Affinage

EYA2

Protein phosphatase EYA2 · UniProt O00167

Length
538 aa
Mass
59.2 kDa
Annotated
2026-06-09
44 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EYA2 is a dual-function protein that operates both as a SIX-recruited transcriptional co-activator and as a HAD-family tyrosine phosphatase, integrating developmental and oncogenic transcriptional programs with phosphatase-dependent control of cell migration and mitosis (PMID:10617572, PMID:19858093). Intrinsically cytosolic, EYA2 is translocated to the nucleus by SIX-family homeodomain proteins, where it forms bipartite complexes with SIX1/SIX4 and DACH proteins to drive transcription from MEF3 promoter elements; this complex governs PAX3-initiated myogenic and somitic programs during development (PMID:10906137, PMID:17098221). Crystallographic analysis places the catalytic site and the SIX-interacting surface on opposite faces of the EYA domain with the DACH-binding site between them, and a high-resolution SIX1-EYA2 co-structure shows SIX1 engages EYA2 through a single helix whose single-residue disruption blocks SIX1-driven EMT and metastasis (PMID:19858093, PMID:23435380). Nuclear access of EYA2 is negatively regulated by activated Gαi/Gαz proteins, which bind its C-terminal Eya domain and sequester it at the plasma membrane, while EYA2 reciprocally relieves Gαi2-mediated inhibition of adenylyl cyclase (PMID:10906137, PMID:15308761). The intrinsic tyrosine phosphatase activity dephosphorylates H2AX and is required for cell cycle progression, mitotic spindle assembly at centrosomes, cell migration, invadopodia formation, and invasion, as established by allosteric inhibitors that bind a pocket distant from the active site and abrogate Mg2+ coordination (PMID:22820394, PMID:24755226, PMID:31285279, PMID:32142407, PMID:34617969). Through this dual activity EYA2 drives oncogenic phenotypes — SIX1-dependent TGF-β signaling and EMT, ERK/MMP9-mediated invasion, MYC expression and stability, and mesenchymal/immune-evasion programs — and conversely acts as a tumor suppressor in liver by partnering DACH1 to induce SOCS3 and restrain JAK/STAT signaling (PMID:21706047, PMID:28901379, PMID:34044846, PMID:35182481, PMID:37486991). EYA2 protein abundance is set by competing ubiquitin pathways: FBXO7 stabilizes it whereas SCFFBXW7 and Smurf2 promote its ubiquitin-mediated degradation (PMID:35182481, PMID:40556274).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1999 High

    Established that EYA2 functions not in isolation but as a node in a SIX-EYA-DACH regulatory network controlling myogenic differentiation.

    Evidence GST pulldown and co-IP plus chick embryo electroporation epistasis showing EYA2-DACH2 and EYA2-SIX1 interactions

    PMID:10617572

    Open questions at the time
    • Did not define the structural basis of the interactions
    • Catalytic activity of EYA2 not yet known
  2. 2000 High

    Resolved how EYA2 reaches its site of action and how it is restrained, showing it is cytosolic and SIX-imported while Gαz/Gαi2 block nuclear entry.

    Evidence Yeast and mammalian two-hybrid, GST pulldown, localization and MEF3/TATA reporter assays with domain mapping

    PMID:10906137

    Open questions at the time
    • Mechanism by which SIX drives import not detailed
    • Physiological trigger for Gα-mediated sequestration unknown
  3. 2001 Medium

    Placed EYA2 within an ordered myogenic cascade by identifying PAX3 as a necessary and sufficient upstream inducer of SIX1 and EYA2.

    Evidence Gain- and dominant-negative loss-of-function in pluripotent stem cells with RT-PCR readout

    PMID:11262400

    Open questions at the time
    • Direct vs indirect induction of EYA2 by PAX3 not resolved
    • Single lab, expression-level readout only
  4. 2004 High

    Extended Gα regulation to the Gαi family and demonstrated bidirectional crosstalk, with EYA2 relieving Gαi2 inhibition of adenylyl cyclase.

    Evidence In vitro binding, co-IP, localization microscopy, reporter and adenylyl cyclase activity assays

    PMID:15308761

    Open questions at the time
    • In vivo relevance of EYA2-Gαi crosstalk untested
    • Whether phosphatase activity contributes to adenylyl cyclase modulation unknown
  5. 2006 High

    Revealed EYA2 as a developmental regulator acting genetically upstream of PAX3 in hypaxial myogenesis through SIX-MEF3 site engagement.

    Evidence Eya1/Eya2 double-knockout mice, in situ hybridization, ChIP/reporter MEF3 binding

    PMID:17098221

    Open questions at the time
    • Functional redundancy with EYA1 prevents EYA2-specific dissection
    • Phosphatase contribution to this developmental role untested
  6. 2009 High

    Defined the structural and catalytic nature of EYA2, identifying it as a HAD-family phosphatase with spatially segregated catalytic, SIX, and DACH surfaces.

    Evidence 2.4-Å X-ray crystallography of the EYA domain with reaction-intermediate capture

    PMID:19858093

    Open questions at the time
    • Physiological substrates not identified in this study
    • Proposed DACH switch model not functionally tested here
  7. 2009 Medium

    Connected EYA2 to organ physiology by showing it protects against pathological cardiac remodeling via SIX1-complexed signaling.

    Evidence Cardiac-specific transgenic mice, pressure-overload surgery, expression profiling, co-IP

    PMID:19272299

    Open questions at the time
    • Direct transcriptional targets not identified in this study
    • Phosphatase vs co-activator contribution not separated
  8. 2011 High

    Identified mTOR as a direct EYA2-SIX1 transcriptional target mediating physiological hypertrophy, providing a concrete promoter readout.

    Evidence Luciferase reporter, ChIP, EMSA, co-IP and transgenic mice

    PMID:22197309

    Open questions at the time
    • Whether phosphatase activity is required for mTOR promoter activation unknown
    • Single lab
  9. 2011 Medium

    Established EYA2 as an obligatory co-factor for SIX1's oncogenic functions, linking it to TGF-β-driven EMT and cancer stem cell properties.

    Evidence siRNA knockdown in MCF7 cells with TGF-β, EMT marker, and stem-cell assays

    PMID:21706047

    Open questions at the time
    • Did not separate phosphatase from co-activator requirement
    • Single cell line, single lab
  10. 2012 Medium

    Provided the first selective chemical probes of EYA2 phosphatase and confirmed H2AX as a substrate, enabling functional dissection of catalytic activity.

    Evidence HTS, in vitro phosphatase assays, selectivity panel

    PMID:22820394

    Open questions at the time
    • Modest potency (IC50 1.8–79 µM)
    • Cellular target engagement not yet shown
  11. 2013 High

    Defined the SIX1-EYA2 interface at atomic resolution and proved a single interface residue controls EMT and metastasis, validating the complex as a therapeutic target.

    Evidence 2.0-Å crystallography, site-directed mutagenesis, co-IP, in vivo metastasis models

    PMID:23435380

    Open questions at the time
    • Did not address phosphatase-dependent functions
    • BOR mutation consequences inferred structurally
  12. 2013 Low

    Suggested cell-cycle kinase control of EYA2 abundance by identifying CDK6-promoted degradation.

    Evidence Co-IP and protein degradation assays

    PMID:24196439

    Open questions at the time
    • Single co-IP and degradation assay without reciprocal or mechanistic validation
    • Ubiquitin pathway not defined
  13. 2014 High

    Demonstrated the inhibitors act allosterically rather than at the active site, separating EYA2 phosphatase-driven migration from EYA3 and defining a druggable regulatory pocket.

    Evidence In vitro phosphatase assay, mutagenesis, reversibility and migration assays

    PMID:24755226

    Open questions at the time
    • Allosteric mechanism structurally undefined at this stage
    • Single lab
  14. 2014 Medium

    Placed EYA2 under post-transcriptional control by miR-30a and linked it to G1/S progression via cyclin and c-Myc regulation.

    Evidence 3'-UTR reporter, knockdown, rescue overexpression, proliferation/migration and flow cytometry assays

    PMID:24508260

    Open questions at the time
    • Mechanism of cyclin/c-Myc regulation not defined
    • Single lab
  15. 2017 Medium

    Showed EYA2 drives invasion through SIX1-dependent ERK activation and MMP9 induction in astrocytoma.

    Evidence Co-IP, siRNA knockdown, ERK inhibitor, invasion assay, MMP9 Western blot

    PMID:28901379

    Open questions at the time
    • Direct vs indirect link between EYA2 and ERK unresolved
    • Single lab
  16. 2019 High

    Captured the inhibitor-bound EYA2 structure revealing an induced allosteric pocket and genetically confirmed phosphatase-dependent invasion in lung cancer.

    Evidence X-ray crystallography, F290Y mutagenesis, migration/invasion/invadopodia and loss-of-function assays

    PMID:31285279

    Open questions at the time
    • Phosphatase substrate driving invasion not identified
    • Phosphatase dispensable for growth/survival in this model
  17. 2020 High

    Demonstrated in vivo that EYA2 phosphatase controls H2AX phosphorylation and cell cycle progression during regeneration, generalizing its catalytic role beyond cancer.

    Evidence Eya2 mutant axolotl, pharmacological inhibition, phospho-H2AX immunostaining, cell cycle analysis

    PMID:32142407

    Open questions at the time
    • Whether H2AX is the direct in vivo substrate not formally proven
    • Co-activator contribution to regeneration untested
  18. 2020 High

    Validated pharmacological disruption of the SIX1/EYA2 complex as antimetastatic, showing it reverses EMT and TGF-β programs without affecting primary tumor growth.

    Evidence PPI assay, transcriptomics, metabolomics, EMT analysis, in vivo metastasis model

    PMID:32341035

    Open questions at the time
    • Whether residual phosphatase activity persists with PPI disruption unknown
    • Single lab
  19. 2021 High

    Identified EYA2 as a context-dependent tumor suppressor in liver, acting with DACH1 to induce SOCS3 and dampen JAK/STAT signaling.

    Evidence Co-IP, RNA-seq, hepatocyte-specific KO mice, UPR assays of the A510E mutant

    PMID:34044846

    Open questions at the time
    • Reconciliation of tumor-suppressive vs oncogenic roles across tissues unresolved
    • Role of phosphatase activity in SOCS3 regulation not defined
  20. 2021 High

    Revealed a centrosomal localization and a phosphatase-dependent role in mitotic spindle assembly essential for glioblastoma stem cell survival.

    Evidence Immunofluorescence, genetic KO/KD, pharmacological inhibition, cell cycle/apoptosis assays, in vivo tumor model

    PMID:34617969

    Open questions at the time
    • Centrosomal substrate of EYA2 not identified
    • Link to H2AX dephosphorylation at centrosome unclear
  21. 2022 High

    Defined competing ubiquitin pathways controlling EYA2 stability and linked phosphatase-driven EYA2 to mesenchymal and immune-evasion programs downstream of GAS6/AXL.

    Evidence Reciprocal co-IP, ubiquitination assays, genetic perturbation, transcriptomics, in vivo immune phenotyping with anti-PD-1

    PMID:35182481

    Open questions at the time
    • Direct phosphatase substrate driving immune evasion not identified
    • Interplay between FBXW7 and Smurf2 degradation not compared
  22. 2023 Medium

    Connected EYA2 phosphatase activity to MYC expression and stability, defining a targetable axis in Group 3 medulloblastoma.

    Evidence Genetic knockdown, pharmacological phosphatase inhibition, MYC expression/stability assays, in vivo tumor models

    PMID:37486991

    Open questions at the time
    • Direct mechanism of MYC stabilization by EYA2 phosphatase not resolved
    • Single lab
  23. 2025 Medium

    Added Smurf2 as an EYA2 ubiquitin ligase relevant to diabetic nephropathy, with EYA2 placed downstream as the effector of fibrosis and proliferation.

    Evidence Co-IP, ubiquitination Western blot, siRNA knockdown, in vitro fibrosis assays, in vivo diabetic nephropathy model

    PMID:40556274

    Open questions at the time
    • Smurf2 degron on EYA2 not mapped
    • Single lab, recently published

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological tyrosine phosphatase substrates beyond H2AX and the basis for EYA2's opposite (oncogenic vs tumor-suppressive) roles across tissues remain undefined.
  • No direct centrosomal or MYC-stabilizing phosphatase substrate identified
  • Switch between co-activator and phosphatase functions not mechanistically resolved
  • Tissue-specific determinants of oncogenic vs suppressive output unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0140110 transcription regulator activity 4 GO:0016787 hydrolase activity 3 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 2 GO:0005886 plasma membrane 2 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 2
Partners
DACH1DACH2FBXO7FBXW7GNAI2SIX1SIX4SMURF2
Complex memberships
EYA2-DACH1 complexSIX1-EYA2-DACH transcriptional complexSIX4-EYA2 complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 EYA2 physically interacts with DACH2 and SIX1 proteins, and these interactions synergistically regulate myogenic differentiation; EYA2-DACH2 and EYA2-SIX1 direct physical interactions were demonstrated by pulldown/co-immunoprecipitation assays. GST pulldown and co-immunoprecipitation assays; functional synergy assays in chick embryo electroporation Genes & development High 10617572
2000 EYA2 is an intrinsically cytosolic protein that is translocated to the nucleus by SIX family homeodomain proteins; activated Gαz and Gαi2 interact with the C-terminal Eya consensus domain of EYA2, prevent its nuclear translocation, and inhibit SIX/EYA2-mediated transcription from MEF3/TATA promoter elements. Yeast two-hybrid, mammalian two-hybrid, GST pulldown, subcellular localization assays, reporter gene assays The Journal of biological chemistry High 10906137
2001 PAX3 is necessary and sufficient to induce expression of SIX1 and its cofactor EYA2 prior to MyoD and myogenin induction during myogenesis; dominant-negative PAX3 abolishes SIX1 and EYA2 expression, placing PAX3 upstream of EYA2 in the myogenic transcriptional cascade. Gain-of-function and dominant-negative loss-of-function in pluripotent stem cells; RT-PCR expression analysis The Journal of biological chemistry Medium 11262400
2004 Gαi1, Gαi2, and Gαi3 (but not Gαo) interact with EYA2 in an activation-dependent manner; coexpression of activated Gαi family members recruits EYA2 to the plasma membrane, prevents nuclear translocation, abrogates EYA2/SIX4-mediated transcription, and EYA2 reciprocally relieves Gαi2-mediated inhibition of adenylyl cyclase. In vitro binding assays, co-immunoprecipitation, subcellular localization by microscopy, transcriptional reporter assays, adenylyl cyclase activity assay Molecular pharmacology High 15308761
2006 EYA1 and EYA2 act genetically upstream of PAX3 in hypaxial dermomyotome formation; SIX proteins recruit EYA proteins to MEF3 DNA sites to drive transcription during somitogenesis; compound Eya1/Eya2 double-knockout embryos lose PAX3 expression in ventrolateral dermomyotomes and lack hypaxial myogenic progenitors, phenocopying Six1/Six4 double knockouts. Genetic epistasis (double knockout mice), in situ hybridization, ChIP/reporter assays showing SIX-EYA binding to MEF3 sites Developmental biology High 17098221
2009 Crystal structure of the EYA domain (ED) of human EYA2 at 2.4-Å resolution reveals it belongs to the haloacid dehalogenase (HAD) family with an elongated helix-bundle motif; catalytic and SIX-interacting sites are on opposite faces, and the DACH-binding site lies between them, suggesting DACH acts as a transcriptional switch linking phosphatase activity to SIX binding; two reaction intermediates (acyl-phosphate and hydrolysis transition state) were captured. X-ray crystallography (2.4 Å), active-site intermediate capture FASEB journal High 19858093
2009 EYA2 overexpression in transgenic mice prevents pressure-overload-induced adverse cardiac remodeling, preserves the PI3K/Akt/mTOR signaling cascade, and alters metabolic gene expression; EYA2 forms a complex with SIX1 during physiological hypertrophy. Cardiac-specific transgenic mice, pressure overload surgery, gene expression profiling, co-immunoprecipitation Journal of molecular and cellular cardiology Medium 19272299
2011 EYA2 directly binds to the mTOR promoter and activates mTOR expression; the EYA2-SIX1 complex binds the mTOR promoter synergistically; this pathway mediates physiological cardiac hypertrophy with preservation of mitochondrial integrity. Luciferase reporter assays, chromatin immunoprecipitation (ChIP), EMSA, transgenic mice, co-immunoprecipitation Journal of molecular and cellular cardiology High 22197309
2011 EYA2 is required for SIX1 to induce TGF-β signaling, epithelial-mesenchymal transition, and cancer stem cell properties in breast cancer cells; knockdown of EYA2 reverses SIX1-mediated pro-metastatic characteristics, establishing EYA2 as a necessary co-factor for SIX1's oncogenic functions. siRNA knockdown in MCF7 cells, TGF-β signaling assays, EMT marker analysis, cancer stem cell assays Oncogene Medium 21706047
2012 A class of N-arylidenebenzohydrazide compounds selectively inhibits EYA2 phosphatase activity with IC50 values of 1.8–79 µM and does not significantly inhibit other cellular phosphatases; H2AX is confirmed as a known EYA2 substrate in this assay context. High-throughput screening, in vitro phosphatase assay (OMFP and malachite green), selectivity panel against other phosphatases Journal of biomolecular screening Medium 22820394
2013 Crystal structure of the human SIX1-EYA2 complex at 2.0-Å resolution reveals SIX1 uses predominantly a single helix to interact with EYA2; substitution of a single amino acid in this helix disrupts SIX1-EYA2 interaction, SIX1-mediated EMT, and metastasis in mouse models; structure provides rationale for BOR syndrome mutations. X-ray crystallography (2.0 Å), site-directed mutagenesis, co-immunoprecipitation, in vivo mouse metastasis models Nature structural & molecular biology High 23435380
2013 CDK6 binds to and promotes the degradation of the EYA2 protein, suggesting CDK6 regulates EYA2 activity. Co-immunoprecipitation, protein degradation assays Cell cycle (Georgetown, Tex.) Low 24196439
2014 N-arylidenebenzohydrazide compounds are reversible, allosteric inhibitors of EYA2 phosphatase that do not bind the active site and do not require Mg2+ coordination; mutagenesis indicates binding occurs on the opposite face from the active site; these compounds inhibit EYA2 phosphatase-mediated cell migration selectively over EYA3. In vitro phosphatase assay, site-directed mutagenesis, reversibility assays, cell migration assay The Journal of biological chemistry High 24755226
2014 miR-30a represses EYA2 expression by binding to the 3'-UTR of EYA2; EYA2 overexpression rescues the inhibition of breast cancer cell proliferation and migration caused by miR-30a, and EYA2 mediates G1/S cell cycle progression via regulation of cyclin A, cyclin D1, cyclin E, and c-Myc. 3'-UTR reporter assay, siRNA knockdown, rescue overexpression, cell proliferation and migration assays, flow cytometry Biochemical and biophysical research communications Medium 24508260
2017 EYA2 interacts with SIX1 protein in astrocytoma cells; EYA2 positively regulates ERK activity and MMP9 expression; blockade of ERK signaling abolishes EYA2-induced MMP9 production and invasion; EYA2 fails to upregulate MMP9 expression when SIX1 is silenced, indicating EYA2 requires SIX1 for this function. Co-immunoprecipitation, siRNA knockdown, ERK inhibitor treatment, invasion assay, Western blot for MMP9 International journal of molecular medicine Medium 28901379
2019 Crystal structure of EYA2 ED in complex with allosteric inhibitor NCGC00249987 reveals it binds an induced pocket distant from the active site; inhibitor binding causes a conformational change unfavorable for Mg2+ binding, inhibiting tyrosine phosphatase activity; EYA2 tyrosine phosphatase activity is required for migration, invadopodia formation, and invasion of lung adenocarcinoma cells but not for growth or survival; EYA2 F290Y mutant abolishes compound binding, confirming on-target activity. X-ray crystallography, site-directed mutagenesis (F290Y), cell migration/invasion/invadopodia assays, genetic loss-of-function Molecular cancer therapeutics High 31285279
2020 EYA2 phosphatase activity regulates H2AX phosphorylation during blastema cell proliferation in axolotl limb regeneration; loss of eya2 (genetic ablation or pharmacological phosphatase inhibition) impairs cell cycle progression at G1/S and G2/M transitions and reduces regeneration rate. Eya2 mutant axolotl generation, pharmacological Eya2 phosphatase inhibition, phospho-H2AX immunostaining, cell cycle analysis eLife High 32142407
2020 Small molecule NCGC00378430 (8430) reduces the SIX1/EYA2 protein-protein interaction; 8430 partially reverses SIX1-mediated transcriptional and metabolic profiles and reverses SIX1-induced TGF-β signaling and EMT; treatment significantly suppresses breast cancer metastasis in vivo without significantly altering primary tumor growth. Protein-protein interaction assay, transcriptomics, metabolomics, TGF-β signaling assays, EMT marker analysis, in vivo mouse metastasis model Cancer research High 32341035
2021 EYA2 combines with DACH1 to transcriptionally regulate SOCS3 expression, suppressing JAK/STAT signaling; hepatocyte-specific deletion of EYA2 in mice promotes diethylnitrosamine-induced HCC development; EYA2(A510E) mutation leads to protein degradation via the unfolded protein response, weakening EYA2's tumor-suppressive function. Co-immunoprecipitation (EYA2-DACH1 complex), RNA sequencing, loss- and gain-of-function in cell lines, hepatocyte-specific knockout mice, unfolded protein response assays Molecular cancer High 34044846
2021 EYA2 localizes to centrosomes in glioblastoma stem cells (GSCs); EYA2 tyrosine phosphatase activity is essential for proper mitotic spindle assembly and survival of GSCs; genetic or pharmacological inhibition of EYA2 Tyr phosphatase causes mitotic catastrophe, cell cycle arrest, apoptosis, and loss of self-renewal in GSCs. Immunofluorescence localization to centrosomes, genetic EYA2 knockout/knockdown, pharmacological Tyr phosphatase inhibition, cell cycle analysis, apoptosis assays, in vivo mouse tumor model The Journal of experimental medicine High 34617969
2022 FBXO7 binds and stabilizes EYA2, stimulating mesenchymal gene expression and suppressing IFN/chemokine/antigen-presentation pathways; ubiquitin ligase SCFFBXW7 antagonizes this by promoting EYA2 ubiquitin-mediated degradation; EYA2 Tyr phosphatase activity drives mesenchymal phenotypes and immune evasion; the AXL ligand GAS6 drives the FBXO7/EYA2 axis. Co-immunoprecipitation (FBXO7-EYA2), ubiquitination assays, genetic knockdown/knockout, transcriptomics, in vivo mouse tumor/immune infiltration assays, anti-PD-1 combination experiments Molecular cell High 35182481
2023 EYA2 regulates MYC expression and protein stability in Group 3 medulloblastoma; inhibition of EYA2 tyrosine phosphatase activity decreases MYC expression and global MYC transcriptional activity both in vitro and in vivo, reducing tumor growth. Genetic EYA2 knockdown, pharmacological Tyr phosphatase inhibition (NCGC00249987), MYC expression/stability assays, in vivo flank and intracranial tumor models Neuro-oncology Medium 37486991
2025 Smurf2 ubiquitin ligase promotes EYA2 ubiquitination and degradation; Smurf2 knockdown suppresses EYA2 ubiquitination, elevates EYA2 protein levels, and inhibits mesangial cell proliferation and fibrosis under high glucose; EYA2 knockdown reverses the protective effects of Smurf2 knockdown, placing EYA2 downstream of Smurf2-mediated ubiquitination in diabetic nephropathy. Co-immunoprecipitation (Smurf2-EYA2), ubiquitination Western blot, siRNA knockdown, in vitro cell proliferation/fibrosis assays, in vivo diabetic nephropathy mouse model Renal failure Medium 40556274

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation. Genes & development 292 10617572
2006 Eya1 and Eya2 proteins are required for hypaxial somitic myogenesis in the mouse embryo. Developmental biology 123 17098221
2001 Pax3 is essential for skeletal myogenesis and the expression of Six1 and Eya2. The Journal of biological chemistry 122 11262400
2011 Eya2 is required to mediate the pro-metastatic functions of Six1 via the induction of TGF-β signaling, epithelial-mesenchymal transition, and cancer stem cell properties. Oncogene 119 21706047
2017 The EGFR/miR-338-3p/EYA2 axis controls breast tumor growth and lung metastasis. Cell death & disease 99 28703807
2013 Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome. Nature structural & molecular biology 96 23435380
2012 Focal aberrations indicate EYA2 and hsa-miR-375 as oncogene and tumor suppressor in cervical carcinogenesis. Genes, chromosomes & cancer 74 22987659
2014 miR-30a suppresses breast cancer cell proliferation and migration by targeting Eya2. Biochemical and biophysical research communications 71 24508260
2014 Allosteric inhibitors of the Eya2 phosphatase are selective and inhibit Eya2-mediated cell migration. The Journal of biological chemistry 51 24755226
2000 The alpha subunits of Gz and Gi interact with the eyes absent transcription cofactor Eya2, preventing its interaction with the six class of homeodomain-containing proteins. The Journal of biological chemistry 49 10906137
2021 EYA2 suppresses the progression of hepatocellular carcinoma via SOCS3-mediated blockade of JAK/STAT signaling. Molecular cancer 46 34044846
2012 Identification of a selective small-molecule inhibitor series targeting the eyes absent 2 (Eya2) phosphatase activity. Journal of biomolecular screening 43 22820394
2020 Identification of a Small-Molecule Inhibitor That Disrupts the SIX1/EYA2 Complex, EMT, and Metastasis. Cancer research 42 32341035
2009 Crystal structure of ED-Eya2: insight into dual roles as a protein tyrosine phosphatase and a transcription factor. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37 19858093
2019 Structural and Functional Analyses of an Allosteric EYA2 Phosphatase Inhibitor That Has On-Target Effects in Human Lung Cancer Cells. Molecular cancer therapeutics 34 31285279
2020 Eya2 promotes cell cycle progression by regulating DNA damage response during vertebrate limb regeneration. eLife 30 32142407
2016 Overexpression of miR-30a in lung adenocarcinoma A549 cell line inhibits migration and invasion via targeting EYA2. Acta biochimica et biophysica Sinica 30 26837415
2014 Epigenetic silencing of EYA2 in pancreatic adenocarcinomas promotes tumor growth. Oncotarget 28 24810906
2017 EYA2 promotes lung cancer cell proliferation by downregulating the expression of PTEN. Oncotarget 27 29340020
2008 Differential expression of Eya1 and Eya2 during chick early embryonic development. Gene expression patterns : GEP 27 18316249
2004 Reciprocal signaling between the transcriptional co-factor Eya2 and specific members of the Galphai family. Molecular pharmacology 24 15308761
2022 A FBXO7/EYA2-SCFFBXW7 axis promotes AXL-mediated maintenance of mesenchymal and immune evasion phenotypes of cancer cells. Molecular cell 22 35182481
2017 Eya2 overexpression promotes the invasion of human astrocytoma through the regulation of ERK/MMP9 signaling. International journal of molecular medicine 21 28901379
2021 Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe. The Journal of experimental medicine 18 34617969
2017 Eya2, a Target Activated by Plzf, Is Critical for PLZF-RARA-Induced Leukemogenesis. Molecular and cellular biology 18 28416638
2011 Transcription coactivator Eya2 is a critical regulator of physiological hypertrophy. Journal of molecular and cellular cardiology 17 22197309
2009 The transcription factor Eya2 prevents pressure overload-induced adverse cardiac remodeling. Journal of molecular and cellular cardiology 17 19272299
2021 Eya2 expression during mouse embryonic development revealed by Eya2lacZ knockin reporter and homozygous mice show mild hearing loss. Developmental dynamics : an official publication of the American Association of Anatomists 15 33715274
2023 EYA2 tyrosine phosphatase inhibition reduces MYC and prevents medulloblastoma progression. Neuro-oncology 12 37486991
2019 Eya2 Is Overexpressed in Human Prostate Cancer and Regulates Docetaxel Sensitivity and Mitochondrial Membrane Potential through AKT/Bcl-2 Signaling. BioMed research international 12 31317026
2018 miR-219a-5p represses migration and invasion of osteosarcoma cells via targeting EYA2. Artificial cells, nanomedicine, and biotechnology 12 30449183
2013 CDK6 binds and promotes the degradation of the EYA2 protein. Cell cycle (Georgetown, Tex.) 12 24196439
2021 EYA2 upregulates miR-93 to promote tumorigenesis of breast cancer by targeting and inhibiting the STING signaling pathway. Carcinogenesis 9 33449106
2021 Structure-activity relationship studies of allosteric inhibitors of EYA2 tyrosine phosphatase. Protein science : a publication of the Protein Society 8 34761455
2009 [Expression of EYA2 in non-small cell lang cancer]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 7 19950702
2021 Role of SIX1, EYA2, and E-cadherin in ovarian carcinoma. Evidence on epithelial-mesenchymal transition from an immunohistochemical study. Annals of diagnostic pathology 6 34534789
2012 Structure-based de novo design of Eya2 phosphatase inhibitors. Journal of molecular graphics & modelling 6 23085179
2023 The role of Eya1 and Eya2 in the taste system of mice from embryonic stage to adulthood. Frontiers in cell and developmental biology 4 37181748
2019 Eya2 is critical for the E2A‑HLF‑mediated immortalization of mouse hematopoietic stem/progenitor cells. International journal of oncology 4 30628662
2020 MicroRNA-219 inhibits cell viability and metastasis in papillary thyroid carcinoma by targeting EYA2. European review for medical and pharmacological sciences 2 33015798
2024 In Vitro Phosphatase Assays for the Eya2 Tyrosine Phosphatase. Methods in molecular biology (Clifton, N.J.) 1 38147222
2026 A genome-wide association study identifies EYA2 as a contributing gene for diabetic retinopathy in type 2 diabetes. Communications medicine 0 41741574
2025 Smurf2 knockdown attenuates the progression of diabetic nephropathy by inhibiting mesangial cell proliferation and fibrosis through suppressing EYA2 ubiquitination. Renal failure 0 40556274
2024 Rational Design of Novel Allosteric EYA2 Inhibitors as Potential Therapeutics for Multiple Brain Cancers. ChemMedChem 0 38861151

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