Human urate transporter 1 (URAT1)

Human urate transporter 1 (URAT1, SLC22A12) is an integral membrane protein localized in the apical membrane of renal proximal tubule epithelial cells. It operates as an antiporter, exchanging intracellular organic anions or chloride ions for extracellular urate, thus crucially controlling urate reabsorption into the bloodstream. The transporter’s activity depends on a network of highly conserved amino acid residues that form a hydrophobic binding pocket, ensuring selective urate transport, and undergoes conformational changes between inward, outward, and occluded states during the transport cycle. This mechanism can be pharmacologically inhibited, and several drugs target URAT1 directly to lower serum urate, making it a prime target for treating gout and hyperuricemia. Genetic variations in URAT1 can influence urate affinity and transport efficiency, potentially affecting drug response and disease risk.

Other names

SLC22A12solute carrier family 22 member 12urate channelurate transporter 1 (URAT1)

Pharmacological inhibition of urate reabsorption (reducing serum urate by blocking URAT1; drug binding interferes with urate or counteranion binding in the transport cycle)