Dbfetch

Transglutaminases catalyse the post-translational modification of proteins at glutamine residues, with formation of isopeptide bonds. Members of the transglutaminase family usually have three domains: N-terminal ( ), middle ( ) and C-terminal. The middle domain is usually well conserved, but family members can display major differences in their N- and C-terminal domains, although their overall structure is conserved [ ]. This entry represents the C-terminal domain found in transglutaminases, which consists of an immunoglobulin-like β-sandwich consisting of seven strands in two sheets with a Greek key topology.

The best known transglutaminase is blood coagulation factor XIII, a plasma tetrameric protein composed of two catalytic A subunits and two non-catalytic B subunits. Factor XIII is responsible for cross-linking fibrin chains, thus stabilising the fibrin clot. Protein-glutamine gamma-glutamyltransferases ( ) are calcium-dependent enzymes that catalyse the cross-linking of proteins by promoting the formation of isopeptide bonds between the γ-carboxyl group of a glutamine in one polypeptide chain and the ε-amino group of a lysine in a second polypeptide chain. TGases also catalyse the conjugation of polyamines to proteins [ , ].

Proteins containing this domain also include Protein 4.2 (also known as Epb42), which is one of the most abundant protein components of the erythrocyte membrane. The protein shares significant sequence homology with transglutaminases, but lacks the catalytic triad residues required for transglutaminase activity [ ]. The complete or nearly complete absence of protein 4.2 is associated with an atypical form of hereditary spherocytosis (HS) [ ].