YES proto-oncogene 1, Src family tyrosine kinase | Src family | IUPHAR/BPS Guide to PHARMACOLOGY

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YES proto-oncogene 1, Src family tyrosine kinase

target has curated data in GtoImmuPdb

Target id: 2284

Nomenclature: YES proto-oncogene 1, Src family tyrosine kinase

Abbreviated Name: Yes

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 - 543 18p11.31-p11.21 YES1 YES proto-oncogene 1, Src family tyrosine kinase
Mouse - 541 5 B1 Yes1 YES proto-oncogene 1, Src family tyrosine kinase
Rat - 489 9 q38 Yes1 YES proto-oncogene 1
Previous and Unofficial Names
c-yes | p60c-yes | p61-Yes | v-yes-1 Yamaguchi sarcoma viral oncogene homolog 1 | Yamaguchi sarcoma viral (v-yes) oncogene homolog 1 | YES proto-oncogene 1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank 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:  Yes SH3 domain.
PDB Id:  2HDA
Resolution:  1.9Å
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
eCF506 Hs Inhibition >9.3 pIC50 6
pIC50 >9.3 (IC50 <5x10-10 M) [6]
rebastinib Hs Inhibition 8.6 – 8.8 pIC50 11
pIC50 8.6 – 8.8 (IC50 2.5x10-9 – 1.5x10-9 M) [11]
saracatinib Hs Inhibition 8.4 pIC50 8
pIC50 8.4 (IC50 4x10-9 M) [8]
ibrutinib Hs Inhibition 8.4 pIC50 2
pIC50 8.4 (IC50 4.1x10-9 M) [2]
SU6656 Hs Inhibition 7.7 pIC50 5
pIC50 7.7 (IC50 2x10-8 M) [5]
theliatinib Hs Inhibition 6.5 pIC50 12
pIC50 6.5 (IC50 3.34x10-7 M) [12]
spebrutinib Hs Inhibition 6.1 pIC50 4
pIC50 6.1 (IC50 7.23x10-7 M) [4]
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: 3,13

Key to terms and symbols Click column headers to sort
Target used in screen: YES
Ligand Sp. Type Action Value Parameter
dasatinib Hs Inhibitor Inhibition 9.5 pKd
PD-173955 Hs Inhibitor Inhibition 8.6 pKd
bosutinib Hs Inhibitor Inhibition 8.4 pKd
KW-2449 Hs Inhibitor Inhibition 7.7 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.6 pKd
tamatinib Hs Inhibitor Inhibition 7.5 pKd
foretinib Hs Inhibitor Inhibition 7.3 pKd
staurosporine Hs Inhibitor Inhibition 7.3 pKd
fedratinib Hs Inhibitor Inhibition 6.9 pKd
sunitinib Hs Inhibitor Inhibition 6.9 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: 1,7

Key to terms and symbols Click column headers to sort
Target used in screen: Tes/YES(YES1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Lck inhibitor Hs Inhibitor Inhibition 0.7 0.0 0.0
dasatinib Hs Inhibitor Inhibition 1.9
staurosporine Hs Inhibitor Inhibition 4.5 1.0 -0.5
SU11652 Hs Inhibitor Inhibition 5.3 2.0 -1.0
sunitinib Hs Inhibitor Inhibition 5.9
TWS119 Hs Inhibitor Inhibition 6.0 1.0 -1.0
dovitinib Hs Inhibitor Inhibition 6.3
aminopurvalanol A Hs Inhibitor Inhibition 7.0 5.0 0.0
bosutinib Hs Inhibitor Inhibition 7.3
Src kinase inhibitor I Hs Inhibitor Inhibition 8.0 9.0 4.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system.
Cell Type Associations
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Comment:  Low expression level
References:  9
Immuno Cell Type:  Natural killer cells
Cell Ontology Term:   natural killer cell (CL:0000623)
Comment:  Low expression level
References:  9
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   monocyte (CL:0000576)
macrophage (CL:0000235)
Comment:  Low expression level
References:  9
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0050900 leukocyte migration TAS
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0031295 T cell costimulation TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0031295 T cell costimulation TAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
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 2 GO processes
GO:0031295 T cell costimulation TAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS

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. 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]

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. Evans E, Tester R, Aslanian S, Mazdiyasn H, Ponader S, Tesar B, Chaturvedi P, Nacht M, Stiede K, Witowski S et al.. Clinical Development of AVL - 292: A Potent, Selective Covalent Btk Inhibitor for the Treatment of B Cell Malignancies. Accessed on 29/10/2014. Modified on 29/10/2014. http://www.celgene.com, http://www.celgene.com/content/uploads/pdf/2011_ASH_AVL-292.pdf

5. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc. Natl. Acad. Sci. U.S.A., 104 (51): 20523-8. [PMID:18077363]

6. 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]

7. 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]

8. Hennequin LF, Allen J, Breed J, Curwen J, Fennell M, Green TP, Lambert-van der Brempt C, Morgentin R, Norman RA, Olivier A et al.. (2006) N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. J. Med. Chem., 49 (22): 6465-88. [PMID:17064066]

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

10. Martín-García JM, Luque I, Mateo PL, Ruiz-Sanz J, Cámara-Artigas A. (2007) Crystallographic structure of the SH3 domain of the human c-Yes tyrosine kinase: loop flexibility and amyloid aggregation. FEBS Lett., 581 (9): 1701-6. [PMID:17418139]

11. Patel PR, Sun H, Li SQ, Shen M, Khan J, Thomas CJ, Davis MI. (2013) Identification of potent Yes1 kinase inhibitors using a library screening approach. Bioorg. Med. Chem. Lett., 23 (15): 4398-403. [PMID:23787099]

12. Ren Y, Zheng J, Fan S, Wang L, Cheng M, Shi D, Zhang W, Tang R, Yu Y, Jiao L et al.. (2017) Anti-tumor efficacy of theliatinib in esophageal cancer patient-derived xenografts models with epidermal growth factor receptor (EGFR) overexpression and gene amplification. Oncotarget, 8 (31): 50832-50844. [PMID:28881608]

13. 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: YES proto-oncogene 1, Src family tyrosine kinase. Last modified on 26/04/2018. Accessed on 20/07/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2284.