EPH receptor A4 | Type XIII RTKs: Ephrin receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

EPH receptor A4

target has curated data in GtoImmuPdb

Target id: 1824

Nomenclature: EPH receptor A4

Abbreviated Name: EphA4

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 1 986 2q36.3 EPHA4 EPH receptor A4
Mouse 1 986 1 C1-C5 Epha4 Eph receptor A4
Rat - 986 9q33 Epha4 Eph receptor A4
Previous and Unofficial Names
Hek8 | TYRO1 | Tyrosine-protein kinase receptor MPK-3 | Tyrosine-protein kinase receptor SEK-1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
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
EC Number: 2.7.10.1

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

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] Hs Inhibition 8.5 pIC50 6
pIC50 8.5 (IC50 3.3x10-9 M) [6]
compound 20 [PMID: 23489211] Mm Inhibition 5.6 pIC50 5
pIC50 5.6 (IC50 2.7x10-6 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: 3,8

Key to terms and symbols Click column headers to sort
Target used in screen: EPHA4
Ligand Sp. Type Action Value Parameter
dasatinib Hs Inhibitor Inhibition 8.9 pKd
foretinib Hs Inhibitor Inhibition 8.7 pKd
PD-173955 Hs Inhibitor Inhibition 8.1 pKd
bosutinib Hs Inhibitor Inhibition 7.7 pKd
tamatinib Hs Inhibitor Inhibition 6.8 pKd
staurosporine Hs Inhibitor Inhibition 6.5 pKd
nilotinib Hs Inhibitor Inhibition 6.5 pKd
crizotinib Hs Inhibitor Inhibition 6.4 pKd
AST-487 Hs Inhibitor Inhibition 6.4 pKd
MLN-8054 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
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 Hs Inhibitor Inhibition 1.6
staurosporine Hs Inhibitor Inhibition 6.7 17.0 1.0
nilotinib Hs Inhibitor Inhibition 12.0
bosutinib Hs Inhibitor Inhibition 27.0
vandetanib Hs Inhibitor Inhibition 33.7
dorsomorphin Hs Inhibitor Inhibition 37.7 95.0 39.0
TWS119 Hs Inhibitor Inhibition 48.3 48.0 4.0
PP1 analog II Hs Inhibitor Inhibition 48.9 47.0 5.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 54.8 97.0 86.0
PDK1/Akt/Flt dual pathway inhibitor 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

Show »

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 05/04/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1824.