal-binding
• Non-syndromic deafness
• Nucleus
• Phosphoprotein
• Protein phosphatase
• Transcription
• Transcription regulation
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of EYA4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SIX3