Biology:SLC19A2

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A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
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

  1. ↑ "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. 
  2. ↑ "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. ↑ 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.
  4. ↑ "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. 
  5. ↑ "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. 
  6. ↑ "SLC19A2 - Thiamine transporter 1". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). https://amino.heartproteome.org/web/protein/O60779. 
  7. ↑ 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. ↑ 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. PMC 5210571. https://doi.org/10.1093/nar/gkw1099. 
  9. ↑ 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. PMID 10542220. 
  10. ↑ 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. ↑ 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/
  12. ↑ "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. 
  13. ↑ IntAct. "https://www.ebi.ac.uk/intact/interactors/id:O60779*#" (in en). https://www.ebi.ac.uk/intact/interactors/id:O60779*#. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.




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