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Missense mutations affecting a conserved cysteine pair in the TH domain of Btk
Author(s) -
Vihinen Mauno,
Nore Beston F.,
Mattsson Pekka T.,
Bäckesjö Carl-Magnus,
Nars Martin,
Koutaniemi Sanna,
Watanabe Chiaki,
Lester Tracy,
Jones Allison,
Ochs Hans D.,
Smith C.I.Edvard
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00912-5
Subject(s) - missense mutation , bruton's tyrosine kinase , cysteine , mutation , genetics , chemistry , biochemistry , biology , gene , receptor , tyrosine kinase , enzyme
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 Zn 2+ binding and thereby the mutations alter protein folding and stability.