BTK - Tyrosine-protein kinase BTK - human protein (Function)
 
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BTK »  Tyrosine-protein kinase BTK   [ EC 2.7.10.2 ]
 
Protein also known as:  Agammaglobulinemia tyrosine kinase (ATK).
Gene name:  BTK
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
7
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • HGNC
Identical protein bindingdefinition[GO:0042802]  
1
  • IntAct
Metal ion bindingdefinition[GO:0046872]  
1
  • UniProtKB KW
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
2
  • UniProtKB
  • RefGenome
Phosphatidylinositol-3,4,5-trisphosphate bindingdefinition[GO:0005547]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
10
  • IntAct
  • UniProtKB
  • BHF-UCL
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • HGNC
Not  Receptor bindingdefinition[GO:0005102]  
1
  • RefGenome
GO biological process 
Adaptive immune responsedefinition[GO:0002250]  
2
  • UniProtKB
  • RefGenome
Apoptotic signaling pathwaydefinition[GO:0097190]  
1
  • PINC
B cell activationdefinition[GO:0042113]  
1
  • UniProtKB
B cell receptor signaling pathwaydefinition[GO:0050853]  
2
  • UniProtKB
  • RefGenome
Cell differentiationdefinition[GO:0030154]  
1
  • RefGenome
Innate immune responsedefinition[GO:0045087]  
2
  • UniProtKB
  • RefGenome
Intracellular signal transductiondefinition[GO:0035556]  
1
  • HGNC
Mesoderm developmentdefinition[GO:0007498]  
1
  • PINC
Peptidyl-tyrosine autophosphorylationdefinition[GO:0038083]  
1
  • RefGenome
Positive regulation of B cell differentiationdefinition[GO:0045579]  
1
  • UniProtKB
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
1
  • UniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • HGNC
Regulation of B cell apoptotic processdefinition[GO:0002902]  
1
  • UniProtKB
Regulation of B cell cytokine productiondefinition[GO:0002721]  
1
  • UniProtKB
Regulation of cell proliferationdefinition[GO:0042127]  
1
  • RefGenome
Not  T cell receptor signaling pathwaydefinition[GO:0050852]  
1
  • RefGenome
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • UniProtKB KW
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169]  
1
  • RefGenome
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
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  • PROSITE-ProRule
  • UniProtKB
It requires the following cofactor
 Zn(2+) : Binds 1 zinc ion per subunit.  
1
  • UniProtKB
It is regulated in the following manner
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.  
9
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
B cell receptor signaling pathway  hsa04662+695  
Fc epsilon RI signaling pathway  hsa04664+695  
Osteoclast differentiation  hsa04380+695  
Primary immunodeficiency  hsa05340+695  
According to Reactome, this protein belongs to the following pathways:
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers  REACT_118700  
DAP12 signaling  REACT_147814  
FCERI mediated Ca+2 mobilization  REACT_163834  
MyD88:Mal cascade initiated on plasma membrane  REACT_6788  
Regulation of actin dynamics for phagocytic cup formation  REACT_160086  
 

Keywords

Biological process 
Adaptive immunity  definition   [KW-1064]
Apoptosis  definition   [KW-0053]
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Bruton%27s_tyrosine_kinase
GenomeRNAi: 695
PRO: PR:Q06187
Chemistry
GuidetoPHARMACOLOGY: 1948