Tyrosine-protein kinase BTK

Details

Name
Tyrosine-protein kinase BTK
Synonyms
  • 2.7.10.2
  • Agammaglobulinemia tyrosine kinase
  • AGMX1
  • ATK
  • B-cell progenitor kinase
  • BPK
  • Bruton tyrosine kinase
Gene Name
BTK
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002554|Tyrosine-protein kinase BTK
MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEK
ITCVETVVPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEEL
RKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSS
HRKTKKPLPPTPEEDQILKKPLPPEPAAAPVSTSELKKVVALYDYMPMNANDLQLRKGDE
YFILEESNLPWWRARDKNGQEGYIPSNYVTEAEDSIEMYEWYSKHMTRSQAEQLLKQEGK
EGGFIVRDSSKAGKYTVSVFAKSTGDPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELIN
YHQHNSAGLISRLKYPVSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGK
WRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANG
CLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDF
GLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYER
FTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES
Number of residues
659
Molecular Weight
76280.71
Theoretical pI
7.86
GO Classification
Functions
ATP binding / identical protein binding / metal ion binding / non-membrane spanning protein tyrosine kinase activity / phosphatidylinositol-3,4,5-trisphosphate binding / protein tyrosine kinase activity
Processes
adaptive immune response / apoptotic signaling pathway / B cell activation / B cell receptor signaling pathway / calcium-mediated signaling / cell differentiation / cell maturation / Fc-epsilon receptor signaling pathway / I-kappaB kinase/NF-kappaB signaling / innate immune response / intracellular signal transduction / mesoderm development / MyD88-dependent toll-like receptor signaling pathway / negative regulation of cytokine production / peptidyl-tyrosine autophosphorylation / peptidyl-tyrosine phosphorylation / positive regulation of B cell differentiation / positive regulation of NF-kappaB transcription factor activity / protein phosphorylation / regulation of B cell apoptotic process / regulation of B cell cytokine production / regulation of cell proliferation / toll-like receptor 2 signaling pathway / toll-like receptor 4 signaling pathway / toll-like receptor signaling pathway / toll-like receptor TLR1 / toll-like receptor TLR6 / transcription, DNA-templated / transmembrane receptor protein tyrosine kinase signaling pathway
Components
cytoplasm / cytoplasmic vesicle / cytosol / extrinsic component of cytoplasmic side of plasma membrane / intracellular membrane-bounded organelle / membrane raft / nucleus / plasma membrane
General Function
Protein tyrosine kinase activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0020522|Tyrosine-protein kinase BTK (BTK)
ATGGCCGCAGTGATTCTGGAGAGCATCTTTCTGAAGCGATCCCAACAGAAAAAGAAAACA
TCACCTCTAAACTTCAAGAAGCGCCTGTTTCTCTTGACCGTGCACAAACTCTCCTACTAT
GAGTATGACTTTGAACGTGGGAGAAGAGGCAGTAAGAAGGGTTCAATAGATGTTGAGAAG
ATCACTTGTGTTGAAACAGTGGTTCCTGAAAAAAATCCTCCTCCAGAAAGACAGATTCCG
AGAAGAGGTGAAGAGTCCAGTGAAATGGAGCAAATTTCAATCATTGAAAGGTTCCCTTAT
CCCTTCCAGGTTGTATATGATGAAGGGCCTCTCTACGTCTTCTCCCCAACTGAAGAACTA
AGGAAGCGGTGGATTCACCAGCTCAAAAACGTAATCCGGTACAACAGTGATCTGGTTCAG
AAATATCACCCTTGCTTCTGGATCGATGGGCAGTATCTCTGCTGCTCTCAGACAGCCAAA
AATGCTATGGGCTGCCAAATTTTGGAGAACAGGAATGGAAGCTTAAAACCTGGGAGTTCT
CACCGGAAGACAAAAAAGCCTCTTCCCCCAACGCCTGAGGAGGACCAGATCTTGAAAAAG
CCACTACCGCCTGAGCCAGCAGCAGCACCAGTCTCCACAAGTGAGCTGAAAAAGGTTGTG
GCCCTTTATGATTACATGCCAATGAATGCAAATGATCTACAGCTGCGGAAGGGTGATGAA
TATTTTATCTTGGAGGAAAGCAACTTACCATGGTGGAGAGCACGAGATAAAAATGGGCAG
GAAGGCTACATTCCTAGTAACTATGTCACTGAAGCAGAAGACTCCATAGAAATGTATGAG
TGGTATTCCAAACACATGACTCGGAGTCAGGCTGAGCAACTGCTAAAGCAAGAGGGGAAA
GAAGGAGGTTTCATTGTCAGAGACTCCAGCAAAGCTGGCAAATATACAGTGTCTGTGTTT
GCTAAATCCACAGGGGACCCTCAAGGGGTGATACGTCATTATGTTGTGTGTTCCACACCT
CAGAGCCAGTATTACCTGGCTGAGAAGCACCTTTTCAGCACCATCCCTGAGCTCATTAAC
TACCATCAGCACAACTCTGCAGGACTCATATCCAGGCTCAAATATCCAGTGTCTCAACAA
AACAAGAATGCACCTTCCACTGCAGGCCTGGGATACGGATCATGGGAAATTGATCCAAAG
GACCTGACCTTCTTGAAGGAGCTGGGGACTGGACAATTTGGGGTAGTGAAGTATGGGAAA
TGGAGAGGCCAGTACGACGTGGCCATCAAGATGATCAAAGAAGGCTCCATGTCTGAAGAT
GAATTCATTGAAGAAGCCAAAGTCATGATGAATCTTTCCCATGAGAAGCTGGTGCAGTTG
TATGGCGTCTGCACCAAGCAGCGCCCCATCTTCATCATCACTGAGTACATGGCCAATGGC
TGCCTCCTGAACTACCTGAGGGAGATGCGCCACCGCTTCCAGACTCAGCAGCTGCTAGAG
ATGTGCAAGGATGTCTGTGAAGCCATGGAATACCTGGAGTCAAAGCAGTTCCTTCACCGA
GACCTGGCAGCTCGAAACTGTTTGGTAAACGATCAAGGAGTTGTTAAAGTATCTGATTTC
GGCCTGTCCAGGTATGTCCTGGATGATGAATACACAAGCTCAGTAGGCTCCAAATTTCCA
GTCCGGTGGTCCCCACCGGAAGTCCTGATGTATAGCAAGTTCAGCAGCAAATCTGACATT
TGGGCTTTTGGGGTTTTGATGTGGGAAATTTACTCCCTGGGGAAGATGCCATATGAGAGA
TTTACTAACAGTGAGACTGCTGAACACATTGCCCAAGGCCTACGTCTCTACAGGCCTCAT
CTGGCTTCAGAGAAGGTATATACCATCATGTACAGTTGCTGGCATGAGAAAGCAGATGAG
CGTCCCACTTTCAAAATTCTTCTGAGCAATATTCTAGATGTCATGGATGAAGAATCCTGA
Chromosome Location
X
Locus
Xq21.33-q22
External Identifiers
ResourceLink
UniProtKB IDQ06187
UniProtKB Entry NameBTK_HUMAN
GenBank Protein ID312467
GenBank Gene IDX58957
GenAtlas IDBTK
HGNC IDHGNC:1133
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01863Inositol 1,3,4,5-TetrakisphosphateexperimentalunknownDetails
DB05204XL418investigationalunknownDetails
DB09053IbrutinibapprovedyesinhibitorDetails
DB01254Dasatinibapproved, investigationalunknownDetails
DB11703Acalabrutinibapproved, investigationalyesinhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails