Solute carrier organic anion transporter 4C subfamily of the Major Facilitator Superfamily of transporters
The Solute carrier organic anion transporter 4C (SLCO4C), also called Organic anion-transporting polypeptide 4C (OATP4C), subfamily has one mammalian member, OATP4C1 (encoded by SLCO4C1). It is capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. It is the only OATP expressed at the basolateral side of proximal tubular cells in human kidney and it mediates the excretion of uremic toxins, which accumulate in patients with chronic kidney diseases (CKDs) and cause further progression of renal damage and cardiovascular diseases. Overexpression of human SLCO4C1 in rat kidney promotes the renal excretion of uremic toxins and reduces hypertension, cardiomegaly, and renal inflammation in renal failure. The SLCO4C/OATP4C subfamily 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.",