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Identification
HMDB Protein ID HMDBP02392
Secondary Accession Numbers
  • 7884
  • HMDBP03622
Name Large neutral amino acids transporter small subunit 2
Synonyms
  1. L-type amino acid transporter 2
  2. Solute carrier family 7 member 8
  3. hLAT2
Gene Name SLC7A8
Protein Type Transporter
Biological Properties
General Function Involved in transport
Specific Function Sodium-independent, high-affinity transport of small and large neutral amino acids such as alanine, serine, threonine, cysteine, phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Acts as an amino acid exchanger. Has higher affinity for L-phenylalanine than LAT1 but lower affinity for glutamine and serine. L-alanine is transported at physiological concentrations. Plays a role in basolateral (re)absorption of neutral amino acids. 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. Plays an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney
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)
  • Glucose Transporter Defect (SGLT2)
  • Hartnup Disorder
  • Hydrochlorothiazide Action Pathway
  • Hydroflumethiazide Action Pathway
  • Iminoglycinuria
  • Indapamide Action Pathway
  • Kidney Function
  • 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. Basolateral cell membrane
  3. Multi- pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 14q11.2
SNPs SLC7A8
Gene Sequence
>1608 bp
ATGGAAGAAGGAGCCAGGCACCGAAACAACACCGAAAAGAAACACCCAGGTGGGGGCGAG
TCGGACGCCAGCCCCGAGGCTGGTTCCGGAGGGGGCGGAGTAGCCCTGAAGAAAGAGATC
GGATTGGTCAGTGCCTGTGGTATCATCGTAGGGAACATCATCGGCTCTGGAATCTTTGTC
TCGCCAAAGGGAGTGCTGGAGAATGCTGGTTCTGTGGGCCTTGCTCTCATCGTCTGGATT
GTGACGGGCTTCATCACAGTTGTGGGAGCCCTCTGCTATGCTGAACTCGGGGTCACCATC
CCCAAATCTGGAGGTGACTACTCCTATGTCAAGGACATCTTCGGAGGACTGGCTGGGTTC
CTGAGGCTGTGGATTGCTGTGCTGGTGATCTACCCCACCAACCAGGCTGTCATCGCCCTC
ACCTTCTCCAACTACGTGCTGCAGCCGCTCTTCCCCACCTGCTTCCCCCCAGAGTCTGGC
CTTCGGCTCCTGGCTGCCATCTGCTTATTGCTCCTCACATGGGTCAACTGTTCCAGTGTG
CGGTGGGCCACCCGGGTTCAAGACATCTTCACAGCTGGGAAGCTCCTGGCCTTGGCCCTG
ATTATCATCATGGGGATTGTACAGATATGCAAAGGAGAGTACTTCTGGCTGGAGCCAAAG
AATGCATTTGAGAATTTCCAGGAACCTGACATCGGCCTCGTCGCACTGGCTTTCCTTCAG
GGCTCCTTTGCCTATGGAGGCTGGAACTTTCTGAATTACGTGACTGAGGAGCTTGTTGAT
CCCTACAAGAACCTTCCCAGAGCCATCTTCATCTCCATCCCACTGGTCACATTTGTGTAT
GTCTTTGCCAATGTCGCTTATGTCACTGCAATGTCCCCCCAGGAGCTGCTGGCATCCAAC
GCCGTCGCTGTGACTTTTGGAGAGAAGCTCCTAGGAGTCATGGCCTGGATCATGCCCATT
TCTGTTGCCCTGTCCACATTTGGAGGAGTTAATGGGTCTCTCTTCACCTCCTCTCGGCTG
TTCTTCGCTGGAGCCCGAGAGGGCCACCTTCCCAGTGTGTTGGCCATGATCCACGTGAAG
CGCTGCACCCCAATCCCAGCCCTGCTCTTCACATGCATCTCCACCCTGCTGATGCTGGTC
ACCAGCGACATGTACACACTCATCAACTACGTGGGCTTCATCAACTACCTCTTCTATGGG
GTCACGGTTGCTGGACAGATAGTCCTTCGCTGGAAGAAGCCTGATATCCCCCGCCCCATC
AAGATCAACCTGCTGTTCCCCATCATCTACTTGCTGTTCTGGGCCTTCCTGCTGGTCTTC
AGCCTGTGGTCAGAGCCGGTGGTGTGTGGCATTGGCCTGGCCATCATGCTGACAGGAGTG
CCTGTCTATTTCCTGGGTGTTTACTGGCAACACAAGCCCAAGTGTTTCAGTGACTTCATT
GAGCTGCTAACCCTGGTGAGCCAGAAGATGTGTGTGGTCGTGTACCCCGAGGTGGAGCGG
GGCTCAGGGACAGAGGAGGCTAATGAGGACATGGAGGAGCAGCAGCAGCCCATGTACCAA
CCCACTCCCACGAAGGACAAGGACGTGGCGGGGCAGCCCCAGCCCTGA
Protein Properties
Number of Residues 535
Molecular Weight 58381.1
Theoretical pI 5.75
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 40-60
  • 72-92
  • 113-133
  • 155-175
  • 189-209
  • 231-251
  • 268-288
  • 310-330
  • 362-382
  • 388-408
  • 424-444
  • 447-467
Protein Sequence
>Large neutral amino acids transporter small subunit 2
MEEGARHRNNTEKKHPGGGESDASPEAGSGGGGVALKKEIGLVSACGIIVGNIIGSGIFV
SPKGVLENAGSVGLALIVWIVTGFITVVGALCYAELGVTIPKSGGDYSYVKDIFGGLAGF
LRLWIAVLVIYPTNQAVIALTFSNYVLQPLFPTCFPPESGLRLLAAICLLLLTWVNCSSV
RWATRVQDIFTAGKLLALALIIIMGIVQICKGEYFWLEPKNAFENFQEPDIGLVALAFLQ
GSFAYGGWNFLNYVTEELVDPYKNLPRAIFISIPLVTFVYVFANVAYVTAMSPQELLASN
AVAVTFGEKLLGVMAWIMPISVALSTFGGVNGSLFTSSRLFFAGAREGHLPSVLAMIHVK
RCTPIPALLFTCISTLLMLVTSDMYTLINYVGFINYLFYGVTVAGQIVLRWKKPDIPRPI
KINLLFPIIYLLFWAFLLVFSLWSEPVVCGIGLAIMLTGVPVYFLGVYWQHKPKCFSDFI
ELLTLVSQKMCVVVYPEVERGSGTEEANEDMEEQQQPMYQPTPTKDKDVAGQPQP
GenBank ID Protein 12597192
UniProtKB/Swiss-Prot ID Q9UHI5
UniProtKB/Swiss-Prot Entry Name LAT2_HUMAN
PDB IDs Not Available
GenBank Gene ID AB037669
GeneCard ID SLC7A8
GenAtlas ID SLC7A8
HGNC ID HGNC:11066
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Borsani G, Bassi MT, Sperandeo MP, De Grandi A, Buoninconti A, Riboni M, Manzoni M, Incerti B, Pepe A, Andria G, Ballabio A, Sebastio G: SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nat Genet. 1999 Mar;21(3):297-301. [PubMed:10080183 ]
  6. Park SY, Kim JK, Kim IJ, Choi BK, Jung KY, Lee S, Park KJ, Chairoungdua A, Kanai Y, Endou H, Kim DK: Reabsorption of neutral amino acids mediated by amino acid transporter LAT2 and TAT1 in the basolateral membrane of proximal tubule. Arch Pharm Res. 2005 Apr;28(4):421-32. [PubMed:15918515 ]
  7. 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 ]
  8. 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 ]
  9. Liu X, Charrier L, Gewirtz A, Sitaraman S, Merlin D: CD98 and intracellular adhesion molecule I regulate the activity of amino acid transporter LAT-2 in polarized intestinal epithelia. J Biol Chem. 2003 Jun 27;278(26):23672-7. Epub 2003 Apr 25. [PubMed:12716892 ]
  10. Gandhi MD, Pal D, Mitra AK: Identification and functional characterization of a Na(+)-independent large neutral amino acid transporter (LAT2) on ARPE-19 cells. Int J Pharm. 2004 May 4;275(1-2):189-200. [PubMed:15081149 ]
  11. 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 ]
  12. 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 ]