Thiamine transporter 1

SLC19A2
Identifiers
Aliases	SLC19A2, TC1, THMD1, THT1, THTR1, TRMA, solute carrier family 19 member 2
External IDs	OMIM: 603941; MGI: 1928761; HomoloGene: 38258; GeneCards: SLC19A2; OMA:SLC19A2 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q24.2 Start 169,463,909 bp[1] End 169,485,944 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 H2.2|1 71.56 cM Start 164,076,615 bp[2] End 164,092,954 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte gastrocnemius muscle tibialis anterior muscle Skeletal muscle tissue of rectus abdominis biceps brachii deltoid muscle muscle of thigh gastric mucosa buccal mucosa cell body of tongue Top expressed in retinal pigment epithelium left lobe of liver facial motor nucleus medullary collecting duct cornea endothelial cell of lymphatic vessel interventricular septum motor neuron cumulus cell spermatocyte More reference expression data BioGPS n/a
Gene ontology Molecular function folic acid transmembrane transporter activity protein binding 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 folic acid transport thiamine transmembrane transport vitamin transport transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 1: 164.08 – 164.09 Mb PubMed search [3] [4]
Wikidata
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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

Further reading

External links

• GeneReviews/NIH/NCBI/UW entry on Thiamine-Responsive Megaloblastic Anemia or Rogers Syndrome
• SLC19A2+protein,+human at the U.S. 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.