Monocarboxylate transporter 8 of the Major Facilitator Superfamily of transporters
Monocarboxylate transporter 8 (MCT8) is also called Solute carrier family 16 member 2 (SLC16A2) or X-linked PEST-containing transporter. MCT8 is a very active and specific thyroid hormone transporter which stimulates the cellular uptake of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine (T2). Inactivating mutations in SLC16A2, the gene that encodes MCT8, lead to an X-linked syndrome with severe neurological impairment known as Allan-Herndon-Dudley syndrome (AHDS). AHDS is characterized by congenital hypotonia that progresses to spasticity with severe psychomotor delays, spastic paraplegia and dystonic movements, global developmental delay, and profound intellectual disability. MCT8 belongs to the Monocarboxylate transporter (MCT) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Feature 1:putative chemical substrate binding pocket [chemical binding site]
Evidence:
Comment:based on the structures of MFS transporters with bound substrates, substrate analogs, and/or inhibitors
Comment:since MFS proteins facilitate the transport of many different substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides, the residues involved in substrate binding may not be strictly conserved among superfamily members
Comment:the substrate binding site or translocation pore has access to both sides of the membrane in an alternating fashion through a conformational change of the MFS transporter
Jiyao W et al.(2023). "The conserved domain database in 2023.",