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EPH receptor A4

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1824

Nomenclature: EPH receptor A4

Abbreviated Name: EphA4

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 1 986 2q36.1 EPHA4 EPH receptor A4
Mouse 1 986 1 39.55 cM Epha4 Eph receptor A4
Rat - 986 9q33 Epha4 Eph receptor A4
Previous and Unofficial Names Click here for help
Hek8 | TYRO1 | Tyrosine-protein kinase receptor MPK-3 | Tyrosine-protein kinase receptor SEK-1
Database Links Click here for help
Alphafold P54764 (Hs), Q03137 (Mm)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.120.260, 2.60.40.10
ChEMBL Target CHEMBL3988 (Hs), CHEMBL1293259 (Mm)
Ensembl Gene ENSG00000116106 (Hs), ENSMUSG00000026235 (Mm), ENSRNOG00000013213 (Rn)
Entrez Gene 2043 (Hs), 13838 (Mm), 316539 (Rn)
Human Protein Atlas ENSG00000116106 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:2043 (Hs), mmu:13838 (Mm), rno:316539 (Rn)
OMIM 602188 (Hs)
Pharos P54764 (Hs)
RefSeq Nucleotide NM_004438 (Hs), NM_007936 (Mm), NM_001162411 (Rn)
RefSeq Protein NP_004429 (Hs), NP_031962 (Mm), NP_001155883 (Rn)
UniProtKB P54764 (Hs), Q03137 (Mm)
Wikipedia EPHA4 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the EPHA4 ligand binding domain
PDB Id:  2WO1
Resolution:  1.85Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the EPHA4-EPHRINA2 complex
PDB Id:  2WO3
Ligand:  ephrin-A2   This ligand is endogenous
Resolution:  2.35Å
Species:  Human
References:  2
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
compound 66 [PMID: 19788238] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 6
⤷ pIC50 8.5 (IC50 3.3x10-9 M) [6]
compound 20 [PMID: 23489211] Small molecule or natural product Click here for species-specific activity table Mm Inhibition 5.6 pIC50 5
⤷ pIC50 5.6 (IC50 2.7x10-6 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: 3,8
Key to terms and symbols Click column headers to sort
Target used in screen: EPHA4
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.9 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.7 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.4 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
MLN-8054 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 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: 1,4
Key to terms and symbols Click column headers to sort
Target used in screen: EphA4/EPHA4
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 1.6
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 17.0 1.0
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 12.0
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 27.0
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 33.7
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 37.7 95.0 39.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 48.3 48.0 4.0
PP1 analog II Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 48.9 47.0 5.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 54.8 97.0 86.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 61.1 115.0 102.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
EPHA4 interaction with the ligand ephrin B2 mediates a forward signal that leads to endothelial cell activation and increased monocyte adhesion to the endothelium [7]. This ephrin B2 pro-adhesion effect is EPHA4 dependent and can be induced by TNF-α treatment (via elevation of ephrin B2 expression).

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. Bowden TA, Aricescu AR, Nettleship JE, Siebold C, Rahman-Huq N, Owens RJ, Stuart DI, Jones EY. (2009) Structural plasticity of eph receptor A4 facilitates cross-class ephrin signaling. Structure, 17 (10): 1386-97. [PMID:19836338]

3. 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]

4. 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]

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. Poitz DM, Ende G, Stütz B, Augstein A, Friedrichs J, Brunssen C, Werner C, Strasser RH, Jellinghaus S. (2015) EphrinB2/EphA4-mediated activation of endothelial cells increases monocyte adhesion. Mol Immunol, 68 (2 Pt C): 648-56. [PMID:26552760]

8. 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 A4. Last modified on 26/02/2018. Accessed on 16/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1824.