title: X-linked agammaglobulinemia (XLA): a genetic tyrosine kinase (Btk) disease.
abstract: X-linked agammaglobulinemia is a heritable immunodeficiency disease caused by a differentiation abnormality, resulting in the virtual absence of B lymphocytes and plasma cells. The affected gene encodes a cytoplasmic protein tyrosine kinase, Bruton's agammaglobulinemia tyrosine kinase, designated Btk. Btk and the other family members, Tec, ltk and Bmx, contain five regions, four of which are common structural and functional modules that are found in other signaling proteins. Mutations affect all domains of the gene, but amino acid substitutions seem to be confined to certain regions. More than 150 unique mutations have been identified and are collected in a mutation database, BTKbase. Here we discuss the three-dimensional structural implications of such mutations and their putative functional role. Of special interest are mutations affecting the pleckstrin homology domain, as Btk is the only disease-associated protein so far reported to carry mutations in this particular module.
authors.affiliation: Department of Bioscience at Novum, Karolinska Institute, Huddinge, Sweden. pekmat@utu.fi
authors.forename: P T
authors.initials: PT
authors.lastname: Mattsson
authors.forename: M
authors.initials: M
authors.lastname: Vihinen
authors.forename: C I
authors.initials: CI
authors.lastname: Smith
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology* / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse