Btk
entrez
12229
canonical
uniprot
P35991
canonical
ensembl
ENSMUSG00000031264
resolver
ensp
ENSMUSP00000033617
resolver
enst
ENSMUST00000033617
resolver
genesymbol
Btk
resolver
genesymbol_syn
Bpk
resolver
uniprot
Q61365
resolver
uniprot_entry
BTK_MOUSE
resolver
uniprot_sec
Q61365
resolver
activity_regulation
ACTIVITY REGULATION: Activated by phosphorylation. In primary B lymphocytes, is almost always non-phosphorylated and is thus catalytically inactive. Stimulation of TLR8 and TLR9 causes BTK activation. As a negative feedback mechanism to fine-tune BCR signaling, activated PRKCB down-modulates BTK function via direct phosphorylation of BTK at Ser-180, resulting in translocation of BTK back to the cytoplasmic fraction. PIN1, SH3BP5, and IBTK were also identified as BTK activity inhibitors. Interaction with CAV1 leads to dramatic down-regulation of the kinase activity of BTK. LFM-13A is a specific inhibitor of BTK. Dasatinib, a cancer drug acting as a tyrosine kinase inhibitor, also blocks BTK activity. {ECO:0000269|PubMed:10852954}.
uniprot
proteins
amino_acid_sequence
MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEKITCVETVIPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEELRKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSSHRKTKKPLPPTPEEDQILKKPLPPEPTAAPISTTELKKVVALYDYMPMNANDLQLRKGEEYFILEESNLPWWRARDKNGQEGYIPSNYITEAEDSIEMYEWYSKHMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSTGEPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELINYHQHNSAGLISRLKYPVSKQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIREGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASERVYTIMYSCWHEKADERPSFKILLSNILDVMDEES
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in Btk are the cause of murine X-linked immunodeficiency (XID).
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
function
FUNCTION: 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). Plays a role in STING1-mediated induction of type I interferon (IFN) response by phosphorylating DDX41 (By similarity). {ECO:0000250|UniProtKB:Q06187, ECO:0000269|PubMed:10852954, ECO:0000269|PubMed:11120822, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17725607, ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:7538439, ECO:0000269|PubMed:8629002}.
uniprot
proteins
mass_dalton
76437
uniprot
proteins
mutagenesis
MUTAGEN 41; /note="E->K: Constitutive activation."; /evidence="ECO:0000269|PubMed:7538439"; MUTAGEN 223; /note="Y->F: No autophosphorylation."; /evidence="ECO:0000269|PubMed:8630736"; MUTAGEN 430; /note="K->R: Loss of activity and no phosphorylation."; /evidence="ECO:0000269|PubMed:7538439, ECO:0000269|PubMed:8630736
uniprot
proteins
post_translational_modification
PTM: Following B-cell receptor (BCR) engagement, translocates to the plasma membrane where it gets phosphorylated at Tyr-551 by LYN and SYK. Phosphorylation at Tyr-551 is followed by autophosphorylation of Tyr-223 which may create a docking site for a SH2 containing protein. Phosphorylation at Ser-180 by PRKCB, leads in translocation of BTK back to the cytoplasmic fraction. Phosphorylation at Ser-21 and Ser-115 creates a binding site for PIN1 at these Ser-Pro motifs, and promotes its recruitment (By similarity). {ECO:0000250|UniProtKB:Q06187}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
TEC subfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10811867
uniprot
proteins
pubmed
10852954
uniprot
proteins
pubmed
11120822
uniprot
proteins
pubmed
16738337
uniprot
proteins
pubmed
17725607
uniprot
proteins
pubmed
17947660
uniprot
proteins
pubmed
19290921
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23478294
uniprot
proteins
pubmed
29348675
uniprot
proteins
pubmed
34554188
uniprot
proteins
pubmed
7538439
uniprot
proteins
pubmed
7626884
uniprot
proteins
pubmed
7989760
uniprot
proteins
pubmed
8332901
uniprot
proteins
pubmed
8425221
uniprot
proteins
pubmed
8476425
uniprot
proteins
pubmed
8629002
uniprot
proteins
pubmed
8630736
uniprot
proteins
pubmed
9240435
uniprot
proteins
pubmed
9751072
uniprot
proteins
sequence_length
659
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11120822}. Cell membrane {ECO:0000269|PubMed:11120822}; Peripheral membrane protein {ECO:0000269|PubMed:11120822}. Nucleus {ECO:0000269|PubMed:11120822}. Membrane raft {ECO:0000269|PubMed:23478294}. Note=In steady state, BTK is predominantly cytosolic. Following B-cell receptor (BCR) engagement by antigen, translocates to the plasma membrane through its PH domain. Plasma membrane localization is a critical step in the activation of BTK. A fraction of BTK also shuttles between the nucleus and the cytoplasm, and nuclear export is mediated by the nuclear export receptor CRM1. {ECO:0000250|UniProtKB:Q06187}.
uniprot
proteins