The interaction enhances the efficiency by which AMPK phosphorylates TBC1D1 on its key regulatory site, Ser<sup>237</sup> Furthermore, the interaction is reduced by a naturally occurring R125W mutation in the PTB1 domain of TBC1D1, previously found to be associated with severe familial obesity in females, with a concomitant reduction in Ser<sup>237</sup> phosphorylation.
The interaction enhances the efficiency by which AMPK phosphorylates TBC1D1 on its key regulatory site, Ser<sup>237</sup> Furthermore, the interaction is reduced by a naturally occurring R125W mutation in the PTB1 domain of TBC1D1, previously found to be associated with severe familial obesity in females, with a concomitant reduction in Ser<sup>237</sup> phosphorylation.
A non-synonymous polymorphism (rs35859249, p.Arg125Trp) in the N-terminal TBC1D1 phosphotyrosine-binding (PTB) domain has shown a replicated association with familial obesity in women.
A non-synonymous polymorphism (rs35859249, p.Arg125Trp) in the N-terminal TBC1D1 phosphotyrosine-binding (PTB) domain has shown a replicated association with familial obesity in women.
In addition, by selecting families that segregated R125W with obes</span>ity, we were able to generate highly significant linkage evidence for an obesity predisposition locus at 4q34-35.
Since mutations within TBC1D1 (R125W) display stronger associations with clinical parameters in women, we further examined possible sex differences in the predisposition to diabetic cardiomyopathy.