Target General Infomation
Target ID
T57278 (Former ID: TTDR01214)
Target Name
Ephrin type-A receptor 2 (EPHA2)
Synonyms
Tyrosine-protein kinase receptor ECK; Epithelial cell kinase; EphA2receptor; ECK
Gene Name
EPHA2
Target Type
Clinical trial target
[1]
Disease [+] 2 Target-related Diseases +
1 Brain cancer [ICD-11: 2A00]
2 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Function
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. 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.
BioChemical Class
Kinase
UniProt ID
EPHA2_HUMAN
EC Number
EC 2.7.10.1
Sequence
MELQAARACFALLWGCALAAAAAAQGKEVVLLDFAAAGGELGWLTHPYGKGWDLMQNIMN
DMPIYMYSVCNVMSGDQDNWLRTNWVYRGEAERIFIELKFTVRDCNSFPGGASSCKETFN
LYYAESDLDYGTNFQKRLFTKIDTIAPDEITVSSDFEARHVKLNVEERSVGPLTRKGFYL
AFQDIGACVALLSVRVYYKKCPELLQGLAHFPETIAGSDAPSLATVAGTCVDHAVVPPGG
EEPRMHCAVDGEWLVPIGQCLCQAGYEKVEDACQACSPGFFKFEASESPCLECPEHTLPS
PEGATSCECEEGFFRAPQDPASMPCTRPPSAPHYLTAVGMGAKVELRWTPPQDSGGREDI
VYSVTCEQCWPESGECGPCEASVRYSEPPHGLTRTSVTVSDLEPHMNYTFTVEARNGVSG
LVTSRSFRTASVSINQTEPPKVRLEGRSTTSLSVSWSIPPPQQSRVWKYEVTYRKKGDSN
SYNVRRTEGFSVTLDDLAPDTTYLVQVQALTQEGQGAGSKVHEFQTLSPEGSGNLAVIGG
VAVGVVLLLVLAGVGFFIHRRRKNQRARQSPEDVYFSKSEQLKPLKTYVDPHTYEDPNQA
VLKFTTEIHPSCVTRQKVIGAGEFGEVYKGMLKTSSGKKEVPVAIKTLKAGYTEKQRVDF
LGEAGIMGQFSHHNIIRLEGVISKYKPMMIITEYMENGALDKFLREKDGEFSVLQLVGML
RGIAAGMKYLANMNYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDPEATYTTSGGKIP
IRWTAPEAISYRKFTSASDVWSFGIVMWEVMTYGERPYWELSNHEVMKAINDGFRLPTPM
DCPSAIYQLMMQCWQQERARRPKFADIVSILDKLIRAPDSLKTLADFDPRVSIRLPSTSG
SEGVPFRTVSEWLESIKMQQYTEHFMAAGYTAIEKVVQMTNDDIKRIGVRLPGHQKRIAY
SLLGLKDQVNTVGIPI
Drugs and Modes of Action
Clinical Trial Drug(s) [+] 3 Clinical Trial Drugs +
1 CAR-T cells targeting EphA2 Drug Info Phase 1/2 Malignant glioma [1]
2 DS-8895 Drug Info Phase 1 Solid tumour/cancer [2]
3 MEDI-547 Drug Info Phase 1 Solid tumour/cancer [3]
Preclinical Drug(s) [+] 1 Preclinical Drugs +
1 MEDI-543 Drug Info Preclinical Solid tumour/cancer [4]
Mode of Action [+] 3 Modes of Action +
CAR-T-Cell-Therapy [+] 1 CAR-T-Cell-Therapy drugs +
1 CAR-T cells targeting EphA2 Drug Info [1]
Inhibitor [+] 4 Inhibitor drugs +
1 AMP-PNP Drug Info [9]
2 PMID19788238C66 Drug Info [10]
3 PMID21561767C8h Drug Info [11]
4 PMID23489211C20 Drug Info [12]
Modulator [+] 1 Modulator drugs +
1 EphA2-targeting BiTE molecules Drug Info [7]
Target Regulators
Target-regulating microRNAs
Target-interacting Proteins
Target Affiliated Biological Pathways
KEGG Pathway [+] 4 KEGG Pathways +
1 Ras signaling pathway
2 Rap1 signaling pathway
3 PI3K-Akt signaling pathway
4 Axon guidance
NetPath Pathway [+] 1 NetPath Pathways +
1 TGF_beta_Receptor Signaling Pathway
PID Pathway [+] 6 PID Pathways +
1 EphrinA-EPHA pathway
2 Arf6 signaling events
3 Direct p53 effectors
4 EPHA forward signaling
5 Stabilization and expansion of the E-cadherin adherens junction
6 EPHA2 forward signaling
Reactome [+] 3 Reactome Pathways +
1 EPH-Ephrin signaling
2 EPHA-mediated growth cone collapse
3 EPH-ephrin mediated repulsion of cells
WikiPathways [+] 1 WikiPathways +
1 NRF2 pathway
References
REF 1 ClinicalTrials.gov (NCT02575261) CAR-T Cell Immunotherapy for EphA2 Positive Malignant Glioma Patients
REF 2 ClinicalTrials.gov (NCT02252211) Safety and Bio-Imaging Trial of DS-8895a in Patients With Advanced EphA2 Positive Cancers. U.S. National Institutes of Health.
REF 3 ClinicalTrials.gov (NCT00796055) Study of MEDI-547 to Evaluate the Safety, Tolerability, and Biologic Activity of IV Administration in Subjects With Relapsed or Refractory Solid Tumors. U.S. NationalInstitutes of Health.
REF 4 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016645)
REF 5 Clinical pipeline report, company report or official report of Daiichi Sankyo.
REF 6 Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
REF 7 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1822).
REF 8 Clinical and biological impact of EphA2 overexpression and angiogenesis in endometrial cancer. Cancer Biol Ther. 2010 Dec 15;10(12):1306-14.
REF 9 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
REF 10 Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem. 2009 Oct 22;52(20):6433-46.
REF 11 Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3743-8.
REF 12 Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.

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