{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC36A1, also known as hPAT1, is a proton‐coupled amino acid transporter primarily expressed at the apical membrane of intestinal epithelial cells where it facilitates the uptake of small neutral amino acids. It mediates transport by harnessing the inwardly directed H⁺ gradient, functioning in a Na⁺‐independent manner to carry substrates such as α‐aminoisobutyric acid (AIB), glycine, L‐alanine, β‐alanine, and taurine. In addition, hPAT1 appears to contribute to the imino acid transport process through a functional interplay with the Na⁺/H⁺ exchanger NHE3 and has been implicated in the uptake of certain guanidine derivatives (e.g. beta‐guanidinopropionic acid), potentially influencing oral drug absorption. Furthermore, selected dipeptides can inhibit hPAT1 transport function in vitro, underscoring its role in nutrient–drug interactions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role at the plasma membrane, hPAT1 is also localized to intracellular compartments—particularly late endosomes—where it plays an important part in modulating mTORC1 signaling in response to extracellular amino acids. hPAT1 physically interacts with components such as Rag GTPases and is required for proper amino acid–dependent mTORC1 activation and subcellular mTOR relocalization, positioning it as a key intracellular amino acid sensor that contributes to cell growth regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDetailed structural and biochemical analyses of hPAT1 reveal that specific amino acid residues and post‐translational modifications are critical for its function. For instance, the conserved His‐55 residue is essential for H⁺ binding and the catalytic activity of the transporter. Moreover, N‐linked glycosylation at specific asparagine sites, while not strictly required for substrate translocation, is important for proper membrane targeting. In addition, the formation of an intramolecular disulfide bridge between extracellular cysteines (notably between Cys‑180 and Cys‑329) is necessary for maintaining the substrate binding site configuration, thereby ensuring efficient transport."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhong Chen, You-Jun Fei, Catriona M H Anderson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure, function and immunolocalization of a proton-coupled amino acid transporter (hPAT1) in the human intestinal cell line Caco-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/jphysiol.2002.026500"}], "href": "https://doi.org/10.1113/jphysiol.2002.026500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12527723"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12527723"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Catriona M H Anderson, Danielle S Grenade, Michael Boll, et al. "}, {"type": "b", "children": [{"type": "t", "text": "H+/amino acid transporter 1 (PAT1) is the imino acid carrier: An intestinal nutrient/drug transporter in human and rat."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2004.08.017"}], "href": "https://doi.org/10.1053/j.gastro.2004.08.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15521011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15521011"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Catriona M H Anderson, David T Thwaites "}, {"type": "b", "children": [{"type": "t", "text": "Indirect regulation of the intestinal H+-coupled amino acid transporter hPAT1 (SLC36A1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.20337"}], "href": "https://doi.org/10.1002/jcp.20337"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15754324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15754324"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Catriona M H Anderson, Alison Howard, Julian R F Walters, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Taurine uptake across the human intestinal brush-border membrane is via two transporters: H+-coupled PAT1 (SLC36A1) and Na+- and Cl(-)-dependent TauT (SLC6A6)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/jphysiol.2008.164228"}], "href": "https://doi.org/10.1113/jphysiol.2008.164228"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19074966"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19074966"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Linda Metzner, Madlen Dorn, Fritz Markwardt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The orally active antihyperglycemic drug beta-guanidinopropionic acid is transported by the human proton-coupled amino acid transporter hPAT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharm (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/mp9000684"}], "href": "https://doi.org/10.1021/mp9000684"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19358571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19358571"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sidsel Frølund, Louise Langthaler, Morten A Kall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intestinal drug transport via the proton-coupled amino acid transporter PAT1 (SLC36A1) is inhibited by Gly-X(aa) dipeptides."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharm (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/mp300345e"}], "href": "https://doi.org/10.1021/mp300345e"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22853447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22853447"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "S Heublein, S Kazi, M H Ogmundsdóttir, et al. 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