BTK
entrez
695
canonical
uniprot
Q06187
canonical
ensembl
ENSG00000010671
resolver
ensp
ENSP00000308176
resolver
ensp
ENSP00000483570
resolver
ensp
ENSP00000512057
resolver
enst
ENST00000703407
resolver
genesymbol
BTK
resolver
genesymbol_syn
AGMX1
resolver
genesymbol_syn
ATK
resolver
genesymbol_syn
BPK
resolver
hgnc
HGNC:1133
resolver
uniprot
A0A8Q3WKL1
resolver
uniprot
B2RAW1
resolver
uniprot
Q32ML5
resolver
uniprot
Q5JY90
resolver
uniprot_entry
A0A8Q3WKL1_HUMAN
resolver
uniprot_entry
BTK_HUMAN
resolver
uniprot_entry
Q5JY90_HUMAN
resolver
uniprot_sec
B2RAW1
resolver
uniprot_sec
Q32ML5
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:10339589, ECO:0000269|PubMed:11577348, ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:11751885, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16644721, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:8630736}.
uniprot
proteins
amino_acid_sequence
MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEKITCVETVVPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEELRKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSSHRKTKKPLPPTPEEDQILKKPLPPEPAAAPVSTSELKKVVALYDYMPMNANDLQLRKGDEYFILEESNLPWWRARDKNGQEGYIPSNYVTEAEDSIEMYEWYSKHMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSTGDPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELINYHQHNSAGLISRLKYPVSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES
uniprot
proteins
disease_involvement
DISEASE: X-linked agammaglobulinemia (XLA) [MIM:300755]: Humoral immunodeficiency disease which results in developmental defects in the maturation pathway of B-cells. Affected boys have normal levels of pre-B-cells in their bone marrow but virtually no circulating mature B-lymphocytes. This results in a lack of immunoglobulins of all classes and leads to recurrent bacterial infections like otitis, conjunctivitis, dermatitis, sinusitis in the first few years of life, or even some patients present overwhelming sepsis or meningitis, resulting in death in a few hours. Treatment in most cases is by infusion of intravenous immunoglobulin. {ECO:0000269|PubMed:10220140, ECO:0000269|PubMed:10612838, ECO:0000269|PubMed:10678660, ECO:0000269|PubMed:11472359, ECO:0000269|PubMed:12204007, ECO:0000269|PubMed:12768435, ECO:0000269|PubMed:15024743, ECO:0000269|PubMed:15661032, ECO:0000269|PubMed:18241230, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:7627183, ECO:0000269|PubMed:7633420, ECO:0000269|PubMed:7633429, ECO:0000269|PubMed:7711734, ECO:0000269|PubMed:7809124, ECO:0000269|PubMed:7849006, ECO:0000269|PubMed:7849697, ECO:0000269|PubMed:7849721, ECO:0000269|PubMed:7880320, ECO:0000269|PubMed:7897635, ECO:0000269|PubMed:8013627, ECO:0000269|PubMed:8162018, ECO:0000269|PubMed:8162056, ECO:0000269|PubMed:8594569, ECO:0000269|PubMed:8634718, ECO:0000269|PubMed:8695804, ECO:0000269|PubMed:8723128, ECO:0000269|PubMed:8834236, ECO:0000269|PubMed:8938104, ECO:0000269|PubMed:9016530, ECO:0000269|PubMed:9192269, ECO:0000269|PubMed:9260159, ECO:0000269|PubMed:9280283, ECO:0000269|PubMed:9445504, ECO:0000269|PubMed:9545398}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 3, with agammaglobulinemia (IGHD3) [MIM:307200]: An X-linked recessive disorder characterized by growth hormone deficiency, short stature, delayed bone age, agammaglobulinemia with markedly reduced numbers of B cells, and good response to treatment with growth hormone. {ECO:0000269|PubMed:8013627}. Note=The disease may be caused by variants affecting the gene represented in this entry.
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:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:19290921). 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 (PubMed:11606584). PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (PubMed:11606584). BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (PubMed:16517732, PubMed:17932028). 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:16517732). The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (PubMed:16517732). Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (PubMed:16517732, PubMed:17932028). Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (PubMed:16415872). BTK also plays a critical role in transcription regulation (PubMed:19290921). Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (PubMed:19290921). BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921). 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:9012831). GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:9012831). ARID3A and NFAT are other transcriptional target of BTK (PubMed:16738337). BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:16738337). There is however no evidence that BTK itself binds directly to DNA (PubMed:16738337). BTK has a dual role in the regulation of apoptosis (PubMed:9751072). Plays a role in STING1-mediated induction of type I interferon (IFN) response by phosphorylating DDX41 (PubMed:25704810). {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:9012831, ECO:0000303|PubMed:19290921, ECO:0000303|PubMed:9751072}.
uniprot
proteins
mass_dalton
76281
uniprot
proteins
mutagenesis
MUTAGEN 41; /note="E->K: No effect on phosphorylation of GTF2I."; /evidence="ECO:0000269|PubMed:9012831"; MUTAGEN 189; /note="P->A: No effect on phosphorylation of GTF2I."; /evidence="ECO:0000269|PubMed:9012831"; MUTAGEN 223; /note="Y->F: Loss of phosphorylation of GTF2I."; /evidence="ECO:0000269|PubMed:8630736, ECO:0000269|PubMed:9012831"; MUTAGEN 251..252; /note="WW->LL: Large decrease in binding by SH3BP5."; /evidence="ECO:0000269|PubMed:9571151"; MUTAGEN 251; /note="W->L: No effect on phosphorylation of GTF2I."; /evidence="ECO:0000269|PubMed:9012831"; MUTAGEN 307; /note="R->K: Loss of phosphorylation of GTF2I."; /evidence="ECO:0000269|PubMed:9012831"; MUTAGEN 551; /note="Y->F: Loss of phosphorylation of GTF2I."; /evidence="ECO:0000269|PubMed:9012831"; MUTAGEN 617; /note="Y->E: Defective in mediating calcium response."; /evidence="ECO:0000269|PubMed:15375214
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. {ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:12573241, ECO:0000269|PubMed:15375214, ECO:0000269|PubMed:16644721, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:8630736, ECO:0000269|PubMed:9012831}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
TEC subfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10196129
uniprot
proteins
pubmed
10196179
uniprot
proteins
pubmed
10220140
uniprot
proteins
pubmed
10339589
uniprot
proteins
pubmed
10602036
uniprot
proteins
pubmed
10612838
uniprot
proteins
pubmed
10678660
uniprot
proteins
pubmed
10826882
uniprot
proteins
pubmed
11016936
uniprot
proteins
pubmed
11472359
uniprot
proteins
pubmed
11527964
uniprot
proteins
pubmed
11577348
uniprot
proteins
pubmed
11598012
uniprot
proteins
pubmed
11606584
uniprot
proteins
pubmed
11751885
uniprot
proteins
pubmed
12204007
uniprot
proteins
pubmed
12573241
uniprot
proteins
pubmed
12768435
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15024743
uniprot
proteins
pubmed
15375214
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15661032
uniprot
proteins
pubmed
15772651
uniprot
proteins
pubmed
16415872
uniprot
proteins
pubmed
16517732
uniprot
proteins
pubmed
16644721
uniprot
proteins
pubmed
16738337
uniprot
proteins
pubmed
16969585
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17932028
uniprot
proteins
pubmed
18241230
uniprot
proteins
pubmed
19290921
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19807924
uniprot
proteins
pubmed
20052711
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21280133
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23913792
uniprot
proteins
pubmed
24607955
uniprot
proteins
pubmed
24869597
uniprot
proteins
pubmed
24869598
uniprot
proteins
pubmed
25189416
uniprot
proteins
pubmed
25704810
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
34554188
uniprot
proteins
pubmed
7626884
uniprot
proteins
pubmed
7627183
uniprot
proteins
pubmed
7633420
uniprot
proteins
pubmed
7633429
uniprot
proteins
pubmed
7711734
uniprot
proteins
pubmed
7809124
uniprot
proteins
pubmed
7849006
uniprot
proteins
pubmed
7849697
uniprot
proteins
pubmed
7849721
uniprot
proteins
pubmed
7880320
uniprot
proteins
pubmed
7897635
uniprot
proteins
pubmed
7927535
uniprot
proteins
pubmed
8013627
uniprot
proteins
pubmed
8070576
uniprot
proteins
pubmed
8090769
uniprot
proteins
pubmed
8162018
uniprot
proteins
pubmed
8162056
uniprot
proteins
pubmed
8380905
uniprot
proteins
pubmed
8425221
uniprot
proteins
pubmed
8594569
uniprot
proteins
pubmed
8630736
uniprot
proteins
pubmed
8634718
uniprot
proteins
pubmed
8695804
uniprot
proteins
pubmed
8723128
uniprot
proteins
pubmed
8834236
uniprot
proteins
pubmed
8938104
uniprot
proteins
pubmed
9012831
uniprot
proteins
pubmed
9016530
uniprot
proteins
pubmed
9192269
uniprot
proteins
pubmed
9218782
uniprot
proteins
pubmed
9260159
uniprot
proteins
pubmed
9280283
uniprot
proteins
pubmed
9445504
uniprot
proteins
pubmed
9485443
uniprot
proteins
pubmed
9545398
uniprot
proteins
pubmed
9571151
uniprot
proteins
pubmed
9751072
uniprot
proteins
sequence_length
659
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11016936, ECO:0000269|PubMed:25704810}. Cell membrane {ECO:0000269|PubMed:10196179, ECO:0000269|PubMed:10602036}; Peripheral membrane protein {ECO:0000269|PubMed:10196179, ECO:0000269|PubMed:10602036}. Nucleus {ECO:0000269|PubMed:11016936}. Membrane raft {ECO:0000250|UniProtKB:P35991}. 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:0000303|PubMed:19290921}.
uniprot
proteins