Homo sapiens Gene: BTK
Summary
InnateDB Gene IDBG-79651.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol BTK
Gene Name Bruton agammaglobulinemia tyrosine kinase
Synonyms AGMX1; AT; ATK; BPK; IMD1; PSCTK1; XLA;
Species Homo sapiens
Ensembl Gene ENSG00000010671
Encoded Proteins
Bruton agammaglobulinemia tyrosine kinase
Bruton agammaglobulinemia tyrosine kinase
Bruton agammaglobulinemia tyrosine kinase
Bruton agammaglobulinemia tyrosine kinase
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
BTK is a Toll/interleukin-1 receptor domain-binding protein that participates in NF-kappaB activation by TLR4.
BTK interacts with intracellular MHC class II molecules to activate adaptor molecules MYD88 and TICAM1 to promote TLR signalling. (Demonstrated in murine model)
BTK is a positive regulator in the ITAM-mediated TREM1/TYROBP pathway, which induces pro-inflammatory cytokines such as TNF-alpha, IL8, and activation/differentiation cell surface markers. Patients suffering from X-linked agammaglobulinemia (XLA), which is a rare hereditary disease caused by mutation in the BTK gene, show reduced TNF-alpha induction in PBMCs upon TREM1 engagement.
BTK directly phosphorylates TLR3 and plays a critical role in the induction of inflammatory cytokines and IFNB. (Demonstrated in mice)
BTK is required for the activation of natural killer cells. (Demonstrated in mice)
BTK is a negative regulator of TLR- or TNF-stimulated reactive oxygen species (ROS) production in neutrophils.
BTK regulates TLR9-mediated induction of cytokines in plasmacytoid dendritic cells, but has no role in TLR7 signalling.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Btk interacts with intracellular MHC class II molecules to activate adaptor molecules Myd88 and Ticam1 to promote TLR signalling.
[Mus musculus] Btk is a positive regulator in the ITAM-mediated Trem1/Tyrobp pathway, which induces pro-inflammatory cytokines such as TNF-alpha, Il8, and activation/differentiation cell surface markers.
[Mus musculus] Btk directly phosphorylates Tlr3 and plays a critical role in the induction of inflammatory cytokines and Ifnb.
[Mus musculus] Btk is required for the activation of natural killer cells.
[Mus musculus] Btk is a negative regulator of TLR- or TNF-stimulated reactive oxygen species (ROS) production in neutrophils. (Demonstrated in human)
Entrez Gene
Summary 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. [provided by RefSeq, Nov 2008]
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]
Gene Information
Type Protein coding
Genomic Location Chromosome X:101349447-101390796
Strand Reverse strand
Band q22.1
Transcripts
ENST00000372880 ENSP00000361971
ENST00000308731 ENSP00000308176
ENST00000470069
ENST00000488970
ENST00000478995
ENST00000470329
ENST00000464006
ENST00000464567
ENST00000621635 ENSP00000483570
ENST00000618050 ENSP00000479125
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 106 experimentally validated interaction(s) in this database.
They are also associated with 37 interaction(s) predicted by orthology.
Experimentally validated
Total 106 [view]
Protein-Protein 104 [view]
Protein-DNA 1 [view]
Protein-RNA 0
DNA-DNA 1 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 37 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0042802 identical protein binding
GO:0046872 metal ion binding
Biological Process
GO:0002224 toll-like receptor signaling pathway
GO:0002250 adaptive immune response
GO:0002553 histamine secretion by mast cell
GO:0002721 regulation of B cell cytokine production
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002902 regulation of B cell apoptotic process
GO:0006351 transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007498 mesoderm development
GO:0010033 response to organic substance
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0019722 calcium-mediated signaling
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034614 cellular response to reactive oxygen species
GO:0035556 intracellular signal transduction
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0042113 B cell activation
GO:0045087 innate immune response (InnateDB)
GO:0045579 positive regulation of B cell differentiation
GO:0046777 protein autophosphorylation
GO:0048469 cell maturation
GO:0050853 B cell receptor signaling pathway
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0071226 cellular response to molecule of fungal origin
GO:0097190 apoptotic signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0031410 cytoplasmic vesicle
GO:0042629 mast cell granule
GO:0043231 intracellular membrane-bounded organelle
GO:0045121 membrane raft
GO:0048471 perinuclear region of cytoplasm
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
KitReceptor pathway
BCR pathway
IL4 pathway
IL5 pathway
IL6 pathway
TSLP pathway
REACTOME
Regulation of actin dynamics for phagocytic cup formation pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
DAP12 signaling pathway
Innate Immune System pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
Fc epsilon receptor (FCERI) signaling pathway
Adaptive Immune System pathway
Immune System pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers pathway
Fcgamma receptor (FCGR) dependent phagocytosis pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
FCERI mediated Ca+2 mobilization pathway
Signaling by the B Cell Receptor (BCR) pathway
DAP12 interactions pathway
KEGG
Osteoclast differentiation pathway
B cell receptor signaling pathway pathway
Fc epsilon RI signaling pathway pathway
Primary immunodeficiency pathway
INOH
IL-7 signaling pathway
JAK STAT pathway and regulation pathway
EPO signaling pathway pathway
VEGF signaling pathway pathway
PID BIOCARTA
Bcr signaling pathway [Biocarta view]
Phosphoinositides and their downstream targets [Biocarta view]
Fc epsilon receptor i signaling in mast cells [Biocarta view]
PID NCI
EPO signaling pathway
BCR signaling pathway
Fc-epsilon receptor I signaling in mast cells
FAS (CD95) signaling pathway
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.159494
RefSeq NM_000061 NM_001287344 NM_001287345
HUGO
OMIM
CCDS CCDS14482 CCDS76002 CCDS76003
HPRD 02248
IMGT
EMBL
GenPept
RNA Seq Atlas