InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Btk

Summary

InnateDB Protein

IDBP-171429.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Btk

Protein Name

Bruton agammaglobulinemia tyrosine kinase

Synonyms

AI528679; xid;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000033617

InnateDB Gene

IDBG-171427 (Btk)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10852954, ECO:0000269PubMed:11120822, ECO:0000269PubMed:16738337, ECO:0000269PubMed:17725607, ECO:0000269PubMed:7538439, ECO:0000269PubMed:8629002}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:11120822}. Cell membrane {ECO:0000269PubMed:11120822}; Peripheral membrane protein {ECO:0000269PubMed:11120822}. Nucleus {ECO:0000269PubMed:11120822}. 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. {ECO:0000250}.

Disease Associations

Note=Defects in Btk are the cause of murine X-linked immunodeficiency (XID).

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 47 experimentally validated interaction(s) in this database.
They are also associated with 71 interaction(s) predicted by orthology.

Experimentally validated
Total	47 [view]
Protein-Protein	47 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	71 [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:0000302	response to reactive oxygen species
GO:0002553	histamine secretion by mast cell
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0010033	response to organic substance
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0034614	cellular response to reactive oxygen species
GO:0035556	intracellular signal transduction
GO:0045087	innate immune response (InnateDB)
GO:0046777	protein autophosphorylation
GO:0048469	cell maturation
GO:0071226	cellular response to molecule of fungal origin

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

Protein Structure and Domains

PDB ID

MGI:88216

InterPro

IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001452 SH3 domain
IPR001562 Zinc finger, Btk motif
IPR001849 Pleckstrin homology domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011511 Variant SH3 domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM