Summary | |
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Symbol | BTK |
Name | Bruton agammaglobulinemia tyrosine kinase |
Aliases | ATK; XLA; PSCTK1; AGMX1; IMD1; BPK; B-cell progenitor kinase; agammaglobulinaemia tyrosine kinase; dominant- ...... |
Chromosomal Location | Xq21.33-q22 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway |
Subcellular Location | Cytoplasm. Cell membrane; Peripheral membrane protein. Nucleus. 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. |
Domain |
PF00779 BTK motif PF00169 PH domain PF07714 Protein tyrosine kinase PF00017 SH2 domain PF00018 SH3 domain |
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. |
Biological Process |
GO:0000302 response to reactive oxygen species GO:0001783 B cell apoptotic process GO:0001802 type III hypersensitivity GO:0001803 regulation of type III hypersensitivity GO:0001805 positive regulation of type III hypersensitivity GO:0001810 regulation of type I hypersensitivity GO:0001812 positive regulation of type I hypersensitivity GO:0001818 negative regulation of cytokine production GO:0001821 histamine secretion GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway GO:0002238 response to molecule of fungal origin GO:0002250 adaptive immune response GO:0002263 cell activation involved in immune response GO:0002274 myeloid leukocyte activation GO:0002275 myeloid cell activation involved in immune response GO:0002279 mast cell activation involved in immune response GO:0002349 histamine production involved in inflammatory response GO:0002366 leukocyte activation involved in immune response GO:0002367 cytokine production involved in immune response GO:0002368 B cell cytokine production GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002437 inflammatory response to antigenic stimulus GO:0002438 acute inflammatory response to antigenic stimulus GO:0002440 production of molecular mediator of immune response GO:0002441 histamine secretion involved in inflammatory response GO:0002443 leukocyte mediated immunity GO:0002444 myeloid leukocyte mediated immunity GO:0002448 mast cell mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002521 leukocyte differentiation GO:0002524 hypersensitivity GO:0002526 acute inflammatory response GO:0002532 production of molecular mediator involved in inflammatory response GO:0002553 histamine secretion by mast cell GO:0002673 regulation of acute inflammatory response GO:0002675 positive regulation of acute inflammatory response GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0002697 regulation of immune effector process GO:0002699 positive regulation of immune effector process GO:0002700 regulation of production of molecular mediator of immune response GO:0002703 regulation of leukocyte mediated immunity GO:0002705 positive regulation of leukocyte mediated immunity GO:0002706 regulation of lymphocyte mediated immunity GO:0002708 positive regulation of lymphocyte mediated immunity GO:0002712 regulation of B cell mediated immunity GO:0002714 positive regulation of B cell mediated immunity GO:0002718 regulation of cytokine production involved in immune response GO:0002721 regulation of B cell cytokine production GO:0002755 MyD88-dependent toll-like receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0002819 regulation of adaptive immune response GO:0002821 positive regulation of adaptive immune response GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002861 regulation of inflammatory response to antigenic stimulus GO:0002863 positive regulation of inflammatory response to antigenic stimulus GO:0002864 regulation of acute inflammatory response to antigenic stimulus GO:0002866 positive regulation of acute inflammatory response to antigenic stimulus GO:0002883 regulation of hypersensitivity GO:0002885 positive regulation of hypersensitivity GO:0002886 regulation of myeloid leukocyte mediated immunity GO:0002888 positive regulation of myeloid leukocyte mediated immunity GO:0002889 regulation of immunoglobulin mediated immune response GO:0002891 positive regulation of immunoglobulin mediated immune response GO:0002902 regulation of B cell apoptotic process GO:0006887 exocytosis GO:0006979 response to oxidative stress GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0007498 mesoderm development GO:0009620 response to fungus GO:0009914 hormone transport GO:0010817 regulation of hormone levels GO:0016064 immunoglobulin mediated immune response GO:0016068 type I hypersensitivity GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0019722 calcium-mediated signaling GO:0019724 B cell mediated immunity GO:0019932 second-messenger-mediated signaling GO:0021700 developmental maturation GO:0023061 signal release GO:0030098 lymphocyte differentiation GO:0030183 B cell differentiation GO:0031349 positive regulation of defense response GO:0032103 positive regulation of response to external stimulus GO:0032418 lysosome localization GO:0034599 cellular response to oxidative stress GO:0034614 cellular response to reactive oxygen species GO:0038083 peptidyl-tyrosine autophosphorylation GO:0038093 Fc receptor signaling pathway GO:0038095 Fc-epsilon receptor signaling pathway GO:0042113 B cell activation GO:0043299 leukocyte degranulation GO:0043303 mast cell degranulation GO:0045055 regulated exocytosis GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045117 azole transport GO:0045576 mast cell activation GO:0045577 regulation of B cell differentiation GO:0045579 positive regulation of B cell differentiation GO:0045619 regulation of lymphocyte differentiation GO:0045621 positive regulation of lymphocyte differentiation GO:0046777 protein autophosphorylation GO:0046879 hormone secretion GO:0048469 cell maturation GO:0050727 regulation of inflammatory response GO:0050729 positive regulation of inflammatory response GO:0050851 antigen receptor-mediated signaling pathway GO:0050853 B cell receptor signaling pathway GO:0050864 regulation of B cell activation GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050871 positive regulation of B cell activation GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051249 regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0051608 histamine transport GO:0051640 organelle localization GO:0051656 establishment of organelle localization GO:0070227 lymphocyte apoptotic process GO:0070228 regulation of lymphocyte apoptotic process GO:0071216 cellular response to biotic stimulus GO:0071226 cellular response to molecule of fungal origin GO:0071887 leukocyte apoptotic process GO:1902105 regulation of leukocyte differentiation GO:1902107 positive regulation of leukocyte differentiation GO:1903706 regulation of hemopoiesis GO:1903708 positive regulation of hemopoiesis GO:2000106 regulation of leukocyte apoptotic process |
Molecular Function |
GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine kinase activity GO:0005543 phospholipid binding GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding GO:0035091 phosphatidylinositol binding GO:1901981 phosphatidylinositol phosphate binding |
Cellular Component |
GO:0009898 cytoplasmic side of plasma membrane GO:0019897 extrinsic component of plasma membrane GO:0019898 extrinsic component of membrane GO:0031234 extrinsic component of cytoplasmic side of plasma membrane GO:0042629 mast cell granule GO:0045121 membrane raft GO:0098552 side of membrane GO:0098562 cytoplasmic side of membrane GO:0098589 membrane region GO:0098857 membrane microdomain |
KEGG |
hsa04064 NF-kappa B signaling pathway hsa04380 Osteoclast differentiation hsa04611 Platelet activation hsa04662 B cell receptor signaling pathway hsa04664 Fc epsilon RI signaling pathway |
Reactome |
R-HSA-166054: Activated TLR4 signalling R-HSA-1280218: Adaptive Immune System R-HSA-983695: Antigen activates B Cell Receptor (BCR) leading to generation of second messengers R-HSA-1236975: Antigen processing-Cross presentation R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-2172127: DAP12 interactions R-HSA-2424491: DAP12 signaling R-HSA-1643685: Disease R-HSA-5602358: Diseases associated with the TLR signaling cascade R-HSA-5260271: Diseases of Immune System R-HSA-1236974: ER-Phagosome pathway R-HSA-2871809: FCERI mediated Ca+2 mobilization R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis R-HSA-5603041: IRAK4 deficiency (TLR2/4) R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-5602498: MyD88 deficiency (TLR2/4) R-HSA-166058: MyD88 R-HSA-195258: RHO GTPase Effectors R-HSA-5663213: RHO GTPases Activate WASPs and WAVEs R-HSA-2029482: Regulation of actin dynamics for phagocytic cup formation R-HSA-162582: Signal Transduction R-HSA-194315: Signaling by Rho GTPases R-HSA-983705: Signaling by the B Cell Receptor (BCR) R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade R-HSA-168179: Toll Like Receptor TLR1 R-HSA-168188: Toll Like Receptor TLR6 R-HSA-168898: Toll-Like Receptors Cascades |
Summary | |
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Symbol | BTK |
Name | Bruton agammaglobulinemia tyrosine kinase |
Aliases | ATK; XLA; PSCTK1; AGMX1; IMD1; BPK; B-cell progenitor kinase; agammaglobulinaemia tyrosine kinase; dominant- ...... |
Chromosomal Location | Xq21.33-q22 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Literatures that report relations between BTK and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells. |
Literatures describing the relation between BTK and anti-tumor immunity in human cancer.
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Summary | |
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Symbol | BTK |
Name | Bruton agammaglobulinemia tyrosine kinase |
Aliases | ATK; XLA; PSCTK1; AGMX1; IMD1; BPK; B-cell progenitor kinase; agammaglobulinaemia tyrosine kinase; dominant- ...... |
Chromosomal Location | Xq21.33-q22 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets. |
> High-throughput Screening
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Statistical results of BTK in screening data sets for detecting immune reponses.
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Summary | |
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Symbol | BTK |
Name | Bruton agammaglobulinemia tyrosine kinase |
Aliases | ATK; XLA; PSCTK1; AGMX1; IMD1; BPK; B-cell progenitor kinase; agammaglobulinaemia tyrosine kinase; dominant- ...... |
Chromosomal Location | Xq21.33-q22 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders |
Points in the above scatter plot represent the expression difference of BTK in various data sets.
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Points in the above scatter plot represent the mutation difference of BTK in various data sets.
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Summary | |
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Symbol | BTK |
Name | Bruton agammaglobulinemia tyrosine kinase |
Aliases | ATK; XLA; PSCTK1; AGMX1; IMD1; BPK; B-cell progenitor kinase; agammaglobulinaemia tyrosine kinase; dominant- ...... |
Chromosomal Location | Xq21.33-q22 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of BTK. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene. |
Summary | |
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Symbol | BTK |
Name | Bruton agammaglobulinemia tyrosine kinase |
Aliases | ATK; XLA; PSCTK1; AGMX1; IMD1; BPK; B-cell progenitor kinase; agammaglobulinaemia tyrosine kinase; dominant- ...... |
Chromosomal Location | Xq21.33-q22 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of BTK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by BTK. > Immunoinhibitor > Immunostimulator > MHC molecule |
Summary | |
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Symbol | BTK |
Name | Bruton agammaglobulinemia tyrosine kinase |
Aliases | ATK; XLA; PSCTK1; AGMX1; IMD1; BPK; B-cell progenitor kinase; agammaglobulinaemia tyrosine kinase; dominant- ...... |
Chromosomal Location | Xq21.33-q22 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of BTK. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor |
Summary | |
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Symbol | BTK |
Name | Bruton agammaglobulinemia tyrosine kinase |
Aliases | ATK; XLA; PSCTK1; AGMX1; IMD1; BPK; B-cell progenitor kinase; agammaglobulinaemia tyrosine kinase; dominant- ...... |
Chromosomal Location | Xq21.33-q22 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Distribution of BTK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype |
Summary | |
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Symbol | BTK |
Name | Bruton agammaglobulinemia tyrosine kinase |
Aliases | ATK; XLA; PSCTK1; AGMX1; IMD1; BPK; B-cell progenitor kinase; agammaglobulinaemia tyrosine kinase; dominant- ...... |
Chromosomal Location | Xq21.33-q22 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Associations between BTK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade |
Summary | |
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Symbol | BTK |
Name | Bruton agammaglobulinemia tyrosine kinase |
Aliases | ATK; XLA; PSCTK1; AGMX1; IMD1; BPK; B-cell progenitor kinase; agammaglobulinaemia tyrosine kinase; dominant- ...... |
Chromosomal Location | Xq21.33-q22 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Drugs targeting BTK collected from DrugBank database. |
Details on drugs targeting BTK.
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