Uniprot ID:Q06187	Gene name: BTK AGMX1 ATK BPK	Protein Family:"Protein kinase superfamily, Tyr protein kinase family, TEC subfamily"
Protein name: Tyrosine-protein kinase BTK	Length : 659

Sequnce	>Q06187 660 MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEKITCVETVVPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEELRKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSSHRKTKKPLPPTPEEDQILKKPLPPEPAAAPVSTSELKKVVALYDYMPMNANDLQLRKGDEYFILEESNLPWWRARDKNGQEGYIPSNYVTEAEDSIEMYEWYSKHMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKSTGDPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELINYHQHNSAGLISRLKYPVSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES
Repeated Sequence regions	Length: 15 residues : 2 times from 185 to 216 :0.7222222222222222 region Length:32 KKPLPPTPEEDQI----L KKPLPPEPAAAPVSTSEL
Domains	DOMAIN 3 133 PH. DOMAIN 214 274 SH3. DOMAIN 281 377 SH2. DOMAIN 402 655 Protein kinase
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"
Active Site	ACT_SITE 521 521 Proton acceptor
Motifs	MOTIF 581 588 CAV1-binding
Binding Site	"BINDING 26 26 Inositol-(1,3,4,5)-tetrakisphosphate. BINDING 28 28 Inositol-(1,3,4,5)-tetrakisphosphate. BINDING 39 39 Inositol-(1,3,4,5)-tetrakisphosphate. BINDING 53 53 Inositol-(1,3,4,5)-tetrakisphosphate. via carbonyl oxygen. BINDING 430 430 ATP. BINDING 445 445 Inhibitor. BINDING 461 461 Inhibitor. BINDING 477 477 Inhibitor. BINDING 538 538 Inhibitor. BINDING 539 539 Inhibitor. via amide nitrogen. BINDING 542 542 Inhibitor. via carbonyl oxygen"
Nucleotide Binding	NP_BIND 408 416 ATP
Mutation	41 41 E->K: No effect on phosphorylation of GTF2I 189 189 P->A: No effect on phosphorylation of GTF2I 223 223 Y->F: Loss of phosphorylation of GTF2I 251 252 WW->LL: Large decrease in binding by SH3BP5 251 251 W->L: No effect on phosphorylation of GTF2I 307 307 R->K: Loss of phosphorylation of GTF2I 551 551 Y->F: Loss of phosphorylation of GTF2I 617 617 Y->E: Defective in mediating calcium response
Disease	"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 Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA-IGHD) [MIM:307200]: In rare cases XLA is inherited together with isolated growth hormone deficiency (IGHD) Note=The disease may be caused by mutations affecting the gene represented in this entry"

Q06187 Proteins with novel repeats