EPHA2

Synonyms

EC:2.7.10.1, Epithelial Cell Receptor Protein Tyrosine Kinase, Ephrin type-A receptor 2, Epithelial cell kinase, EPHA2, EPH Receptor A2, Tyrosine-Protein Kinase Receptor ECK, ECK, Soluble EPHA2 Variant 1, EC 2.7.10.1, CTRCT6, ARCC2, CTPP1, CTPA, Receptor, EphA2, EC 2.7.10

Description

Ephrin type-A receptor 2 is a protein that in humans is encoded by the EPHA2 gene.Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.(Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins.

KO Status

RenMab: Antibody Discovery

RenLite: F0

Drug Information

Launched drugs: 2
Drugs in clinical trials: 3
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Regorafenib Monohydrate

BAY-73-4506, DAST

Approved

Bayer Ag

Solid tumours, Rectal Neoplasms, Carcinoma, Renal Cell, Colonic Neoplasms, Colorectal Neoplasms, Gastrointestinal Stromal Tumors, Carcinoma, Hepatocellular, Gastrointestinal Neoplasms

Dasatinib Hydrate

BMS-354825, NSC-732517

Approved

Bristol-Myers Squibb Company

Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Leukemia, Myeloid, Accelerated Phase, Leukemia, Myeloid, Leukemia, Lymphoid, Myelodysplastic Syndromes, Scleroderma, Systemic, Blast Crisis, Prostatic Neoplasms, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Breast Neoplasms, Leukemia, Myeloid, Chronic-Phase, Leukemia, Myeloid, Acute, Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung

BT-5528

BT-5528, BT5528

Phase 2 Clinical

Bicycle Therapeutics

Solid tumours, Carcinoma, Non-Small-Cell Lung

siRNA-EphA2-DOPC

Phase 1 Clinical

The University Of Texas MD Anderson Cancer Center

Ovarian Neoplasms, Pancreatic Neoplasms

Dasatinib nanoparticle formulation (Xspray Pharma)

Phase 1 Clinical

Xspray Pharma

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

MM-310

MM-310

Pending

Merrimack

Solid tumours, Ovarian Neoplasms, Squamous Cell Carcinoma of Head and Neck, Stomach Neoplasms, Carcinoma, Transitional Cell, Triple Negative Breast Neoplasms, Small Cell Lung Carcinoma, Sarcoma, Prostatic Neoplasms, Carcinoma, Pancreatic Ductal, Endometrial Neoplasms, Carcinoma, Non-Small-Cell Lung

MEDI-547

MEDI547

Discontinued

Astrazeneca Plc

Neoplasms

DS-8895

DS-8895, DS-8895a

Discontinued

Daiichi Sankyo Co Ltd

Solid tumours, Neoplasms

References

Title

Authors

Source

The DNA sequence and biological annotation of human chromosome 1

Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Bentley D.R.,

Nature 441:315-321(2006)

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)

Unified nomenclature for Eph family receptors and their ligands, the ephrins

Eph nomenclature committee,

Cell 90:403-404(1997)

Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation

Miao H., Burnett E., Kinch M., Simon E., Wang B.,

Nat. Cell Biol. 2:62-69(2000)

EphA2 overexpression causes tumorigenesis of mammary epithelial cells

Zelinski D.P., Zantek N.D., Stewart J.C., Irizarry A.R., Kinch M.S.,

Cancer Res. 61:2301-2306(2001)

Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation

Kikawa K.D., Vidale D.R., Van Etten R.L., Kinch M.S.,

J. Biol. Chem. 277:39274-39279(2002)

EphA2 phosphorylates the cytoplasmic tail of Claudin-4 and mediates paracellular permeability

Tanaka M., Kamata R., Sakai R.,

J. Biol. Chem. 280:42375-42382(2005)

Ephrin-A1 is a negative regulator in glioma through down-regulation of EphA2 and FAK

Liu D.-P., Wang Y., Koeffler H.P., Xie D.,

Int. J. Oncol. 30:865-871(2007)

Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via phosphatidylinositol 3-Kinase-dependent Rac1 activation

Zhuang G., Hunter S., Hwang Y., Chen J.,

J. Biol. Chem. 282:2683-2694(2007)

Architecture of Eph receptor clusters

Himanen J.P., Yermekbayeva L., Janes P.W., Walker J.R., Xu K., Atapattu L., Rajashankar K.R., Mensinga A., Lackmann M., Nikolov D.B., Dhe-Paganon S.,

Proc. Natl. Acad. Sci. U.S.A. 107:10860-10865(2010)

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