Thiamine transporter 1

The SLC19A2 gene is located on the q arm of chromosome 1 in position 24.2 and spans 22,062 base pairs. The gene produces a 55.4 kDa protein composed of 497 amino acids.{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}{{cite web | url = https://amino.heartproteome.org/web/protein/O60779 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = SLC19A2 - Thiamine transporter 1 | access-date = 2018-08-23 | archive-date = 2018-08-23 | archive-url = https://web.archive.org/web/20180823105447/https://amino.heartproteome.org/web/protein/O60779 | url-status = dead }} In the encoded protein (TC1), a multi-pass membrane protein located in the cell membrane, the N-terminus and C-terminus face the cytosol.{{Cite web|url=https://www.uniprot.org/uniprot/Q9UBX3|title=SLC19A2 - Thiamine transporter 1 - Homo sapiens (Human) - SLC19A2 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-21}}{{CC-notice|cc=by4}}{{cite journal | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158–D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 }} This gene has 6 exons while the protein has 12 putative transmembrane domains, with 3 phosphorylation sites in putative intracellular domains, 2 N-glycolysation sites in putative extracellular domains, and a 17-amino acid long G protein-coupled receptor signature sequence. The thiamine transporter protein encoded by SLC19A2 has a 40% shared amino acid identity with the folate transporter SLC19A1.{{cite journal | vauthors = Dutta B, Huang W, Molero M, Kekuda R, Leibach FH, Devoe LD, Ganapathy V, Prasad PD | title = Cloning of the human thiamine transporter, a member of the folate transporter family | journal = The Journal of Biological Chemistry | volume = 274 | issue = 45 | pages = 31925–9 | date = November 1999 | pmid = 10542220 | doi = 10.1074/jbc.274.45.31925 | doi-access = free }} The N-terminal domain and the sequence between the C-terminal domain and sixth transmembrane domain are required for proper localization of this protein to the cell membrane.{{cite journal | vauthors = Subramanian VS, Marchant JS, Parker I, Said HM | title = Cell biology of the human thiamine transporter-1 (hTHTR1). Intracellular trafficking and membrane targeting mechanisms | journal = The Journal of Biological Chemistry | volume = 278 | issue = 6 | pages = 3976–84 | date = February 2003 | pmid = 12454006 | doi = 10.1074/jbc.M210717200 | doi-access = free }}Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {603941}: {11/22/2017}: . World Wide Web URL: https://omim.org/

The encoded protein is a high-affinity transporter specific to the intake of thiamine. Thiamine transport is not inhibited by other organic cations nor affected by sodium ion concentration; it is stimulated by a proton gradient directed outward, with an optimal pH between 8.0 and 8.5. TC1 is transported to the cell membrane by intracellular vesicles via microtubules.

Mutations in the SLC19A2 gene can cause thiamine-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disease characterized by megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Onset is typically between infancy and adolescence, but all of the cardinal findings are often not present initially. The anemia, and sometimes the diabetes, improves with high doses of thiamine. Other more variable features include optic atrophy, congenital heart defects, short stature, and stroke.

A 3.8 kb transcript is expressed variably in most tissues, highest in skeletal and cardiac muscle, followed by medium expression placenta, heart, liver, kidney cells and low expression in lung cells. In melanocytic cells SLC19A2 gene expression may be regulated by MITF.{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell & Melanoma Research | volume = 21 | issue = 6 | pages = 665–76 | date = December 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x | doi-access = free }}

This protein interacts with CERS2.{{Cite web|url=https://www.ebi.ac.uk/intact/interactors/id:O60779*#|last=IntAct|title=IntAct Portal |website=www.ebi.ac.uk|language=en|access-date=2018-08-23}}

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• {{cite journal | vauthors = Scharfe C, Hauschild M, Klopstock T, Janssen AJ, Heidemann PH, Meitinger T, Jaksch M | title = A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I | journal = Journal of Medical Genetics | volume = 37 | issue = 9 | pages = 669–73 | date = September 2000 | pmid = 10978358 | pmc = 1734685 | doi = 10.1136/jmg.37.9.669 }}
• {{cite journal | vauthors = Guerrini I, Thomson AD, Cook CC, McQuillin A, Sharma V, Kopelman M, Reynolds G, Jauhar P, Harper C, Gurling HM | title = Direct genomic PCR sequencing of the high affinity thiamine transporter (SLC19A2) gene identifies three genetic variants in Wernicke Korsakoff syndrome (WKS) | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 137B | issue = 1 | pages = 17–9 | date = August 2005 | pmid = 16015585 | doi = 10.1002/ajmg.b.30194 | s2cid = 37693278 }}
• {{cite journal | vauthors = Subramanian VS, Mohammed ZM, Molina A, Marchant JS, Vaziri ND, Said HM | title = Vitamin B1 (thiamine) uptake by human retinal pigment epithelial (ARPE-19) cells: mechanism and regulation | journal = The Journal of Physiology | volume = 582 | issue = Pt 1 | pages = 73–85 | date = July 2007 | pmid = 17463047 | pmc = 2075275 | doi = 10.1113/jphysiol.2007.128843 }}
• {{cite journal | vauthors = Ashokkumar B, Vaziri ND, Said HM | title = Thiamin uptake by the human-derived renal epithelial (HEK-293) cells: cellular and molecular mechanisms | journal = American Journal of Physiology. Renal Physiology | volume = 291 | issue = 4 | pages = F796–805 | date = October 2006 | pmid = 16705148 | doi = 10.1152/ajprenal.00078.2006 }}
• {{cite journal | vauthors = Nabokina SM, Reidling JC, Said HM | title = Differentiation-dependent up-regulation of intestinal thiamin uptake: cellular and molecular mechanisms | journal = The Journal of Biological Chemistry | volume = 280 | issue = 38 | pages = 32676–82 | date = September 2005 | pmid = 16055442 | doi = 10.1074/jbc.M505243200 | doi-access = free }}
• {{cite journal | vauthors = Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H | title = Toward a confocal subcellular atlas of the human proteome | journal = Molecular & Cellular Proteomics | volume = 7 | issue = 3 | pages = 499–508 | date = March 2008 | pmid = 18029348 | doi = 10.1074/mcp.M700325-MCP200 | doi-access = free }}
• {{cite journal | vauthors = Ehret GB, O'Connor AA, Weder A, Cooper RS, Chakravarti A | title = Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study | journal = European Journal of Human Genetics | volume = 17 | issue = 12 | pages = 1650–7 | date = December 2009 | pmid = 19536175 | pmc = 2783544 | doi = 10.1038/ejhg.2009.94 }}
• {{cite journal | vauthors = Olsen BS, Hahnemann JM, Schwartz M, Østergaard E | title = Thiamine-responsive megaloblastic anaemia: a cause of syndromic diabetes in childhood | journal = Pediatric Diabetes | volume = 8 | issue = 4 | pages = 239–41 | date = August 2007 | pmid = 17659067 | doi = 10.1111/j.1399-5448.2007.00251.x | s2cid = 24093373 | doi-access = free }}
• {{cite journal | vauthors = Subramanian VS, Marchant JS, Said HM | title = Targeting and intracellular trafficking of clinically relevant hTHTR1 mutations in human cell lines | journal = Clinical Science | volume = 113 | issue = 2 | pages = 93–102 | date = July 2007 | pmid = 17331069 | doi = 10.1042/CS20060331 }}
• {{cite journal | vauthors = Pei LJ, Zhu HP, Li ZW, Zhang W, Ren AG, Zhu JH, Li Z | title = Interaction between maternal periconceptional supplementation of folic acid and reduced folate carrier gene polymorphism of neural tube defects | journal = Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics | volume = 22 | issue = 3 | pages = 284–7 | date = June 2005 | pmid = 15952116 }}
• {{cite journal | vauthors = Haas RH | title = Thiamin and the brain | journal = Annual Review of Nutrition | volume = 8 | pages = 483–515 | year = 1988 | pmid = 3060175 | doi = 10.1146/annurev.nu.08.070188.002411 }}
• {{cite journal | vauthors = Ricketts CJ, Minton JA, Samuel J, Ariyawansa I, Wales JK, Lo IF, Barrett TG | title = Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families | journal = Acta Paediatrica | volume = 95 | issue = 1 | pages = 99–104 | date = January 2006 | pmid = 16373304 | doi = 10.1080/08035250500323715 }}
• {{cite journal | vauthors = Lagarde WH, Underwood LE, Moats-Staats BM, Calikoglu AS | title = Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome | journal = American Journal of Medical Genetics. Part A | volume = 125A | issue = 3 | pages = 299–305 | date = March 2004 | pmid = 14994241 | doi = 10.1002/ajmg.a.20506 | s2cid = 12191136 }}
• {{cite journal | vauthors = Ashton LJ, Gifford AJ, Kwan E, Lingwood A, Lau DT, Marshall GM, Haber M, Norris MD | title = Reduced folate carrier and methylenetetrahydrofolate reductase gene polymorphisms: associations with clinical outcome in childhood acute lymphoblastic leukemia | journal = Leukemia | volume = 23 | issue = 7 | pages = 1348–51 | date = July 2009 | pmid = 19340000 | doi = 10.1038/leu.2009.67 | doi-access = free }}
• {{cite journal | vauthors = Bergmann AK, Campagna DR, McLoughlin EM, Agarwal S, Fleming MD, Bottomley SS, Neufeld EJ | title = Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations | journal = Pediatric Blood & Cancer | volume = 54 | issue = 2 | pages = 273–8 | date = February 2010 | pmid = 19731322 | pmc = 2843911 | doi = 10.1002/pbc.22244 }}
• {{cite journal | vauthors = Subramanian VS, Marchant JS, Said HM | title = Targeting and trafficking of the human thiamine transporter-2 in epithelial cells | journal = The Journal of Biological Chemistry | volume = 281 | issue = 8 | pages = 5233–45 | date = February 2006 | pmid = 16371350 | doi = 10.1074/jbc.M512765200 | doi-access = free }}
• {{cite journal | vauthors = Mee L, Nabokina SM, Sekar VT, Subramanian VS, Maedler K, Said HM | title = Pancreatic beta cells and islets take up thiamin by a regulated carrier-mediated process: studies using mice and human pancreatic preparations | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 297 | issue = 1 | pages = G197–206 | date = July 2009 | pmid = 19423748 | pmc = 2711754 | doi = 10.1152/ajpgi.00092.2009 }}
• {{cite journal | vauthors = Cheung CL, Chan BY, Chan V, Ikegawa S, Kou I, Ngai H, Smith D, Luk KD, Huang QY, Mori S, Sham PC, Kung AW | title = Pre-B-cell leukemia homeobox 1 (PBX1) shows functional and possible genetic association with bone mineral density variation | journal = Human Molecular Genetics | volume = 18 | issue = 4 | pages = 679–87 | date = February 2009 | pmid = 19064610 | doi = 10.1093/hmg/ddn397 | doi-access = free }}
• {{cite journal | vauthors = Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, Keavney B, Yusuf S, Gerstein HC, Engert JC, Anand S | title = Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study | journal = Diabetes Care | volume = 33 | issue = 10 | pages = 2250–3 | date = October 2010 | pmid = 20628086 | pmc = 2945168 | doi = 10.2337/dc10-0452 }}

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• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=trma GeneReviews/NIH/NCBI/UW entry on Thiamine-Responsive Megaloblastic Anemia or Rogers Syndrome]
• {{MeshName|SLC19A2+protein,+human}}

{{Membrane transport proteins}}

{{NLM content}}

Category:Solute carrier family