Biology:Thiamine transporter 1
Generic protein structure example |
Thiamine transporter 1, also known as thiamine carrier 1 (TC1) or solute carrier family 19 member 2 (SLC19A2) is a protein that in humans is encoded by the SLC19A2 gene.[1] SLC19A2 is a thiamine transporter. Mutations in this gene cause thiamine-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural deafness.[2][3][4]
Structure
The SLC19A2 gene is located on the q arm of chromosome 1 in position 24.2 and spans 22,062 base pairs.[3] The gene produces a 55.4 kDa protein composed of 497 amino acids.[5][6] In the encoded protein (TC1), a multi-pass membrane protein located in the cell membrane, the N-terminus and C-terminus face the cytosol.[7][8] 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.[9] 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.[10][11]
Function
The encoded protein is a high-affinity transporter specific to the intake of thiamine.[7][8] 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.[9] TC1 is transported to the cell membrane by intracellular vesicles via microtubules.[10][11]
Clinical significance
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.[7][8]
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.[12]
Interactions
This protein interacts with CERS2.[13]
References
- ↑ "Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping". American Journal of Human Genetics 61 (6): 1335–41. December 1997. doi:10.1086/301642. PMID 9399900.
- ↑ "Thiamine-responsive megaloblastic anemia syndrome". International Journal of Hematology 92 (3): 524–6. October 2010. doi:10.1007/s12185-010-0681-y. PMID 20835854.
- ↑ 3.0 3.1 "Entrez Gene: solute carrier family 19 (thiamine transporter)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10560. This article incorporates text from this source, which is in the public domain.
- ↑ "Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness". Nature Genetics 22 (3): 300–4. July 1999. doi:10.1038/10372. PMID 10391221.
- ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338.
- ↑ "SLC19A2 - Thiamine transporter 1". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). https://amino.heartproteome.org/web/protein/O60779.
- ↑ 7.0 7.1 7.2 "SLC19A2 - Thiamine transporter 1 - Homo sapiens (Human) - SLC19A2 gene & protein" (in en). https://www.uniprot.org/uniprot/Q9UBX3. This article incorporates text available under the CC BY 4.0 license.
- ↑ 8.0 8.1 8.2 "UniProt: the universal protein knowledgebase". Nucleic Acids Research 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMID 27899622.
- ↑ 9.0 9.1 "Cloning of the human thiamine transporter, a member of the folate transporter family". The Journal of Biological Chemistry 274 (45): 31925–9. November 1999. doi:10.1074/jbc.274.45.31925. PMID 10542220.
- ↑ 10.0 10.1 "Cell biology of the human thiamine transporter-1 (hTHTR1). Intracellular trafficking and membrane targeting mechanisms". The Journal of Biological Chemistry 278 (6): 3976–84. February 2003. doi:10.1074/jbc.M210717200. PMID 12454006.
- ↑ 11.0 11.1 Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {603941}: {11/22/2017}: . World Wide Web URL: https://omim.org/
- ↑ "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research 21 (6): 665–76. December 2008. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ↑ IntAct. "IntAct Portal" (in en). https://www.ebi.ac.uk/intact/interactors/id:O60779*#.
Further reading
- "A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I". Journal of Medical Genetics 37 (9): 669–73. September 2000. doi:10.1136/jmg.37.9.669. PMID 10978358.
- "Direct genomic PCR sequencing of the high affinity thiamine transporter (SLC19A2) gene identifies three genetic variants in Wernicke Korsakoff syndrome (WKS)". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 137B (1): 17–9. August 2005. doi:10.1002/ajmg.b.30194. PMID 16015585.
- "Vitamin B1 (thiamine) uptake by human retinal pigment epithelial (ARPE-19) cells: mechanism and regulation". The Journal of Physiology 582 (Pt 1): 73–85. July 2007. doi:10.1113/jphysiol.2007.128843. PMID 17463047.
- "Thiamin uptake by the human-derived renal epithelial (HEK-293) cells: cellular and molecular mechanisms". American Journal of Physiology. Renal Physiology 291 (4): F796–805. October 2006. doi:10.1152/ajprenal.00078.2006. PMID 16705148.
- "Differentiation-dependent up-regulation of intestinal thiamin uptake: cellular and molecular mechanisms". The Journal of Biological Chemistry 280 (38): 32676–82. September 2005. doi:10.1074/jbc.M505243200. PMID 16055442.
- "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics 7 (3): 499–508. March 2008. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
- "Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study". European Journal of Human Genetics 17 (12): 1650–7. December 2009. doi:10.1038/ejhg.2009.94. PMID 19536175.
- "Thiamine-responsive megaloblastic anaemia: a cause of syndromic diabetes in childhood". Pediatric Diabetes 8 (4): 239–41. August 2007. doi:10.1111/j.1399-5448.2007.00251.x. PMID 17659067.
- "Targeting and intracellular trafficking of clinically relevant hTHTR1 mutations in human cell lines". Clinical Science 113 (2): 93–102. July 2007. doi:10.1042/CS20060331. PMID 17331069.
- "Interaction between maternal periconceptional supplementation of folic acid and reduced folate carrier gene polymorphism of neural tube defects". Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics 22 (3): 284–7. June 2005. PMID 15952116.
- "Thiamin and the brain". Annual Review of Nutrition 8: 483–515. 1988. doi:10.1146/annurev.nu.08.070188.002411. PMID 3060175.
- "Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families". Acta Paediatrica 95 (1): 99–104. January 2006. doi:10.1080/08035250500323715. PMID 16373304.
- "Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome". American Journal of Medical Genetics. Part A 125A (3): 299–305. March 2004. doi:10.1002/ajmg.a.20506. PMID 14994241.
- "Reduced folate carrier and methylenetetrahydrofolate reductase gene polymorphisms: associations with clinical outcome in childhood acute lymphoblastic leukemia". Leukemia 23 (7): 1348–51. July 2009. doi:10.1038/leu.2009.67. PMID 19340000.
- "Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations". Pediatric Blood & Cancer 54 (2): 273–8. February 2010. doi:10.1002/pbc.22244. PMID 19731322.
- "Targeting and trafficking of the human thiamine transporter-2 in epithelial cells". The Journal of Biological Chemistry 281 (8): 5233–45. February 2006. doi:10.1074/jbc.M512765200. PMID 16371350.
- "Pancreatic beta cells and islets take up thiamin by a regulated carrier-mediated process: studies using mice and human pancreatic preparations". American Journal of Physiology. Gastrointestinal and Liver Physiology 297 (1): G197–206. July 2009. doi:10.1152/ajpgi.00092.2009. PMID 19423748.
- "Pre-B-cell leukemia homeobox 1 (PBX1) shows functional and possible genetic association with bone mineral density variation". Human Molecular Genetics 18 (4): 679–87. February 2009. doi:10.1093/hmg/ddn397. PMID 19064610.
- "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study". Diabetes Care 33 (10): 2250–3. October 2010. doi:10.2337/dc10-0452. PMID 20628086.
External links
- GeneReviews/NIH/NCBI/UW entry on Thiamine-Responsive Megaloblastic Anemia or Rogers Syndrome
- SLC19A2+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.
Original source: https://en.wikipedia.org/wiki/Thiamine transporter 1.
Read more |