Thiamine transporter 2 (ThTr-2), also known as solute carrier family 19 member 3, is a protein that in humans is encoded by the SLC19A3gene.[5][6][7] SLC19A3 is a thiamine transporter.
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.[5]
References
^ abcGRCh38: Ensembl release 89: ENSG00000135917 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000038496 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Eudy JD, Spiegelstein O, Barber RC, Wlodarczyk BJ, Talbot J, Finnell RH (December 2000). "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. doi:10.1006/mgme.2000.3112. PMID 11136550.
^Zeng WQ, Al-Yamani E, Acierno JS, Slaugenhaupt S, Gillis T, MacDonald ME, Ozand PT, Gusella JF (July 2005). "Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3". Am. J. Hum. Genet. 77 (1): 16–26. doi:10.1086/431216. PMC1226189. PMID 15871139.
^Huang Z, Srinivasan S, Zhang J, Chen K, Li Y, Li W, Quiocho FA, Pan X (2012). "Discovering thiamine transporters as targets of chloroquine using a novel functional genomics strategy". PLOS Genet. 8 (11): e1003083. doi:10.1371/journal.pgen.1003083. PMC3510038. PMID 23209439.
Further reading
Subramanian VS, Marchant JS, Said HM (2006). "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. doi:10.1152/ajpcell.00105.2006. PMID 16790503. S2CID 44058.
Subramanian VS, Mohammed ZM, Molina A, et al. (2007). "Vitamin B1 (thiamine) uptake by human retinal pigment epithelial (ARPE-19) cells: mechanism and regulation". J. Physiol. 582 (Pt 1): 73–85. doi:10.1113/jphysiol.2007.128843. PMC2075275. PMID 17463047.
Vlasova TI, Stratton SL, Wells AM, et al. (2005). "Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood". J. Nutr. 135 (1): 42–7. doi:10.1093/jn/135.1.42. PMC1307527. PMID 15623830.
Nabokina SM, Said HM (2004). "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. doi:10.1152/ajpgi.00234.2004. PMID 15217784. S2CID 22973189.
Liu S, Stromberg A, Tai HH, Moscow JA (2004). "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. doi:10.1158/1541-7786.477.2.8. PMID 15328374. S2CID 2963046.
Ashokkumar B, Vaziri ND, Said HM (2006). "Thiamin uptake by the human-derived renal epithelial (HEK-293) cells: cellular and molecular mechanisms". Am. J. Physiol. Renal Physiol. 291 (4): F796-805. doi:10.1152/ajprenal.00078.2006. PMID 16705148.
Nabokina SM, Reidling JC, Said HM (2005). "Differentiation-dependent up-regulation of intestinal thiamin uptake: cellular and molecular mechanisms". J. Biol. Chem. 280 (38): 32676–82. doi:10.1074/jbc.M505243200. PMID 16055442.
Rajgopal A, Edmondnson A, Goldman ID, Zhao R (2001). "SLC19A3 encodes a second thiamine transporter ThTr2". Biochim. Biophys. Acta. 1537 (3): 175–8. doi:10.1016/s0925-4439(01)00073-4. PMID 11731220.
Liu X, Lam EK, Wang X, et al. (2009). "Promoter hypermethylation mediates downregulation of thiamine receptor SLC19A3 in gastric cancer". Tumour Biol. 30 (5–6): 242–8. doi:10.1159/000243767. PMID 19816091. S2CID 33408137.
Haas RH (1988). "Thiamin and the brain". Annu. Rev. Nutr. 8: 483–515. doi:10.1146/annurev.nu.08.070188.002411. PMID 3060175.
Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature. 434 (7034): 724–31. Bibcode:2005Natur.434..724H. doi:10.1038/nature03466. PMID 15815621.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC528928. PMID 15489334.
Subramanian VS, Marchant JS, Said HM (2006). "Targeting and trafficking of the human thiamine transporter-2 in epithelial cells". J. Biol. Chem. 281 (8): 5233–45. doi:10.1074/jbc.M512765200. PMID 16371350.
Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
Mee L, Nabokina SM, Sekar VT, et al. (2009). "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. doi:10.1152/ajpgi.00092.2009. PMC2711754. PMID 19423748.
Liu S, Huang H, Lu X, et al. (2003). "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. PMID 12861052.
thiamine, transporter, thtr, also, known, solute, carrier, family, member, protein, that, humans, encoded, slc19a3, gene, slc19a3, thiamine, transporter, slc19a3identifiersaliasesslc19a3, bbgd, thmd2, thtr2, solute, carrier, family, member, thtr, 2external, id. 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 5 6 7 SLC19A3 is a thiamine transporter SLC19A3IdentifiersAliasesSLC19A3 BBGD THMD2 THTR2 solute carrier family 19 member 3 thTr 2External IDsOMIM 606152 MGI 1931307 HomoloGene 23530 GeneCards SLC19A3Gene location Human Chr Chromosome 2 human 1 Band2q36 3Start227 683 763 bp 1 End227 718 028 bp 1 Gene location Mouse Chr Chromosome 1 mouse 2 Band1 C5 1 42 65 cMStart82 990 244 bp 2 End83 016 169 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed insubcutaneous adipose tissueabdominal fatplacentaright lungright lobe of liverjejunal mucosagallbladderduodenumendothelial cellupper lobe of left lungTop expressed induodenumproximal tubulemorulakidneyvisual cortexyolk sacsuperior frontal gyrusleft lung lobeprimitive streakatrioventricular valveMore reference expression dataBioGPSn aGene ontologyMolecular functionthiamine transmembrane transporter activity vitamin transmembrane transporter activityCellular componentintegral component of membrane plasma membrane membraneBiological processthiamine containing compound metabolic process thiamine transport thiamine transmembrane transport vitamin transport transmembrane transportSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez8070480721EnsemblENSG00000135917ENSMUSG00000038496UniProtQ9BZV2Q99PL8RefSeq mRNA NM 025243NM 001371411NM 001371412NM 001371413NM 001371414NM 030556RefSeq protein NP 079519NP 001358340NP 001358341NP 001358342NP 001358343NP 085033Location UCSC Chr 2 227 68 227 72 MbChr 1 82 99 83 02 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 References 4 Further reading 5 External linksFunction EditThTr 2 is a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity 5 It is specifically inhibited by chloroquine 8 Clinical significance EditMutations 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 5 References Edit a b c GRCh38 Ensembl release 89 ENSG00000135917 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000038496 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b c Entrez Gene solute carrier family 19 Eudy JD Spiegelstein O Barber RC Wlodarczyk BJ Talbot J Finnell RH December 2000 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 doi 10 1006 mgme 2000 3112 PMID 11136550 Zeng WQ Al Yamani E Acierno JS Slaugenhaupt S Gillis T MacDonald ME Ozand PT Gusella JF July 2005 Biotin responsive basal ganglia disease maps to 2q36 3 and is due to mutations in SLC19A3 Am J Hum Genet 77 1 16 26 doi 10 1086 431216 PMC 1226189 PMID 15871139 Huang Z Srinivasan S Zhang J Chen K Li Y Li W Quiocho FA Pan X 2012 Discovering thiamine transporters as targets of chloroquine using a novel functional genomics strategy PLOS Genet 8 11 e1003083 doi 10 1371 journal pgen 1003083 PMC 3510038 PMID 23209439 Further reading EditSubramanian VS Marchant JS Said HM 2006 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 doi 10 1152 ajpcell 00105 2006 PMID 16790503 S2CID 44058 Subramanian VS Mohammed ZM Molina A et al 2007 Vitamin B1 thiamine uptake by human retinal pigment epithelial ARPE 19 cells mechanism and regulation J Physiol 582 Pt 1 73 85 doi 10 1113 jphysiol 2007 128843 PMC 2075275 PMID 17463047 Vlasova TI Stratton SL Wells AM et al 2005 Biotin deficiency reduces expression of SLC19A3 a potential biotin transporter in leukocytes from human blood J Nutr 135 1 42 7 doi 10 1093 jn 135 1 42 PMC 1307527 PMID 15623830 Nabokina SM Said HM 2004 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 doi 10 1152 ajpgi 00234 2004 PMID 15217784 S2CID 22973189 Liu S Stromberg A Tai HH Moscow JA 2004 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 doi 10 1158 1541 7786 477 2 8 PMID 15328374 S2CID 2963046 Ganapathy V Smith SB Prasad PD 2004 SLC19 the folate thiamine transporter family Pflugers Arch 447 5 641 6 doi 10 1007 s00424 003 1068 1 PMID 14770311 S2CID 7410075 Ashokkumar B Vaziri ND Said HM 2006 Thiamin uptake by the human derived renal epithelial HEK 293 cells cellular and molecular mechanisms Am J Physiol Renal Physiol 291 4 F796 805 doi 10 1152 ajprenal 00078 2006 PMID 16705148 Nabokina SM Reidling JC Said HM 2005 Differentiation dependent up regulation of intestinal thiamin uptake cellular and molecular mechanisms J Biol Chem 280 38 32676 82 doi 10 1074 jbc M505243200 PMID 16055442 Rajgopal A Edmondnson A Goldman ID Zhao R 2001 SLC19A3 encodes a second thiamine transporter ThTr2 Biochim Biophys Acta 1537 3 175 8 doi 10 1016 s0925 4439 01 00073 4 PMID 11731220 Liu X Lam EK Wang X et al 2009 Promoter hypermethylation mediates downregulation of thiamine receptor SLC19A3 in gastric cancer Tumour Biol 30 5 6 242 8 doi 10 1159 000243767 PMID 19816091 S2CID 33408137 Haas RH 1988 Thiamin and the brain Annu Rev Nutr 8 483 515 doi 10 1146 annurev nu 08 070188 002411 PMID 3060175 Hillier LW Graves TA Fulton RS et al 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4 Nature 434 7034 724 31 Bibcode 2005Natur 434 724H doi 10 1038 nature03466 PMID 15815621 Gerhard DS Wagner L Feingold EA et al 2004 The status quality and expansion of the NIH full length cDNA project the Mammalian Gene Collection MGC Genome Res 14 10B 2121 7 doi 10 1101 gr 2596504 PMC 528928 PMID 15489334 Subramanian VS Marchant JS Said HM 2006 Targeting and trafficking of the human thiamine transporter 2 in epithelial cells J Biol Chem 281 8 5233 45 doi 10 1074 jbc M512765200 PMID 16371350 Strausberg RL Feingold EA Grouse LH et al 2002 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 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Mee L Nabokina SM Sekar VT et al 2009 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 doi 10 1152 ajpgi 00092 2009 PMC 2711754 PMID 19423748 Liu S Huang H Lu X et al 2003 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 PMID 12861052 External links EditSLC19A3 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 This membrane protein related article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia 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