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EPH receptor A2

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Target not currently curated in GtoImmuPdb

Target id: 1822

Nomenclature: EPH receptor A2

Abbreviated Name: EphA2

Family: Type XIII RTKs: Ephrin receptor family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 976 1p36.13 EPHA2 EPH receptor A2
Mouse 1 977 4 73.67 cM Epha2 Eph receptor A2
Rat - 977 5q36 Epha2 Eph receptor A2
Previous and Unofficial Names Click here for help
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 Click here for help
Alphafold P29317 (Hs), Q03145 (Mm)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.40.10, 2.60.120.260
ChEMBL Target CHEMBL2068 (Hs), CHEMBL4105859 (Mm)
DrugBank Target P29317 (Hs)
Ensembl Gene ENSG00000142627 (Hs), ENSMUSG00000006445 (Mm), ENSRNOG00000009222 (Rn)
Entrez Gene 1969 (Hs), 13836 (Mm), 366492 (Rn)
Human Protein Atlas ENSG00000142627 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:1969 (Hs), mmu:13836 (Mm), rno:366492 (Rn)
OMIM 176946 (Hs)
Orphanet ORPHA209474 (Hs)
Pharos P29317 (Hs)
RefSeq Nucleotide NM_004431 (Hs), NM_010139 (Mm), NM_001108977 (Rn)
RefSeq Protein NP_004422 (Hs), NP_034269 (Mm), NP_001102447 (Rn)
UniProtKB P29317 (Hs), Q03145 (Mm)
Wikipedia EPHA2 (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.10.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
DDR1/2 inhibitor 5n Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.6 pKd 10
⤷ pKd 6.6 (Kd 2.6x10-7 M) [10]
compound 8h [PMID: 21561767] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.2 pIC50 9
⤷ pIC50 9.2 (IC50 6x10-10 M) [9]
compound 66 [PMID: 19788238] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 pIC50 6
⤷ pIC50 8.6 (IC50 2.3x10-9 M) [6]
dorsomorphin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure 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] Small molecule or natural product Click here for species-specific activity table Mm Inhibition 5.7 pIC50 5
⤷ pIC50 5.7 (IC50 2.2x10-6 M) [5]
View species-specific inhibitor tables
DiscoveRx KINOMEscan® screen Click here for help
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 Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.1 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.7 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.8 pKd
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
MLN-8054 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure 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 Click here for help
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 Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.6
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 10.8
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 21.3 25.0 2.0
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 21.5
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 29.9 13.0 -2.0
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 34.4
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 36.2 59.0 8.0
IKK-2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 37.5 32.0 4.0
PP1 analog II Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 42.0 33.0 1.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Barrier integrity
Immuno Process:  Immune system development
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Clinically-Relevant Mutations and Pathophysiology Click here for help
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 USA, 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 25/06/2021. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1822.