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TYRO3 protein tyrosine kinase

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1836

Nomenclature: TYRO3 protein tyrosine kinase

Abbreviated Name: Tyro3

Family: Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 890 15q15.1 TYRO3 TYRO3 protein tyrosine kinase
Mouse 1 880 2 59.97 cM Tyro3 TYRO3 protein tyrosine kinase 3
Rat 1 880 3q35 Tyro3 TYRO3 protein tyrosine kinase
Previous and Unofficial Names Click here for help
Brt | Dtk | RSE | Tif | Bruton agammaglobulinemia tyrosine kinase | tyrosine-protein kinase SKY | Etk-2
Database Links Click here for help
Alphafold Q06418 (Hs), P55144 (Mm), P55146 (Rn)
BRENDA 2.7.10.1
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL5314 (Hs)
Ensembl Gene ENSG00000092445 (Hs), ENSMUSG00000027298 (Mm), ENSRNOG00000058586 (Rn)
Entrez Gene 7301 (Hs), 22174 (Mm), 25232 (Rn)
Human Protein Atlas ENSG00000092445 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:7301 (Hs), mmu:22174 (Mm), rno:25232 (Rn)
OMIM 600341 (Hs)
Pharos Q06418 (Hs)
RefSeq Nucleotide NM_006293 (Hs), NM_019392 (Mm), NM_017092 (Rn)
RefSeq Protein NP_006284 (Hs), NP_062265 (Mm), NP_058788 (Rn)
UniProtKB Q06418 (Hs), P55144 (Mm), P55146 (Rn)
Wikipedia TYRO3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human Tyro3-D1D2.
PDB Id:  1RHF
Resolution:  1.96Å
Species:  Human
References:  5
Enzyme Reaction Click here for help
EC Number: 2.7.10.1
Natural/Endogenous Ligands Click here for help
growth arrest specific protein 6 {Sp: Human}
protein S {Sp: Human}

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
UNC4203 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.4 pKi 12
⤷ pKi 8.4 (Ki 3.87x10-9 M) [12]
compound 21 [PMID: 23312943] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.1 pIC50 8
⤷ pIC50 9.1 (IC50 7x10-10 M) [8]
BMS-777607 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pIC50 9
⤷ pIC50 8.4 (IC50 4.3x10-9 M) [9]
LDC1267 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 7
⤷ pIC50 8.1 (IC50 8x10-9 M) [7]
UNC8969 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 6
⤷ pIC50 7.2 (IC50 6.6x10-8 M) [6]
SLC-391 Small molecule or natural product Click here for species-specific activity table Hs Inhibition >6.3 pIC50 11
⤷ pIC50 >6.3 (IC50 <5x10-7 M) [11]
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: 3,10
Key to terms and symbols Click column headers to sort
Target used in screen: TYRO3
Ligand Sp. Type Action Value Parameter
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.2 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.0 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: Rse/TYRO3(SKY)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 1.5 -0.5
K-252a Small molecule or natural product Hs Inhibitor Inhibition 20.4 6.0 2.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 23.2 24.0 -1.0
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 23.8
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 28.3
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 29.8 14.0 -1.0
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 33.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 33.3 106.0 114.0
SU11274 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 34.7 48.0 30.0
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 47.8
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
TYRO3 is a negative regulator of type 2 immunity [2].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Immuno Process:  Barrier integrity
Immuno Process:  Immune system development

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. Chan PY, Carrera Silva EA, De Kouchkovsky D, Joannas LD, Hao L, Hu D, Huntsman S, Eng C, Licona-Limón P, Weinstein JS et al.. (2016) The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity. Science, 352 (6281): 99-103. [PMID:27034374]

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. Heiring C, Dahlbäck B, Muller YA. (2004) Ligand recognition and homophilic interactions in Tyro3: structural insights into the Axl/Tyro3 receptor tyrosine kinase family. J Biol Chem, 279 (8): 6952-8. [PMID:14623883]

6. Kong D, Tian Q, Chen Z, Zheng H, Stashko MA, Yan D, Earp HS, Frye SV, DeRyckere D, Kireev D et al.. (2024) Discovery of Novel Macrocyclic MERTK/AXL Dual Inhibitors. J Med Chem, 67 (7): 5866-5882. [PMID:38556760]

7. Paolino M, Choidas A, Wallner S, Pranjic B, Uribesalgo I, Loeser S, Jamieson AM, Langdon WY, Ikeda F, Fededa JP et al.. (2014) The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature, 507 (7493): 508-12. [PMID:24553136]

8. Powell NA, Hoffman JK, Ciske FL, Kohrt JT, Baxi SM, Peng YW, Zhong M, Catana C, Ohren J, Perrin LA et al.. (2013) Optimization of highly selective 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase. Bioorg Med Chem Lett, 23 (4): 1051-5. [PMID:23312943]

9. Schroeder GM, An Y, Cai ZW, Chen XT, Clark C, Cornelius LA, Dai J, Gullo-Brown J, Gupta A, Henley B et al.. (2009) Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily. J Med Chem, 52 (5): 1251-4. [PMID:19260711]

10. 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]

11. Zhang Z. (2015) Aminopyridine derivatives as tam family kinase inhibitors. Patent number: WO2015081257A2. Assignee: Signalchem Lifesciences Corporation. Priority date: 26/11/2014. Publication date: 04/06/2015.

12. Zhao J, Zhang D, Zhang W, Stashko MA, DeRyckere D, Vasileiadi E, Parker RE, Hunter D, Liu Q, Zhang Y et al.. (2018) Highly Selective MERTK Inhibitors Achieved by a Single Methyl Group. J Med Chem, 61 (22): 10242-10254. [PMID:30347155]

How to cite this page

Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family: TYRO3 protein tyrosine kinase. Last modified on 02/04/2024. Accessed on 16/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1836.