BTK

Tyrosine-protein kinase BTK ;
Agammaglobulinaemia tyrosine kinase ;
ATK ;
B-cell progenitor kinase ;
BPK ;
Bruton tyrosine kinase ;

catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ,cofactor:Binds 1 zinc ion per subunit. ,disease:Defects in BTK are the cause of X-linked agammaglobulinemia (XLA) [MIM:300755]; also called X-linked agammaglobulinemia type 1 (AGMX1) or immunodeficiency type 1 (IMD1) . XLA is a 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. ,disease:Defects in BTK may be the cause of X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA-IGHD) [MIM:307200]; also known as agammaglobulinemia and isolated growth hormone deficiency or Fleisher syndrome or isolated growth hormone deficiency type 3 (IGHD3) . In rare cases XLA is inherited together with isolated growth hormone deficiency (IGHD) . ,enzyme regulation:Inhibited by IBTK. Activated by phosphorylation. ,function:Plays a crucial role in B-cell ontogeny. Transiently phosphorylates GTF2I on tyrosine residues in response to B-cell receptor cross-linking. Required for the formation of functional ARID3A DNA-binding complexes. ,online information:BTK mutation db ,PTM:Autophosphorylated on Tyr-223 and Tyr-551. Phosphorylation of Tyr-223 may create a docking site for a SH2 containing protein. ,similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. ,similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily. ,similarity:Contains 1 Btk-type zinc finger. ,similarity:Contains 1 PH domain. ,similarity:Contains 1 protein kinase domain. ,similarity:Contains 1 SH2 domain. ,similarity:Contains 1 SH3 domain. ,subunit:Binds GTF2I through the PH domain. Interacts with SH3BP5 via the SH3 domain. Interacts with IBTK via its PH domain. Interacts with GTF2I and ARID3A. ,

protein amino acid phosphorylation , phosphorus metabolic process , phosphate metabolic process , induction of apoptosis , intracellular signaling cascade , protein kinase cascade , I-kappaB kinase/NF-kappaB cascade , mesoderm development , induction of apoptosis by extracellular signals , regulation of cell death , positive regulation of cell death ,induction of programmed cell death , phosphorylation , peptidyl-tyrosine phosphorylation , peptidyl-tyrosine modification , calcium-mediated signaling , second-messenger-mediated signaling , developmental maturation ,regulation of apoptosis , positive regulation of apoptosis , regulation of programmed cell death , positive regulation of programmed cell death , cell maturation ,

Cytoplasm. Cell membrane; Peripheral membrane protein. Nucleus. 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.