The munc-18 interacting (Mint) protein family is a group of evolutionarily conserved adaptor proteins that function in membrane transport and organization. In mammals, there exist three mint isoforms, Mint 1, 2, and 3. Although there is little amino acid sequence conservation in the amino-terminal half, the carboxy-terminal half of these proteins is highly conserved. Within this conserved portion there exists a phosphotyrosine-binding (PTB) and a PSD-95/DLG-A/ZO-1 (PDZ) domain, which function as protein interaction modules. Mint 1 and 2 appear to be expressed exclusively in the brain and are found to bind to munc-18, an essential component of the synaptic vesicle fusion machinery. Mint 3 is ubiquitously expressed in all tissues and is expressed at the lowest levels in the brain and testis. Studies show that Mint 3 does not interact with munc-18. Mint 3 has been found to interact with the Alzheimer’s Disease-related amyloid precursor protein (APP) and does so through its PTB and PDZ domains. It has been suggested that Mint 3 links APP to other transport machinery components, thereby regulating it transport, endocytosis, and metabolism. Abnormal APP metabolism has been shown to be the cause of an early-onset type of Alzheimer’s disease.
Composed of an N-terminal domain, a middle phosphotyrosine-binding domain (PID/PTB) that mediates binding with the cytoplasmic domain of the beta-amyloid precursor protein, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane.