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

BTK (Q06187) - Overview - Molecular Target Synopsis

Protein


BTK, Tyrosine-protein kinase BTK
Enzyme Classification 2.7.10.2
UniProt Q06187

Also Known as BTK_HUMAN, BTK, AGMX1, ATK, BPK

Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK plays also a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis. Binds GTF2I through the PH domain. Interacts with SH3BP5 via the SH3 domain. Interacts with IBTK via its PH domain. Interacts with ARID3A, CAV1, FASLG, PIN1, TLR8 and TLR9.

6O8I
BTK IN COMPLEX WITH INHIBITOR
RCSB/PDB
Inspect Structure
See all 3D Structures for BTK

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
693Q06187-2
659ENSG00000010671ENST00000308731ENSP00000308176Q06187-1
483ENSG00000010671ENST00000372880ENSP00000361971

Drugs


BTK is targeted by Approved Drug Ibrutinib. (see details)
Ibrutinib

Sub-cellular localization


UniProt: BTK is active in the following subcellular-locations: cell membrane, cytoplasm, nucleus.
GO terms: BTK is active in the following subcellular-locations: cytoplasm, cytoplasmic vesicle, cytosol, mast cell granule, membrane raft, nucleus, perinuclear region of cytoplasm, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project BTK has gain in 1 cell-lines, loss in 31 cell-lines and no signal in 973 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HL_60, K_562, MCF7

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Toledo, WSU-FSCCL, HEL

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: K562, CD20-positive B cell, CD14-positive monocyte

(see details)

RNA Interference


BTK was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CAL120, CAL51. (see details)

3D Structures


For BTK there are:
75 structures (97 chains) solved
68 are solved in complex with at least one small molecule ligand
2 are solved with an approved drug

BTK is solved in complex with the approved drug(s):

1N1/DASATINIB (3K54_A, 3OCT_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


BTK has been screened with 1882 compounds (2799 bioactivities), 773 compounds have bioactivities that show binding affinity of <= 500nM (954 bioactivities). (see details)