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Target has curated data in GtoImmuPdb
Target id: 1940
Nomenclature: BLK proto-oncogene, Src family tyrosine kinase
Abbreviated Name: Blk
Family: Src family
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 505 | 8p23.1 | BLK | BLK proto-oncogene, Src family tyrosine kinase | |
Mouse | - | 499 | 14 33.25 cM | Blk | B lymphoid kinase | |
Rat | - | 499 | 15p12 | Blk | BLK proto-oncogene, Src family tyrosine kinase |
Previous and Unofficial Names |
B lymphocyte kinase | p55-Blk | BLK proto-oncogene |
Database Links | |
Alphafold | P51451 (Hs), P16277 (Mm) |
BRENDA | 2.7.10.2 |
CATH/Gene3D | 3.30.505.10 |
ChEMBL Target | CHEMBL2250 (Hs), CHEMBL3343 (Mm) |
Ensembl Gene | ENSG00000136573 (Hs), ENSMUSG00000014453 (Mm), ENSRNOG00000010798 (Rn) |
Entrez Gene | 640 (Hs), 12143 (Mm), 364403 (Rn) |
Human Protein Atlas | ENSG00000136573 (Hs) |
KEGG Enzyme | 2.7.10.2 |
KEGG Gene | hsa:640 (Hs), mmu:12143 (Mm), rno:364403 (Rn) |
OMIM | 191305 (Hs) |
Orphanet | ORPHA227384 (Hs) |
Pharos | P51451 (Hs) |
RefSeq Nucleotide | NM_001715 (Hs), NM_007549 (Mm), NM_001025751 (Rn) |
RefSeq Protein | NP_001706 (Hs), NP_031575 (Mm), NP_001020922 (Rn) |
UniProtKB | P51451 (Hs), P16277 (Mm) |
Wikipedia | BLK (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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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: 6,20 |
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Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Target used in screen: BLK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 1,8 |
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Target used in screen: Blk/BLK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immunopharmacology Comments |
BLK is a B cell-specific kinase. In Blk knockout mice B cells develop normally and show unaltered in vitro activation and humoral immune responses to T cell-dependent and -independent antigens, a result which is indicative of functional redundancy of Blk in B cell development and immune responses [18]. Genetic variants in BLK have been reported to associate with autoimmune conditions [25], including systemic lupus erythematosus (SLE) [5], primary Sjögren's syndrome [16-17], asthma and allergic rhinitis [11]. |
Cell Type Associations | ||||||||
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Immuno Process Associations | ||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||||
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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. Bradshaw JM, McFarland JM, Paavilainen VO, Bisconte A, Tam D, Phan VT, Romanov S, Finkle D, Shu J, Patel V et al.. (2015) Prolonged and tunable residence time using reversible covalent kinase inhibitors. Nat Chem Biol, 11 (7): 525-31. [PMID:26006010]
3. 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]
4. 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]
5. Chen Y, Wu Q, Shao Y, Zhang J, Guan M, Wan J, Yu B, Zhang W. (2012) Identify the association between polymorphisms of BLK and systemic lupus erythematosus through unlabelled probe-based high-resolution melting analysis. Int J Immunogenet, 39 (4): 321-7. [PMID:22313735]
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. Hudkins RL, Becknell NC, Zulli AL, Underiner TL, Angeles TS, Aimone LD, Albom MS, Chang H, Miknyoczki SJ, Hunter K et al.. (2012) Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent. J Med Chem, 55 (2): 903-13. [PMID:22148921]
10. Li X, Zuo Y, Tang G, Wang Y, Zhou Y, Wang X, Guo T, Xia M, Ding N, Pan Z. (2014) Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem, 57 (12): 5112-28. [PMID:24915291]
11. Liu Y, Ke X, Kang HY, Wang XQ, Shen Y, Hong SL. (2016) Genetic risk of TNFSF4 and FAM167A-BLK polymorphisms in children with asthma and allergic rhinitis in a Han Chinese population. J Asthma, 53 (6): 567-75. [PMID:27088737]
12. Lou Y, Owens TD, Kuglstatter A, Kondru RK, Goldstein DM. (2012) Bruton's tyrosine kinase inhibitors: approaches to potent and selective inhibition, preclinical and clinical evaluation for inflammatory diseases and B cell malignancies. J Med Chem, 55 (10): 4539-50. [PMID:22394077]
13. Lowell CA. (2004) Src-family kinases: rheostats of immune cell signaling. Mol Immunol, 41 (6-7): 631-43. [PMID:15220000]
14. Metzler WJ, Leiting B, Pryor K, Mueller L, Farmer BT. (1996) The three-dimensional solution structure of the SH2 domain from p55blk kinase. Biochemistry, 35 (20): 6201-11. [PMID:8639560]
15. Reiff SD, Mantel R, Smith LL, Greene JT, Muhowski EM, Fabian CA, Goettl VM, Tran M, Harrington BK, Rogers KA et al.. (2018) The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation. Cancer Discov, 8 (10): 1300-1315. [PMID:30093506]
16. Sun F, Li P, Chen H, Wu Z, Xu J, Shen M, Leng X, Shi Q, Zhang W, Tian X et al.. (2013) Association studies of TNFSF4, TNFAIP3 and FAM167A-BLK polymorphisms with primary Sjogren's syndrome in Han Chinese. J Hum Genet, 58 (7): 475-9. [PMID:23635951]
17. Sun F, Xu J, Wu Z, Li P, Chen H, Su J, You X, Li M, Zhao Y, Tian X et al.. (2013) Polymorphisms in the FAM167A-BLK, but not BANK1, are associated with primary Sjögren's syndrome in a Han Chinese population. Clin Exp Rheumatol, 31 (5): 704-10. [PMID:23899688]
18. Texido G, Su IH, Mecklenbräuker I, Saijo K, Malek SN, Desiderio S, Rajewsky K, Tarakhovsky A. (2000) The B-cell-specific Src-family kinase Blk is dispensable for B-cell development and activation. Mol Cell Biol, 20 (4): 1227-33. [PMID:10648608]
19. Tichenor MS, Wiener JJM, Rao NL, Bacani GM, Wei J, Pooley Deckhut C, Barbay JK, Kreutter KD, Chang L, Clancy KW et al.. (2022) Discovery of JNJ-64264681: A Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem, 65 (21): 14326-14336. [PMID:36314537]
20. 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]
21. Yang J, Shibu MA, Kong L, Luo J, BadrealamKhan F, Huang Y, Tu ZC, Yun CH, Huang CY, Ding K et al.. (2020) Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors. J Med Chem, 63 (5): 2114-2130. [PMID:31244114]
22. 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]
23. Zhong Y, Dong S, Strattan E, Ren L, Butchar JP, Thornton K, Mishra A, Porcu P, Bradshaw JM, Bisconte A et al.. (2015) Targeting interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK) using a novel covalent inhibitor PRN694. J Biol Chem, 290 (10): 5960-78. [PMID:25593320]
24. Zhou W, Ercan D, Chen L, Yun CH, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE, Padera R et al.. (2009) Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature, 462 (7276): 1070-4. [PMID:20033049]
25. Zhou Y, Li X, Wang G, Li X. (2016) Association of FAM167A-BLK rs2736340 Polymorphism with Susceptibility to Autoimmune Diseases: A Meta-Analysis. Immunol Invest, 45 (4): 336-48. [PMID:27105348]
Src family: BLK proto-oncogene, Src family tyrosine kinase. Last modified on 02/11/2022. Accessed on 02/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1940.