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Target id: 2060
Nomenclature: LYN proto-oncogene, Src family tyrosine kinase
Abbreviated Name: Lyn
Family: Src family
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 512 | 8q12.1 | LYN | LYN proto-oncogene, Src family tyrosine kinase | |
Mouse | - | 512 | 4 2.05 cM | Lyn | LYN proto-oncogene, Src family tyrosine kinase | |
Rat | - | 512 | 5q12 | Lyn | LYN proto-oncogene, Src family tyrosine kinase | |
Gene and Protein Information Comments | ||||||
A shorter 491 amino acid isoform has been identified in human, mouse and rat. This shorter isoform is termed isoform B, and in all species is 21 amino acids shorter than the cononical isoform (known as isoform A). |
Previous and Unofficial Names |
Hck-2 | JTK8 | p53Lyn | p56Lyn | v-yes-1 Yamaguchi sarcoma viral related oncogene homolog | LYN proto-oncogene |
Database Links | |
Alphafold | P07948 (Hs), P25911 (Mm), Q07014 (Rn) |
BRENDA | 2.7.10.2 |
CATH/Gene3D | 3.30.505.10 |
ChEMBL Target | CHEMBL3905 (Hs), CHEMBL2258 (Mm), CHEMBL4363 (Rn) |
Ensembl Gene | ENSG00000254087 (Hs), ENSMUSG00000042228 (Mm), ENSRNOG00000008180 (Rn) |
Entrez Gene | 4067 (Hs), 17096 (Mm), 81515 (Rn) |
Human Protein Atlas | ENSG00000254087 (Hs) |
KEGG Enzyme | 2.7.10.2 |
KEGG Gene | hsa:4067 (Hs), mmu:17096 (Mm), rno:81515 (Rn) |
OMIM | 165120 (Hs) |
Pharos | P07948 (Hs) |
RefSeq Nucleotide | NM_001111097 (Hs), NM_001111098 (Hs), NM_010747 (Mm), NM_002350 (Mm), NM_030857 (Rn), NM_001111098 (Rn) |
RefSeq Protein | NP_001104567 (Hs), NP_002341 (Hs), NP_034877 (Mm), NP_001104566 (Mm), NP_001104568 (Rn), NP_110484 (Rn) |
UniProtKB | P07948 (Hs), P25911 (Mm), Q07014 (Rn) |
Wikipedia | LYN (Hs) |
Selected 3D Structures | |||||||||||
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Enzyme Reaction | ||||
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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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Inhibitor Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Note that bosutinib has inhibitory activity at other kinases including HCK, ABL1 and SRC. |
Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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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: 7,22 |
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Target used in screen: LYN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 1,12 |
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Target used in screen: Lyn/LYN | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Target used in screen: nd/LYN B | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immunopharmacology Comments |
LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [10-11,21]. |
Cell Type Associations | ||||||
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Immuno Process Associations | ||
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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. Bamborough P, Angell RM, Bhamra I, Brown D, Bull J, Christopher JA, Cooper AW, Fazal LH, Giordano I, Hind L et al.. (2007) N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics. Bioorg Med Chem Lett, 17 (15): 4363-8. [PMID:17600705]
4. 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.
5. Bauer F, Schweimer K, Meiselbach H, Hoffmann S, Rösch P, Sticht H. (2005) Structural characterization of Lyn-SH3 domain in complex with a herpesviral protein reveals an extended recognition motif that enhances binding affinity. Protein Sci, 14 (10): 2487-98. [PMID:16155203]
6. 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]
7. 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]
8. 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 USA, 104 (51): 20523-8. [PMID:18077363]
9. 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]
10. Freedman TS, Tan YX, Skrzypczynska KM, Manz BN, Sjaastad FV, Goodridge HS, Lowell CA, Weiss A. (2015) LynA regulates an inflammation-sensitive signaling checkpoint in macrophages. Elife, 4. [PMID:26517880]
11. Gao R, Ma Z, Ma M, Yu J, Chen J, Li Z, Shetty S, Fu J. (2015) Deletion of Src family kinase Lyn aggravates endotoxin-induced lung inflammation. Am J Physiol Lung Cell Mol Physiol, 309 (11): L1376-81. [PMID:26453518]
12. 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]
13. Horio T, Hamasaki T, Inoue T, Wakayama T, Itou S, Naito H, Asaki T, Hayase H, Niwa T. (2007) Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives. Bioorg Med Chem Lett, 17 (10): 2712-7. [PMID:17376680]
14. Kim KH, Maderna A, Schnute ME, Hegen M, Mohan S, Miyashiro J, Lin L, Li E, Keegan S, Lussier J et al.. (2011) Imidazo[1,5-a]quinoxalines as irreversible BTK inhibitors for the treatment of rheumatoid arthritis. Bioorg Med Chem Lett, 21 (21): 6258-63. [PMID:21958547]
15. Lowell CA. (2004) Src-family kinases: rheostats of immune cell signaling. Mol Immunol, 41 (6-7): 631-43. [PMID:15220000]
16. Miyano N, Kinoshita T, Nakai R, Kirii Y, Yokota K, Tada T. (2009) Structural basis for the inhibitor recognition of human Lyn kinase domain. Bioorg Med Chem Lett, 19 (23): 6557-60. [PMID:19857964]
17. 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]
18. 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]
19. Saporito MS, Ochman AR, Lipinski CA, Handler JA, Reaume AG. (2012) MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo. J Pharmacol Exp Ther, 342 (1): 15-22. [PMID:22473614]
20. Tan L, Nomanbhoy T, Gurbani D, Patricelli M, Hunter J, Geng J, Herhaus L, Zhang J, Pauls E, Ham Y et al.. (2015) Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2). J Med Chem, 58 (1): 183-96. [PMID:25075558]
21. Toubiana J, Rossi AL, Belaidouni N, Grimaldi D, Pene F, Chafey P, Comba B, Camoin L, Bismuth G, Claessens YE et al.. (2015) Src-family-tyrosine kinase Lyn is critical for TLR2-mediated NF-κB activation through the PI 3-kinase signaling pathway. Innate Immun, 21 (7): 685-97. [PMID:26055819]
22. 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]
Src family: LYN proto-oncogene, Src family tyrosine kinase. Last modified on 26/04/2018. Accessed on 11/11/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2060.