Figure 3

Functional domains of the CHIP protein and illustration of amino acid substitutions/deletions found in patients. Presentation of the CHIP E3-Ligase with its three functional domains: Tetratricopeptide repeat (TPR), coiled-coil (CC) and U-box. Patient 1 (P1[II-1]) is homozygous for a point mutation resulting in CHIP-N65S located in the TPR domain. Patient 2 (P2) is compound heterozygous for two point mutations; one resulting in CHIP-E28K in the TPR domain and another causing the deletion mutant CHIP-K144*, a truncated protein lacking most of the CC domain and the entire U-box domain. The mutation resulting in the CHIP-T246M mutant is located in the U-box domain and has previously been described [5] and indicated here in Patient 3 (P3).