BTK [The Human Chemical-Genetic Interaction Map Project]

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======= BTK =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: BTK
  * **<color #00a2e8>Official Name</color>**: Bruton tyrosine kinase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=695|695]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q06187|Q06187]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=BTK&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20BTK|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/300300|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene plays a crucial role in B-cell development. Mutations in this gene cause X-linked agammaglobulinemia type 1, which is an immunodeficiency characterized by the failure to produce mature B lymphocytes, and associated with a failure of Ig heavy chain rearrangement. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:9012831}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|PH|
|SH3 2|
|BTK|
|Pkinase Tyr|
|SH2|
|SH3 1|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|B cell affinity maturation|
|regulation of B cell cytokine production|
|peripheral B cell selection|
|positive regulation of type III hypersensitivity|
|positive regulation of type I hypersensitivity|
|regulation of type III hypersensitivity|
|histamine production involved in inflammatory response|
|cellular response to molecule of fungal origin|
|B cell selection|
|histamine secretion involved in inflammatory response|
|response to molecule of fungal origin|
|regulation of type I hypersensitivity|
|histamine secretion by mast cell|
|positive regulation of hypersensitivity|
|histamine secretion|
|positive regulation of acute inflammatory response to antigenic stimulus|
|regulation of hypersensitivity|
|histamine transport|
|positive regulation of inflammatory response to antigenic stimulus|
|positive regulation of B cell differentiation|
|regulation of acute inflammatory response to antigenic stimulus|
|negative regulation of B cell proliferation|
|production of molecular mediator involved in inflammatory response|
|mast cell degranulation|
|mast cell activation involved in immune response|
|regulation of B cell apoptotic process|
|azole transport|
|mast cell mediated immunity|
|mast cell granule|
|mast cell activation|
|regulation of inflammatory response to antigenic stimulus|
|immunoglobulin production involved in immunoglobulin mediated immune response|
|regulation of B cell differentiation|
|response to interleukin-7|
|positive regulation of acute inflammatory response|
|cellular response to interleukin-7|
|negative regulation of B cell activation|
|positive regulation of myeloid leukocyte mediated immunity|
|MyD88-dependent toll-like receptor signaling pathway|
|peptidyl-tyrosine autophosphorylation|
|positive regulation of immunoglobulin mediated immune response|
|positive regulation of B cell mediated immunity|
|phosphatidylinositol-3,4,5-trisphosphate binding|
|lysosome localization|
|regulation of acute inflammatory response|
|non-membrane spanning protein tyrosine kinase activity|
|response to fungus|
|regulation of immunoglobulin mediated immune response|
|regulation of B cell mediated immunity|
|regulation of lymphocyte apoptotic process|
|ammonium transport|
|regulation of myeloid leukocyte mediated immunity|
|regulation of B cell proliferation|
|exocytic process|
|I-kappaB kinase/NF-kappaB signaling|
|hormone secretion|
|negative regulation of lymphocyte proliferation|
|negative regulation of mononuclear cell proliferation|
|negative regulation of leukocyte proliferation|
|hormone transport|
|regulation of leukocyte apoptotic process|
|regulation of cytokine production involved in immune response|
|protein tyrosine kinase activity|
|positive regulation of lymphocyte differentiation|
|toll-like receptor signaling pathway|
|positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|positive regulation of adaptive immune response|
|positive regulation of lymphocyte mediated immunity|
|B cell differentiation|
|mesoderm development|
|B cell receptor signaling pathway|
|pattern recognition receptor signaling pathway|
|cellular response to reactive oxygen species|
|positive regulation of leukocyte mediated immunity|
|positive regulation of inflammatory response|
|regulation of production of molecular mediator of immune response|
|peptidyl-tyrosine phosphorylation|
|negative regulation of lymphocyte activation|
|regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|calcium-mediated signaling|
|peptidyl-tyrosine modification|
|positive regulation of leukocyte differentiation|
|regulation of lymphocyte mediated immunity|
|positive regulation of NF-kappaB transcription factor activity|
|B cell activation|
|immunoglobulin production|
|cell maturation|
|regulation of adaptive immune response|
|positive regulation of B cell activation|
|regulation of lymphocyte differentiation|
|signal release|
|Fc-epsilon receptor signaling pathway|
|negative regulation of leukocyte activation|
|T cell receptor signaling pathway|
|neurotransmitter transport|
|production of molecular mediator of immune response|
|positive regulation of hemopoiesis|
|protein autophosphorylation|
|response to reactive oxygen species|
|negative regulation of cell activation|
|regulation of leukocyte mediated immunity|
|immunoglobulin mediated immune response|
|regulation of B cell activation|
|B cell mediated immunity|
|regulation of lymphocyte proliferation|
|regulation of mononuclear cell proliferation|
|cellular response to biotic stimulus|
|positive regulation of immune effector process|
|regulation of leukocyte proliferation|
|membrane raft|
|innate immune response-activating signal transduction|
|lymphocyte differentiation|
|developmental maturation|
|cellular response to oxidative stress|
|Fc receptor signaling pathway|
|cytoplasmic vesicle|
|activation of innate immune response|
|positive regulation of DNA-binding transcription factor activity|
|lymphocyte mediated immunity|
|regulation of leukocyte differentiation|
|negative regulation of cytokine production|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|apoptotic signaling pathway|
|antigen receptor-mediated signaling pathway|
|leukocyte differentiation|
|second-messenger-mediated signaling|
|regulation of inflammatory response|
|positive regulation of innate immune response|
|positive regulation of lymphocyte activation|
|positive regulation of response to biotic stimulus|
|establishment of organelle localization|
|lymphocyte activation|
|response to oxidative stress|
|positive regulation of leukocyte activation|
|positive regulation of cell activation|
|regulation of DNA-binding transcription factor activity|
|negative regulation of immune system process|
|immune response-activating cell surface receptor signaling pathway|
|regulation of hemopoiesis|
|regulation of innate immune response|
|regulation of immune effector process|
|positive regulation of defense response|
|immune response-regulating cell surface receptor signaling pathway|
|inflammatory response|
|positive regulation of multi-organism process|
|leukocyte degranulation|
|regulation of lymphocyte activation|
|myeloid leukocyte mediated immunity|
|myeloid cell activation involved in immune response|
|regulation of response to biotic stimulus|
|regulation of hormone levels|
|hemopoiesis|
|immune response-activating signal transduction|
|organelle localization|
|myeloid leukocyte activation|
|immune response-regulating signaling pathway|
|regulation of leukocyte activation|
|positive regulation of response to external stimulus|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|activation of immune response|
|regulation of cell activation|
|immune system development|
|negative regulation of cell population proliferation|
|regulation of cytokine production|
|perinuclear region of cytoplasm|
|regulated exocytosis|
|regulation of defense response|
|leukocyte mediated immunity|
|innate immune response|
|regulation of multi-organism process|
|exocytosis|
|cation transport|
|positive regulation of immune response|
|peptidyl-amino acid modification|
|apoptotic process|
|leukocyte activation|
|defense response to other organism|
|positive regulation of cell differentiation|
|protein phosphorylation|
|secretion by cell|
|cellular response to cytokine stimulus|
|export from cell|
|programmed cell death|
|cellular response to oxygen-containing compound|
|identical protein binding|
|cell activation|
|cell death|
|immune effector process|
|regulation of response to external stimulus|
|response to cytokine|
|cell-cell signaling|
|secretion|
|positive regulation of immune system process|
|regulation of immune response|
|negative regulation of multicellular organismal process|
|phosphorylation|
|response to other organism|
|response to external biotic stimulus|
|G protein-coupled receptor signaling pathway|
|response to biotic stimulus|
|defense response|
|positive regulation of developmental process|
|ion transport|
|regulation of response to stress|
|ATP binding|
|intracellular transport|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|regulation of cell population proliferation|
|cell development|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of multicellular organismal process|
|tissue development|
|positive regulation of molecular function|
|regulation of cell differentiation|
|establishment of localization in cell|
|nitrogen compound transport|
|immune response|
|vesicle-mediated transport|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp116|AICAR 240μM R03 exp116]]|-2.26|
|[[:results:exp443|SNS-032 15μM R08 exp443]]|-2.25|
|[[:results:exp126|GSK461364A 0.1μM R03 exp126]]|-2.01|
|[[:results:exp526|Sulforaphane 9μM R08 exp526 no dilution day6]]|-2|
|[[:results:exp434|Vemurafenib 6.6μM R08 exp434]]|-1.93|
|[[:results:exp499|LY2090314 0.003μM R08 exp499]]|-1.91|
|[[:results:exp435|JQ1 0.8μM R08 exp435]]|-1.86|
|[[:results:exp451|Atovaquone 15μM R08 exp451]]|-1.83|
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|-1.8|
|[[:results:exp355|Dinaciclib 0.007μM R07 exp355]]|-1.79|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|-1.79|
|[[:results:exp89|Vemurafenib 6.6μM R02 exp89]]|-1.78|
|[[:results:exp418|Tunicamycin 0.04μM R07 exp418]]|1.7|
|[[:results:exp15|Cycloheximide 0.2μM R00 exp15]]|1.78|
|[[:results:exp248|UM0131023 0.05μM R05 exp248]]|1.78|
|[[:results:exp16|DABN 2μM R00 exp16]]|1.8|
|[[:results:exp27|Pimelic-diphenylamide-106 0.5μM R00 exp27]]|1.81|
|[[:results:exp100|NFN1 1μM R03 exp100]]|1.92|
|[[:results:exp420|Tunicamycin 0.04 to 0.125μM  on day4 R07 exp420]]|1.93|
|[[:results:exp14|Cycloheximide 0.02μM R00 exp14]]|2.04|
|[[:results:exp70|INK128 0.2μM R02 exp70]]|2.09|
|[[:results:exp283|Glyphosate 1000μM R06 exp283]]|2.31|
|[[:results:exp71|KU-0063794 3.8μM R02 exp71]]|2.39|
|[[:results:exp82|Torin1 0.08μM R02 exp82]]|2.57|
|[[:results:exp29|Rapamycin 1μM R00 exp29]]|2.84|
|[[:results:exp306|Rapamycin 2μM R07 exp306]]|2.98|
|[[:results:exp30|Rapamycin 10μM R00 exp30]]|3.69|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:r:rrm1|RRM1]]|0.62|
|[[:human genes:b:blnk|BLNK]]|0.6|
|[[:human genes:p:plcg2|PLCG2]]|0.577|
|[[:human genes:n:nck1|NCK1]]|0.539|
|[[:human genes:p:psmd1|PSMD1]]|0.419|
|[[:human genes:l:lrmp|LRMP]]|0.409|
|[[:human genes:f:fkbp1a|FKBP1A]]|0.409|
|[[:human genes:e:elof1|ELOF1]]|0.406|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/694
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/26|
|bone|0/26|
|breast|0/30|
|central nervous system|0/49|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/11|
|fibroblast|0/1|
|gastric|0/14|
|kidney|0/18|
|liver|0/19|
|lung|0/72|
|lymphocyte|0/16|
|ovary|0/25|
|pancreas|0/22|
|peripheral nervous system|0/15|
|plasma cell|0/12|
|prostate|0/1|
|skin|0/20|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/28|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 2439
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.55 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='BTK Expression in NALM6 Cells: 7.55'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>