Thiamine transporter 1

SLC19A2
Identifiers
AliasesSLC19A2, TC1, THMD1, THT1, THTR1, TRMA, solute carrier family 19 member 2
External IDsOMIM: 603941; MGI: 1928761; HomoloGene: 38258; GeneCards: SLC19A2; OMA:SLC19A2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

10560

116914

Ensembl

ENSG00000117479

ENSMUSG00000040918

UniProt

O60779

Q9EQN9

RefSeq (mRNA)

NM_006996
NM_001319667

NM_001276455
NM_054087

RefSeq (protein)

NP_001306596
NP_008927

NP_001263384
NP_473428

Location (UCSC)Chr 1: 169.46 – 169.49 MbChr 1: 164.08 – 164.09 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5] 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.[6][7][8]

Structure

The SLC19A2 gene is located on the q arm of chromosome 1 in position 24.2 and spans 22,062 base pairs.[7] The gene produces a 55.4 kDa protein composed of 497 amino acids.[9][10] In the encoded protein (TC1), a multi-pass membrane protein located in the cell membrane, the N-terminus and C-terminus face the cytosol.[11][12] 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.[13] 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.[14][15]

Function

The encoded protein is a high-affinity transporter specific to the intake of thiamine.[11][12] 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.[13] TC1 is transported to the cell membrane by intracellular vesicles via microtubules.[14][15]

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.[11][12]

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.[16]

Interactions

This protein interacts with CERS2.[17]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000117479 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040918 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Neufeld EJ, Mandel H, Raz T, Szargel R, Yandava CN, Stagg A, Fauré S, Barrett T, Buist N, Cohen N (December 1997). "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. doi:10.1086/301642. PMC 1716091. PMID 9399900.
  6. ^ Bay A, Keskin M, Hizli S, Uygun H, Dai A, Gumruk F (October 2010). "Thiamine-responsive megaloblastic anemia syndrome". International Journal of Hematology. 92 (3): 524–6. doi:10.1007/s12185-010-0681-y. PMID 20835854. S2CID 21487938.
  7. ^ a b "Entrez Gene: solute carrier family 19 (thiamine transporter)".Public Domain This article incorporates text from this source, which is in the public domain.
  8. ^ Labay V, Raz T, Baron D, Mandel H, Williams H, Barrett T, Szargel R, McDonald L, Shalata A, Nosaka K, Gregory S, Cohen N (July 1999). "Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness". Nature Genetics. 22 (3): 300–4. doi:10.1038/10372. PMID 10391221. S2CID 26615141.
  9. ^ 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 (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  10. ^ "SLC19A2 - Thiamine transporter 1". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2018-08-23. Retrieved 2018-08-23.
  11. ^ a b c "SLC19A2 - Thiamine transporter 1 - Homo sapiens (Human) - SLC19A2 gene & protein". www.uniprot.org. Retrieved 2018-08-21. This article incorporates text available under the CC BY 4.0 license.
  12. ^ a b c "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  13. ^ a b Dutta B, Huang W, Molero M, Kekuda R, Leibach FH, Devoe LD, Ganapathy V, Prasad PD (November 1999). "Cloning of the human thiamine transporter, a member of the folate transporter family". The Journal of Biological Chemistry. 274 (45): 31925–9. doi:10.1074/jbc.274.45.31925. PMID 10542220.
  14. ^ a b Subramanian VS, Marchant JS, Parker I, Said HM (February 2003). "Cell biology of the human thiamine transporter-1 (hTHTR1). Intracellular trafficking and membrane targeting mechanisms". The Journal of Biological Chemistry. 278 (6): 3976–84. doi:10.1074/jbc.M210717200. PMID 12454006.
  15. ^ a b Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {603941}: {11/22/2017}: . World Wide Web URL: https://omim.org/
  16. ^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
  17. ^ IntAct. "IntAct Portal". www.ebi.ac.uk. Retrieved 2018-08-23.

Further reading

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