L-type amino acid transporter 1
Target has curated data in GtoImmuPdb
Target id: 896
Nomenclature: L-type amino acid transporter 1
Abbreviated Name: LAT1
Systematic Nomenclature: SLC7A5
Family: SLC7 family
Contents:
Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 12 | 507 | 16q24.2 | SLC7A5 | solute carrier family 7 member 5 | |
| Mouse | 12 | 512 | 8 | Slc7a5 | solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 | |
| Rat | 12 | 512 | 19q12 | Slc7a5 | solute carrier family 7 member 5 | |
| Previous and Unofficial Names |
| 4F2 light chain | 4F2LC | integral membrane protein E16 | Large neutral amino acids transporter small subunit 1 | CD98 | MPE16 | solute carrier family 7 (amino acid transporter light chain, L system), member 5 | TA1 | solute carrier family 7 member 5 | tumor-associated protein 1 | solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 | solute carrier family 7 (cationic amino acid transporter |
| Database Links |
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| Specialist databases | |
| Bioparadigms SLC Tables | SLC7A5 (Hs) |
| RESOLUTE | SLC7A5 (Hs) |
| Other databases | |
| Alphafold | Q01650 (Hs), Q9Z127 (Mm), Q63016 (Rn) |
| ChEMBL Target | CHEMBL4459 (Hs), CHEMBL4523516 (Mm), CHEMBL4149 (Rn) |
| Ensembl Gene | ENSG00000103257 (Hs), ENSMUSG00000040010 (Mm), ENSRNOG00000018824 (Rn) |
| Entrez Gene | 8140 (Hs), 20539 (Mm), 50719 (Rn) |
| Human Protein Atlas | ENSG00000103257 (Hs) |
| KEGG Gene | hsa:8140 (Hs), mmu:20539 (Mm), rno:50719 (Rn) |
| OMIM | 600182 (Hs) |
| Pharos | Q01650 (Hs) |
| UniProtKB | Q01650 (Hs), Q9Z127 (Mm), Q63016 (Rn) |
| Wikipedia | SLC7A5 (Hs) |
| Selected 3D Structures |
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Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Immunopharmacology Comments |
| LAT1 has been identified as being a key transporter of the essential amino acids [3] that are required to support the nutritional demands of activated human T cells when mounting an immune response, and LAT1 expression is upregulated to meet this demand [2,13,18]. These findings suggest LAT1 as a novel target for the development of drugs with immuno-suppressive potential. |
| General Comments |
| LAT1 is a key transporter of essential amino acids [3]. LAT1 is used by many types of cancer cells to meet their high nutritional requirements [4,11]. Consequently, LAT1 inhbitors that would functionally starve cancers of essential nutrients, are being designed as potential anti-cancer therapeutics [1,5,7-9,12], and as adjuncts which enhance the efficacy of conventional chemotherapeutics [19]. LAT1 expression on cancer cells is also being used to target anti-cancer drugs to tumours using so-called 'LAT1-utilizing prodrugs' [6,16], and of particular clinical interest is the ability of some of these prodrugs to cross the blood-brain-barrier and the benefit this could bring to the treatment of brain tumours [15,17]. |
References
1. Hayashi K, Anzai N. (2017) Novel therapeutic approaches targeting L-type amino acid transporters for cancer treatment. World J Gastrointest Oncol, 9 (1): 21-29. [PMID:28144396]
2. Hayashi K, Jutabha P, Endou H, Sagara H, Anzai N. (2013) LAT1 is a critical transporter of essential amino acids for immune reactions in activated human T cells. J Immunol, 191 (8): 4080-5. [PMID:24038088]
3. Hayashi K, Jutabha P, Kamai T, Endou H, Anzai N. (2014) LAT1 is a central transporter of essential amino acids in human umbilical vein endothelial cells. J Pharmacol Sci, 124 (4): 511-3. [PMID:24671056]
4. Hayashi K, Jutabha P, Maeda S, Supak Y, Ouchi M, Endou H, Fujita T, Chida M, Anzai N. (2016) LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells. J Pharmacol Sci, 132 (3): 201-204. [PMID:27567475]
5. Huttunen KM, Gynther M, Huttunen J, Puris E, Spicer JA, Denny WA. (2016) A Selective and Slowly Reversible Inhibitor of l-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells. J Med Chem, 59 (12): 5740-51. [PMID:27253989]
6. Huttunen KM, Huttunen J, Aufderhaar I, Gynther M, Denny WA, Spicer JA. (2016) L-Type amino acid transporter 1 (lat1)-mediated targeted delivery of perforin inhibitors. Int J Pharm, 498 (1-2): 205-16. [PMID:26705152]
7. Imai H, Kaira K, Oriuchi N, Shimizu K, Tominaga H, Yanagitani N, Sunaga N, Ishizuka T, Nagamori S, Promchan K et al.. (2010) Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer. Anticancer Res, 30 (12): 4819-28. [PMID:21187458]
8. Kanai Y. (2022) Amino acid transporter LAT1 (SLC7A5) as a molecular target for cancer diagnosis and therapeutics. Pharmacol Ther, 230: 107964. [PMID:34390745]
9. Kongpracha P, Nagamori S, Wiriyasermkul P, Tanaka Y, Kaneda K, Okuda S, Ohgaki R, Kanai Y. (2017) Structure-activity relationship of a novel series of inhibitors for cancer type transporter L-type amino acid transporter 1 (LAT1). J Pharmacol Sci, 133 (2): 96-102. [PMID:28242177]
10. Lee Y, Wiriyasermkul P, Jin C, Quan L, Ohgaki R, Okuda S, Kusakizako T, Nishizawa T, Oda K, Ishitani R et al.. (2019) Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc. Nat Struct Mol Biol, 26 (6): 510-517. [PMID:31160781]
11. Marshall AD, van Geldermalsen M, Otte NJ, Anderson LA, Lum T, Vellozzi MA, Zhang BK, Thoeng A, Wang Q, Rasko JE et al.. (2016) LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma. Int J Cancer, 139 (11): 2529-39. [PMID:27486861]
12. Napolitano L, Scalise M, Koyioni M, Koutentis P, Catto M, Eberini I, Parravicini C, Palazzolo L, Pisani L, Galluccio M et al.. (2017) Potent inhibitors of human LAT1 (SLC7A5) transporter based on dithiazole and dithiazine compounds for development of anticancer drugs. Biochem Pharmacol, 143: 39-52. [PMID:28709952]
13. Nii T, Segawa H, Taketani Y, Tani Y, Ohkido M, Kishida S, Ito M, Endou H, Kanai Y, Takeda E et al.. (2001) Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation. Biochem J, 358 (Pt 3): 693-704. [PMID:11535130]
14. Oda K, Hosoda N, Endo H, Saito K, Tsujihara K, Yamamura M, Sakata T, Anzai N, Wempe MF, Kanai Y et al.. (2010) L-type amino acid transporter 1 inhibitors inhibit tumor cell growth. Cancer Sci, 101 (1): 173-9. [PMID:19900191]
15. Papin-Michault C, Bonnetaud C, Dufour M, Almairac F, Coutts M, Patouraux S, Virolle T, Darcourt J, Burel-Vandenbos F. (2016) Study of LAT1 Expression in Brain Metastases: Towards a Better Understanding of the Results of Positron Emission Tomography Using Amino Acid Tracers. PLoS ONE, 11 (6): e0157139. [PMID:27276226]
16. Park K. (2017) Insight into brain-targeted drug delivery via LAT1-utilizing prodrugs. J Control Release, 261: 368. [PMID:28780138]
17. Puris E, Gynther M, Huttunen J, Petsalo A, Huttunen KM. (2017) L-type amino acid transporter 1 utilizing prodrugs: How to achieve effective brain delivery and low systemic exposure of drugs. J Control Release, 261: 93-104. [PMID:28662899]
18. Ren W, Liu G, Yin J, Tan B, Wu G, Bazer FW, Peng Y, Yin Y. (2017) Amino-acid transporters in T-cell activation and differentiation. Cell Death Dis, 8 (3): e2655. [PMID:28252650]
19. Yamauchi K, Sakurai H, Kimura T, Wiriyasermkul P, Nagamori S, Kanai Y, Kohno N. (2009) System L amino acid transporter inhibitor enhances anti-tumor activity of cisplatin in a head and neck squamous cell carcinoma cell line. Cancer Lett, 276 (1): 95-101. [PMID:19058911]
20. Yan R, Zhao X, Lei J, Zhou Q. (2019) Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex. Nature, 568 (7750): 127-130. [PMID:30867591]
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