Biology:SLC19A3
 Generic protein structure example |
Thiamine transporter 2 (ThTr-2), also known as solute carrier family 19 member 3, is a protein that in humans is encoded by the SLC19A3 gene.[1][2][3] SLC19A3 is a thiamine transporter.
Function
ThTr-2 is a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity.[1]
It is specifically inhibited by chloroquine.[4]
Clinical significance
Mutations in this gene cause biotin-responsive basal ganglia disease (BBGD); a recessive disorder manifested in childhood that progresses to chronic encephalopathy, dystonia, quadriparesis, and death if untreated. Patients with BBGD have bilateral necrosis in the head of the caudate nucleus and in the putamen. Administration of high doses of biotin in the early progression of the disorder eliminates pathological symptoms while delayed treatment results in residual paraparesis, mild mental retardation, or dystonia. Administration of thiamine is ineffective in the treatment of this disorder. Experiments have failed to show that this protein can transport biotin. Mutations in this gene also cause a Wernicke's-like encephalopathy.[1]
References
- ↑ 1.0 1.1 1.2 "Entrez Gene: solute carrier family 19". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=80704.
- ↑ "Identification and characterization of the human and mouse SLC19A3 gene: a novel member of the reduced folate family of micronutrient transporter genes". Mol. Genet. Metab. 71 (4): 581–90. December 2000. doi:10.1006/mgme.2000.3112. PMID 11136550.
- ↑ "Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3". Am. J. Hum. Genet. 77 (1): 16–26. July 2005. doi:10.1086/431216. PMID 15871139.
- ↑ "Discovering thiamine transporters as targets of chloroquine using a novel functional genomics strategy". PLoS Genet. 8 (11): e1003083. 2012. doi:10.1371/journal.pgen.1003083. PMID 23209439.
Further reading
- "Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2.". Am. J. Physiol., Cell Physiol. 291 (5): C851-9. 2006. doi:10.1152/ajpcell.00105.2006. PMID 16790503.
- "Vitamin B1 (thiamine) uptake by human retinal pigment epithelial (ARPE-19) cells: mechanism and regulation.". J. Physiol. 582 (Pt 1): 73–85. 2007. doi:10.1113/jphysiol.2007.128843. PMID 17463047.
- "Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood.". J. Nutr. 135 (1): 42–7. 2005. PMID 15623830.
- "Characterization of the 5'-regulatory region of the human thiamin transporter SLC19A3: in vitro and in vivo studies.". Am. J. Physiol. Gastrointest. Liver Physiol. 287 (4): G822-9. 2004. doi:10.1152/ajpgi.00234.2004. PMID 15217784.
- "Thiamine transporter gene expression and exogenous thiamine modulate the expression of genes involved in drug and prostaglandin metabolism in breast cancer cells.". Mol. Cancer Res. 2 (8): 477–87. 2004. PMID 15328374.
- "SLC19: the folate/thiamine transporter family.". Pflügers Arch. 447 (5): 641–6. 2004. doi:10.1007/s00424-003-1068-1. PMID 14770311.
- "Thiamin uptake by the human-derived renal epithelial (HEK-293) cells: cellular and molecular mechanisms.". Am. J. Physiol. Renal Physiol. 291 (4): F796-805. 2006. doi:10.1152/ajprenal.00078.2006. PMID 16705148.
- "Differentiation-dependent up-regulation of intestinal thiamin uptake: cellular and molecular mechanisms.". J. Biol. Chem. 280 (38): 32676–82. 2005. doi:10.1074/jbc.M505243200. PMID 16055442.
- "SLC19A3 encodes a second thiamine transporter ThTr2.". Biochim. Biophys. Acta 1537 (3): 175–8. 2001. doi:10.1016/s0925-4439(01)00073-4. PMID 11731220.
- "Promoter hypermethylation mediates downregulation of thiamine receptor SLC19A3 in gastric cancer.". Tumour Biol. 30 (5-6): 242–8. 2009. doi:10.1159/000243767. PMID 19816091.
- Haas RH (1988). "Thiamin and the brain.". Annu. Rev. Nutr. 8: 483–515. doi:10.1146/annurev.nu.08.070188.002411. PMID 3060175.
- "Generation and annotation of the DNA sequences of human chromosomes 2 and 4.". Nature 434 (7034): 724–31. 2005. doi:10.1038/nature03466. PMID 15815621.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "Targeting and trafficking of the human thiamine transporter-2 in epithelial cells.". J. Biol. Chem. 281 (8): 5233–45. 2006. doi:10.1074/jbc.M512765200. PMID 16371350.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2002. doi:10.1073/pnas.242603899. PMID 12477932.
- "Pancreatic beta cells and islets take up thiamin by a regulated carrier-mediated process: studies using mice and human pancreatic preparations.". Am. J. Physiol. Gastrointest. Liver Physiol. 297 (1): G197-206. 2009. doi:10.1152/ajpgi.00092.2009. PMID 19423748.
- "Down-regulation of thiamine transporter THTR2 gene expression in breast cancer and its association with resistance to apoptosis.". Mol. Cancer Res. 1 (9): 665–73. 2003. PMID 12861052.
External links
- SLC19A3+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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