UniProtKB - O00167 (EYA2_HUMAN)
Eyes absent homolog 2
EYA2
Functioni
Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5 (PubMed:12500905, PubMed:23435380).
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:19351884).
Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis. Plays an important role in hypaxial muscle development together with SIX1 and DACH2; in this it is functionally redundant with EYA1 (PubMed:12500905).
4 PublicationsCatalytic activityi
- EC:3.1.3.481 Publication
Cofactori
Kineticsi
- KM=1.9 µM for H2AXY142ph1 Publication
- KM=80 µM for H2AXS139ph1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 274 | Nucleophile1 Publication | 1 | |
Metal bindingi | 274 | Magnesium1 Publication | 1 | |
Active sitei | 276 | Proton donor1 Publication | 1 | |
Metal bindingi | 276 | Magnesium; via carbonyl oxygen1 Publication | 1 | |
Metal bindingi | 502 | Magnesium1 Publication | 1 |
GO - Molecular functioni
- magnesium ion binding Source: UniProtKB
- protein tyrosine phosphatase activity Source: UniProtKB
GO - Biological processi
- anatomical structure development Source: GO_Central
- cell differentiation Source: GO_Central
- chromatin organization Source: UniProtKB-KW
- DNA repair Source: UniProtKB-KW
- extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
- histone dephosphorylation Source: UniProtKB
- mesodermal cell fate specification Source: ProtInc
- mitochondrial outer membrane permeabilization Source: Ensembl
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central
- positive regulation of DNA repair Source: GO_Central
- striated muscle tissue development Source: Ensembl
Keywordsi
Molecular function | Activator, Chromatin regulator, Developmental protein, Hydrolase, Protein phosphatase |
Biological process | DNA damage, DNA repair, Transcription, Transcription regulation |
Ligand | Magnesium, Metal-binding |
Enzyme and pathway databases
BRENDAi | 3.1.3.48, 2681 |
PathwayCommonsi | O00167 |
Reactomei | R-HSA-5693565, Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks |
SABIO-RKi | O00167 |
SignaLinki | O00167 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:EYA2 Synonyms:EAB1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3520, EYA2 |
MIMi | 601654, gene |
neXtProti | NX_O00167 |
VEuPathDBi | HostDB:ENSG00000064655 |
Subcellular locationi
Cytosol
- cytosol Source: HPA
Mitochondrion
- mitochondrion Source: GOC
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 516 | P → R: Strongly reduces SIX1 binding. 1 Publication | 1 | |
Mutagenesisi | 532 | A → R: Abolishes interaction with SIX1. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 2139 |
OpenTargetsi | ENSG00000064655 |
PharmGKBi | PA27932 |
Miscellaneous databases
Pharosi | O00167, Tbio |
Chemistry databases
ChEMBLi | CHEMBL1293275 |
Genetic variation databases
BioMutai | EYA2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000218646 | 1 – 538 | Eyes absent homolog 2Add BLAST | 538 |
Proteomic databases
jPOSTi | O00167 |
MassIVEi | O00167 |
PaxDbi | O00167 |
PeptideAtlasi | O00167 |
PRIDEi | O00167 |
ProteomicsDBi | 47756 [O00167-1] 47757 [O00167-2] 47758 [O00167-3] |
PTM databases
DEPODi | EYA2 |
iPTMneti | O00167 |
PhosphoSitePlusi | O00167 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSG00000064655, Expressed in calcaneal tendon and 168 other tissues |
ExpressionAtlasi | O00167, baseline and differential |
Genevisiblei | O00167, HS |
Organism-specific databases
HPAi | ENSG00000064655, Tissue enhanced (cervix) |
Interactioni
Subunit structurei
Interacts with DACH2 and SIX1, and probably with SIX2, SIX4 and SIX5.
Interacts with CAPN8 (By similarity).
Interacts with GNAZ and GNAI2; this precludes interaction with SIX1.
By similarity5 PublicationsBinary interactionsi
O00167
With | #Exp. | IntAct |
---|---|---|
SIX1 [Q15475] | 4 | EBI-750211,EBI-743675 |
Isoform 1 [O00167-1]
With | #Exp. | IntAct |
---|---|---|
SIX1 [Q15475] | 3 | EBI-16038245,EBI-743675 |
Isoform 2 [O00167-2]
Protein-protein interaction databases
BioGRIDi | 108440, 122 interactors |
DIPi | DIP-40707N |
IntActi | O00167, 72 interactors |
MINTi | O00167 |
STRINGi | 9606.ENSP00000333640 |
Miscellaneous databases
RNActi | O00167, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | O00167 |
SMRi | O00167 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O00167 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 209 – 263 | DisorderedSequence analysisAdd BLAST | 55 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 209 – 232 | Polar residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 233 – 262 | Basic and acidic residuesSequence analysisAdd BLAST | 30 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3107, Eukaryota |
GeneTreei | ENSGT00950000182978 |
HOGENOMi | CLU_021184_2_0_1 |
InParanoidi | O00167 |
OMAi | HTQGYSV |
OrthoDBi | 1030296at2759 |
PhylomeDBi | O00167 |
TreeFami | TF319337 |
Family and domain databases
CDDi | cd02601, HAD_Eya, 1 hit |
Gene3Di | 3.40.50.12350, 1 hit |
InterProi | View protein in InterPro IPR028473, EYA2 IPR006545, EYA_dom IPR042577, EYA_dom_metazoan IPR038102, EYA_dom_sf IPR028472, EYA_fam IPR036412, HAD-like_sf |
PANTHERi | PTHR10190, PTHR10190, 1 hit PTHR10190:SF7, PTHR10190:SF7, 1 hit |
SUPFAMi | SSF56784, SSF56784, 1 hit |
TIGRFAMsi | TIGR01658, EYA-cons_domain, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MVELVISPSL TVNSDCLDKL KFNRADAAVW TLSDRQGITK SAPLRVSQLF
60 70 80 90 100
SRSCPRVLPR QPSTAMAAYG QTQYSAGIQQ ATPYTAYPPP AQAYGIPSYS
110 120 130 140 150
IKTEDSLNHS PGQSGFLSYG SSFSTSPTGQ SPYTYQMHGT TGFYQGGNGL
160 170 180 190 200
GNAAGFGSVH QDYPSYPGFP QSQYPQYYGS SYNPPYVPAS SICPSPLSTS
210 220 230 240 250
TYVLQEASHN VPNQSSESLA GEYNTHNGPS TPAKEGDTDR PHRASDGKLR
260 270 280 290 300
GRSKRSSDPS PAGDNEIERV FVWDLDETII IFHSLLTGTF ASRYGKDTTT
310 320 330 340 350
SVRIGLMMEE MIFNLADTHL FFNDLEDCDQ IHVDDVSSDD NGQDLSTYNF
360 370 380 390 400
SADGFHSSAP GANLCLGSGV HGGVDWMRKL AFRYRRVKEM YNTYKNNVGG
410 420 430 440 450
LIGTPKRETW LQLRAELEAL TDLWLTHSLK ALNLINSRPN CVNVLVTTTQ
460 470 480 490 500
LIPALAKVLL YGLGSVFPIE NIYSATKTGK ESCFERIMQR FGRKAVYVVI
510 520 530
GDGVEEEQGA KKHNMPFWRI SCHADLEALR HALELEYL
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE7ETN2 | E7ETN2_HUMAN | Eyes absent homolog | EYA2 | 508 | Annotation score: | ||
B1AKW3 | B1AKW3_HUMAN | Eyes absent homolog | EYA2 | 197 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 296 | K → E in AAB42065 (PubMed:9049631).Curated | 1 | |
Sequence conflicti | 361 | G → A in AAP35328 (Ref. 4) Curated | 1 | |
Sequence conflicti | 361 | G → A in AAH08803 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 381 | A → S in AAB42065 (PubMed:9049631).Curated | 1 | |
Sequence conflicti | 419 | A → V in CAA07815 (PubMed:9887327).Curated | 1 | |
Sequence conflicti | 525 | D → N in AAB51120 (PubMed:9195991).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_048964 | 83 | P → S. Corresponds to variant dbSNP:rs2275596Ensembl. | 1 | |
Natural variantiVAR_048965 | 238 | T → A. Corresponds to variant dbSNP:rs866936EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_001490 | 99 – 122 | Missing in isoform 2. 2 PublicationsAdd BLAST | 24 | |
Alternative sequenceiVSP_001491 | 401 – 479 | Missing in isoform 3. 1 PublicationAdd BLAST | 79 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U71207 mRNA Translation: AAB51120.1 Y10261 Genomic DNA Translation: CAA71310.1 BT006682 mRNA Translation: AAP35328.1 AL049540 , AL121776, AL359434, AL022342 Genomic DNA Translation: CAI23166.1 BC000289 mRNA Translation: AAH00289.2 BC008803 mRNA Translation: AAH08803.1 BC013882 mRNA Translation: AAH13882.2 Different initiation. U81601 mRNA Translation: AAB42065.1 AJ007992 mRNA Translation: CAA07815.1 |
CCDSi | CCDS13403.1 [O00167-1] CCDS54471.1 [O00167-3] |
RefSeqi | NP_005235.3, NM_005244.4 [O00167-1] NP_742108.2, NM_172110.3 [O00167-3] |
Genome annotation databases
Ensembli | ENST00000327619.10; ENSP00000333640.5; ENSG00000064655.19 ENST00000357410.7; ENSP00000349986.3; ENSG00000064655.19 [O00167-3] ENST00000497062.6; ENSP00000417105.3; ENSG00000064655.19 [O00167-2] |
GeneIDi | 2139 |
KEGGi | hsa:2139 |
MANE-Selecti | ENST00000327619.10; ENSP00000333640.5; NM_005244.5; NP_005235.3 |
UCSCi | uc002xsm.3, human [O00167-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U71207 mRNA Translation: AAB51120.1 Y10261 Genomic DNA Translation: CAA71310.1 BT006682 mRNA Translation: AAP35328.1 AL049540 , AL121776, AL359434, AL022342 Genomic DNA Translation: CAI23166.1 BC000289 mRNA Translation: AAH00289.2 BC008803 mRNA Translation: AAH08803.1 BC013882 mRNA Translation: AAH13882.2 Different initiation. U81601 mRNA Translation: AAB42065.1 AJ007992 mRNA Translation: CAA07815.1 |
CCDSi | CCDS13403.1 [O00167-1] CCDS54471.1 [O00167-3] |
RefSeqi | NP_005235.3, NM_005244.4 [O00167-1] NP_742108.2, NM_172110.3 [O00167-3] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3GEB | X-ray | 2.40 | A/B/C/D | 268-538 | [»] | |
3HB0 | X-ray | 2.50 | A/B/C/D | 268-538 | [»] | |
3HB1 | X-ray | 2.51 | A/B/C/D | 268-538 | [»] | |
4EGC | X-ray | 1.99 | B | 253-538 | [»] | |
5ZMA | X-ray | 3.17 | A/B/C | 253-538 | [»] | |
7F8G | X-ray | 3.49 | A/B | 253-538 | [»] | |
7F8H | X-ray | 3.30 | A/B/C | 253-538 | [»] | |
AlphaFoldDBi | O00167 | |||||
SMRi | O00167 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108440, 122 interactors |
DIPi | DIP-40707N |
IntActi | O00167, 72 interactors |
MINTi | O00167 |
STRINGi | 9606.ENSP00000333640 |
Chemistry databases
ChEMBLi | CHEMBL1293275 |
PTM databases
DEPODi | EYA2 |
iPTMneti | O00167 |
PhosphoSitePlusi | O00167 |
Genetic variation databases
BioMutai | EYA2 |
Proteomic databases
jPOSTi | O00167 |
MassIVEi | O00167 |
PaxDbi | O00167 |
PeptideAtlasi | O00167 |
PRIDEi | O00167 |
ProteomicsDBi | 47756 [O00167-1] 47757 [O00167-2] 47758 [O00167-3] |
Protocols and materials databases
Antibodypediai | 13258, 268 antibodies from 29 providers |
DNASUi | 2139 |
Genome annotation databases
Ensembli | ENST00000327619.10; ENSP00000333640.5; ENSG00000064655.19 ENST00000357410.7; ENSP00000349986.3; ENSG00000064655.19 [O00167-3] ENST00000497062.6; ENSP00000417105.3; ENSG00000064655.19 [O00167-2] |
GeneIDi | 2139 |
KEGGi | hsa:2139 |
MANE-Selecti | ENST00000327619.10; ENSP00000333640.5; NM_005244.5; NP_005235.3 |
UCSCi | uc002xsm.3, human [O00167-1] |
Organism-specific databases
CTDi | 2139 |
DisGeNETi | 2139 |
GeneCardsi | EYA2 |
HGNCi | HGNC:3520, EYA2 |
HPAi | ENSG00000064655, Tissue enhanced (cervix) |
MIMi | 601654, gene |
neXtProti | NX_O00167 |
OpenTargetsi | ENSG00000064655 |
PharmGKBi | PA27932 |
VEuPathDBi | HostDB:ENSG00000064655 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3107, Eukaryota |
GeneTreei | ENSGT00950000182978 |
HOGENOMi | CLU_021184_2_0_1 |
InParanoidi | O00167 |
OMAi | HTQGYSV |
OrthoDBi | 1030296at2759 |
PhylomeDBi | O00167 |
TreeFami | TF319337 |
Enzyme and pathway databases
BRENDAi | 3.1.3.48, 2681 |
PathwayCommonsi | O00167 |
Reactomei | R-HSA-5693565, Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks |
SABIO-RKi | O00167 |
SignaLinki | O00167 |
Miscellaneous databases
BioGRID-ORCSi | 2139, 14 hits in 1075 CRISPR screens |
ChiTaRSi | EYA2, human |
EvolutionaryTracei | O00167 |
GeneWikii | EYA2 |
GenomeRNAii | 2139 |
Pharosi | O00167, Tbio |
PROi | PR:O00167 |
RNActi | O00167, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000064655, Expressed in calcaneal tendon and 168 other tissues |
ExpressionAtlasi | O00167, baseline and differential |
Genevisiblei | O00167, HS |
Family and domain databases
CDDi | cd02601, HAD_Eya, 1 hit |
Gene3Di | 3.40.50.12350, 1 hit |
InterProi | View protein in InterPro IPR028473, EYA2 IPR006545, EYA_dom IPR042577, EYA_dom_metazoan IPR038102, EYA_dom_sf IPR028472, EYA_fam IPR036412, HAD-like_sf |
PANTHERi | PTHR10190, PTHR10190, 1 hit PTHR10190:SF7, PTHR10190:SF7, 1 hit |
SUPFAMi | SSF56784, SSF56784, 1 hit |
TIGRFAMsi | TIGR01658, EYA-cons_domain, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | EYA2_HUMAN | |
Accessioni | O00167Primary (citable) accession number: O00167 Secondary accession number(s): Q5JSW8 Q9UIX7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | May 2, 2002 | |
Last modified: | May 25, 2022 | |
This is version 196 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 20
Human chromosome 20: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families