Members of the SLC36 family of proton-coupled amino acid transporters are involved in membrane transport of amino acids and derivatives. 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 [3]. In lysosomes, PAT1 functions as an efflux mechanism for amino acids produced during intralysosomal proteolysis [2,17]. PAT2 is expressed at the apical membrane of the renal proximal tubule [6] and at the plasma-membrane in brown/beige adipocytes [19]. PAT1 and PAT4 are involved in regulation of the mTORC1 pathway [10]. More comprehensive lists of substrates can be found within the reviews under Further Reading and in the references [3].

* Key recommended reading is highlighted with an asterisk

Anderson CM, Thwaites DT. (2010) Hijacking solute carriers for proton-coupled drug transport. Physiology (Bethesda), 25 (6): 364-77. [PMID:21186281]

Bermingham JR, Pennington J. (2004) Organization and expression of the SLC36 cluster of amino acid transporter genes. Mamm Genome, 15 (2): 114-25. [PMID:15058382]

Boll M, Daniel H, Gasnier B. (2004) The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis. Pflugers Arch, 447 (5): 776-9. [PMID:12748860]

Bröer S. (2008) Amino acid transport across mammalian intestinal and renal epithelia. Physiol Rev, 88 (1): 249-86. [PMID:18195088]

Bröer S. (2008) Apical transporters for neutral amino acids: physiology and pathophysiology. Physiology (Bethesda), 23: 95-103. [PMID:18400692]

* Schiöth HB, Roshanbin S, Hägglund MG, Fredriksson R. (2013) Evolutionary origin of amino acid transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects. Mol Aspects Med, 34 (2-3): 571-85. [PMID:23506890]

* Thwaites DT, Anderson CM. (2007) Deciphering the mechanisms of intestinal imino (and amino) acid transport: the redemption of SLC36A1. Biochim Biophys Acta, 1768 (2): 179-97. [PMID:17123464]

Thwaites DT, Anderson CM. (2007) H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine. Exp Physiol, 92 (4): 603-19. [PMID:17468205]

* Thwaites DT, Anderson CM. (2011) The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport. Br J Pharmacol, 164 (7): 1802-16. [PMID:21501141]

1. Abbot EL, Grenade DS, Kennedy DJ, Gatfield KM, Thwaites DT. (2006) Vigabatrin transport across the human intestinal epithelial (Caco-2) brush-border membrane is via the H+ -coupled amino-acid transporter hPAT1. Br J Pharmacol, 147 (3): 298-306. [PMID:16331283]

2. Agulhon C, Rostaing P, Ravassard P, Sagné C, Triller A, Giros B. (2003) Lysosomal amino acid transporter LYAAT-1 in the rat central nervous system: an in situ hybridization and immunohistochemical study. J Comp Neurol, 462 (1): 71-89. [PMID:12761825]

3. Alexander SPH, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL et al.. (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters. Br J Pharmacol, 176 Suppl 1: S397-S493. [PMID:31710713]

4. Anderson CM, Grenade DS, Boll M, Foltz M, Wake KA, Kennedy DJ, Munck LK, Miyauchi S, Taylor PM, Campbell FC et al.. (2004) H+/amino acid transporter 1 (PAT1) is the imino acid carrier: An intestinal nutrient/drug transporter in human and rat. Gastroenterology, 127 (5): 1410-22. [PMID:15521011]

5. Anderson CM, Thwaites DT. (2005) Indirect regulation of the intestinal H+-coupled amino acid transporter hPAT1 (SLC36A1). J Cell Physiol, 204 (2): 604-13. [PMID:15754324]

6. Bröer S, Bailey CG, Kowalczuk S, Ng C, Vanslambrouck JM, Rodgers H, Auray-Blais C, Cavanaugh JA, Bröer A, Rasko JE. (2008) Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters. J Clin Invest, 118 (12): 3881-92. [PMID:19033659]

7. Chen Z, Kennedy DJ, Wake KA, Zhuang L, Ganapathy V, Thwaites DT. (2003) Structure, tissue expression pattern, and function of the amino acid transporter rat PAT2. Biochem Biophys Res Commun, 304 (4): 747-54. [PMID:12727219]

8. Edwards N, Anderson CM, Gatfield KM, Jevons MP, Ganapathy V, Thwaites DT. (2011) Amino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2). Biochim Biophys Acta, 1808 (1): 260-70. [PMID:20691150]

9. Edwards N, Anderson CMH, Conlon NJ, Watson AK, Hall RJ, Cheek TR, Embley TM, Thwaites DT. (2018) Resculpting the binding pocket of APC superfamily LeuT-fold amino acid transporters. Cell Mol Life Sci, 75 (5): 921-938. [PMID:29058016]

10. Fan SJ, Goberdhan DCI. (2018) PATs and SNATs: Amino Acid Sensors in Disguise. Front Pharmacol, 9: 640. [PMID:29971004]

11. Fan SJ, Snell C, Turley H, Li JL, McCormick R, Perera SM, Heublein S, Kazi S, Azad A, Wilson C et al.. (2016) PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer. Oncogene, 35 (23): 3004-15. [PMID:26434594]

12. Foltz M, Boll M, Raschka L, Kottra G, Daniel H. (2004) A novel bifunctionality: PAT1 and PAT2 mediate electrogenic proton/amino acid and electroneutral proton/fatty acid symport. FASEB J, 18 (14): 1758-60. [PMID:15345686]

13. Kennedy DJ, Gatfield KM, Winpenny JP, Ganapathy V, Thwaites DT. (2005) Substrate specificity and functional characterisation of the H+/amino acid transporter rat PAT2 (Slc36a2). Br J Pharmacol, 144 (1): 28-41. [PMID:15644866]

14. Larsen M, Holm R, Jensen KG, Brodin B, Nielsen CU. (2009) Intestinal gaboxadol absorption via PAT1 (SLC36A1): modified absorption in vivo following co-administration of L-tryptophan. Br J Pharmacol, 157 (8): 1380-9. [PMID:19594759]

15. Metzner L, Kottra G, Neubert K, Daniel H, Brandsch M. (2005) Serotonin, L-tryptophan, and tryptamine are effective inhibitors of the amino acid transport system PAT1. FASEB J, 19 (11): 1468-73. [PMID:16126914]

16. Pillai SM, Meredith D. (2011) SLC36A4 (hPAT4) is a high affinity amino acid transporter when expressed in Xenopus laevis oocytes. J Biol Chem, 286 (4): 2455-60. [PMID:21097500]

17. Sagné C, Agulhon C, Ravassard P, Darmon M, Hamon M, El Mestikawy S, Gasnier B, Giros B. (2001) Identification and characterization of a lysosomal transporter for small neutral amino acids. Proc Natl Acad Sci USA, 98 (13): 7206-11. [PMID:11390972]

18. Thwaites DT, Anderson CM. (2011) The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport. Br J Pharmacol, 164 (7): 1802-16. [PMID:21501141]

19. Ussar S, Lee KY, Dankel SN, Boucher J, Haering MF, Kleinridders A, Thomou T, Xue R, Macotela Y, Cypess AM et al.. (2014) ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes. Sci Transl Med, 6 (247): 247ra103. [PMID:25080478]

Subcommittee members: David T. Thwaites (Chairperson) Newcastle University Biosciences Institute Faculty of Medical Sciences Framlington Place Newcastle University Newcastle upon Tyne, NE2 4HH UK Catriona M.H. Anderson Newcastle University Biosciences Institute Faculty of Medical Sciences Framlington Place Newcastle University Newcastle upon Tyne, NE2 4HH UK