Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Eyes absent homolog 1

Gene

EYA1

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

Functioni

Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5 (By similarity). Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. '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 (PubMed:19234442). Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis (By similarity). Has also phosphatase activity with proteins phosphorylated on Ser and Thr residues (in vitro) (By similarity). Required for normal embryonic development of the craniofacial and trunk skeleton, kidneys and ears (By similarity). Together with SIX1, it plays an important role in hypaxial muscle development; in this it is functionally redundant with EYA2 (By similarity).By similarity1 Publication

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.1 Publication
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.1 Publication

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei328NucleophileBy similarity1
Metal bindingi328MagnesiumBy similarity1
Active sitei330Proton donorBy similarity1
Metal bindingi330Magnesium; via carbonyl oxygenBy similarity1
Metal bindingi556MagnesiumBy similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • protein tyrosine phosphatase activity Source: UniProtKB
  • RNA binding Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionActivator, Chromatin regulator, Developmental protein, Hydrolase, Protein phosphatase
Biological processDNA damage, DNA repair, Transcription, Transcription regulation
LigandMagnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
SIGNORiQ99502

Names & Taxonomyi

Protein namesi
Recommended name:
Eyes absent homolog 1 (EC:3.1.3.161 Publication, EC:3.1.3.481 Publication)
Gene namesi
Name:EYA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104313.17
HGNCiHGNC:3519 EYA1
MIMi601653 gene
neXtProtiNX_Q99502

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Branchiootorenal syndrome 1 (BOR1)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, structural defects of the outer, middle or inner ear, and renal malformations.
See also OMIM:113650
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06494295P → S in BOR1. 1 Publication1
Natural variantiVAR_064943140G → S in BOR1. 1 Publication1
Natural variantiVAR_064944363E → V in BOR1. 1 Publication1
Natural variantiVAR_016865426G → S in BOR1; with cataract. 1 PublicationCorresponds to variant dbSNP:rs121909199EnsemblClinVar.1
Natural variantiVAR_016866429D → G in BOR1. 1 Publication1
Natural variantiVAR_016867440R → Q in BOR1. 2 PublicationsCorresponds to variant dbSNP:rs121909196EnsemblClinVar.1
Natural variantiVAR_005203487S → P in BOR1. 1 PublicationCorresponds to variant dbSNP:rs121909200EnsemblClinVar.1
Natural variantiVAR_005204505L → R in BOR1. 1 PublicationCorresponds to variant dbSNP:rs121909201EnsemblClinVar.1
Natural variantiVAR_064945514L → P in BOR1. 1 PublicationCorresponds to variant dbSNP:rs112340154Ensembl.1
Natural variantiVAR_064946527Y → C in BOR1. 1 Publication1
Natural variantiVAR_064947569M → T in BOR1. 1 Publication1
Natural variantiVAR_016869583L → P in BOR1. 1 PublicationCorresponds to variant dbSNP:rs397517920EnsemblClinVar.1
Otofaciocervical syndrome 1 (OTFCS1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by facial dysmorphism, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability.
See also OMIM:166780
Branchiootic syndrome 1 (BOS1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by usually bilateral branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, and structural defects of the outer, middle or inner ear. Otic defects include malformed and hypoplastic pinnae, a narrowed external ear canal, bulbous internal auditory canal, stapes fixation, malformed and hypoplastic cochlea. Branchial and otic anomalies overlap with those seen in individuals with the branchiootorenal syndrome. However renal anomalies are absent in branchiootic syndrome patients.
See also OMIM:602588
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_044452242S → G in BOS1. 1 PublicationCorresponds to variant dbSNP:rs191838840Ensembl.1
Anterior segment anomalies with or without cataract (ASA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by various types of developmental eye anomalies, in the absence of other abnormalities. The phenotypic spectrum of anterior segment anomalies include central corneal opacity, Peters anomaly, and bilateral persistence of the pupillary membrane. Some patients have cataract.
See also OMIM:602588
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_016864363E → K in ASA. 1 PublicationCorresponds to variant dbSNP:rs121909198EnsemblClinVar.1
Natural variantiVAR_016868547R → G in ASA; with cataract. 1 PublicationCorresponds to variant dbSNP:rs121909197EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi328D → A: Loss of tyrosine phosphatase activity toward H2AX. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi2138
GeneReviewsiEYA1
MalaCardsiEYA1
MIMi113650 phenotype
166780 phenotype
602588 phenotype
OpenTargetsiENSG00000104313
Orphaneti107 BOR syndrome
52429 Branchio-otic syndrome
2792 Otofaciocervical syndrome
PharmGKBiPA27931

Polymorphism and mutation databases

DMDMi3183005

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002186431 – 592Eyes absent homolog 1Add BLAST592

Post-translational modificationi

Sumoylated with SUMO1.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ99502
PaxDbiQ99502
PeptideAtlasiQ99502
PRIDEiQ99502
ProteomicsDBi78303
78304 [Q99502-2]

PTM databases

DEPODiQ99502
iPTMnetiQ99502
PhosphoSitePlusiQ99502

Expressioni

Tissue specificityi

In the embryo, highly expressed in kidney with lower levels in brain. Weakly expressed in lung. In the adult, highly expressed in heart and skeletal muscle. Weakly expressed in brain and liver. No expression in eye or kidney.

Developmental stagei

Detected in cytoplasm of somite cells at the beginning of fourth week of development. Detected in cytoplasm of limb bud cell between the sixth and eighth week of development.1 Publication

Gene expression databases

BgeeiENSG00000104313 Expressed in 145 organ(s), highest expression level in kidney
CleanExiHS_EYA1
ExpressionAtlasiQ99502 baseline and differential
GenevisibleiQ99502 HS

Organism-specific databases

HPAiHPA028917

Interactioni

Subunit structurei

Probably interacts with SIX2, SIX4 and SIX5. Interacts with H2AX in response to DNA damage. Interacts with SIX3; promotes EYA1 translocation to the nucleus.By similarity

Protein-protein interaction databases

BioGridi108439, 20 interactors
DIPiDIP-60446N
IntActiQ99502, 3 interactors
STRINGi9606.ENSP00000342626

Structurei

3D structure databases

ProteinModelPortaliQ99502
SMRiQ99502
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3107 Eukaryota
ENOG410XT12 LUCA
GeneTreeiENSGT00390000008860
HOGENOMiHOG000293149
HOVERGENiHBG002447
InParanoidiQ99502
KOiK15616
OMAiYATYPQP
OrthoDBiEOG091G04YD
PhylomeDBiQ99502
TreeFamiTF319337

Family and domain databases

CDDicd02601 HAD_Eya, 1 hit
Gene3Di3.40.50.12350, 1 hit
InterProiView protein in InterPro
IPR006545 EYA_dom
IPR038102 EYA_dom_sf
IPR028472 EYA_fam
IPR028471 Eyes_absent_h1
PANTHERiPTHR10190 PTHR10190, 1 hit
PTHR10190:SF11 PTHR10190:SF11, 1 hit
TIGRFAMsiTIGR01658 EYA-cons_domain, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 10 potential isoforms that are computationally mapped.iShow all

Isoform EYA1A (identifier: Q99502-1) [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
MEMQDLTSPH SRLSGSSESP SGPKLGNSHI NSNSMTPNGT EVKTEPMSSS
60 70 80 90 100
ETASTTADGS LNNFSGSAIG SSSFSPRPTH QFSPPQIYPS NRPYPHILPT
110 120 130 140 150
PSSQTMAAYG QTQFTTGMQQ ATAYATYPQP GQPYGISSYG ALWAGIKTEG
160 170 180 190 200
GLSQSQSPGQ TGFLSYGTSF STPQPGQAPY SYQMQGSSFT TSSGIYTGNN
210 220 230 240 250
SLTNSSGFNS SQQDYPSYPS FGQGQYAQYY NSSPYPAHYM TSSNTSPTTP
260 270 280 290 300
STNATYQLQE PPSGITSQAV TDPTAEYSTI HSPSTPIKDS DSDRLRRGSD
310 320 330 340 350
GKSRGRGRRN NNPSPPPDSD LERVFIWDLD ETIIVFHSLL TGSYANRYGR
360 370 380 390 400
DPPTSVSLGL RMEEMIFNLA DTHLFFNDLE ECDQVHIDDV SSDDNGQDLS
410 420 430 440 450
TYNFGTDGFP AAATSANLCL ATGVRGGVDW MRKLAFRYRR VKEIYNTYKN
460 470 480 490 500
NVGGLLGPAK REAWLQLRAE IEALTDSWLT LALKALSLIH SRTNCVNILV
510 520 530 540 550
TTTQLIPALA KVLLYGLGIV FPIENIYSAT KIGKESCFER IIQRFGRKVV
560 570 580 590
YVVIGDGVEE EQGAKKHAMP FWRISSHSDL MALHHALELE YL
Length:592
Mass (Da):64,593
Last modified:July 15, 1998 - v2
Checksum:iD62365F81EB692E2
GO
Isoform EYA1B (identifier: Q99502-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-41: MEMQDLTSPHSRLSGSSESPSGPKLGNSHINSNSMTPNGTE → MLLFPQVA

Show »
Length:559
Mass (Da):61,211
Checksum:i6B638C22438309A8
GO
Isoform EYA1D (identifier: Q99502-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     140-144: Missing.
     351-380: Missing.

Show »
Length:557
Mass (Da):60,660
Checksum:i7AAB97F0AAE440CC
GO

Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8WB53F8WB53_HUMAN
Eyes absent homolog
EYA1
591Annotation score:
A6NCB9A6NCB9_HUMAN
Eyes absent homolog
EYA1
586Annotation score:
E7EQM5E7EQM5_HUMAN
Eyes absent homolog
EYA1
558Annotation score:
E5RHZ7E5RHZ7_HUMAN
Eyes absent homolog
EYA1
148Annotation score:
E5RIQ7E5RIQ7_HUMAN
Eyes absent homolog
EYA1
212Annotation score:
A0A2R8Y6K4A0A2R8Y6K4_HUMAN
Eyes absent homolog
EYA1
621Annotation score:
A0A2R8YGM9A0A2R8YGM9_HUMAN
Eyes absent homolog
EYA1
585Annotation score:
A0A2R8YET7A0A2R8YET7_HUMAN
Eyes absent homolog
EYA1
586Annotation score:
A0A2R8YFS6A0A2R8YFS6_HUMAN
Eyes absent homolog
EYA1
82Annotation score:
A0A2R8YF73A0A2R8YF73_HUMAN
Eyes absent homolog
EYA1
90Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti33N → D in AAL73437 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02443920P → A. Corresponds to variant dbSNP:rs1445404EnsemblClinVar.1
Natural variantiVAR_07003341E → K Found in a patient with congenital cataract. 1 PublicationCorresponds to variant dbSNP:rs561111097Ensembl.1
Natural variantiVAR_06494295P → S in BOR1. 1 Publication1
Natural variantiVAR_064943140G → S in BOR1. 1 Publication1
Natural variantiVAR_044452242S → G in BOS1. 1 PublicationCorresponds to variant dbSNP:rs191838840Ensembl.1
Natural variantiVAR_016864363E → K in ASA. 1 PublicationCorresponds to variant dbSNP:rs121909198EnsemblClinVar.1
Natural variantiVAR_064944363E → V in BOR1. 1 Publication1
Natural variantiVAR_016865426G → S in BOR1; with cataract. 1 PublicationCorresponds to variant dbSNP:rs121909199EnsemblClinVar.1
Natural variantiVAR_016866429D → G in BOR1. 1 Publication1
Natural variantiVAR_016867440R → Q in BOR1. 2 PublicationsCorresponds to variant dbSNP:rs121909196EnsemblClinVar.1
Natural variantiVAR_005203487S → P in BOR1. 1 PublicationCorresponds to variant dbSNP:rs121909200EnsemblClinVar.1
Natural variantiVAR_005204505L → R in BOR1. 1 PublicationCorresponds to variant dbSNP:rs121909201EnsemblClinVar.1
Natural variantiVAR_064945514L → P in BOR1. 1 PublicationCorresponds to variant dbSNP:rs112340154Ensembl.1
Natural variantiVAR_064946527Y → C in BOR1. 1 Publication1
Natural variantiVAR_016868547R → G in ASA; with cataract. 1 PublicationCorresponds to variant dbSNP:rs121909197EnsemblClinVar.1
Natural variantiVAR_064947569M → T in BOR1. 1 Publication1
Natural variantiVAR_016869583L → P in BOR1. 1 PublicationCorresponds to variant dbSNP:rs397517920EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0014861 – 41MEMQD…PNGTE → MLLFPQVA in isoform EYA1B. CuratedAdd BLAST41
Alternative sequenceiVSP_045793140 – 144Missing in isoform EYA1D. 1 Publication5
Alternative sequenceiVSP_045794351 – 380Missing in isoform EYA1D. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10260 Genomic DNA Translation: CAA71309.1
AJ000097 mRNA Translation: CAA03922.1
AJ000098 mRNA Translation: CAA03923.1
AF467247 mRNA Translation: AAL73437.1
AC016465 Genomic DNA No translation available.
AC022858 Genomic DNA No translation available.
CH471068 Genomic DNA Translation: EAW86976.1
BC121799 mRNA Translation: AAI21800.1
CCDSiCCDS34906.1 [Q99502-1]
RefSeqiNP_000494.2, NM_000503.5 [Q99502-1]
NP_001275503.1, NM_001288574.1
NP_001275504.1, NM_001288575.1
NP_742055.1, NM_172058.3 [Q99502-1]
NP_742056.1, NM_172059.3
NP_742057.1, NM_172060.3
XP_016868695.1, XM_017013206.1 [Q99502-1]
XP_016868701.1, XM_017013212.1 [Q99502-2]
UniGeneiHs.444971
Hs.491997
Hs.612611

Genome annotation databases

EnsembliENST00000340726; ENSP00000342626; ENSG00000104313 [Q99502-1]
ENST00000388740; ENSP00000373392; ENSG00000104313 [Q99502-2]
ENST00000388742; ENSP00000373394; ENSG00000104313 [Q99502-1]
ENST00000419131; ENSP00000410176; ENSG00000104313 [Q99502-3]
ENST00000644427; ENSP00000496702; ENSG00000104313 [Q99502-1]
ENST00000645793; ENSP00000496255; ENSG00000104313 [Q99502-1]
ENST00000647540; ENSP00000494438; ENSG00000104313 [Q99502-1]
GeneIDi2138
KEGGihsa:2138
UCSCiuc003xyr.6 human [Q99502-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiEYA1_HUMAN
AccessioniPrimary (citable) accession number: Q99502
Secondary accession number(s): A6NHQ0
, G5E9R4, Q0P516, Q8WX80
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: September 12, 2018
This is version 164 of the entry and version 2 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again