Thiamine transporter 2

Protein-coding gene in the species Homo sapiens
SLC19A3
Identifiers
AliasesSLC19A3, BBGD, THMD2, THTR2, solute carrier family 19 member 3, thTr-2
External IDsOMIM: 606152; MGI: 1931307; HomoloGene: 23530; GeneCards: SLC19A3; OMA:SLC19A3 - orthologs
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for SLC19A3
Genomic location for SLC19A3
Band2q36.3Start227,683,763 bp[1]
End227,718,028 bp[1]
Gene location (Mouse)
Chromosome 1 (mouse)
Chr.Chromosome 1 (mouse)[2]
Chromosome 1 (mouse)
Genomic location for SLC19A3
Genomic location for SLC19A3
Band1 C5|1 42.65 cMStart82,990,244 bp[2]
End83,016,169 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • subcutaneous adipose tissue

  • abdominal fat

  • placenta

  • right lung

  • right lobe of liver

  • jejunal mucosa

  • gallbladder

  • duodenum

  • epithelium of colon

  • testicle
Top expressed in
  • duodenum

  • right kidney

  • proximal tubule

  • morula

  • lumbar subsegment of spinal cord

  • human kidney

  • epithelium of lens

  • embryo

  • embryo

  • visual cortex
More reference expression data
BioGPS
n/a
Gene ontology
Molecular function
  • thiamine transmembrane transporter activity
  • vitamin transmembrane transporter activity
Cellular component
  • integral component of membrane
  • plasma membrane
  • membrane
Biological process
  • thiamine-containing compound metabolic process
  • thiamine transport
  • thiamine transmembrane transport
  • vitamin transport
  • transmembrane transport
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

80704

80721

Ensembl

ENSG00000135917

ENSMUSG00000038496

UniProt

Q9BZV2

Q99PL8

RefSeq (mRNA)

NM_025243
NM_001371411
NM_001371412
NM_001371413
NM_001371414

NM_030556

RefSeq (protein)

NP_079519
NP_001358340
NP_001358341
NP_001358342
NP_001358343

NP_085033

Location (UCSC)Chr 2: 227.68 – 227.72 MbChr 1: 82.99 – 83.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

Function

ThTr-2 is a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity.[5]

It is specifically inhibited by chloroquine.[8]

Clinical significance

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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135917 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038496 – 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. ^ a b c "Entrez Gene: solute carrier family 19".
  6. ^ 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.
  7. ^ 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.
  8. ^ 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. Open access icon

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. 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". Pflügers 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

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

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By group
SLC1–10
(1):
(2):
(3):
(4):
(5):
(6):
(7):
(8):
  • Na+/Ca2+ exchanger
(9):
(10):
SLC11–20
(11):
(12):
(13):
(14):
(15):
(16):
(17):
(18):
(19):
(20):
SLC21–30
(21):
(22):
(23):
  • Na+-dependent ascorbic acid transporter
(24):
  • Na+/(Ca2+-K+) exchanger
(25):
(26):
(27):
(28):
(29):
(30):
SLC31–40
(31):
(32):
(33):
(34):
(35):
(36):
(37):
(38):
(39):
(40):
  • basolateral iron transporter
SLC41–48
(41):
(42):
(43):
  • Na+-independent, system-L like amino-acid transporter
(44):
(45):
(46):
(47):
(48):
SLCO1–4
Symporter, Cotransporter
  • Na+/K+,Cl−
  • Na+/Pi3
  • Na+/Cl−
  • Na+/glucose
  • Na+/I−
  • Cl−/K+
Antiporter (exchanger)
  • Na+/H+
  • Na+/Ca2+
    • Na+/(Ca2+-K+) - Cl−/HCO−
      3       (Band 3)
  • Cl−-formate
  • Cl−-oxalate
see also solute carrier disorders


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