Primary external reference:
PTEN missense mutation that results in the substitution of cysteine at position 124 with arginine affects the conserved H-C-K/R-A-G-K-G-R sequence (corresponding to HCXXGXXR motif of protein tyrosine phosphatases) in the catalytic cleft of the PTEN phosphatase domain. The cystein residue in this motif, corresponding to C124 of human PTEN, 'attacks' the phosphate group of a substrate and forms a thio-phosphate intermediate during dephosphorylation reaction (Guan and Dixon 1991, Barford et al. 1994, Lee et al. 1999). PTEN C124R (Cys124Arg) mutant shows markedly decreased phosphoinositide phosphatase activity (Han et al. 2000). PTEN C124R is found as a germline mutation in Cowden syndrome, an autosomal dominant cancer syndrome (Nelen et al. 1997).