Ephrin type-A receptor 2

UniProt P29317 Organism Homo sapiens Gene ECK, EPHA2 EC 2.7.10.1

Also known as: ECK, EPHA2

Function

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.

Classification

Family (Pfam): PF14575 EphA2_TM, PF25599 Ephrin_CRD, PF01404 Ephrin_lbd, PF00041 fn3, PF07714 PK_Tyr_Ser-Thr, PF00536 SAM_1
InterPro: Eph_TM, EphA2_rcpt_lig-bd, Ephrin_rcpt_lig-bd_dom, Ephrin_rcpt_TKs, FN3_dom, FN3_sf, Galactose-bd-like_sf, Growth_fac_rcpt_cys_sf, Ig-like_fold, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, SAM, SAM/pointed_sf, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_ephrin_rcpt, Tyr_kinase_rcpt_V_CS
Functional cluster: Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 103

1MQB X-ray 2.30A
2E8N NMR
2K9Y NMR
2KSO NMR
2X10 X-ray 3.00A
2X11 X-ray 4.83A
3C8X X-ray 1.95A
3CZU X-ray 2.65A
3FL7 X-ray 2.50A
3HEI X-ray 2.00A
3HPN X-ray 2.52A
3KKA X-ray 2.40A
… and 91 more

A predicted model is available from AlphaFold.

Gene Ontology · 43

Disease associations

cataract 6 multiple types MONDO:0007288

Drugs targeting this protein · 3

DASATINIB ANHYDROUS inhibitor
REGORAFENIB inhibitor
VANDETANIB inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Ephrin-A1 4 shared papers
Ankyrin repeat and SAM domain-containing protein 1A 1 shared papers
T-cell immunoglobulin and mucin domain-containing protein 4 1 shared papers
Low molecular weight phosphotyrosine protein phosphatase 1 shared papers
Envelope glycoprotein L 2 shared papers
Envelope glycoprotein L 1 shared papers
Envelope glycoprotein H 1 shared papers
Envelope glycoprotein H 2 shared papers
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 1 shared papers
Cell migration-inducing and hyaluronan-binding protein 1 shared papers
Envelope glycoprotein L 1 shared papers
Receptor-type tyrosine-protein phosphatase F 1 shared papers

Literature · 44 cited papers

EphA2 is a functional entry receptor for HCMV infection of glioblastoma cells. PLoS Pathog. · 2023
EphA2 Interacts with Tim-4 through Association between Its FN3 Domain and the IgV Domain of Tim-4. Cells · 2021
Ephrin receptor A2 is a functional entry receptor for Epstein-Barr virus. Nat. Microbiol. · 2018
Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry. Nat. Microbiol. · 2018
Protein kinase A can block EphA2 receptor-mediated cell repulsion by increasing EphA2 S897 phosphorylation. Mol. Biol. Cell · 2016
Crucial roles of RSK in cell motility by catalysing serine phosphorylation of EphA2. Nat. Commun. · 2015
Early insights into the function of KIAA1199, a markedly overexpressed protein in human colorectal tumors. PLoS ONE · 2013
Receptor protein tyrosine phosphatase-receptor tyrosine kinase substrate screen identifies EphA2 as a target for LAR in cell migration. Mol. Cell. Biol. · 2013
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi's sarcoma-associated herpesvirus. Nat. Med. · 2012
Human cataract mutations in EPHA2 SAM domain alter receptor stability and function. PLoS ONE · 2012
Solution structure of the first Sam domain of Odin and binding studies with the EphA2 receptor. Biochemistry · 2012
… and 32 more in the literature graph

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