| basic FUNCTION
| involved in short-range contact-mediated axonal guidance |
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promotes tumor malignancy through a mechanism involving RhoA-dependent destabilization of adherens junctions |
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modulates the localization and function of claudin-4, a constituent of tight junctions (associates with claudin-4 via their extracellular domains) |
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play an important role in tumor metastasis and angiogenesis  |
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having a functional role in EGFR-expressing cancer cells |
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promotes tumor malignancy through a mechanism involving RhoA-dependent destabilization of adherens junctions |
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bidirectional EFNA2-EPHA2 signaling regulates bone remodeling at the initiation phase |
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playing an important role in maintaining lens clarity with age |
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its function is required for mammary epithelial growth and branching morphogenesis |
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positive role for EphA2 during normal mammary epithelial proliferation and branching morphogenesis |
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may be a previously unrecognized contributor to the pathophysiology of lung injury |
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functions as a tumor suppressor when its signaling ability is activated by ephrin ligands, whereas its tumor promoting effects may be ligand-independent |
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receptor tyrosine kinase that is engaged and activated by membrane-linked ephrin-A ligands residing on adjacent cell surfaces |
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can inhibit Akt phosphorylation induced by oncogenic mutations of not only PTEN but also PI3 kinase |
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contributes to malignant cellular behavior, including resistance to anoikis, in several different types of cancer cells |
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the frequencies of EPHA2 and MAGE6A-specific CD4+ T cells in cancerous patients were significantly correlated with active disease |
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EPHA2 is a key downstream target of the MEK/ERK/RSK signaling pathway in the regulation of glioblastoma cell proliferation |
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plays a critical role in oncogenic signaling |
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promotes angiogenesis in Ewing sarcoma (ES) cells via ligand-dependent signaling |
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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 |
| protein
| ephrin A1 binding |
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interacting with TIAM1 (mediates neurite outgrowth induced by EPHB1 and EPHA2) |
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associates with claudin-4 via their extracellular domains |
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interacted with both SRC and ACP1, and the interactions increased in EPHA2-overexpressing cells |
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EFNA2-EPHA2 interaction facilitates the initiation phase of bone remodeling by enhancing osteoclast differentiation and suppressing osteoblast differentiation |
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link between EPHA2 and Rac activation that contributes to the cell motility and invasiveness of breast cancer cells |
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ARHGEF16 is a guanine nucleotide exchange factor (GEF) for RHOG that interacts with EPHA2 in breast cancer cells |
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ligand targeting of EPHA2 enhancing keratinocyte adhesion and differentiation via desmoglein 1 |
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interacting with EFNA1 (promotes the motility of EPHA2-positive cardiac stem cells, facilitates their migration to the area of damage, and enhances cardiac repair) |
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ARHGEF16 mediates resistance to anoikis through activation of RHOG and PI3K downstream of EPHA2 |
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EPHA2 is a new direct target gene of HIC1 |
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MMP14 cleaved EPHA2 at its Fibronectin type-III domain 1 |
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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) |
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functional signaling receptor for progranulin |
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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 |
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EPHA2 is a critical player for EBV epithelial cell entry |
| 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)
|
| Type | Gene Modification | Chromosome rearrangement | Protein expression | Protein 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 |
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EPHA2 targeted therapy reduces angiogenesis and tumor growth in endometrial cancer uterine cancer models and should be considered for future clinical trials |
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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
|
|
| System | Type | Disorder | Pubmed |
|---|
| cancer | | | |
| 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 | | cancer | | | |
| 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 | | cancer | digestive | colon | |
| as a potential therapeutic target in metastatic colorectal cancer | | 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 |
