Q06187

Background

Protein Name
Tyrosine-protein kinase BTK
Gene Name
BTK
Organism
Homo sapiens

Annotations

Function
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.

Mapping Statistics

Site Maximum Consensus Site Population Minimum Consensus Site Population Median Consensus Site Population
MPP 28 1 11.0
AAS 28 2 5.0
MT3 38 2 12.5
ATP 25 2 13.0
DEF 4 4 4.0
DFG 18 12 14.0
CMP 17 2 5.5
EDI 2 2 2.0
DRS 10 10 10.0
PDIG 13 3 8.5
PIF 25 2 8.5

Mapping Results

PDB ID Maximum Consensus Site Population
MPP site AAS site MT3 site LBP site ATP site DEF site DFG site CMP site PMP site EDI site DRS site PDIG site PIF site
Total Druggable Structures per Site 15 1 16 0 8 0 3 1 0 0 0 0 1
4OTF 20 4 19 0 13 0 0 0 0 0 0 9 0
3PJ3 17 5 0 0 19 0 16 17 0 0 0 0 0
4OTR 3 5 27 0 8 0 0 0 0 0 0 0 0
3PIY 17 5 0 0 13 0 14 0 0 0 0 4 0
4OT5 12 0 22 0 12 0 0 0 0 0 0 12 0
4OT6 15 7 14 0 12 0 0 0 0 0 0 0 0
4ZLZ 18 9 28 0 0 0 0 0 0 0 0 0 0
3PIZ 18 0 0 0 18 0 13 4 0 2 0 0 0
5FBO 17 5 11 0 20 0 14 0 0 0 0 0 0
4OTQ 11 4 15 0 13 0 0 0 0 0 0 0 0
3OCS 15 5 4 0 14 0 0 0 0 0 0 8 0
4RFY 11 5 38 0 13 0 0 0 0 0 0 0 0
AFQ06187 0 0 0 0 0 0 0 0 0 0 0 0 0
4YHF 17 6 22 0 16 0 16 0 0 0 0 0 2
3PJ2 16 12 13 0 12 0 0 0 0 0 0 0 10
3GEN 18 6 17 0 16 0 0 0 0 0 0 0 0
5FBN 20 3 15 0 15 0 18 0 0 0 0 0 0
4NWM 6 7 28 0 14 0 0 7 0 0 0 0 0
4Z3V 15 6 28 0 0 0 0 0 0 0 0 0 0
4RX5 17 4 22 0 0 0 0 0 0 0 0 13 0
3P08 0 4 20 0 8 4 0 2 0 0 10 7 0
3OCT 14 12 20 0 15 0 0 0 0 0 0 11 0
3PJ1 15 5 0 0 15 0 12 6 0 0 0 0 0
5BQ0 15 4 12 0 0 0 0 0 0 0 0 0 0
4RG0 11 5 13 0 13 0 0 0 0 0 0 0 0
5BPY 16 2 30 0 0 0 0 0 0 0 0 0 0
3PIX 0 14 16 0 0 0 0 0 0 0 0 0 25
3K54 24 15 0 0 16 0 13 5 0 0 0 0 0
4RFZ 11 5 15 0 18 0 0 0 0 0 0 0 0
4ZLY 28 6 17 0 0 0 0 0 0 0 0 0 0
1K2P 19 28 27 0 25 0 0 0 0 0 0 3 0