FYN proto-oncogene, Src family tyrosine kinase | Src family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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FYN proto-oncogene, Src family tyrosine kinase

  Target has curated data in GtoImmuPdb

Target id: 2026

Nomenclature: FYN proto-oncogene, Src family tyrosine kinase

Abbreviated Name: Fyn

Family: Src 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 - 537 6q21 FYN FYN proto-oncogene, Src family tyrosine kinase
Mouse - 534 10 B1 Fyn Fyn proto-oncogene
Rat - 537 20 q13 Fyn FYN proto-oncogene
Previous and Unofficial Names
FGR | p59-Fyn | SLK | Src Kinase p59 | SYN | FYN oncogene related to SRC, FGR, YES | FYN proto-oncogene
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 the Human Fyn SH3 domain
PDB Id:  3UA6
Resolution:  1.85Å
Species:  Human
References:  12
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Fyn kinase domain complexed with staurosporine
PDB Id:  2DQ7
Ligand:  staurosporine
Resolution:  2.8Å
Species:  Human
References:  10
Enzyme Reaction
EC Number: 2.7.10.2

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
acalabrutinib Hs Inhibition <6.0 pEC50 3
pEC50 <6.0 (EC50 >1x10-6 M) [3]
compound 2 [PMID: 15546730] Hs Inhibition 9.0 pIC50 5
pIC50 9.0 (IC50 1x10-9 M) [5]
bosutinib Hs Inhibition 8.7 pIC50 14
pIC50 8.7 (IC50 1.8x10-9 M) [14]
eCF506 Hs Inhibition 8.7 pIC50 7
pIC50 8.7 (IC50 2.1x10-9 M) [7]
PP2 Hs Inhibition 8.3 pIC50 9
pIC50 8.3 (IC50 5x10-9 M) [9]
PP1 Hs Inhibition 8.2 pIC50 9
pIC50 8.2 (IC50 6x10-9 M) [9]
ibrutinib Hs Inhibition 7.5 pIC50 4
pIC50 7.5 (IC50 2.9x10-8 M) [4]
pexmetinib Hs Inhibition 7.4 pIC50 2
pIC50 7.4 (IC50 4.1x10-8 M) [2]
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: 6,15

Key to terms and symbols Click column headers to sort
Target used in screen: FYN
Ligand Sp. Type Action Value Parameter
dasatinib Hs Inhibitor Inhibition 9.1 pKd
PD-173955 Hs Inhibitor Inhibition 8.3 pKd
bosutinib Hs Inhibitor Inhibition 8.0 pKd
tamatinib Hs Inhibitor Inhibition 7.6 pKd
staurosporine Hs Inhibitor Inhibition 7.5 pKd
fedratinib Hs Inhibitor Inhibition 7.4 pKd
AST-487 Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Hs Inhibitor Inhibition 7.1 pKd
foretinib Hs Inhibitor Inhibition 7.1 pKd
masitinib Hs Inhibitor Inhibition 6.8 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: 1,8

Key to terms and symbols Click column headers to sort
Target used in screen: Fyn/FYN
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Hs Inhibitor Inhibition 2.0
Lck inhibitor Hs Inhibitor Inhibition 3.5 0.0 0.0
staurosporine Hs Inhibitor Inhibition 3.6 -0.5 -1.0
GSK-3 inhibitor IX Hs Inhibitor Inhibition 5.1 1.0 2.0
TWS119 Hs Inhibitor Inhibition 7.9 0.0 -2.0
indirubin derivative E804 Hs Inhibitor Inhibition 13.0 -1.0 2.0
aminopurvalanol A Hs Inhibitor Inhibition 18.9 9.0 0.0
GSK-3 inhibitor X Hs Inhibitor Inhibition 20.9 1.0 0.0
dorsomorphin Hs Inhibitor Inhibition 20.9 11.0 1.0
dovitinib Hs Inhibitor Inhibition 22.5
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [13]. TCR-based signals are required at several stages of T-cell development. Note that is thought that the related Src tyrosine kinase Lck is the major contributor to TCR signal transduction.
Cell Type Associations
Immuno Cell Type:  T cells
References:  11
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
References:  11
Immuno Cell Type:  Natural killer cells
Cell Ontology Term:   natural killer cell (CL:0000623)
References:  11
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
References:  11
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 3 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0050900 leukocyte migration TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0019221 cytokine-mediated signaling pathway TAS
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 3 GO processes
GO:0031295 T cell costimulation TAS
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
GO:0050798 activated T cell proliferation IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 4 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0031295 T cell costimulation TAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0050852 T cell receptor signaling pathway IDA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes
GO:0031295 T cell costimulation TAS
GO:0050900 leukocyte migration TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 6 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0031295 T cell costimulation TAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0050852 T cell receptor signaling pathway IDA
click arrow to show/hide IEA associations
GO:0031397 negative regulation of protein ubiquitination IEA
GO:0050798 activated T cell proliferation IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response 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. Bachegowda L, Morrone K, Winski SL, Mantzaris I, Bartenstein M, Ramachandra N, Giricz O, Sukrithan V, Nwankwo G, Shahnaz S et al.. (2016) Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Cancer Res., 76 (16): 4841-4849. [PMID:27287719]

3. Barf TA, Jans CGJM, Man PADeA, Oubrie AA, Raaijmakers HCA, Rewinkel JBM, Sterrenburg J-G, Wijkmans JCHM. (2014) 4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides as btk inhibitors. Patent number: US20140155385 A1. Assignee: Barf TA, Jans CGJM, Man PADeA, Oubrie AA, Raaijmakers HCA, Rewinkel JBM, Sterrenburg J-G, Wijkmans JCHM. Priority date: 19/07/2011. Publication date: 05/06/2014.

4. Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR et al.. (2016) Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N. Engl. J. Med., 374 (4): 323-32. [PMID:26641137]

5. Chen P, Norris D, Das J, Spergel SH, Wityak J, Leith L, Zhao R, Chen BC, Pitt S, Pang S et al.. (2004) Discovery of novel 2-(aminoheteroaryl)-thiazole-5-carboxamides as potent and orally active Src-family kinase p56(Lck) inhibitors. Bioorg. Med. Chem. Lett., 14 (24): 6061-6. [PMID:15546730]

6. 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]

7. Fraser C, Dawson JC, Dowling R, Houston DR, Weiss JT, Munro AF, Muir M, Harrington L, Webster SP, Frame MC et al.. (2016) Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase. J. Med. Chem., 59 (10): 4697-710. [PMID:27115835]

8. 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]

9. Hanke JH, Gardner JP, Dow RL, Changelian PS, Brissette WH, Weringer EJ, Pollok BA, Connelly PA. (1996) Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation. J. Biol. Chem., 271 (2): 695-701. [PMID:8557675]

10. Kinoshita T, Matsubara M, Ishiguro H, Okita K, Tada T. (2006) Structure of human Fyn kinase domain complexed with staurosporine. Biochem. Biophys. Res. Commun., 346 (3): 840-4. [PMID:16782058]

11. Lowell CA. (2004) Src-family kinases: rheostats of immune cell signaling. Mol. Immunol., 41 (6-7): 631-43. [PMID:15220000]

12. Martin-Garcia JM, Luque I, Ruiz-Sanz J, Camara-Artigas A. (2012) The promiscuous binding of the Fyn SH3 domain to a peptide from the NS5A protein. Acta Crystallogr. D Biol. Crystallogr., 68 (Pt 8): 1030-40. [PMID:22868769]

13. Palacios EH, Weiss A. (2004) Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene, 23 (48): 7990-8000. [PMID:15489916]

14. Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Müller A, Baumgartner C, Valent P, Augustin M et al.. (2009) Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia, 23 (3): 477-85. [PMID:19039322]

15. 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

Src family: FYN proto-oncogene, Src family tyrosine kinase. Last modified on 24/04/2018. Accessed on 20/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2026.