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Gene Review

SLC5A6  -  solute carrier family 5...

Homo sapiens

Synonyms: Na(+)-dependent multivitamin transporter, SMVT, Sodium-dependent multivitamin transporter, Solute carrier family 5 member 6
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Disease relevance of SLC5A6

  • We have cloned the human Na+-dependent multivitamin transporter (SMVT), which transports the water-soluble vitamins pantothenate, biotin, and lipoate, from a placental choriocarcinoma cell line (JAR) [1].
  • Of 40 MI patients, SMVT was inducible in 14, sustained polymorphic VT in three, nonsustained monomorphic VT in three, nonsustained polymorphic VT in two, and no inducible arrhythmia was obtained in 18 [2].
  • Nine myocardial infarction (MI) patients with clinically documented sustained monomorphic VT (SMVT), 40 MI patients without clinical VT, and 30 normal healthy control subjects were evaluated [2].
  • In patients without prior symptomatic ventricular arrhythmias a history of unexplained syncope, severely impaired right ventricular hemodynamics, frequent spontaneous ventricular ectopy or NSVT, and inducible SMVT may help identify those at greatest risk of dying suddenly [3].
  • Left ventricular ejection fraction was highest among patients with inducible VF (35 +/- 13), lowest for patients with inducible sustained monomorphic ventricular tachycardia (SMVT; 27 +/- 9), and intermediate for patients with inducible ventricular flutter (30 +/- 10) [4].

High impact information on SLC5A6


Chemical compound and disease context of SLC5A6


Biological context of SLC5A6

  • The nucleotide sequence of the cDNA (sodium-dependent multivitamin transporter (SMVT)) predicts a protein of 68.6 kDa with 634 amino acids and 12 potential transmembrane domains [6].
  • Maintaining the HK-2 cells in a biotin-deficient growth medium led to a marked upregulation in biotin transport, which was associated with an increase in hSMVT protein and RNA levels and an increase in activity of the hSMVT promoters [8].
  • We also employed a molecular biology approach of selectively silencing the endogenous SMVT of these cells with specific small interfering RNAs (siRNAs), then examining carrier-mediated biotin uptake [9].
  • We cloned and functionally characterized the 5' regulatory region of the human sodium-dependent multivitamin transporter (hSMVT) gene, a remarkably versatile carrier responsible for uptake of biotin, pantothenic acid and lipoate [10].
  • The increase in mRNA levels was not due to an increase in RNA stability but was associated with an increase in activity of the hSMVT promoter in transfected human intestinal cells [11].

Anatomical context of SLC5A6

  • These results demonstrate that biotin uptake by human renal epithelial cells occurs via the hSMVT system and that the process is regulated by intracellular PKC- and Ca(2+)/calmodulin-mediated pathways [8].
  • The SMVT-specific transcripts of 3.2 kbp are equally distributed throughout the small intestine [12].
  • Keratinocytes join forces with immune cells in the prosecution of SMVT as a "false" biotin transporter [13].
  • Using promoter deletion constructs and mutational analysis in transiently transfected HuTu-80 and Caco-2 cells, a biotin deficiency-responsive region was mapped to a 103-bp area within the hSMVT promoter that contains gut-enriched Kruppel-like factor (GKLF) sites that confer the response to biotin deficiency [11].
  • Uptake of these two compounds was also determined in CHO cells transfected with human SMVT (CHO/hSMVT) and control cells (CHO/pSPORT) over the concentration ranges of 0.05-12.5 microM and 0.003-30 microM, respectively [14].

Associations of SLC5A6 with chemical compounds


Analytical, diagnostic and therapeutic context of SLC5A6

  • Northern blot analysis shows that SMVT transcripts are present in all of the tissues that were tested [6].
  • To understand the role of SMVT in the control of biotin utilization, we have studied the effect of biotin availability on SMVT protein and mRNA expression levels in HepG2 cells by Western blot analysis and rtPCR, respectively; and their functional impact on the rate of [3H]biotin uptake in human cells [17].
  • A human sodium-dependant multivitamin transporter, hSMVT, was identified by RT-PCR in Y-79 [18].
  • There was no significant difference in time-domain variables among fast SMVT, no VT, and normal control groups [19].
  • Reverse transcription polymerase chain reaction (RT-PCR) was performed to confirm the molecular identity of human sodium-dependent multivitamin transporter (hSMVT) [18].


  1. Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. Wang, H., Huang, W., Fei, Y.J., Xia, H., Yang-Feng, T.L., Leibach, F.H., Devoe, L.D., Ganapathy, V., Prasad, P.D. J. Biol. Chem. (1999) [Pubmed]
  2. Combined use of time and frequency domain variables in signal-averaged ECG as a predictor of inducible sustained monomorphic ventricular tachycardia in myocardial infarction. Nogami, A., Iesaka, Y., Akiyama, J., Takahashi, A., Nitta, J., Chun, Y., Aonuma, K., Hiroe, M., Marumo, F., Hiraoka, M. Circulation (1992) [Pubmed]
  3. Sudden death in idiopathic dilated cardiomyopathy. Tamburro, P., Wilber, D. Am. Heart J. (1992) [Pubmed]
  4. Ventricular flutter induced during electrophysiologic studies in patients with old myocardial infarction: clinical and electrophysiologic predictors, and prognostic significance. Viskin, S., Ish-Shalom, M., Koifman, E., Rozovski, U., Zeltser, D., Glick, A., Finkelstein, A., Halkin, A., Fish, R., Belhassen, B. J. Cardiovasc. Electrophysiol. (2003) [Pubmed]
  5. Uptake, localization, and noncarboxylase roles of biotin. Zempleni, J. Annu. Rev. Nutr. (2005) [Pubmed]
  6. Cloning and functional expression of a cDNA encoding a mammalian sodium-dependent vitamin transporter mediating the uptake of pantothenate, biotin, and lipoate. Prasad, P.D., Wang, H., Kekuda, R., Fujita, T., Fei, Y.J., Devoe, L.D., Leibach, F.H., Ganapathy, V. J. Biol. Chem. (1998) [Pubmed]
  7. Biotin supply affects rates of cell proliferation, biotinylation of carboxylases and histones, and expression of the gene encoding the sodium-dependent multivitamin transporter in JAr choriocarcinoma cells. Crisp, S.E., Griffin, J.B., White, B.R., Toombs, C.F., Camporeale, G., Said, H.M., Zempleni, J. European journal of nutrition. (2004) [Pubmed]
  8. Biotin uptake by human proximal tubular epithelial cells: cellular and molecular aspects. Balamurugan, K., Vaziri, N.D., Said, H.M. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  9. Biotin uptake by human intestinal and liver epithelial cells: role of the SMVT system. Balamurugan, K., Ortiz, A., Said, H.M. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  10. Characterization of the 5' regulatory region of the human sodium-dependent multivitamin transporter, hSMVT. Dey, S., Subramanian, V.S., Chatterjee, N.S., Rubin, S.A., Said, H.M. Biochim. Biophys. Acta (2002) [Pubmed]
  11. Molecular mechanisms involved in the adaptive regulation of human intestinal biotin uptake: a study of the hSMVT system. Reidling, J.C., Nabokina, S.M., Said, H.M. Am. J. Physiol. Gastrointest. Liver Physiol. (2007) [Pubmed]
  12. Molecular and functional characterization of the intestinal Na+-dependent multivitamin transporter. Prasad, P.D., Wang, H., Huang, W., Fei, Y.J., Leibach, F.H., Devoe, L.D., Ganapathy, V. Arch. Biochem. Biophys. (1999) [Pubmed]
  13. Keratinocytes join forces with immune cells in the prosecution of SMVT as a "false" biotin transporter. Prasad, P.D., Ganapathy, V. J. Invest. Dermatol. (2003) [Pubmed]
  14. Targeted PEG-based bioconjugates enhance the cellular uptake and transport of a HIV-1 TAT nonapeptide. Ramanathan, S., Qiu, B., Pooyan, S., Zhang, G., Stein, S., Leibowitz, M.J., Sinko, P.J. Journal of controlled release : official journal of the Controlled Release Society. (2001) [Pubmed]
  15. XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: I. Design, synthesis, enzymatic conversion to gabapentin, and transport by intestinal solute transporters. Cundy, K.C., Branch, R., Chernov-Rogan, T., Dias, T., Estrada, T., Hold, K., Koller, K., Liu, X., Mann, A., Panuwat, M., Raillard, S.P., Upadhyay, S., Wu, Q.Q., Xiang, J.N., Yan, H., Zerangue, N., Zhou, C.X., Barrett, R.W., Gallop, M.A. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  16. Targeting the sodium-dependent multivitamin transporter (SMVT) for improving the oral absorption properties of a retro-inverso Tat nonapeptide. Ramanathan, S., Pooyan, S., Stein, S., Prasad, P.D., Wang, J., Leibowitz, M.J., Ganapathy, V., Sinko, P.J. Pharm. Res. (2001) [Pubmed]
  17. Biotin availability regulates expression of the sodium-dependent multivitamin transporter and the rate of biotin uptake in HepG2 cells. Pacheco-Alvarez, D., Solórzano-Vargas, R.S., González-Noriega, A., Michalak, C., Zempleni, J., León-Del-Río, A. Mol. Genet. Metab. (2005) [Pubmed]
  18. Biotin uptake and cellular translocation in human derived retinoblastoma cell line (Y-79): a role of hSMVT system. Kansara, V., Luo, S., Balasubrahmanyam, B., Pal, D., Mitra, A.K. International journal of pharmaceutics. (2006) [Pubmed]
  19. Time- versus frequency-domain analysis in predicting cycle length of inducible ventricular tachycardia after myocardial infarction. Nogami, A., Iesaka, Y., Yamauchi, Y., Goya, M., Takahashi, A., Koike, A., Ito, H., Aonuma, K., Hiroe, M. Pacing and clinical electrophysiology : PACE. (1996) [Pubmed]
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