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Gene Review

SLC38A5  -  solute carrier family 38, member 5

Homo sapiens

Synonyms: JM24, PP7194, SN2, SNAT5, Sodium-coupled neutral amino acid transporter 5, ...
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Disease relevance of SLC38A5


High impact information on SLC38A5

  • The single-strand damage processed by AlkB was primarily cytotoxic and not mutagenic and was induced by SN2 methylating agents, MMS, DMS, and MeI but not by SN1 agent N-methyl-N-nitrosourea or by gamma irradiation [4].
  • Nonenzymatic and enzymatic hydrolysis of alkyl halides: a theoretical study of the SN2 reactions of acetate and hydroxide ions with alkyl chlorides [5].
  • A self-consistent reaction field solvation model was used to examine the SN2 reactions between methyl chloride and hydroxide ion and between 1,2-dichloroethane and acetate in solution [5].
  • It is proposed that the increase in cis-adduct formation due to salt results from SN1 attack of chloride ion on the BPDE carbocation, forming a trans chlorohydrin, followed by SN2 attack of DNA [6].
  • Reactions proceed by a SN2-like reaction through the cooperation of acid catalysis by the imidazolyl cation and nucleophilic attack by the serine [7].

Chemical compound and disease context of SLC38A5

  • Although the growth of all hepatomas was glutamine dependent, competitive inhibition of ATB(0)-mediated glutamine uptake blocked proliferation only in poorly differentiated cells lacking SN1 or SN2 expression and exhibiting low glutamine synthetase mRNA levels [2].

Biological context of SLC38A5

  • The sizes of the transcripts vary in different tissues, indicating tissue-specific alternative splicing of the SN2 mRNA [8].
  • The gene coding for SN2 is located on human chromosome Xp11.23 [8].
  • This transporter, designated SN2, consists of 472 amino acids and exhibits 62% identity with human SN1 at the level of amino acid sequence [8].
  • Non-enzymatic and enzymatic hydrolysis of alkyl halides: a haloalkane dehalogenation enzyme evolved to stabilize the gas-phase transition state of an SN2 displacement reaction [9].
  • Deuterated analogs of the two metabolites have been synthesized, namely N,N-bis(2,2-dideutero-2-chloroethyl)-phosphorodiamidic acid and N,N-bis(2,2-dideutero-2-chloroethyl)amine and used to determine that alkylation proceeds directly via an aziridinium intermediate rather than a direct SN2 displacement of the chlorine atom [10].

Anatomical context of SLC38A5

  • These immunotoxins were prepared by conjugating ricin A chain (RIA) with our recently generated murine monoclonal antibodies, SN1 and SN2, the latter of which was obtained from a hybridoma clone N6/D11 described previously by Negoro and Seon (Cancer Res., 42: 4259-4262, 1982), directed to two unique human T-cell leukemia antigens [11].
  • In the rat, SN2 mRNA is most abundant in the liver but is detectable in the brain, lung, stomach, kidney, testis, and spleen [12].
  • When expressed in Xenopus laevis oocytes and in mammalian cells, rat SN2 mediates Na(+)-dependent transport of several neutral amino acids, including glycine, asparagine, alanine, serine, glutamine, and histidine [12].
  • These results suggest that SN2 DNA-alkylating agent-induced phosphorylation of p53 on Ser15 and Ser392 increases its DNA-binding properties to cause an increased expression of p21 that may play a role in cell cycle arrest and/or apoptosis of HCT-116 cells [13].

Associations of SLC38A5 with chemical compounds

  • In addition, SN2 also transports serine, alanine, and glycine [8].
  • The Michaelis-Menten constant for histidine uptake via human SN2 is 0.6 +/- 0.1 mM [8].
  • When expressed in mammalian cells, the cloned human SN2 mediates Na(+)-coupled transport of system N-specific amino acid substrates (glutamine, asparagine, and histidine) [8].
  • It appears that the transition states for phosphoryl transfer have no more than one negative charge on the nonbridge oxygens, so that reactions of monoesters are dissociative, reactions of triesters are associative, and reactions of diesters are SN2 with half bond order to entering and leaving groups [14].
  • The results described here strongly indicate that transfer of methyl group to carbon monoxide dehydrogenase/acetyl-CoA synthase occurs by an SN2 pathway [15].

Analytical, diagnostic and therapeutic context of SLC38A5

  • We conclude that: (1) ventilation distribution in the lung periphery is normal in HLT recipients with adequate allograft function; (2) the airflow obstruction elicited by OB and acute episodes of lung infection or rejection is accompanied by increases in SN2, SSF6, and S(He) and decreases in SSF6-(He)).(ABSTRACT TRUNCATED AT 250 WORDS)[16]
  • This radiopharmaceutical is prepared in a three-step synthesis (preparation of [18F]-tetrabutylammonium fluoride, SN2 displacement of a triflate, and ketone reduction) and is purified by high performance liquid chromatography (HPLC) [17].
  • A model is proposed in which different DNA lesions are involved in AP site formation after treatment with SN2 or SN2 alkylating agents [18].
  • The circular dichroism spectral studies with R and S 3,4-epoxy-1-butene revealed that the reaction mechanism at aqueous neutral pH media is more similar to SN2-type rather than SN1-type [19].


  1. Molecular cloning and functional analysis of a human cDNA encoding an Escherichia coli AlkB homolog, a protein involved in DNA alkylation damage repair. Wei, Y.F., Carter, K.C., Wang, R.P., Shell, B.K. Nucleic Acids Res. (1996) [Pubmed]
  2. Molecular and functional analysis of glutamine uptake in human hepatoma and liver-derived cells. Bode, B.P., Fuchs, B.C., Hurley, B.P., Conroy, J.L., Suetterlin, J.E., Tanabe, K.K., Rhoads, D.B., Abcouwer, S.F., Souba, W.W. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  3. Number and location of radiolabeled, intraoperatively identified sentinel nodes in 48 head and neck cancer patients with clinically staged N0 and N1 neck. Werner, J.A., Dünne, A.A., Ramaswamy, A., Folz, B.J., Brandt, D., Külkens, C., Moll, R., Lippert, B.M. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. (2002) [Pubmed]
  4. Defective processing of methylated single-stranded DNA by E. coli AlkB mutants. Dinglay, S., Trewick, S.C., Lindahl, T., Sedgwick, B. Genes Dev. (2000) [Pubmed]
  5. Nonenzymatic and enzymatic hydrolysis of alkyl halides: a theoretical study of the SN2 reactions of acetate and hydroxide ions with alkyl chlorides. Maulitz, A.H., Lightstone, F.C., Zheng, Y.J., Bruice, T.C. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  6. Chloride ions catalyze the formation of cis adducts in the binding of anti-benzo[a]pyrene diol epoxide to nucleic acids. Wolfe, A.R., Yamamoto, J., Meehan, T. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  7. Do cleavages of amides by serine proteases occur through a stepwise pathway involving tetrahedral intermediates? Komiyama, M., Bender, M.L. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  8. Structure, function, and tissue expression pattern of human SN2, a subtype of the amino acid transport system N. Nakanishi, T., Sugawara, M., Huang, W., Martindale, R.G., Leibach, F.H., Ganapathy, M.E., Prasad, P.D., Ganapathy, V. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  9. Non-enzymatic and enzymatic hydrolysis of alkyl halides: a haloalkane dehalogenation enzyme evolved to stabilize the gas-phase transition state of an SN2 displacement reaction. Lightstone, F.C., Zheng, Y.J., Maulitz, A.H., Bruice, T.C. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  10. Alkylating properties of phosphoramide mustard. Colvin, M., Brundrett, R.B., Kan, M.N., Jardine, I., Fenselau, C. Cancer Res. (1976) [Pubmed]
  11. Specific killing of human T-leukemia cells by immunotoxins prepared with ricin A chain and monoclonal anti-human T-cell leukemia antibodies. Seon, B.K. Cancer Res. (1984) [Pubmed]
  12. Cloning and functional characterization of a new subtype of the amino acid transport system N. Nakanishi, T., Kekuda, R., Fei, Y.J., Hatanaka, T., Sugawara, M., Martindale, R.G., Leibach, F.H., Prasad, P.D., Ganapathy, V. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
  13. SN2 DNA-alkylating agent-induced phosphorylation of p53 and activation of p21 gene expression. Jaiswal, A.S., Narayan, S. Mutat. Res. (2002) [Pubmed]
  14. Secondary 18O isotope effects as a tool for studying reactions of phosphate mono-, di-, and triesters. Cleland, W.W. FASEB J. (1990) [Pubmed]
  15. The role of an iron-sulfur cluster in an enzymatic methylation reaction. Methylation of CO dehydrogenase/acetyl-CoA synthase by the methylated corrinoid iron-sulfur protein. Menon, S., Ragsdale, S.W. J. Biol. Chem. (1999) [Pubmed]
  16. Inert gas single-breath washout after heart-lung transplantation. Van Muylem, A., Antoine, M., Yernault, J.C., Paiva, M., Estenne, M. Am. J. Respir. Crit. Care Med. (1995) [Pubmed]
  17. Application of robotics to radiopharmaceutical preparation: controlled synthesis of fluorine-18 16 alpha-fluoroestradiol-17 beta. Brodack, J.W., Kilbourn, M.R., Welch, M.J., Katzenellenbogen, J.A. J. Nucl. Med. (1986) [Pubmed]
  18. Methoxyamine modification of abasic sites protects CHO cells from the cytotoxic and mutagenic effects of oxygen alkylation. Fortini, P., Rosa, S., Zijno, A., Calcagnile, A., Bignami, M., Dogliotti, E. Carcinogenesis (1992) [Pubmed]
  19. Butadiene monoxide and deoxyguanosine alkylation products at the N7-position. Neagu, I., Koivisto, P., Neagu, C., Kostiainen, R., Stenby, K., Peltonen, K. Carcinogenesis (1995) [Pubmed]
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