Tyrosine-protein kinase BTK

CovInDB Protein

P35991

Name

Tyrosine-protein kinase BTK

Encoding Gene

Btk

Synonyms

• Agammaglobulinemia tyrosine kinase (ATK)
• B-cell progenitor kinase (BPK)
• Bruton tyrosine kinase
• Kinase EMB

Taxonomy

Mus musculus (Mouse)

Description

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Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:10852954, PubMed:7538439, PubMed:8629002).
Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity).
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 (By similarity).
PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (By similarity).
BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (By similarity).
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 (PubMed:17725607).
The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (By similarity).
Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (By similarity).
Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (By similarity).
BTK also plays a critical role in transcription regulation (By similarity).
Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (By similarity).
BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (By similarity).
Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188).
Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:11120822, PubMed:16738337).
GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:11120822, PubMed:16738337).
ARID3A and NFAT are other transcriptional target of BTK (PubMed:11120822, PubMed:16738337).
BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:11120822, PubMed:16738337).
There is however no evidence that BTK itself binds directly to DNA (PubMed:11120822, PubMed:16738337).
BTK has a dual role in the regulation of apoptosis (By similarity).

Sequence

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MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEKITCVETVIPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEELRKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSSHRKTKKPLPPTPEEDQILKKPLPPEPTAAPISTTELKKVVALYDYMPMNANDLQLRKGEEYFILEESNLPWWRARDKNGQEGYIPSNYITEAEDSIEMYEWYSKHMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSTGEPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELINYHQHNSAGLISRLKYPVSKQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASERVYTIMYSCWHEKADERPSFKILLSNILDVMDEES

Active Site

Feature Key	Position(s)	Description
Binding site	143	Zn
Binding site	154	Zn
Binding site	155	Zn
Binding site	165	Zn
Binding site	26	1D-myo-inositol 1,3,4,5-tetrakisphosphate
Binding site	28	1D-myo-inositol 1,3,4,5-tetrakisphosphate
Binding site	39	1D-myo-inositol 1,3,4,5-tetrakisphosphate
Binding site	408-416	ATP
Binding site	430	ATP
Active site	521	Proton acceptor
Binding site	53	1D-myo-inositol 1,3,4,5-tetrakisphosphate

Structure

PDB:  6MNY

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Reference

UniProt

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