Details of the Target

General Information of Target

Target ID LDTP04414
Target Name Tyrosine-protein kinase Blk (BLK)
Gene Name BLK
Gene ID 640
Synonyms
Tyrosine-protein kinase Blk; EC 2.7.10.2; B lymphocyte kinase; p55-Blk
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGLVSSKKPDKEKPIKEKDKGQWSPLKVSAQDKDAPPLPPLVVFNHLTPPPPDEHLDEDK
HFVVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVARVESLE
MERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVTTQGELIKHYKIR
CLDEGGYYISPRITFPSLQALVQHYSKKGDGLCQRLTLPCVRPAPQNPWAQDEWEIPRQS
LRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLY
AVVTKEPIYIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRD
LRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWS
FGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRGVIAECWRSRPEER
PTFEFLQSVLEDFYTATERQYELQP
Target Type
Patented-recorded
Target Bioclass
Enzyme
Family
Protein kinase superfamily, Tyr protein kinase family, SRC subfamily
Subcellular location
Cell membrane
Function
Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207'. Phosphorylates also the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose. Phosphorylates CGAS, promoting retention of CGAS in the cytosol.
TTD ID
T74307
Uniprot ID
P51451
DrugMap ID
TTNDSC3
Ensemble ID
ENST00000259089.9
HGNC ID
HGNC:1057
ChEMBL ID
CHEMBL2250

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IBr-1b
 Probe Info  		20.00  LDD0306  [1]
DBIA
 Probe Info  		C319(17.88)  LDD0204  [2]
Acrolein
 Probe Info  		N.A.  LDD0231  [3]
IA-alkyne
 Probe Info  		N.A.  LDD0036  [4]
PAL-AfBPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STS-1
 Probe Info  		1.17  LDD0137  [5]
STS-2
 Probe Info  		1.00  LDD0139  [5]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0102  BDHI 8 Jurkat C319(17.88)  LDD0204  [2]
 LDCM0206  EV-99 T cell C319(20.00)  LDD0521  [6]
 LDCM0625  F8 Ramos C181(1.12); C319(0.32); C472(1.59); C213(1.38)  LDD2187  [7]
 LDCM0572  Fragment10 Ramos C181(1.07); C319(1.61); C472(1.78); C213(1.74)  LDD2189  [7]
 LDCM0573  Fragment11 Ramos C181(0.69); C319(3.94); C472(0.39); C213(0.93)  LDD2190  [7]
 LDCM0574  Fragment12 Ramos C181(1.20); C319(3.76); C472(0.77); C213(1.51)  LDD2191  [7]
 LDCM0575  Fragment13 Ramos C181(0.99); C319(2.25); C213(0.80); C220(0.32)  LDD2192  [7]
 LDCM0576  Fragment14 Ramos C181(1.17); C472(0.97); C213(1.93); 1.44  LDD2193  [7]
 LDCM0579  Fragment20 Ramos C181(1.28); C319(4.35); C472(1.58); C460(0.59)  LDD2194  [7]
 LDCM0580  Fragment21 Ramos C181(1.03); C319(0.95); C472(0.76); C213(0.82)  LDD2195  [7]
 LDCM0582  Fragment23 Ramos C181(1.09); C319(0.63); C472(0.85); C213(1.19)  LDD2196  [7]
 LDCM0578  Fragment27 Ramos C181(0.98); C319(0.85); C472(0.95); C213(0.91)  LDD2197  [7]
 LDCM0586  Fragment28 Ramos C181(0.82); C319(0.94); C472(0.62); C213(0.43)  LDD2198  [7]
 LDCM0588  Fragment30 Ramos C181(1.01); C319(20.00); C472(0.78); C213(1.04)  LDD2199  [7]
 LDCM0589  Fragment31 Ramos C181(1.02); C319(0.84); C472(0.90); C213(0.84)  LDD2200  [7]
 LDCM0590  Fragment32 Ramos C181(1.03); C319(6.73); C472(0.58); C460(1.20)  LDD2201  [7]
 LDCM0468  Fragment33 Ramos C181(0.80); C319(1.05); C472(0.69); C213(0.73)  LDD2202  [7]
 LDCM0596  Fragment38 Ramos C181(0.77); C319(0.80); C472(0.55); C213(1.38)  LDD2203  [7]
 LDCM0566  Fragment4 Ramos C181(1.14); C319(1.53); C472(2.33); C213(1.70)  LDD2184  [7]
 LDCM0610  Fragment52 Ramos C181(0.98); C472(0.76); C213(1.21); C220(0.37)  LDD2204  [7]
 LDCM0614  Fragment56 Ramos C181(1.01); C319(0.94); C472(0.72); C213(1.21)  LDD2205  [7]
 LDCM0569  Fragment7 Ramos C181(1.50); C319(7.56); C472(1.44); C213(2.19)  LDD2186  [7]
 LDCM0571  Fragment9 Ramos C181(1.11); C319(2.42); C472(3.61); C460(6.18)  LDD2188  [7]
 LDCM0022  KB02 Ramos C181(1.24); C319(4.79); C472(1.17); C213(2.17)  LDD2182  [7]
 LDCM0023  KB03 Jurkat C319(69.57)  LDD0209  [2]
 LDCM0024  KB05 NALM-6 C181(2.13); C319(4.39); C472(1.41); C220(1.28)  LDD3339  [8]
 LDCM0109  NEM HeLa N.A.  LDD0231  [3]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Tyrosyl-DNA phosphodiesterase 2 (TDP2) CCR4/nocturin family O95551
Baculoviral IAP repeat-containing protein 2 (BIRC2) IAP family Q13490
Mast/stem cell growth factor receptor Kit (KIT) Tyr protein kinase family P10721
Epidermal growth factor receptor (EGFR) Tyr protein kinase family P00533
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Heat shock protein HSP 90-beta (HSP90AB1) Heat shock protein 90 family P08238
Transcription factor
Click To Hide/Show 6 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Zinc finger protein Aiolos (IKZF3) Ikaros C2H2-type zinc-finger protein family Q9UKT9
Zinc finger protein 774 (ZNF774) Krueppel C2H2-type zinc-finger protein family Q6NX45
Zinc finger and BTB domain-containing protein 42 (ZBTB42) Krueppel C2H2-type zinc-finger protein family B2RXF5
Androgen receptor (AR) Nuclear hormone receptor family P10275
Signal transducer and activator of transcription 3 (STAT3) Transcription factor STAT family P40763
Zinc finger and BTB domain-containing protein 8A (ZBTB8A) . Q96BR9
Other
Click To Hide/Show 14 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Embryonal Fyn-associated substrate (EFS) CAS family O43281
Crk-like protein (CRKL) CRK family P46109
RNA-binding protein FXR2 (FXR2) FMR1 family P51116
GRB2-associated-binding protein 1 (GAB1) GAB family Q13480
Vimentin (VIM) Intermediate filament family P08670
Janus kinase and microtubule-interacting protein 1 (JAKMIP1) JAKMIP family Q96N16
Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3) PI3K p85 subunit family Q92569
B-cell scaffold protein with ankyrin repeats (BANK1) . Q8NDB2
Heat shock factor 2-binding protein (HSF2BP) . O75031
PRKCA-binding protein (PICK1) . Q9NRD5
SH2 domain-containing protein 1B (SH2D1B) . O14796
Signal-transducing adaptor protein 2 (STAP2) . Q9UGK3
Single-stranded DNA-binding protein 3 (SSBP3) . Q9BWW4
Suppressor of cytokine signaling 3 (SOCS3) . O14543

The Drug(s) Related To This Target

Approved
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fostamatinib Small molecular drug DB12010
Zanubrutinib . DB15035
Investigative
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pmid15546730c2 Small molecular drug D08RZB
Pmid24915291c31 Small molecular drug D01RHR
Pmid24915291c38 Small molecular drug D06BJG
Patented
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pyrazolo[4,3-c]Pyridine Derivative 2 . D09PIS

References

1 Site-Specific Labeling of Endogenous Proteins Using CoLDR Chemistry. J Am Chem Soc. 2021 Dec 8;143(48):20095-20108. doi: 10.1021/jacs.1c06167. Epub 2021 Nov 24.
2 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.
3 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
4 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
5 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.
6 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.
7 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
8 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840