Protein-4.2 homology model. Ribbon representation of the model of protein 4.2. Space-filled residues are the 3 mutation sites (Nippon, A142T; Komatsu, D175Y; Tozeur, R310Q) and the palmitoylation site (C203). The proposed band-3–binding site on protein 4.2⁴³  is located on a hairpin region (red) that also contains the known palmitoylation site of protein 4.2⁴³  (C203 in the hairpin reverse turn). Transglutaminases such as 1G0D,³³  1KV3,³⁴  and 1EVU⁴⁴  (factor XIII) have a catalytic triad comprising H332, C333, and D355 (1G0D numbering). The corresponding residues in the model of protein 4.2 are T, Q, and D, hence the catalytic triad is missing and no transglutaminase activity is expected. It has been shown that protein 4.2 binds adenosine triphosphate and that binding is associated with a P-loop type sequence GEGQRGR (residues 346-352; green).⁴⁵  The protein-4.2 model has 2 conserved glutamate residues whose side chains coordinate a calcium ion in other family members (protein 4.2: E469, E474; 1L9N: E443, E448⁴⁶ ; 1EVU: E485, E490⁴⁴ ). This putative calcium-binding site (cyan) is at the N-terminus of a 3-turn helix corresponding to helix-14 in the 1G0D template. The template structure has a stretch of 10 residues that do not appear in the crystal structure (due to disorder) connecting the C-terminal end of this helix (G0D1 residue) to the first strand of domain 3. Protein 4.2 also has a sequence insertion of 9 residues with respect to the template in this region. Hence the protein-4.2 model required a 19-residue linker between domains 2 and 3 to be modeled ab initio and must be considered as the least reliable part of the model with respect to structural detail. Interestingly, this region (colored orange) contains the sequence (482 EKEKMEREKD 491) that is responsible for the binding of spectrin by protein 4.2.¹⁶  The proximity of the calcium-binding loop to the spectrin-binding loop is suggestive of a role for calcium in controlling spectrin binding.