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FYN proto-oncogene, Src family tyrosine kinase

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Target id: 2026

Nomenclature: FYN proto-oncogene, Src family tyrosine kinase

Abbreviated Name: Fyn

Family: Src family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 537 6q21 FYN FYN proto-oncogene, Src family tyrosine kinase
Mouse - 537 10 20.51 cM Fyn Fyn proto-oncogene
Rat - 537 20q12 Fyn FYN proto-oncogene, Src family tyrosine kinase
Previous and Unofficial Names Click here for help
FGR | p59-Fyn | SLK | Src Kinase p59 | SYN | FYN oncogene related to SRC, FGR, YES | FYN proto-oncogene
Database Links Click here for help
Alphafold P06241 (Hs), P39688 (Mm), Q62844 (Rn)
BRENDA 2.7.10.2
CATH/Gene3D 3.30.505.10
ChEMBL Target CHEMBL1841 (Hs), CHEMBL4517 (Mm)
Ensembl Gene ENSG00000010810 (Hs), ENSMUSG00000019843 (Mm), ENSRNOG00000000596 (Rn)
Entrez Gene 2534 (Hs), 14360 (Mm), 25150 (Rn)
Human Protein Atlas ENSG00000010810 (Hs)
KEGG Enzyme 2.7.10.2
KEGG Gene hsa:2534 (Hs), mmu:14360 (Mm), rno:25150 (Rn)
OMIM 137025 (Hs)
Pharos P06241 (Hs)
RefSeq Nucleotide NM_002037 (Hs), NM_001122892 (Mm), NM_012755 (Rn)
RefSeq Protein NP_002028 (Hs), NP_001116364 (Mm), NP_036887 (Rn)
UniProtKB P06241 (Hs), P39688 (Mm), Q62844 (Rn)
Wikipedia FYN (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.10.2

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
acalabrutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition <6.0 pEC50 3
⤷ pEC50 <6.0 (EC50 >1x10-6 M) [3]
compound 2 [PMID: 15546730] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 5
⤷ pIC50 9.0 (IC50 1x10-9 M) [5]
bosutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 14
⤷ pIC50 8.7 (IC50 1.8x10-9 M) [14]
eCF506 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 7
⤷ pIC50 8.7 (IC50 2.1x10-9 M) [7]
PP2 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 9
⤷ pIC50 8.3 (IC50 5x10-9 M) [9]
PP1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 9
⤷ pIC50 8.2 (IC50 6x10-9 M) [9]
ibrutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.5 pIC50 4
⤷ pIC50 7.5 (IC50 2.9x10-8 M) [4]
pexmetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 2
⤷ pIC50 7.4 (IC50 4.1x10-8 M) [2]
compound 25 [PMID: 31260299] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.8 pIC50 16
⤷ pIC50 6.8 (IC50 1.652x10-7 M) [16]
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: 6,15
Key to terms and symbols Click column headers to sort
Target used in screen: FYN
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.1 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.0 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
masitinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand 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 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: 1,8
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 Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 2.0
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.5 0.0 0.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.6 -0.5 -1.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 5.1 1.0 2.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 7.9 0.0 -2.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 13.0 -1.0 2.0
aminopurvalanol A Small molecule or natural product Hs Inhibitor Inhibition 18.9 9.0 0.0
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 20.9 11.0 1.0
GSK-3 inhibitor X Small molecule or natural product Hs Inhibitor Inhibition 20.9 1.0 0.0
dovitinib Small molecule or natural product 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
Immuno Process:  Cytokine production & signalling
Immuno Process:  T cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Immuno Process:  B cell (activation)

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]

16. Yao X, Sun X, Jin S, Yang L, Xu H, Rao Y. (2019) Discovery of 4-Aminoquinoline-3-carboxamide Derivatives as Potent Reversible Bruton's Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis. J Med Chem, 62 (14): 6561-6574. [PMID:31260299]

How to cite this page

Src family: FYN proto-oncogene, Src family tyrosine kinase. Last modified on 16/07/2019. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2026.