Solute carrier organic anion transporter 4 family of the Major Facilitator Superfamily of transporters
The Solute carrier organic anion transporter 4 (SLCO4) or Organic anion transporting polypeptide 4 (OATP4) family contains two families: OATP4A and OATP4C, each containing one mammalian member, OATP4A1 and OATP4C1, respectively. OATP4A1 (encoded by SLCO4A1), is ubiquitously expressed and mediates the Na(+)-independent transport of the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and other organic anions such as estrone sulfate and taurocholate. OATP4C1 (encoded by SLCO4C1) is capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate, cAMP, and uremic toxins, which accumulate in patients with chronic kidney diseases (CKDs). The SLCO4/OATP4 family belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. 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.",