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Symbol EPHA2 contributors: mct/pgu - updated : 09-06-2020
HGNC name EPH receptor A2
HGNC id 3386
Corresponding disease
CPP1 cataract, posterior, polar, congenital type
Location 1p36.13      Physical location : 16.450.831 - 16.482.582
Synonym name
  • EPH related tyrosine kinase receptor 2
  • ephrin receptor A2
  • epithelial cell receptor protein tyrosine kinase
  • soluble EPHA2 variant 1
  • Synonym symbol(s) ECK, EVI63, EPA2, ARCC2, CTPA, CTPP1, CTRCT6
    TYPE functioning gene
    STRUCTURE 31.77 kb     17 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 3963 - 976 - 2008 18198190
    16 - 3878 - 922 - 2008 18198190
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
     liver   highly
    Endocrinepancreas   highly
    Reproductivefemale systembreastmammary gland highly Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoblast Homo sapiens
    Skeletonosteoclast Homo sapiens
    Skin/Tegumentkeratinocyte Homo sapiens
    cell lineage
    cell lines highly, in metastatic melanoma cells
    at STAGE
  • one sterile alpha motif, SAM domain known to be important for receptor function, that inhibits receptor dimerization and decreases EPHA2 tyrosine phosphorylation
  • a vestigial Ig-l domain
  • a single cystein rich region
  • two FNIII domains in the extracellular region
  • two fibronectin type 2 domain
    interspecies homolog to murine Epha2
  • protein kinase superfamily
  • Tyr protein kinase family
  • ephrin receptor subfamily
  • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
    basic FUNCTION
  • involved in short-range contact-mediated axonal guidance
  • promotes tumor malignancy through a mechanism involving RhoA-dependent destabilization of adherens junctions
  • modulates the localization and function of claudin-4, a constituent of tight junctions (associates with claudin-4 via their extracellular domains)
  • play an important role in tumor metastasis and angiogenesis
  • having a functional role in EGFR-expressing cancer cells
  • promotes tumor malignancy through a mechanism involving RhoA-dependent destabilization of adherens junctions
  • bidirectional EFNA2-EPHA2 signaling regulates bone remodeling at the initiation phase
  • playing an important role in maintaining lens clarity with age
  • its function is required for mammary epithelial growth and branching morphogenesis
  • positive role for EphA2 during normal mammary epithelial proliferation and branching morphogenesis
  • may be a previously unrecognized contributor to the pathophysiology of lung injury
  • functions as a tumor suppressor when its signaling ability is activated by ephrin ligands, whereas its tumor promoting effects may be ligand-independent
  • receptor tyrosine kinase that is engaged and activated by membrane-linked ephrin-A ligands residing on adjacent cell surfaces
  • can inhibit Akt phosphorylation induced by oncogenic mutations of not only PTEN but also PI3 kinase
  • contributes to malignant cellular behavior, including resistance to anoikis, in several different types of cancer cells
  • the frequencies of EPHA2 and MAGE6A-specific CD4+ T cells in cancerous patients were significantly correlated with active disease
  • EPHA2 is a key downstream target of the MEK/ERK/RSK signaling pathway in the regulation of glioblastoma cell proliferation
  • plays a critical role in oncogenic signaling
  • promotes angiogenesis in Ewing sarcoma (ES) cells via ligand-dependent signaling
  • EPHA2 and EFNA5 participate likely in the complex, global patterning of lens fiber cells that is necessary for maximal optical quality
    a component
  • EPHA2 forms higher-order oligomers and two different types of dimers that all lead to increased EPHA2 tyrosine phosphorylation, which is indicative of increased kinase-dependent signaling
    small molecule
  • ephrin A1 binding
  • interacting with TIAM1 (mediates neurite outgrowth induced by EPHB1 and EPHA2)
  • associates with claudin-4 via their extracellular domains
  • interacted with both SRC and ACP1, and the interactions increased in EPHA2-overexpressing cells
  • EFNA2-EPHA2 interaction facilitates the initiation phase of bone remodeling by enhancing osteoclast differentiation and suppressing osteoblast differentiation
  • link between EPHA2 and Rac activation that contributes to the cell motility and invasiveness of breast cancer cells
  • ARHGEF16 is a guanine nucleotide exchange factor (GEF) for RHOG that interacts with EPHA2 in breast cancer cells
  • ligand targeting of EPHA2 enhancing keratinocyte adhesion and differentiation via desmoglein 1
  • interacting with EFNA1 (promotes the motility of EPHA2-positive cardiac stem cells, facilitates their migration to the area of damage, and enhances cardiac repair)
  • ARHGEF16 mediates resistance to anoikis through activation of RHOG and PI3K downstream of EPHA2
  • EPHA2 is a new direct target gene of HIC1
  • MMP14 cleaved EPHA2 at its Fibronectin type-III domain 1
  • CLDN4 serves to restrain pro-oncogenic signaling from EPHA2 by limiting the activity of CTNNB1 and PI3K and preventing phosphorylation of EPHA2 on S897 by AKT1 0)
  • functional signaling receptor for progranulin
  • SOCS2-interacting protein, and binding requires the SOCS2 SH2 domain and EPHA2 activation loop autophosphorylation, which is stimulated by EFNA1 or by phosphotyrosine phosphatase inhibition
  • EPHA2 is a critical player for EBV epithelial cell entry
  • cell & other
    activated by by ephrin-A1 ligands (presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer)
    corresponding disease(s) CPP1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    associated with angiogenesis in ovarian cancer
    tumoral     --over  
    in many cancer types, including breast, ovarian, prostate, pancreatic, and lung cancer
    tumoral     --over  
    predicts poor prognosis in endometrial cancer
    constitutional     --over  
    in lung injury, contributes to vascular leak in the injured lung, and is regulated in endothelial cells by endothelin
    tumoral     --other  
    absence of EPHA2 in normal bone, and de novo expression in osteosarcomas
    tumoral     --over  
    of EPHA2 and EFNA1 plays an important role in the progression of gastric adenocarcinoma
    constitutional germinal mutation      
    lead to disorganized lens cells that subsequently contribute to altered refractive index and cataracts
    Susceptibility to cortical cataract, age-related
    Variant & Polymorphism SNP rs6678616 was the most frequent in cortical cataract, age-related
    Candidate gene
  • could be useful for cancer diagnosis, particularly because EPHA2 appears to be overexpressed starting from early stages of cancer
  • EPHA2 targeted therapy reduces angiogenesis and tumor growth in endometrial cancer uterine cancer models and should be considered for future clinical trials
  • EPHA2 could be a promising candidate as a therapeutic target for Small-cell lung cancer (SCLC)
  • Marker
  • EFNA1 and EPHA2 may be useful serum markers for the detection of hepatocellular carcinoma development and progression, respectively
  • Therapy target
    peptides of the YSA/SWL series could be used in cancer (breast, ovarian, prostate, pancreatic, and lung) therapeutic strategies to target EPHA2, a receptor widely expressed not only in cancer cells but also in the tumor vasculature
    activation of EPHA2 signaling represents a possible new avenue for anti-cancer therapies that exploit the remarkable ability of this receptor to counteract multiple oncogenic signaling pathways
    as a potential therapeutic target in metastatic colorectal cancer
    therapeutic strategy that aims at the stabilization of EPHA2 dimers may be beneficial for the treatment of cancers linked to EPHA2 overexpression
  • mice Epha2-null, Efna5-null, or both receptor and ligand (Epha2/Efna5-null) consistently develop mostly transparent lenses with an internal refractive disturbance and a grossly disturbed cellular architecture