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Identification
HMDB Protein ID HMDBP03158
Secondary Accession Numbers
  • 8711
Name Large neutral amino acids transporter small subunit 1
Synonyms
  1. 4F2 LC
  2. 4F2 light chain
  3. 4F2LC
  4. CD98 light chain
  5. Integral membrane protein E16
  6. L-type amino acid transporter 1
  7. Solute carrier family 7 member 5
  8. hLAT1
  9. y+ system cationic amino acid transporter
Gene Name SLC7A5
Protein Type Unknown
Biological Properties
General Function Involved in transport
Specific Function Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Involved in cellular amino acid uptake. Acts as an amino acid exchanger. Involved in the transport of L-DOPA across the blood- brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Plays a role in neuronal cell proliferation (neurogenesis) in brain. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L- nitrosocysteine (L-CNSO) across the transmembrane. May play an important role in high-grade gliomas. Mediates blood-to-retina L- leucine transport across the inner blood-retinal barrier which in turn may play a key role in maintaining large neutral amino acids as well as neurotransmitters in the neural retina. Acts as the major transporter of tyrosine in fibroblasts
Pathways
  • Amiloride Action Pathway
  • Bendroflumethiazide Action Pathway
  • Blue diaper syndrome
  • Bumetanide Action Pathway
  • Chlorothiazide Action Pathway
  • Chlorthalidone Action Pathway
  • Cyclothiazide Action Pathway
  • Cystinuria
  • Eplerenone Action Pathway
  • Ethacrynic Acid Action Pathway
  • Furosemide Action Pathway
  • Glucose Transporter Defect (SGLT2)
  • Hartnup Disorder
  • Hydrochlorothiazide Action Pathway
  • Hydroflumethiazide Action Pathway
  • Iminoglycinuria
  • Indapamide Action Pathway
  • Kidney Function
  • Leucine Stimulation on Insulin Signaling
  • Lysinuric Protein Intolerance
  • Lysinuric protein intolerance (LPI)
  • Methyclothiazide Action Pathway
  • Metolazone Action Pathway
  • Polythiazide Action Pathway
  • Quinethazone Action Pathway
  • Spironolactone Action Pathway
  • Torsemide Action Pathway
  • Triamterene Action Pathway
  • Trichlormethiazide Action Pathway
Reactions Not Available
GO Classification
Component
membrane
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
active transmembrane transporter activity
transmembrane transporter activity
amine transmembrane transporter activity
amino acid transmembrane transporter activity
transporter activity
Process
establishment of localization
transport
amine transport
amino acid transport
transmembrane transport
Cellular Location
  1. Cytoplasm
  2. Multi-pass membrane protein
  3. Apical cell membrane
  4. cytosol
Gene Properties
Chromosome Location Chromosome:1
Locus 16q24.3
SNPs SLC7A5
Gene Sequence
>1524 bp
ATGGCGGGTGCGGGCCCGAAGCGGCGGGCGCTAGCGGCCCCGGTGGCCGAGGAGAAGGAA
GAGGCGCGGGAGAAGATGCTGGCCTCCAAGCGCGCGGACGGCGCGGCGCCGGCAGGCGAG
GGCGAGGGCGTGACCCTGCAGCGGAACATCACGCTACTCAACGGCGTGGCCATCATCGTG
GGCGCCATCATCGGCTCGGGCATCTTCGTGACGCCCACGGGCGTGCTTAAGGAGGCAGGC
TCGCCGGGGCTGGCGCTGGTGATGTGGGCCGCGTGCGGCGTCTTCTCCATCGTGGGCGCG
CTCTGCTACGCGGAGCTCGGCACCACCATCTCCAAATCGGGCGGCGACTACGCCTACATG
CTGGAGGTCTACGGCTCGCTGCCCGCCTTCCTCAAGCTCTGGATCGAGCTGCTCATCATC
CGGCCTTCATCGCAGTACATCGTGGCCCTGGTCTTCGCCGCCTACCTGCTCAAGCCGCTC
TTCCCCACCTGCCCGGTGCCCGAGGAGGCAGCCAAGCTCGTGGCCTGCCTCTGCGTGCTG
CTGCTCACGGCCGTGAACTGCTACAGCGTGAAGGCCGCCACCCGGGTCCAGGATGCCTTT
GCCGCCGCCAAGCTCCTGGCCCTGGCCCTGATCATCCTGCTGGGCTTCGTCCAGATCGGG
AAGGGTGATGTGTCCAATCTAGATCCCAACTTCTCATTTGAAGGCACCAAACTGGATGTG
GGGAACATTGTGCTGGCATTATACAGCGGCCTCTTTGCCTATGGAGGATGGAATTACTTG
AATTTCGTCACAGAGGAAATGATCAACCCCTACAGAAACCTGCCCCTGGCCATCATCATC
TCCCTGCCCATCGTGACGCTGGTGTACGTGCTGACCAACCTGGCCTACTTCACCACCCTG
TCCACCGAGCAGATGCTGTCGTCCGAGGCCGTGGCCGTGGACTTCGGGAACTATCACCTG
GGCGTCATGTCCTGGATCATCCCCGTCTTCGTGGGCCTGTCCTGCTTCGGCTCCGTCAAT
GGGTCCCTGTTCACATCCTCCAGGCTCTTCTTCGTGGGGTCCCGGGAAGGCCACCTGCCC
TCCATCCTCTCCATGATCCACCCACAGCTCCTCACCCCCGTGCCGTCCCTCGTGTTCACG
TGTGTGATGACGCTGCTCTACGCCTTCTCCAAGGACATCTTCTCCGTCATCAACTTCTTC
AGCTTCTTCAACTGGCTCTGCGTGGCCCTGGCCATCATCGGCATGATCTGGCTGCGCCAC
AGAAAGCCTGAGCTTGAGCGGCCCATCAAGGTGAACCTGGCCCTGCCTGTGTTCTTCATC
CTGGCCTGCCTCTTCCTGATCGCCGTCTCCTTCTGGAAGACACCCGTGGAGTGTGGCATC
GGCTTCACCATCATCCTCAGCGGGCTGCCCGTCTACTTCTTCGGGGTCTGGTGGAAAAAC
AAGCCCAAGTGGCTCCTCCAGGGCATCTTCTCCACGACCGTCCTGTGTCAGAAGCTCATG
CAGGTGGTCCCCCAGGAGACATAG
Protein Properties
Number of Residues 507
Molecular Weight 55009.6
Theoretical pI 7.79
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 50-70
  • 84-104
  • 120-140
  • 146-166
  • 170-190
  • 199-219
  • 243-263
  • 274-294
  • 319-339
  • 396-416
  • 431-451
  • 458-478
Protein Sequence
>Large neutral amino acids transporter small subunit 1
MAGAGPKRRALAAPAAEEKEEAREKMLAAKSADGSAPAGEGEGVTLQRNITLLNGVAIIV
GTIIGSGIFVTPTGVLKEAGSPGLALVVWAACGVFSIVGALCYAELGTTISKSGGDYAYM
LEVYGSLPAFLKLWIELLIIRPSSQYIVALVFATYLLKPLFPTCPVPEEAAKLVACLCVL
LLTAVNCYSVKAATRVQDAFAAAKLLALALIILLGFVQIGKGDVSNLDPNFSFEGTKLDV
GNIVLALYSGLFAYGGWNYLNFVTEEMINPYRNLPLAIIISLPIVTLVYVLTNLAYFTTL
STEQMLSSEAVAVDFGNYHLGVMSWIIPVFVGLSCFGSVNGSLFTSSRLFFVGSREGHLP
SILSMIHPQLLTPVPSLVFTCVMTLLYAFSKDIFSVINFFSFFNWLCVALAIIGMIWLRH
RKPELERPIKVNLALPVFFILACLFLIAVSFWKTPVECGIGFTIILSGLPVYFFGVWWKN
KPKWLLQGIFSTTVLCQKLMQVVPQET
GenBank ID Protein 4519803
UniProtKB/Swiss-Prot ID Q01650
UniProtKB/Swiss-Prot Entry Name LAT1_HUMAN
PDB IDs Not Available
GenBank Gene ID AB017908
GeneCard ID SLC7A5
GenAtlas ID SLC7A5
HGNC ID HGNC:11063
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  3. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP: Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5. Epub 2004 Aug 9. [PubMed:15302935 ]
  4. Meierhofer D, Wang X, Huang L, Kaiser P: Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry. J Proteome Res. 2008 Oct;7(10):4566-76. doi: 10.1021/pr800468j. Epub 2008 Sep 10. [PubMed:18781797 ]
  5. Gevaert K, Staes A, Van Damme J, De Groot S, Hugelier K, Demol H, Martens L, Goethals M, Vandekerckhove J: Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC. Proteomics. 2005 Sep;5(14):3589-99. [PubMed:16097034 ]
  6. Pineda M, Fernandez E, Torrents D, Estevez R, Lopez C, Camps M, Lloberas J, Zorzano A, Palacin M: Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids. J Biol Chem. 1999 Jul 9;274(28):19738-44. [PubMed:10391915 ]
  7. Rossier G, Meier C, Bauch C, Summa V, Sordat B, Verrey F, Kuhn LC: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine. J Biol Chem. 1999 Dec 3;274(49):34948-54. [PubMed:10574970 ]
  8. Broer A, Friedrich B, Wagner CA, Fillon S, Ganapathy V, Lang F, Broer S: Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains. Biochem J. 2001 May 1;355(Pt 3):725-31. [PubMed:11311135 ]
  9. Simmons-Willis TA, Koh AS, Clarkson TW, Ballatori N: Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2. Biochem J. 2002 Oct 1;367(Pt 1):239-46. [PubMed:12117417 ]
  10. Fraga S, Pinho MJ, Soares-da-Silva P: Expression of LAT1 and LAT2 amino acid transporters in human and rat intestinal epithelial cells. Amino Acids. 2005 Nov;29(3):229-33. Epub 2005 Jul 20. [PubMed:16027961 ]
  11. Li S, Whorton AR: Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols. J Biol Chem. 2005 May 20;280(20):20102-10. Epub 2005 Mar 15. [PubMed:15769744 ]
  12. Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T, Cha SH, Matsuo H, Fukushima J, Fukasawa Y, Tani Y, Taketani Y, Uchino H, Kim JY, Inatomi J, Okayasu I, Miyamoto K, Takeda E, Goya T, Endou H: Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001 Oct 1;1514(2):291-302. [PubMed:11557028 ]
  13. Mastroberardino L, Spindler B, Pfeiffer R, Skelly PJ, Loffing J, Shoemaker CB, Verrey F: Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family. Nature. 1998 Sep 17;395(6699):288-91. [PubMed:9751058 ]
  14. Ritchie JW, Taylor PM: Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta. Biochem J. 2001 Jun 15;356(Pt 3):719-25. [PubMed:11389679 ]
  15. Friesema EC, Docter R, Moerings EP, Verrey F, Krenning EP, Hennemann G, Visser TJ: Thyroid hormone transport by the heterodimeric human system L amino acid transporter. Endocrinology. 2001 Oct;142(10):4339-48. [PubMed:11564694 ]
  16. Okamoto Y, Sakata M, Ogura K, Yamamoto T, Yamaguchi M, Tasaka K, Kurachi H, Tsurudome M, Murata Y: Expression and regulation of 4F2hc and hLAT1 in human trophoblasts. Am J Physiol Cell Physiol. 2002 Jan;282(1):C196-204. [PubMed:11742812 ]
  17. Kim DK, Kanai Y, Choi HW, Tangtrongsup S, Chairoungdua A, Babu E, Tachampa K, Anzai N, Iribe Y, Endou H: Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells. Biochim Biophys Acta. 2002 Sep 20;1565(1):112-21. [PubMed:12225859 ]
  18. Nawashiro H, Otani N, Shinomiya N, Fukui S, Ooigawa H, Shima K, Matsuo H, Kanai Y, Endou H: L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. Int J Cancer. 2006 Aug 1;119(3):484-92. [PubMed:16496379 ]
  19. Prasad PD, Wang H, Huang W, Kekuda R, Rajan DP, Leibach FH, Ganapathy V: Human LAT1, a subunit of system L amino acid transporter: molecular cloning and transport function. Biochem Biophys Res Commun. 1999 Feb 16;255(2):283-8. [PubMed:10049700 ]
  20. Tsurudome M, Ito M, Takebayashi S, Okumura K, Nishio M, Kawano M, Kusagawa S, Komada H, Ito Y: Cutting edge: primary structure of the light chain of fusion regulatory protein-1/CD98/4F2 predicts a protein with multiple transmembrane domains that is almost identical to the amino acid transporter E16. J Immunol. 1999 Mar 1;162(5):2462-6. [PubMed:10072483 ]
  21. Gaugitsch HW, Prieschl EE, Kalthoff F, Huber NE, Baumruker T: A novel transiently expressed, integral membrane protein linked to cell activation. Molecular cloning via the rapid degradation signal AUUUA. J Biol Chem. 1992 Jun 5;267(16):11267-73. [PubMed:1597461 ]
  22. Jain-Vakkalagadda B, Dey S, Pal D, Mitra AK: Identification and functional characterization of a Na+-independent large neutral amino acid transporter, LAT1, in human and rabbit cornea. Invest Ophthalmol Vis Sci. 2003 Jul;44(7):2919-27. [PubMed:12824232 ]
  23. Vumma R, Wiesel FA, Flyckt L, Bjerkenstedt L, Venizelos N: Functional characterization of tyrosine transport in fibroblast cells from healthy controls. Neurosci Lett. 2008 Mar 21;434(1):56-60. doi: 10.1016/j.neulet.2008.01.028. Epub 2008 Jan 17. [PubMed:18262359 ]