Proton-dependent oligopeptide transporter (POT)

The proton-dependent oligopeptide transporter (often called PEPT1 and PEPT2 in humans) is a membrane transporter belonging to the solute carrier family SLC15, which facilitates the uptake of short peptides (di- and tripeptides) and peptidomimetic drugs across the plasma membranes of various cell types. In mammals, PEPT1 is primarily found in the small intestine, aiding in nutrient absorption, while PEPT2 is predominantly expressed in the kidney, mediating peptide reabsorption[2][4][9]. These transporters are part of the major facilitator superfamily (MFS), operating via proton symport mechanisms and displaying broad substrate specificity[5][7]. The functional importance of oligopeptide transporters extends from nutrient uptake and conservation to serving as gateways for peptide-based drug delivery. Overexpression of PEPT1 is implicated in inflammatory conditions such as IBD, and its pharmacological modulation can enhance the bioavailability of certain drugs or reduce toxicity by blocking uptake of deleterious bacterial peptides[4][6]. The versatility and pathophysiological relevance of these transporters make them key targets for therapeutic intervention, biomarker development, and drug formulation strategies. In bacteria, ABC-type oligopeptide transport systems, although mechanistically distinct, play critical roles in pathogenicity, antibiotic resistance, and metabolic adaptation[1][3].

Other names

Oligopeptide transporterProton-coupled oligopeptide transporterPEPT1 (SLC15A1), PEPT2 (SLC15A2)PHT1 (SLC15A4), PHT2 (SLC15A3)SLC15 familyPTR family (proton-dependent peptide transporter family)

Facilitated uptake (transmembrane symport of drugs and peptides coupled to proton gradient); Drug absorption optimization (targeting intestinal PEPT1 for better bioavailability); Inhibition of transporter (blocking uptake of harmful peptides in IBD); Substrate competition (drugs outcompete endogenous peptides for absorption)