Affinage

EPHA5

Ephrin type-A receptor 5 · UniProt P54756

Length
1037 aa
Mass
114.8 kDa
Annotated
2026-06-09
63 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EPHA5 is a receptor tyrosine kinase of the ephrin-A signaling system that translates contact-mediated ligand engagement into forward signals governing axon guidance, synapse formation, and a broad range of cell-adhesion and proliferative responses (PMID:7876076, PMID:20824214). Its ligand-binding domain adopts a pre-organized open ephrin-binding pocket with fast loop dynamics but no slow conformational exchange, a feature that restricts the receptor to ephrin-A ligands and distinguishes it from EphA4 (PMID:24086308). Ligand binding (ELF-1/ephrin-A, ephrin-A5) induces receptor autophosphorylation and forward signaling (PMID:7876076). In the nervous system, EPHA5 and its ephrin-A ligands are arranged in complementary gradients that drive topographic axon guidance through selective repulsion of inappropriate neurites (PMID:9321686, PMID:10660883), while ephrin-A5 engagement during hippocampal development triggers a Ca²⁺/PKA/CaMKII/PI3K/CREB cascade that builds NMDA receptor–PSD-95 complexes and matures spines (PMID:20824214), and EPHA5 activation is recruited during hippocampal LTP (PMID:9698392). Downstream effectors are context-dependent: CREB and RhoA in neurite outgrowth (PMID:33912567), Rac1/WAVE1 in hematopoietic progenitor adhesion and migration (PMID:27988259), and Erk1/2 in striatal cocaine responses (PMID:21628570). In the ventromedial hypothalamus, EPHA5 activation amplifies counterregulatory hormone release during hypoglycemia in conjunction with glutamate/glutamine cycling (PMID:23274893, PMID:24222347). EPHA5 also acts in the nucleus, where after irradiation it translocates and associates with activated ATM to support the G1/S checkpoint and DNA damage resolution (PMID:25623065). In innate immunity, EPHA5 phosphorylates EPHB2 and Dectin-1 to drive Syk-dependent antifungal signaling, and its loss increases susceptibility to Candida albicans (PMID:40489568). Its expression is controlled transcriptionally by KLF16 and c-Fos binding to its promoter and silenced by promoter CpG methylation (PMID:27402841, PMID:29330744), and post-translationally stabilized through PIAS2-mediated SUMOylation that opposes ubiquitin-driven degradation (PMID:37481078).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Established that EphA5 is a functional receptor tyrosine kinase activated by an ephrin-A ligand, defining the basic ligand-receptor signaling unit.

    Evidence cDNA cloning and in vitro receptor autophosphorylation assay with ELF-1/ephrin-A

    PMID:7876076

    Open questions at the time
    • Did not map downstream effectors
    • In vitro biochemistry without cellular context
  2. 1997 Medium

    Showed that complementary EphA5/ephrin-A gradients and selective neurite inhibition specify topographic projections, casting EphA5 as a guidance receptor.

    Evidence Gradient expression mapping and neurite outgrowth assays with selective ligand inhibition in hippocamposeptal system

    PMID:9321686

    Open questions at the time
    • Intracellular signaling not delineated
    • Single-system correlation between expression and function
  3. 1998 High

    Demonstrated EphA5 activation is engaged during synaptic plasticity, extending its role beyond development into adult hippocampal LTP.

    Evidence Hippocampal slice electrophysiology with EphA5-IgG antagonist and ephrin-A5-IgG agonist, including occlusion of LTP

    PMID:9698392

    Open questions at the time
    • Molecular link between receptor activation and synaptic strengthening not resolved
  4. 2010 High

    Defined the synaptogenic signaling cascade downstream of EphA5, answering how ligand engagement builds functional synapses.

    Evidence EphA5 knockout mice, hippocampal neuron culture, pharmacological dissection, electrophysiology, and biochemistry tracing Ca²⁺/PKA/CaMKII/PI3K/CREB to NMDAR-PSD-95 complex formation

    PMID:20824214

    Open questions at the time
    • Direct receptor substrate(s) initiating the cascade not identified
  5. 2012 High

    Identified a systemic-physiology role: VMH EphA5 activation tunes counterregulatory hormone responses to hypoglycemia via glutamate/glutamine cycling.

    Evidence Hyperinsulinemic-hypoglycemic clamps with VMH microinjection, AAV manipulation, and microdialysis

    PMID:23274893

    Open questions at the time
    • Cell-type-specific signaling within VMH not resolved
    • Mechanistic link to neurotransmitter cycling correlative
  6. 2013 High

    Resolved the structural basis of ephrin-A binding specificity, explaining why EphA5 is restricted to ephrin-A ligands.

    Evidence X-ray crystallography of the LBD validated by NMR H/D exchange and MD simulations

    PMID:24086308

    Open questions at the time
    • Full-length receptor and kinase-domain conformations not addressed
    • No structure of a ligand-bound complex
  7. 2013 Medium

    Showed EphA5 acts as a contact-dependent inhibitor of osteogenic differentiation, broadening its role into stromal cell fate.

    Evidence siRNA knockdown and co-culture assays in bone marrow stromal cells measuring ALP expression

    PMID:24029132 PMID:27057165

    Open questions at the time
    • Downstream signaling in osteogenic suppression not defined
    • Single-lab cellular models
  8. 2015 High

    Revealed a noncanonical nuclear function in which EphA5 supports the DNA damage response by interacting with activated ATM.

    Evidence Nuclear fractionation, Co-IP with ATM, γ-H2AX foci, cell cycle analysis, and xenograft radiotherapy in lung cancer cells

    PMID:25623065

    Open questions at the time
    • Mechanism of nuclear translocation unknown
    • Whether kinase activity is required not established
  9. 2016 Medium

    Connected forward signaling to cytoskeletal regulation, identifying Rac1/WAVE1 as effectors of EphA5-driven HSPC adhesion and migration.

    Evidence Ephrin-A5-Fc stimulation, blocking peptides, and Rac1 inhibition with adhesion/migration assays

    PMID:27988259

    Open questions at the time
    • Direct link from receptor to Rac1 activation not biochemically resolved
  10. 2016 High

    Established direct transcriptional control of EphA5 by KLF16 and methylation-sensitive promoter regulation governing guidance responses.

    Evidence ChIP, EMSA, methylation-specific reporter assays with mutagenesis, and RGC neurite/growth-cone assays

    PMID:27402841

    Open questions at the time
    • In vivo relevance of specific CpG methylation not tested
  11. 2018 Medium

    Identified c-Fos as a direct transcriptional activator of EphA5, linking receptor expression to neuronal activity states.

    Evidence ChIP, dual-luciferase reporter assays, and c-Fos overexpression in hippocampal neurons of hypothyroid rats

    PMID:29330744

    Open questions at the time
    • Functional consequence of c-Fos-driven expression on circuits not measured
  12. 2021 Medium

    Defined CREB and RhoA as the critical downstream effectors of EphA5 signaling required for neurite outgrowth.

    Evidence RNA-seq, EPHA5 overexpression rescue after RF-EMF exposure, and CREB/RhoA pathway analysis in neural cell models

    PMID:33912567

    Open questions at the time
    • Mechanistic coupling of receptor to RhoA not shown
    • Single-lab cell-line models
  13. 2023 Medium

    Uncovered post-transcriptional and post-translational control of EPHA5 by an IL-17/TRAF2/PIAS2/ELAVL1 axis stabilizing mRNA and protein.

    Evidence Co-IP, RNA-IP, and knockdown of pathway components with proliferation/invasion assays in melanoma

    PMID:37481078

    Open questions at the time
    • Direct SUMOylation site on EPHA5 not mapped
    • Single-lab single-cancer context
  14. 2025 High

    Placed EPHA5 in innate antifungal immunity as a kinase that phosphorylates EPHB2 and Dectin-1 to activate Syk signaling.

    Evidence Phosphorylation assays, Co-IP, and EphA5-deficient mouse Candida albicans infection model

    PMID:40489568

    Open questions at the time
    • Direct phosphosite mapping on Dectin-1 not detailed
    • Receptor activation trigger during infection unclear
  15. 2025 Medium

    Showed EPHA5 can act as a pro-proliferative driver via STAT3 in follicular thyroid carcinoma, contrasting with its tumor-suppressive roles elsewhere.

    Evidence EphA5 gain/loss-of-function with STAT3 inhibitor (SH-4-54) and proliferation/apoptosis assays

    PMID:40263257

    Open questions at the time
    • Mechanism of context-dependent oncogenic vs suppressive switching unresolved
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single receptor reconciles tumor-suppressive (breast, esophageal) and tumor-promoting (thyroid) outputs, and what determines forward versus nuclear versus cross-phosphorylation modes, remains unresolved.
  • No unifying model linking ligand context to divergent downstream pathways
  • Determinants of nuclear translocation vs membrane forward signaling unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0016740 transferase activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 1 R-HSA-73894 DNA Repair 1
Partners
ATMCLEC7AEFNA1EFNA5ELAVL1EPHB2PIAS2TRAF2

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 The Cek7 (EphA5) ligand (ELF-1/ephrin-A) was cloned and shown to be functionally active, inducing autophosphorylation of the Cek7/EphA5 receptor protein tyrosine kinase. cDNA cloning, in vitro receptor autophosphorylation assay The Journal of biological chemistry High 7876076
1997 EphA5 (Bsk) and its ligands (Elf-1, LERK3/Ehk1-L, AL-1/RAGS/LERK7) are expressed in complementary gradients in hippocampal neurons and their septal targets; the ligands selectively inhibit growth of topographically inappropriate medial hippocampal neurites while sustaining appropriate lateral neurite growth, placing EphA5 as a guidance receptor specifying hippocamposeptal topographic projection. Gradient expression analysis, neurite outgrowth assay with selective ligand inhibition Cell and tissue research Medium 9321686
1998 Soluble EphA5-IgG (antagonist) impairs induction of LTP in hippocampal slices without affecting basal synaptic transmission; conversely, ephrin-A5-IgG (EphA5 agonist) induces a sustained potentiation of synaptic transmission that occludes subsequent LTP, demonstrating EphA5 activation is recruited during LTP. Hippocampal slice electrophysiology, LTP induction with pharmacological agonist/antagonist, immunohistochemistry Molecular and cellular neurosciences High 9698392
1999 Activation of EphA5 receptor using ephrin-A1 recombinant fusion protein results in time-dependent tyrosine phosphorylation of EphA5 in glioblastoma U-118 MG cells, but does not promote cell proliferation. Receptor activation with recombinant ephrin-A1-Fc, Western blot for phosphotyrosine, proliferation assay Brain research Medium 10064801
2000 EphA5 expressed on mitral cells and its ligands on olfactory neurons; blocking EphA5-ligand interactions with anti-EphA5 antibodies or recombinant EphA5 protein in explant cultures reduced neurite outgrowth, suggesting intrafascicular axon repulsion limits adhesion and promotes axon growth. Antibody blocking, recombinant protein perturbation in explant cultures, neurite outgrowth quantification The Journal of comparative neurology Medium 10660883
2010 Ephrin-A5 interaction with EphA5 during early hippocampal development induces synaptogenesis: specifically, it drives expression of NMDA receptor-PSD-95 complexes and spine morphological maturation via voltage-sensitive calcium channel Ca2+ fluxes that activate PKA, CaMKII, and PI3 kinase, leading to CREB phosphorylation and a synaptogenic gene expression program. EphA5 functional knockout mice at P6 showed no NMDA receptor currents upon stimulation. Hippocampal neuron culture, EphA5 knockout mice, electrophysiology, pharmacological inhibition, Western blot for signaling intermediates PloS one High 20824214
2013 The crystal structure of the EphA5 ligand-binding domain (LBD) was determined by X-ray crystallography and validated by NMR and MD simulations; the unbound EphA5 LBD adopts an open ephrin-binding pocket with helical conformation over the J-K loop resembling ephrin-bound states of other Eph receptors. NMR H/D exchange and MD simulations revealed rapid picosecond-nanosecond conformational dynamics over loops but no global microsecond-millisecond exchanges, contrasting with EphA4 LBD dynamics and explaining EphA5's restriction to ephrin-A binding. X-ray crystallography, NMR (H/D exchange, relaxation), molecular dynamics simulations PloS one High 24086308
2012 EphA5 receptors in the ventromedial hypothalamus (VMH) regulate counterregulatory hormone release during hypoglycemia: VMH microinjection of ephrin-A5-Fc (EphA5 agonist) or AAV-mediated ephrin-A5 overexpression increased counterregulatory responses and transiently elevated local glutamate, while ephrin-A5 knockdown reduced responses and suppressed VMH glutamine concentrations. Hyperinsulinemic-hypoglycemic clamp, in vivo VMH microinjection, AAV-mediated knockdown/overexpression, microdialysis for glutamate/glutamine Diabetes High 23274893
2013 Recurrent hypoglycemia reduces ephrin-A5 (but not EphA5 receptor) expression in the VMH, increases synaptic connections, and reduces astroglial synaptic coverage; targeted VMH activation of EphA5 receptors by ephrin-A5-Fc restored counterregulatory responses and increased glucagon release by 150% in rats with recurrent hypoglycemia. Hyperinsulinemic-hypoglycemic clamp with recurrent hypoglycemia protocol, VMH microinjection, immunofluorescence for synaptic markers, glucagon RIA Diabetes Medium 24222347
2015 EphA5 is specifically overexpressed in lung cancer and upon irradiation is transported into the nucleus where it interacts with activated ATM at sites of DNA repair; EphA5-deficient lung cancer cells display defective G1/S checkpoint, inability to resolve DNA damage, and increased radiosensitivity. siRNA knockdown, nuclear fractionation, co-immunoprecipitation of EphA5 with ATM, γ-H2AX foci, cell cycle analysis, xenograft radiotherapy The Journal of biological chemistry High 25623065
2011 EphA5 was identified as a direct target of miR-34a during chondrogenesis; miR-34a downregulates EphA5 expression, and upregulation of EphA5 overcomes miR-34a inhibition of chondroblast migration and precartilage condensation. PNA-based antisense oligonucleotide blockade of miR-34a, EphA5 overexpression rescue, migration and condensation assays Biochemical and biophysical research communications Medium 22079638
2016 EphA5 forward signaling in human hematopoietic stem and progenitor cells (HSPCs), stimulated by soluble ephrin-A5-Fc, promotes colony formation, adhesion, and migration via activation of Rac1 and its downstream target WAVE1; functional blocking peptides against EphA5 inhibit HSPC adhesion and migration. Ephrin-A5-Fc stimulation, functional blocking peptides, Rac1 inhibitor, gene/protein expression analysis, adhesion/migration assays Experimental hematology Medium 27988259
2016 KLF16 transcription factor binds directly to a KLF site near the EphA5 transcription start site (confirmed by ChIP and EMSA) and transactivates EphA5 expression; methylation of only 6 of 98 CpG dinucleotides within the EphA5 promoter blocks KLF16-mediated transactivation while enabling transactivation by KLF2 and KLF15. KLF16 overexpression inhibits RGC neurite outgrowth and enhances growth cone collapse in response to ephrin-A5. ChIP assay, EMSA, promoter luciferase assays with site-directed mutagenesis, methylation-specific promoter variants, neurite outgrowth assay The Journal of biological chemistry High 27402841
2011 The ephrin-A5–EphA4/EphA5 system in the substantia nigra pars reticulata (SNr) is upregulated specifically in the direct pathway during cocaine responses; immunoadhesin-mediated activation of EphA4 and EphA5 in the SNr suppressed the adaptive response to repeated cocaine; cocaine stimulated phosphorylation of Erk1/2 in ephrin-A5-expressing SNr cells in a direct pathway-dependent manner. Genome-wide expression profiling, pathway-specific neurotransmission blocking (RNB) mice, immunoadhesin EphA4/EphA5 activation in vivo, Erk1/2 phosphorylation immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 21628570
2013 EphA5 expressed on bone marrow stromal cells (BMSCs) is upregulated with repeated passaging and acts as an inhibitory factor for osteogenesis; siRNA knockdown of EphA5 in long-term passaged BMSCs increased ALP mRNA expression, and co-culture assays showed inhibitory signals require cell-cell contact. siRNA knockdown, co-culture assay, microarray, quantitative PCR, alkaline phosphatase mRNA measurement Bone Medium 24029132
2016 Forced expression of EphA5 in human BMSCs diminishes osteoblast phenotypic marker expression; dexamethasone treatment downregulates EphA5 and promotes osteoblast marker expression; EphA5 promoter is largely unmethylated in hBMSCs but histone deacetylation partially suppresses EphA5 in early-passage cultures. EphA5 overexpression, dexamethasone treatment, ALP mRNA quantification, bisulfite sequencing, histone deacetylase inhibitor treatment Stem cells international Medium 27057165
2019 EPHA5 deficiency (CRISPR knockout) in HER2-positive breast cancer cells increases cancer stem cell-like properties (elevated NANOG, CD133+, CD44+/CD24-/low phenotype, mammosphere formation) and activates Notch1 and PTEN/AKT signaling, leading to trastuzumab resistance in xenografts. CRISPR-Cas9 knockout, mammosphere assay, flow cytometry, Western blot for Notch1/PTEN/AKT, xenograft model FASEB journal Medium 30620624
2020 EphA5 knockdown in esophageal squamous cell carcinoma cells enhances invasion and migration via epithelial-mesenchymal transition, associated with elevated β-catenin and p-GSK-3βSer9 protein levels, indicating activation of the Wnt/β-catenin pathway. siRNA knockdown, Transwell invasion/migration assay, Western blot and immunofluorescence for EMT markers and Wnt pathway components Cancer cell international Medium 31956298
2020 EphA5 silencing in ESCC cells increases radiosensitivity through impaired ATM-dependent pathway: EphA5 knockdown after ionizing radiation results in defective G1/S checkpoint, impaired γ-H2AX foci formation, reduced ATM activation, and downstream reduction in p-Chk2, p-p53, and p21. siRNA knockdown, clonogenic assay, flow cytometry (cell cycle/apoptosis), Western blot for ATM/Chk2/p53/p21, γ-H2AX immunofluorescence Cancer management and research Low 33061640
2021 EphA5 signaling is required for neurite outgrowth; RF-EMF exposure inhibits EPHA5 expression and impairs neurite outgrowth, which is rescued by enhancing EPHA5 signaling; CREB and RhoA were identified as critical downstream factors of EPHA5 signaling mediating neurite outgrowth. RNA sequencing, EPHA5 overexpression rescue, CREB and RhoA pathway analysis, neurite length/branching quantification in neural stem cell-derived neurons and Neuro-2A cells Frontiers in cell and developmental biology Medium 33912567
2023 IL-17 signaling through TRAF2 as a scaffold recruits PIAS2 (SUMO E3 ligase) and ELAVL1 (RNA-binding protein) to induce EPHA5 expression in melanoma: ELAVL1 binds AU-rich elements in the 3'-UTR of EPHA5 mRNA to enhance its stability, and PIAS2 induces EPHA5 SUMOylation which suppresses its ubiquitination and degradation; EPHA5 knockdown suppresses IL-17A-induced melanoma proliferation and invasion. Co-immunoprecipitation, RNA immunoprecipitation, siRNA knockdown of pathway components, proliferation/invasion assays Biochimica et biophysica acta. Molecular cell research Medium 37481078
2025 EPHA5 phosphorylates EPHB2 and Dectin-1 after fungal infection, facilitating recruitment and activation of Syk and subsequent activation of downstream antifungal signaling pathways; EphA5-deficient mice show increased susceptibility to Candida albicans infection with increased fungal burdens and impaired immune cell recruitment. Phosphorylation assays, co-immunoprecipitation, EphA5-deficient mouse infection model, fungal burden quantification, immune cell recruitment analysis PLoS pathogens High 40489568
2025 EPHA5 promotes proliferation and inhibits apoptosis in follicular thyroid carcinoma via activation of the STAT3 signaling pathway; STAT3 inhibitor (SH-4-54) reduces the effects of EPHA5 on proliferation and apoptosis. EphA5 overexpression/knockdown, STAT3 inhibitor (SH-4-54) treatment, proliferation and apoptosis assays Oncogenesis Medium 40263257
2018 c-Fos transcription factor directly binds to the EphA5 promoter at three binding sites (confirmed by ChIP and luciferase assay) and positively regulates EphA5 expression; c-Fos overexpression upregulates EphA5 in hippocampal neurons of congenital hypothyroid rats. Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, c-Fos overexpression, qPCR and Western blot Journal of molecular histology Medium 29330744

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Ephrin-A5 and EphA5 interaction induces synaptogenesis during early hippocampal development. PloS one 69 20824214
1998 Regulation of hippocampal synaptic plasticity by the tyrosine kinase receptor, REK7/EphA5, and its ligand, AL-1/Ephrin-A5. Molecular and cellular neurosciences 64 9698392
2009 Frequent epigenetic inactivation of the receptor tyrosine kinase EphA5 by promoter methylation in human breast cancer. Human pathology 51 19733895
2001 Expression of ephrin-A2 in the superior colliculus and EphA5 in the retina following optic nerve section in adult rat. The European journal of neuroscience 45 11860487
2009 Distribution of EphA5 receptor protein in the developing and adult mouse nervous system. The Journal of comparative neurology 42 19326470
2015 Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer. The Journal of biological chemistry 41 25623065
2020 EPHA5 mutation predicts the durable clinical benefit of immune checkpoint inhibitors in patients with lung adenocarcinoma. Cancer gene therapy 40 32759987
2015 Downregulation of EphA5 by promoter methylation in human prostate cancer. BMC cancer 40 25609195
1995 cDNA cloning and characterization of a Cek7 receptor protein-tyrosine kinase ligand that is identical to the ligand (ELF-1) for the Mek-4 and Sek receptor protein-tyrosine kinases. The Journal of biological chemistry 38 7876076
2016 EphA5 and EphA6: regulation of neuronal and spine morphology. Cell & bioscience 35 27489614
2000 Expression of EphA5 during development of the olfactory nerve pathway in rat. The Journal of comparative neurology 34 10660883
2003 Transient up-regulation of retinal EphA3 and EphA5, but not ephrin-A2, coincides with re-establishment of a topographic map during optic nerve regeneration in goldfish. Experimental neurology 29 14552900
1997 Regulation of topographic projection by the Eph family receptor Bsk (EphA5) and its ligands. Cell and tissue research 28 9321686
1994 Identification of a complete Cek7 receptor protein tyrosine kinase coding sequence and cDNAs of alternatively spliced transcripts. Gene 28 7958948
2019 EPHA5 mediates trastuzumab resistance in HER2-positive breast cancers through regulating cancer stem cell-like properties. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 30620624
2011 MicroRNA-34a regulates migration of chondroblast and IL-1β-induced degeneration of chondrocytes by targeting EphA5. Biochemical and biophysical research communications 27 22079638
2007 EphA5 and ephrin-A2 expression during optic nerve regeneration: a 'two-edged sword'. The European journal of neuroscience 26 17328773
1999 Functional activation of EphA5 receptor does not promote cell proliferation in the aberrant EphA5 expressing human glioblastoma U-118 MG cell line. Brain research 25 10064801
2021 Long noncoding RNA ZFAS1 suppresses osteogenic differentiation of bone marrow-derived mesenchymal stem cells by upregulating miR-499-EPHA5 axis. Molecular and cellular endocrinology 24 34655661
1999 Immunohistochemical localization of EphA5 in the adult human central nervous system. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 24 10375373
1997 A link between axon guidance and axon fasciculation suggested by studies of the tyrosine kinase receptor EphA5/REK7 and its ligand ephrin-A5/AL-1. Cell and tissue research 23 9321687
2021 Deep learning model reveals potential risk genes for ADHD, especially Ephrin receptor gene EPHA5. Briefings in bioinformatics 22 34109382
2020 PDL1 high expression without TP53, KEAP1 and EPHA5 mutations could better predict survival for patients with NSCLC receiving atezolizumab. Lung cancer (Amsterdam, Netherlands) 22 33246647
2016 EphA5 and EphA7 forward signaling enhances human hematopoietic stem and progenitor cell maintenance, migration, and adhesion via Rac1 activation. Experimental hematology 22 27988259
2013 After repeated division, bone marrow stromal cells express inhibitory factors with osteogenic capabilities, and EphA5 is a primary candidate. Bone 22 24029132
2010 A role for DNA methylation in regulation of EphA5 receptor expression in the mouse retina. Vision research 22 20875442
2004 Neurochemical and behavioral deficits consequent to expression of a dominant negative EphA5 receptor. Brain research. Molecular brain research 22 15046871
2020 EPHA5 mutations predict survival after immunotherapy in lung adenocarcinoma. Aging 19 33288738
2016 Novel Roles and Mechanism for Krüppel-like Factor 16 (KLF16) Regulation of Neurite Outgrowth and Ephrin Receptor A5 (EphA5) Expression in Retinal Ganglion Cells. The Journal of biological chemistry 19 27402841
2020 EphA5 knockdown enhances the invasion and migration ability of esophageal squamous cell carcinoma via epithelial-mesenchymal transition through activating Wnt/β-catenin pathway. Cancer cell international 18 31956298
2020 EPHA5 mutation impairs natural killer cell-mediated cytotoxicity against non-small lung cancer cells and promotes cancer cell migration and invasion. Molecular and cellular probes 18 32234341
2020 CpG Islands Methylation Analysis of CDH11, EphA5, and HS3ST2 Genes in Gastric Adenocarcinoma Patients. Journal of gastrointestinal cancer 17 31407253
2008 Changes in attack behavior and activity in EphA5 knockout mice. Brain research 17 18353288
2013 Unique structure and dynamics of the EphA5 ligand binding domain mediate its binding specificity as revealed by X-ray crystallography, NMR and MD simulations. PloS one 14 24086308
2020 Ephrin Receptors (Eph): EphA1, EphA5, and EphA7 Expression in Uveal Melanoma-Associations with Clinical Parameters and Patient Survival. Life (Basel, Switzerland) 13 33007931
2013 Insertional translocation leading to a 4q13 duplication including the EPHA5 gene in two siblings with attention-deficit hyperactivity disorder. American journal of medical genetics. Part A 13 23824631
2011 Pathway-specific engagement of ephrinA5-EphA4/EphA5 system of the substantia nigra pars reticulata in cocaine-induced responses. Proceedings of the National Academy of Sciences of the United States of America 13 21628570
2016 Dexamethasone Regulates EphA5, a Potential Inhibitory Factor with Osteogenic Capability of Human Bone Marrow Stromal Cells. Stem cells international 12 27057165
2012 EphA5-EphrinA5 interactions within the ventromedial hypothalamus influence counterregulatory hormone release and local glutamine/glutamate balance during hypoglycemia. Diabetes 11 23274893
2023 IL-17 promotes melanoma through TRAF2 as a scaffold protein recruiting PIAS2 and ELAVL1 to induce EPHA5. Biochimica et biophysica acta. Molecular cell research 10 37481078
2007 Expression of the tyrosine kinase receptor EphA5 and its ligand ephrin-A5 during mouse spinal cord development. Neuroscience bulletin 10 17952132
2022 Expression of EPHA5 in lung adenocarcinoma is associated with lymph node metastasis and EGFR mutation. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 9 35332588
2020 EphA5 Silencing Increases the Radiosensitivity of ESCC Cells Through ATM-Dependent Pathway. Cancer management and research 8 33061640
2019 Differential expression of EphA5 protein in gastric carcinoma and its clinical significance. Oncology letters 8 31186729
2015 DNA Methylation of the EphA5 Promoter Is Associated with Rat Congenital Hypothyroidism. Journal of molecular neuroscience : MN 8 26109526
2017 Decreased expression of EphA5 is associated with Fuhrman nuclear grade and pathological tumour stage in ccRCC. International journal of experimental pathology 7 28421649
2023 YB-1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2. Molecular oncology 6 36550787
2013 Analysis of EphA5 receptor in the developing rat brain: an in vivo study in congenital hypothyroidism model. European journal of pediatrics 6 23636281
2013 Role of synaptic plasticity and EphA5-ephrinA5 interaction within the ventromedial hypothalamus in response to recurrent hypoglycemia. Diabetes 6 24222347
2007 Altered EphA5 mRNA expression in rat brain with a single methamphetamine treatment. Neuroscience letters 6 17714871
2021 1800 MHz Radiofrequency Electromagnetic Field Impairs Neurite Outgrowth Through Inhibiting EPHA5 Signaling. Frontiers in cell and developmental biology 5 33912567
2022 Immunohistochemical evaluation of forkhead box A1 and EphA5 markers in serous ovarian carcinomas, and their impact on the clinical outcome of patients. Polish journal of pathology : official journal of the Polish Society of Pathologists 4 36345952
2018 c-Fos downregulation positively regulates EphA5 expression in a congenital hypothyroidism rat model. Journal of molecular histology 3 29330744
2022 EPHA5 mutation was associated with adverse outcome of atezolizumab treatment in late-stage non-small cell lung cancers. BMC pulmonary medicine 2 36123678
2021 EPHA5 Enhances the Stemness of Non-small cell lung cancer Cells Through Activating the Wnt Signaling Pathway. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 2 34761594
2019 Autism spectrum disorder in a patient with a genomic rearrangement that only involves the EPHA5 gene. Psychiatric genetics 2 30724859
2025 EPHA5 promotes cell proliferation and inhibits apoptosis in Follicular Thyroid Cancer via the STAT3 signaling pathway. Oncogenesis 1 40263257
2025 EPHA5 regulates antifungal innate immunity by phosphorylating EPHB2 and Dectin-1. PLoS pathogens 0 40489568
2025 EphA5 Silencing Increases the Radiosensitivity of ESCC Cells Through ATM-Dependent Pathway [Retraction]. Cancer management and research 0 40641952
2025 First-generation and preclinical evaluation of an EphA5-targeted antibody-drug conjugate in solid tumors. The Journal of clinical investigation 0 40662373
2025 EphA5 Expression Predicts Better Survival Despite an Association with Proliferative Activity in Endometrial Cancer. Journal of clinical medicine 0 40806980
2019 Dynamic Alterations of Retinal EphA5 Expression in Retinocollicular Map Plasticity. Developmental neurobiology 0 30916472
2017 [Changes in the expression of EphA5/ephrinA5 in the CA3 region of the hippocampus in rats with epilepsy and their role in the pathogenesis of temporal lobe epilepsy]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 0 29237529

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