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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Members of the SLC36 family of proton-coupled amino acid transporters are involved in membrane transport of amino acids and derivatives [28-29]. The four transporters show variable tissue expression patterns and are expressed in various cell types at the plasma-membrane and in intracellular organelles. PAT1 is expressed at the luminal surface of the small intestine and absorbs amino acids and derivatives [4]. In lysosomes, PAT1 functions as an efflux mechanism for amino acids produced during intralysosomal proteolysis [2,25]. PAT2 is expressed at the apical membrane of the renal proximal tubule [7] and at the plasma-membrane in brown/beige adipocytes [30]. PAT1 and PAT4 are involved in regulation of the mTORC1 pathway [11,27]. More comprehensive lists of substrates can be found within the reviews under Further Reading and in the references [3].
PAT1 (Proton-coupled Amino acid Transporter 1 / SLC36A1) C Show summary »
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PAT2 (Proton-coupled Amino acid Transporter 2 / SLC36A2) C Show summary » |
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PAT3 (Proton-coupled Amino acid Transporter 3 / SLC36A3) C Show summary » |
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PAT4 (Proton-coupled Amino acid Transporter 4 / SLC36A4) C Show summary » |
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Transporters. Br J Pharmacol. 180 Suppl 2:S374-469.
The SLC36 transporters are part of the Amino Acid Auxin Permease (AAAP) family within the Amino Acid-Polyamine-Organocation (APC) superfamily [26,31]. In neuronal tissues, PAT1 is found predominantly in lysosomal membranes and to a lesser extent on neuronal plasma membranes [2,25,33]. PAT1 acts as a driver of mTORC1 signalling, contributing CDK4/6 inhibitor resistance in melanoma [34]. PAT2 is found in myelinated fibres and in the endoplasmic reticulum in spinal cord and brain [6,24]. In brown adipocytes, PAT2 acts as an extracellular amino acid sensor and regulates lysosomal acidification [32]. PAT4 is found in lysosomes in neurones and the plasma membrane of epithelial cells lining the lateral ventricles [23]. High PAT4 expression is associated with reduced relapse-free survival after colorectal cancer surgery [12]. Inhibition of SLC36 transporters by indole-3-propionic acid suppresses proline-dependent tumour growth in Drosophila melanogaster [20]. In C. elegans, a SLC36 transporter is involved in lysosome reformation pathways [13,15].