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Gene Review

SLC7A5  -  solute carrier family 7 (amino acid...

Homo sapiens

Synonyms: 4F2 LC, 4F2 light chain, 4F2LC, CD98, CD98 light chain, ...
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Disease relevance of SLC7A5

  • These findings suggest that LAT1 could be one of the molecular targets in glioma therapy [1].
  • Kaplan-Meier analyses demonstrated that high LAT1 expression correlated with poor survival for the study group as a whole (p<0.0001) and for those with glioblastoma multiforme in particular (p=0.0001) [1].
  • Overexpression of LAT1 in T24 cells using recombinant adenoviruses led to increased uptake of L-CSNO, whereas knockdown using a specific small interfering RNA led to decreased uptake [2].
  • The specific inhibition of LAT1 in oral cancer cells could be a new rationale for anti-cancer therapy [3].
  • LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x- C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after, brain ischemia [4].

Psychiatry related information on SLC7A5


High impact information on SLC7A5

  • Pbx1-/- embryos had pancreatic hypoplasia and marked defects in exocrine and endocrine cell differentiation prior to death at embryonic day (E) 15 or E16 [7].
  • The molecular nature of these transporters remains unknown, although expression of the human cell-surface glycoprotein 4F2 heavy chain (h4F2hc; CD98 in the mouse) is known to induce low levels of L- and/or y(+)L-type transport [8].
  • Complementation of dominant suppression implicates CD98 in integrin activation [9].
  • Here we identify a conserved exonic splicing silencer element (CE(16)) in E16 that interacts with hnRNP A/B proteins and plays a role in repression of E16 splicing during early erythropoiesis [10].
  • The LAT1 and NAT1 factors were released from chromatin by extraction with a low-salt buffer and were soluble in 2% trichloroacetic acid, implying a relationship to high-mobility group (HMG) proteins [11].

Chemical compound and disease context of SLC7A5


Biological context of SLC7A5


Anatomical context of SLC7A5

  • Resting monocytes and lymphocytes expressed CD98LC as analyzed by a newly isolated anti-CD98LC mAb, which showed cross-reactivity with insect Sf9 cells as well as with various mammalian cell lines [15].
  • LAT1 also corresponds to TA1, an oncofetal antigen that is expressed primarily in fetal tissues and cancer cells [1].
  • The affinity and the inhibition profiles of [14C]L-leucine uptake by various amino acids in the FOB and Saos2 cells were comparable with those for the LAT2 and LAT1 expressed in Xenopus oocytes, respectively [16].
  • LAT1 is also essential for the permeation of amino acids and amino acid-related drugs through the blood-brain barrier [18].
  • Northern blot, real-time quantitative PCR and immunofluorescence analyses have reveled that T24 cells express LAT1 in the plasma membrane together with its associating protein 4F2hc, whereas T24 cells do not express the other system L isoform LAT2 [18].

Associations of SLC7A5 with chemical compounds

  • In addition, we show that hLAT1 accepts an amino acid-related anti-cancer agent melphalan [19].
  • When loaded intracellularly, L-leucine and L-glutamine but not L-alanine are effluxed by extracellular substrates, confirming that hLAT1 mediates an amino acid exchange. hLAT1 mRNA is highly expressed in the human fetal liver, bone marrow, placenta, testis and brain [19].
  • When expressed in Xenopus oocytes with human 4F2hc (h4F2hc), hLAT1 transports large neutral amino acids with high affinity (K(m)= approximately 15- approximately 50 microM) and L-glutamine and L-asparagine with low affinity (K(m)= approximately 1.5- approximately 2 mM). hLAT1 also transports D-amino acids such as D-leucine and D-phenylalanine [19].
  • We have demonstrated also that LAT1 response to arginine availability is lost in transformed and tumorigenic cells such that expression is constitutively high [20].
  • Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols [2].

Physical interactions of SLC7A5

  • The 4F2hc/LAT1 complex has been suggested to be the most important molecular component responsible for this transport [21].

Other interactions of SLC7A5


Analytical, diagnostic and therapeutic context of SLC7A5

  • In Western blot analysis, hLAT1 and h4F2hc have been confirmed to be linked to each other via a disulfide bond in T24 human bladder carcinoma cells [19].
  • In addition, by Northern-blot analysis, these increments were found to be due to elevated levels of LAT1 and 4F2hc mRNA [25].
  • Human LAT1, a subunit of system L amino acid transporter: molecular cloning and transport function [26].
  • Consistent with this, anti-TA1/E16 antibodies specifically immunoblotted the approximately 35-40-kDa light chain present upon immunoprecipitation of the human CD98 complex [27].
  • LAT1 was identified by RT-PCR in rabbit corneal, SIRC, and human corneal RNA [28].


  1. L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. Nawashiro, H., Otani, N., Shinomiya, N., Fukui, S., Ooigawa, H., Shima, K., Matsuo, H., Kanai, Y., Endou, H. Int. J. Cancer (2006) [Pubmed]
  2. Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols. Li, S., Whorton, A.R. J. Biol. Chem. (2005) [Pubmed]
  3. Amino acid transport system L is differently expressed in human normal oral keratinocytes and human oral cancer cells. Yoon, J.H., Kim, I.J., Kim, H., Kim, H.J., Jeong, M.J., Ahn, S.G., Kim, S.A., Lee, C.H., Choi, B.K., Kim, J.K., Jung, K.Y., Lee, S., Kanai, Y., Endou, H., Kim, d.o. .K. Cancer Lett. (2005) [Pubmed]
  4. Heterodimeric amino acid transporters: molecular biology and pathological and pharmacological relevance. Kanai, Y., Endou, H. Curr. Drug Metab. (2001) [Pubmed]
  5. Cell proliferation in a peripheral target is required for the induction of central neurogenesis in the leech. Becker, T.S., Bothe, G., Harley, A.R., Macagno, E.R. J. Neurobiol. (1998) [Pubmed]
  6. LAT1 gene variants-potential factors influencing the clinical course of phenylketonuria. Bik-Multanowski, M., Pietrzyk, J.J. J. Inherit. Metab. Dis. (2006) [Pubmed]
  7. Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus. Kim, S.K., Selleri, L., Lee, J.S., Zhang, A.Y., Gu, X., Jacobs, Y., Cleary, M.L. Nat. Genet. (2002) [Pubmed]
  8. Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family. Mastroberardino, L., Spindler, B., Pfeiffer, R., Skelly, P.J., Loffing, J., Shoemaker, C.B., Verrey, F. Nature (1998) [Pubmed]
  9. Complementation of dominant suppression implicates CD98 in integrin activation. Fenczik, C.A., Sethi, T., Ramos, J.W., Hughes, P.E., Ginsberg, M.H. Nature (1997) [Pubmed]
  10. Decrease in hnRNP A/B expression during erythropoiesis mediates a pre-mRNA splicing switch. Hou, V.C., Lersch, R., Gee, S.L., Ponthier, J.L., Lo, A.J., Wu, M., Turck, C.W., Koury, M., Krainer, A.R., Mayeda, A., Conboy, J.G. EMBO J. (2002) [Pubmed]
  11. HMG I-like proteins from leaf and nodule nuclei interact with different AT motifs in soybean nodulin promoters. Jacobsen, K., Laursen, N.B., Jensen, E.O., Marcker, A., Poulsen, C., Marcker, K.A. Plant Cell (1990) [Pubmed]
  12. RhoA-GTPase Facilitates Entry of Kaposi's Sarcoma-Associated Herpesvirus into Adherent Target Cells in a Src-Dependent Manner. Veettil, M.V., Sharma-Walia, N., Sadagopan, S., Raghu, H., Sivakumar, R., Naranatt, P.P., Chandran, B. J. Virol. (2006) [Pubmed]
  13. Human LAT1 single nucleotide polymorphism N230K does not alter phenylalanine transport. Boado, R.J., Li, J.Y., Wise, P., Pardridge, W.M. Mol. Genet. Metab. (2004) [Pubmed]
  14. Human immunodeficiency virus type-1 envelope glycoprotein gp120 induces expression of fusion regulatory protein (FRP)-1/CD98 on CD4+ T cells: a possible regulatory mechanism of HIV-induced syncytium formation. Suga, S., Tsurudome, M., Ito, M., Ohgimoto, S., Tabata, N., Nishio, M., Kawano, M., Komada, H., Ito, M., Sakurai, M., Ito, Y. Med. Microbiol. Immunol. (Berl.) (1997) [Pubmed]
  15. 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. Tsurudome, M., Ito, M., Takebayashi, S., Okumura, K., Nishio, M., Kawano, M., Kusagawa, S., Komada, H., Ito, Y. J. Immunol. (1999) [Pubmed]
  16. Differential expression and functional characterization of system L amino acid transporters in human normal osteoblast cells and osteogenic sarcoma cells. Kim, S.G., Kim, H.H., Kim, H.K., Kim, C.H., Chun, H.S., Kanai, Y., Endou, H., Kim, d.o. .K. Anticancer Res. (2006) [Pubmed]
  17. Ornithine transport via cationic amino Acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells. Kaneko, S., Ando, A., Okuda-Ashitaka, E., Maeda, M., Furuta, K., Suzuki, M., Matsumura, M., Ito, S. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  18. Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells. Kim, d.o. .K., Kanai, Y., Choi, H.W., Tangtrongsup, S., Chairoungdua, A., Babu, E., Tachampa, K., Anzai, N., Iribe, Y., Endou, H. Biochim. Biophys. Acta (2002) [Pubmed]
  19. Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Yanagida, O., Kanai, Y., Chairoungdua, A., Kim, D.K., Segawa, H., Nii, T., Cha, S.H., Matsuo, H., Fukushima, J., Fukasawa, Y., Tani, Y., Taketani, Y., Uchino, H., Kim, J.Y., Inatomi, J., Okayasu, I., Miyamoto, K., Takeda, E., Goya, T., Endou, H. Biochim. Biophys. Acta (2001) [Pubmed]
  20. Overexpression of LAT1/CD98 light chain is sufficient to increase system L-amino acid transport activity in mouse hepatocytes but not fibroblasts. Campbell, W.A., Thompson, N.L. J. Biol. Chem. (2001) [Pubmed]
  21. Inter-individual variation in brain phenylalanine concentration in patients with PKU is not caused by genetic variation in the 4F2hc/LAT1 complex. Møller, L.B., Paulsen, M., Koch, R., Moats, R., Guldberg, P., Güttler, F. Mol. Genet. Metab. (2005) [Pubmed]
  22. Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance. Torrents, D., Estévez, R., Pineda, M., Fernández, E., Lloberas, J., Shi, Y.B., Zorzano, A., Palacín, M. J. Biol. Chem. (1998) [Pubmed]
  23. L-type amino acid transporter 1-mediated L-leucine transport at the inner blood-retinal barrier. Tomi, M., Mori, M., Tachikawa, M., Katayama, K., Terasaki, T., Hosoya, K. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  24. Complex regulation of thyroid hormone action: multiple opportunities for pharmacological intervention. Shi, Y.B., Ritchie, J.W., Taylor, P.M. Pharmacol. Ther. (2002) [Pubmed]
  25. Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation. Nii, T., Segawa, H., Taketani, Y., Tani, Y., Ohkido, M., Kishida, S., Ito, M., Endou, H., Kanai, Y., Takeda, E., Miyamoto Ki, n.u.l.l. Biochem. J. (2001) [Pubmed]
  26. Human LAT1, a subunit of system L amino acid transporter: molecular cloning and transport function. Prasad, P.D., Wang, H., Huang, W., Kekuda, R., Rajan, D.P., Leibach, F.H., Ganapathy, V. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  27. The light chain of CD98 is identified as E16/TA1 protein. Mannion, B.A., Kolesnikova, T.V., Lin, S.H., Wang, S., Thompson, N.L., Hemler, M.E. J. Biol. Chem. (1998) [Pubmed]
  28. Identification and functional characterization of a Na+-independent large neutral amino acid transporter, LAT1, in human and rabbit cornea. Jain-Vakkalagadda, B., Dey, S., Pal, D., Mitra, A.K. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
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