TYRO3 protein tyrosine kinase | Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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TYRO3 protein tyrosine kinase

  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

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 1 890 15q15.1-q21.1 TYRO3 TYRO3 protein tyrosine kinase
Mouse 1 880 2 F Tyro3 TYRO3 protein tyrosine kinase 3
Rat 1 880 3 q36.1 Tyro3 TYRO3 protein tyrosine kinase
Previous and Unofficial Names
Brt | Dtk | RSE | Tif | Bruton agammaglobulinemia tyrosine kinase | tyrosine-protein kinase SKY | Etk-2
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
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
EC Number: 2.7.10.1
Natural/Endogenous Ligands
growth arrest specific protein 6 {Sp: Human}
protein S {Sp: Human}

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
UNC4203 Hs Inhibition 8.4 pKi 10
pKi 8.4 (Ki 3.87x10-9 M) [10]
compound 21 [PMID: 23312943] Hs Inhibition 9.1 pIC50 7
pIC50 9.1 (IC50 7x10-10 M) [7]
BMS-777607 Hs Inhibition 8.4 pIC50 8
pIC50 8.4 (IC50 4.3x10-9 M) [8]
LDC1267 Hs Inhibition 8.1 pIC50 6
pIC50 8.1 (IC50 8x10-9 M) [6]
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: 3,9

Key to terms and symbols Click column headers to sort
Target used in screen: TYRO3
Ligand Sp. Type Action Value Parameter
foretinib Hs Inhibitor Inhibition 8.7 pKd
sunitinib Hs Inhibitor Inhibition 7.3 pKd
bosutinib Hs Inhibitor Inhibition 7.2 pKd
vandetanib Hs Inhibitor Inhibition 7.0 pKd
staurosporine Hs Inhibitor Inhibition 6.6 pKd
PD-173955 Hs Inhibitor Inhibition 6.3 pKd
lestaurtinib Hs Inhibitor Inhibition 6.2 pKd
crizotinib Hs Inhibitor Inhibition 6.1 pKd
cediranib Hs Inhibitor Inhibition 6.1 pKd
canertinib 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
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 Hs Inhibitor Inhibition 7.3 1.5 -0.5
K-252a Hs Inhibitor Inhibition 20.4 6.0 2.0
SU11652 Hs Inhibitor Inhibition 23.2 24.0 -1.0
dovitinib Hs Inhibitor Inhibition 23.8
sunitinib Hs Inhibitor Inhibition 28.3
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 29.8 14.0 -1.0
vandetanib Hs Inhibitor Inhibition 33.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 33.3 106.0 114.0
SU11274 Hs Inhibitor Inhibition 34.7 48.0 30.0
bosutinib 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
GO Annotations:  Associated to 4 GO processes
GO:0034122 negative regulation of toll-like receptor signaling pathway ISS
GO:0043277 apoptotic cell clearance ISS
GO:0045824 negative regulation of innate immune response ISS
GO:0050728 negative regulation of inflammatory response ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 4 GO processes
GO:0034122 negative regulation of toll-like receptor signaling pathway ISS
GO:0045824 negative regulation of innate immune response ISS
GO:0050728 negative regulation of inflammatory response ISS
click arrow to show/hide IEA associations
GO:0051250 negative regulation of lymphocyte activation IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 3 GO processes
GO:0034122 negative regulation of toll-like receptor signaling pathway ISS
click arrow to show/hide IEA associations
GO:0001779 natural killer cell differentiation IEA
GO:0051250 negative regulation of lymphocyte activation IEA
Immuno Process:  Barrier integrity
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001618 virus receptor activity IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001779 natural killer cell differentiation IEA

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. 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]

7. 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]

8. 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]

9. 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]

10. 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 13/11/2018. Accessed on 26/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1836.