title: Missense mutations affecting a conserved cysteine pair in the TH domain of Btk.
abstract: Tec family protein tyrosine kinases have in their N-terminus two domains. The PH domain is followed by Tec homology (TH) domain, which consists of two motifs. The first pattern, Btk motif, is also present in some Ras GAP molecules. C-terminal half of the TH domain, a proline-rich region, has been shown to bind to SH3 domains. Mutations in Bruton's tyrosine kinase (Btk) belonging to the Tec family cause X-linked agammaglobulinemia (XLA) due to developmental arrest of B cells. Here we present the first missense mutations in the TH domain. The substitutions affect a conserved pair of cysteines, residues 154 and 155, involved in Zn2+ binding and thereby the mutations alter protein folding and stability.
authors.affiliation: Department of Biosciences, University of Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Vihinen
authors.forename: B F
authors.initials: BF
authors.lastname: Nore
authors.forename: P T
authors.initials: PT
authors.lastname: Mattsson
authors.forename: C M
authors.initials: CM
authors.lastname: Bäckesjö
authors.forename: M
authors.initials: M
authors.lastname: Nars
authors.forename: S
authors.initials: S
authors.lastname: Koutaniemi
authors.forename: C
authors.initials: C
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Lester
authors.forename: A
authors.initials: A
authors.lastname: Jones
authors.forename: H D
authors.initials: HD
authors.lastname: Ochs
authors.forename: C I
authors.initials: CI
authors.lastname: Smith
mesh_terms: D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics*; D000595:Amino Acid Sequence; D002648:Child; D017124:Conserved Sequence / Q000235:genetics; D003545:Cysteine / Q000235:genetics*; D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D017510:Protein Folding; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D014960:X Chromosome; D016335:Zinc Fingers
chemical_list: D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D003545:Cysteine