[11] The GUK domain that they have is structurally very similar to that of the guanylate kinases, however it is known to be catalytically inactive as the P-Loop which binds ATP is absent.

It is thought that the MAGUKs have subfunctionalized the GUK domain for their own purposes, primarily based on its ability to form protein-protein interactions with cytoskeleton proteins, microtubule/actin based machinery and molecules involved in signal transduction.

The PDZ domain which are contained in the MAGUKs in varying numbers, is replicated three times over in PSD-95.

PDZ domains are short peptide binding sequences commonly found at the C-terminus of interacting proteins.

The three copies within the gene have different binding partners, due to amino acid substitutions within the PSD-95 protein and its ligands.