Proton-coupled amino acid transporter (PAT)

The proton-coupled amino acid transporter (PAT) family, primarily comprising SLC36A1 (PAT1) and SLC36A2 (PAT2), mediates the symport of small zwitterionic amino acids and various pharmacological agents across cellular membranes using a proton gradient (Thwaites & Anderson, 2011). PAT1 is predominantly expressed on the luminal surface of the small intestine and in lysosomal membranes, where it facilitates the absorption of nutrients and drugs like vigabatrin and gaboxadol, as well as the efflux of amino acids from lysosomes to the cytoplasm (Chen et al., 2003; NIH Gene ID: 206358). In contrast, PAT2 is mainly found in the renal proximal tubule, where it is responsible for the reabsorption of glycine and proline, and in brown adipose tissue, where it acts as a nutrient sensor (Boll et al., 2002; Guide to Pharmacology). Beyond their transport roles, these proteins are integral to the mTORC1 signaling pathway, making them relevant in cancer biology, particularly in developing resistance to CDK4/6 inhibitors (Guide to Pharmacology). Mutations in PAT2 are linked to metabolic conditions such as iminoglycinuria and hyperglycinuria (GeneCards). Due to their broad substrate specificity, PATs are significant targets for optimizing the oral bioavailability of amino acid-based therapeutics and are being explored for their roles in neurological and metabolic diseases (Thwaites & Anderson, 2011).

Other names

SLC36 familySolute carrier family 36PAT1PAT2LYAAT1TRAMD1Proton/amino acid symporter

Substrate-mediated symport of drugs and amino acids with protons (H+) across the plasma or lysosomal membranes; competitive or non-competitive inhibition of transporter activity.