InnateDB: Systems Biology of the Innate Immune Response

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

IDBP-79653

Bruton agammaglobulinemia tyrosine kinase

IDBP-79655

Bruton agammaglobulinemia tyrosine kinase

IDBP-811243

Bruton agammaglobulinemia tyrosine kinase

IDBP-811247

Bruton agammaglobulinemia tyrosine kinase

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 12724322

BTK is a Toll/interleukin-1 receptor domain-binding protein that participates in NF-kappaB activation by TLR4.

PMID 21441935

BTK interacts with intracellular MHC class II molecules to activate adaptor molecules MYD88 and TICAM1 to promote TLR signalling. (Demonstrated in murine model)

PMID 21659545

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.

PMID 22454496

BTK directly phosphorylates TLR3 and plays a critical role in the induction of inflammatory cytokines and IFNB. (Demonstrated in mice)

PMID 22589540

BTK is required for the activation of natural killer cells. (Demonstrated in mice)

PMID 22366891

BTK is a negative regulator of TLR- or TNF-stimulated reactive oxygen species (ROS) production in neutrophils.

PMID 24375473

BTK regulates TLR9-mediated induction of cytokines in plasmacytoid dendritic cells, but has no role in TLR7 signalling.

InnateDB Annotation from Orthologs

Summary

PMID 21441935

[Mus musculus] Btk interacts with intracellular MHC class II molecules to activate adaptor molecules Myd88 and Ticam1 to promote TLR signalling.

PMID 21659545

[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.

PMID 22454496

[Mus musculus] Btk directly phosphorylates Tlr3 and plays a critical role in the induction of inflammatory cytokines and Ifnb.

PMID 22589540

[Mus musculus] Btk is required for the activation of natural killer cells.

PMID 22366891

[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