EPH receptor A2 | Type XIII RTKs: Ephrin receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

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EPH receptor A2

Target not currently curated in GtoImmuPdb

Target id: 1822

Nomenclature: EPH receptor A2

Abbreviated Name: EphA2

Family: Type XIII RTKs: Ephrin receptor family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 976 1p36 EPHA2 EPH receptor A2
Mouse 1 977 4 D-E Epha2 Eph receptor A2
Rat - 977 5q36 Epha2 Eph receptor A2
Previous and Unofficial Names
ephrin type-A receptor 2 | Epithelial cell kinase | Tyrosine-protein kinase receptor ECK | Tyrosine-protein kinase receptor MPK-5 | Tyrosine-protein kinase receptor SEK-2 | Myk2
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Ephrin A2 (ephA2) Receptor Protein Kinase
PDB Id:  1MQB
Resolution:  2.3Å
Species:  Human
References:  8
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of EphA2 ectodomain in complex with ephrin-A5
PDB Id:  3MX0
Ligand:  ephrin-A5   This ligand is endogenous
Resolution:  3.51Å
Species:  Human
References:  4
Enzyme Reaction
EC Number: 2.7.10.1

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
DDR1/2 inhibitor 5n Hs Inhibition 6.6 pKd 10
pKd 6.6 (Kd 2.6x10-7 M) [10]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 8h [PMID: 21561767] Hs Inhibition 9.2 pIC50 9
pIC50 9.2 (IC50 6x10-10 M) [9]
compound 66 [PMID: 19788238] Hs Inhibition 8.6 pIC50 6
pIC50 8.6 (IC50 2.3x10-9 M) [6]
dorsomorphin Hs Inhibition 8.0 pIC50 7
pIC50 8.0 (IC50 1.1x10-8 M) [7]
Description: Assayed using AMPK heterotrimeric complex containing α2, β1, γ1 subunits
compound 20 [PMID: 23489211] Mm Inhibition 5.7 pIC50 5
pIC50 5.7 (IC50 2.2x10-6 M) [5]
View species-specific inhibitor tables
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 2,11

Key to terms and symbols Click column headers to sort
Target used in screen: EPHA2
Ligand Sp. Type Action Value Parameter
dasatinib Hs Inhibitor Inhibition 9.1 pKd
foretinib Hs Inhibitor Inhibition 8.4 pKd
PD-173955 Hs Inhibitor Inhibition 8.4 pKd
bosutinib Hs Inhibitor Inhibition 7.7 pKd
crizotinib Hs Inhibitor Inhibition 7.0 pKd
tamatinib Hs Inhibitor Inhibition 6.8 pKd
AST-487 Hs Inhibitor Inhibition 6.8 pKd
nilotinib Hs Inhibitor Inhibition 6.6 pKd
MLN-8054 Hs Inhibitor Inhibition 6.4 pKd
PP-242 Hs Inhibitor Inhibition 6.2 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: 1,3

Key to terms and symbols Click column headers to sort
Target used in screen: EphA2/EPHA2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Hs Inhibitor Inhibition 6.8
bosutinib Hs Inhibitor Inhibition 9.6
nilotinib Hs Inhibitor Inhibition 10.8
staurosporine Hs Inhibitor Inhibition 21.3 25.0 2.0
vandetanib Hs Inhibitor Inhibition 21.5
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 29.9 13.0 -2.0
tozasertib Hs Inhibitor Inhibition 34.4
dorsomorphin Hs Inhibitor Inhibition 36.2 59.0 8.0
IKK-2 inhibitor IV Hs Inhibitor Inhibition 37.5 32.0 4.0
PP1 analog II Hs Inhibitor Inhibition 42.0 33.0 1.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Posterior polar cataract
Synonyms: Cataract 6, multiple types; CTRCT6 [OMIM: 116600]
Posterior subcapsular cataract [Orphanet: ORPHA98993]
Disease Ontology: DOID:0050537
OMIM: 116600
Orphanet: ORPHA98993
Disease:  Total congenital cataract
Synonyms: Cataract 6, multiple types; CTRCT6 [OMIM: 116600]
OMIM: 116600
Orphanet: ORPHA98994

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1039-45. [PMID:22037377]

2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]

3. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J., 451 (2): 313-28. [PMID:23398362]

4. Himanen JP, Yermekbayeva L, Janes PW, Walker JR, Xu K, Atapattu L, Rajashankar KR, Mensinga A, Lackmann M, Nikolov DB et al.. (2010) Architecture of Eph receptor clusters. Proc. Natl. Acad. Sci. U.S.A., 107 (24): 10860-5. [PMID:20505120]

5. Incerti M, Tognolini M, Russo S, Pala D, Giorgio C, Hassan-Mohamed I, Noberini R, Pasquale EB, Vicini P, Piersanti S et al.. (2013) Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J. Med. Chem., 56 (7): 2936-47. [PMID:23489211]

6. Lafleur K, Huang D, Zhou T, Caflisch A, Nevado C. (2009) Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J. Med. Chem., 52 (20): 6433-46. [PMID:19788238]

7. Machrouhi F, Ouhamou N, Laderoute K, Calaoagan J, Bukhtiyarova M, Ehrlich PJ, Klon AE. (2010) The rational design of a novel potent analogue of the 5'-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity. Bioorg. Med. Chem. Lett., 20 (22): 6394-9. [PMID:20932747]

8. Nowakowski J, Cronin CN, McRee DE, Knuth MW, Nelson CG, Pavletich NP, Rogers J, Sang BC, Scheibe DN, Swanson RV et al.. (2002) Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography. Structure, 10 (12): 1659-67. [PMID:12467573]

9. Thomas M, Huang WS, Wen D, Zhu X, Wang Y, Metcalf CA, Liu S, Chen I, Romero J, Zou D et al.. (2011) Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg. Med. Chem. Lett., 21 (12): 3743-8. [PMID:21561767]

10. Wang Z, Zhang Y, Pinkas DM, Fox AE, Luo J, Huang H, Cui S, Xiang Q, Xu T, Xun Q et al.. (2018) Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2. J. Med. Chem., 61 (17): 7977-7990. [PMID:30075624]

11. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol., 17 (11): 1241-9. [PMID:21095574]

How to cite this page

Type XIII RTKs: Ephrin receptor family: EPH receptor A2. Last modified on 16/10/2018. Accessed on 17/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1822.