Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

BLK (P51451) - Overview - Molecular Target Synopsis

Protein


BLK, Tyrosine-protein kinase Blk
Enzyme Classification 2.7.10.2
UniProt P51451

Also Known as BLK_HUMAN, BLK

Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling (By similarity). B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors (By similarity). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity). 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 (By similarity). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (By similarity). Phosphorylates also the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C (PubMed:8756631). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (By similarity). Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (By similarity). 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 (PubMed:19667185). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (PubMed:30356214). Interacts with CBL (via SH2 domain). Interacts with CD79A and CD79B (via SH2 domain).

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
505ENSG00000136573ENST00000259089ENSP00000259089P51451-1
434ENSG00000136573ENST00000529894ENSP00000433663

Drugs


BLK is targeted by Approved Drugs Dasatinib, Vandetanib. (see details)
Dasatinib
Vandetanib

Sub-cellular localization


UniProt: BLK is active in the following subcellular-locations: cell membrane.
GO terms: BLK is active in the following subcellular-locations: cytosol, extrinsic component of cytoplasmic side of plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project BLK has gain in 2 cell-lines, loss in 13 cell-lines and no signal in 990 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: RPMI_8226, SN12C, SNB_19

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OCI-LY-3, SU-DHL-4, Daudi

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: CD20-positive B cell, GM12878, SK-N-SH

(see details)

RNA Interference


BLK was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OVTOKO, DU4475. (see details)

3D Structures


At greater than 75% identity similarity to BLK there are:
1 structures (2 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


BLK has been screened with 776 compounds (1391 bioactivities), 44 compounds have bioactivities that show binding affinity of <= 500nM (65 bioactivities). (see details)