Mouse Anti-Phospho-BTK (Ser180) Recombinant Antibody (3D3) (CBMAB-CP0040-LY)

Bruton Tyrosine Kinase

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]

Bruton Tyrosine Kinase; Bruton Agammaglobulinemia Tyrosine Kinase; B-Cell Progenitor Kinase; Brutons Tyrosine Kinase; EC 2.7.10.2; AGMX1; ATK; BPK; Tyrosine-Protein Kinase BTK Isoform (Lacking Exon 13 To 17); Dominant-Negative Kinase-Deficient Brutons Tyrosine Kinase; Tyrosine-Protein Kinase BTK Isoform (Lacking Exon 14);

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.

Adaptive immune response Source: UniProtKB
Apoptotic signaling pathway Source: ProtInc
B cell activation Source: UniProtKB
B cell affinity maturation Source: Ensembl
B cell receptor signaling pathway Source: UniProtKB
Calcium-mediated signaling Source: HGNC-UCL
Cell maturation Source: Ensembl
Cellular response to interleukin-7 Source: Ensembl
Cellular response to molecule of fungal origin Source: Ensembl
Cellular response to reactive oxygen species Source: Ensembl
Fc-epsilon receptor signaling pathway Source: Reactome
G protein-coupled receptor signaling pathway Source: Reactome
Histamine secretion by mast cell Source: Ensembl
I-kappaB kinase/NF-kappaB signaling Source: Ensembl
Innate immune response Source: UniProtKB
Intracellular signal transduction Source: ARUK-UCL
Mesoderm development Source: ProtInc
MyD88-dependent toll-like receptor signaling pathway Source: Reactome
Negative regulation of B cell proliferation Source: Ensembl
Negative regulation of cytokine production Source: Ensembl
Peptidyl-tyrosine phosphorylation Source: ARUK-UCL
Positive regulation of B cell differentiation Source: UniProtKB
Positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
Positive regulation of type I hypersensitivity Source: Ensembl
Positive regulation of type III hypersensitivity Source: Ensembl
Protein autophosphorylation Source: Ensembl
Protein phosphorylation Source: HGNC-UCL
Regulation of B cell apoptotic process Source: UniProtKB
Regulation of B cell cytokine production Source: UniProtKB

Nucleus; Cell membrane; Cytoplasm. 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.

X-linked agammaglobulinemia (XLA): Humoral immunodeficiency disease which results in developmental defects in the maturation pathway of B-cells. Affected boys have normal levels of pre-B-cells in their bone marrow but virtually no circulating mature B-lymphocytes. This results in a lack of immunoglobulins of all classes and leads to recurrent bacterial infections like otitis, conjunctivitis, dermatitis, sinusitis in the first few years of life, or even some patients present overwhelming sepsis or meningitis, resulting in death in a few hours. Treatment in most cases is by infusion of intravenous immunoglobulin.
Growth hormone deficiency, isolated, 3, with agammaglobulinemia (IGHD3): An X-linked recessive disorder characterized by growth hormone deficiency, short stature, delayed bone age, agammaglobulinemia with markedly reduced numbers of B cells, and good response to treatment with growth hormone.

Following B-cell receptor (BCR) engagement, translocates to the plasma membrane where it gets phosphorylated at Tyr-551 by LYN and SYK. Phosphorylation at Tyr-551 is followed by autophosphorylation of Tyr-223 which may create a docking site for a SH2 containing protein. Phosphorylation at Ser-180 by PRKCB, leads in translocation of BTK back to the cytoplasmic fraction. Phosphorylation at Ser-21 and Ser-115 creates a binding site for PIN1 at these Ser-Pro motifs, and promotes it's recruitment.