Difference between revisions of "SLC19A2"

Jump to: navigation, search
m (Bot: HTTP→HTTPS)
imported>Boghog
(consistent citation formatting and removed further reading citations not specific to this gene)
 
Line 1: Line 1:
 
{{Infobox_gene}}
 
{{Infobox_gene}}
'''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]].<ref name="entrez">{{cite web | title = Entrez Gene: solute carrier family 19 (thiamine transporter)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10560| accessdate = }}</ref><ref name="pmid9399900">{{cite journal |author1=Neufeld EJ |author2=Mandel H |author3=Raz T |author4=Szargel R |author5=Yandava CN |author6=Stagg A |author7=Fauré S |author8=Barrett T |author9=Buist N |author10=Cohen N | title = Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping | journal = Am. J. Hum. Genet. | volume = 61 | issue = 6 | pages = 1335–41 |date=December 1997 | pmid = 9399900 | pmc = 1716091 | doi = 10.1086/301642 | url = | issn = }}</ref><ref name="pmid10391221">{{cite journal |author1=Labay V |author2=Raz T |author3=Baron D |author4=Mandel H |author5=Williams H |author6=Barrett T |author7=Szargel R |author8=McDonald L |author9=Shalata A |author10=Nosaka K |author11=Gregory S |author12=Cohen N | title = Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness | journal = Nat. Genet. | volume = 22 | issue = 3 | pages = 300–4 |date=July 1999 | pmid = 10391221 | doi = 10.1038/10372 | url = | issn = }}</ref> SLC19A2 is a [[thiamine]] transporter.
+
'''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]].<ref name="pmid9399900">{{cite journal | vauthors = Neufeld EJ, Mandel H, Raz T, Szargel R, Yandava CN, Stagg A, Fauré S, Barrett T, Buist N, Cohen N | title = Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping | journal = American Journal of Human Genetics | volume = 61 | issue = 6 | pages = 1335–41 | date = December 1997 | pmid = 9399900 | pmc = 1716091 | doi = 10.1086/301642 }}</ref> SLC19A2 is a [[thiamine]] [[Membrane transport protein|transporter]]. [[Mutation|Mutations]] in this gene cause [[Thiamine responsive megaloblastic anemia syndrome|thiamine-responsive megaloblastic anemia syndrome (TRMA)]], which is an [[Genetic_disorder#Autosomal_recessive|autosomal recessive]] disorder characterized by [[diabetes mellitus]], [[megaloblastic anemia]] and [[Sensorineural hearing loss|sensorineural deafness]].<ref name="pmid20835854">{{cite journal | vauthors = Bay A, Keskin M, Hizli S, Uygun H, Dai A, Gumruk F | title = Thiamine-responsive megaloblastic anemia syndrome | journal = International Journal of Hematology | volume = 92 | issue = 3 | pages = 524–6 | date = October 2010 | pmid = 20835854 | doi = 10.1007/s12185-010-0681-y }}</ref><ref name="entrez">{{cite web|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10560|title=Entrez Gene: solute carrier family 19 (thiamine transporter)|access-date=}}{{PD-notice}}</ref><ref name="pmid10391221">{{cite journal | vauthors = Labay V, Raz T, Baron D, Mandel H, Williams H, Barrett T, Szargel R, McDonald L, Shalata A, Nosaka K, Gregory S, Cohen N | title = Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness | journal = Nature Genetics | volume = 22 | issue = 3 | pages = 300–4 | date = July 1999 | pmid = 10391221 | doi = 10.1038/10372 }}</ref>
  
In melanocytic cells SLC19A2 gene expression may be regulated by [[Microphthalmia-associated transcription factor|MITF]].<ref name="pmid19067971">{{cite journal  |vauthors=Hoek KS, Schlegel NC, Eichhoff OM, etal | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell Melanoma Res. | volume = 21 | issue = 6 | pages = 665–76 | year = 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x | issn = }}</ref>
+
== Structure ==
 +
The ''SLC19A2'' gene is located on the q arm of [[chromosome 1]] in position 24.2 and spans 22,062 base pairs.<ref name = "entrez"/> The gene produces a 55.4 kDa protein composed of 497 [[amino acids]].<ref name=COPaKB>{{cite journal | vauthors = 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 | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref><ref name="url_COPaKB">{{cite web | url = https://amino.heartproteome.org/web/protein/O60779 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = SLC19A2 - Thiamine transporter 1 }}</ref> In the encoded protein (TC1), a [[Integral_membrane_protein#Integral_polytopic_protein|multi-pass]] [[Integral membrane protein|membrane protein]] located in the [[cell membrane]], the [[N-terminus]] and [[C-terminus]] face the [[cytosol]].<ref name=":0">{{Cite web|url=https://www.uniprot.org/uniprot/Q9UBX3|title=SLC19A2 - Thiamine transporter 1 - Homo sapiens (Human) - SLC19A2 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-21}}{{CC-notice|cc=by4}}</ref><ref name=":3">{{cite journal | vauthors = | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158-D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 | url = https://doi.org/10.1093/nar/gkw1099 }}</ref> This gene has 6 [[exon|exons]] while the protein has 12 [[Putative_gene|putative]] [[Transmembrane domain|transmembrane domains]], with 3 [[Protein_phosphorylation#Sites|phosphorylation sites]] in putative intracellular domains, 2 [[N-linked glycosylation|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% [[Sequence_homology#Identity,_similarity,_and_conservation|shared amino acid identity]] with the [[folate]] transporter [[SLC19A1]].<ref name=":1">{{cite journal | vauthors = Dutta B, Huang W, Molero M, Kekuda R, Leibach FH, Devoe LD, Ganapathy V, Prasad PD | title = Cloning of the human thiamine transporter, a member of the folate transporter family | journal = The Journal of Biological Chemistry | volume = 274 | issue = 45 | pages = 31925–9 | date = November 1999 | pmid = 10542220 }}</ref> The N-terminal domain and the sequence between the C-terminal domain and sixth transmembrane domain are required for proper [[Protein subcellular localization prediction|localization]] of this protein to the cell membrane.<ref name=":2">{{cite journal | vauthors = Subramanian VS, Marchant JS, Parker I, Said HM | title = Cell biology of the human thiamine transporter-1 (hTHTR1). Intracellular trafficking and membrane targeting mechanisms | journal = The Journal of Biological Chemistry | volume = 278 | issue = 6 | pages = 3976–84 | date = February 2003 | pmid = 12454006 | doi = 10.1074/jbc.M210717200 }}</ref><ref name=":4">Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {603941}: {11/22/2017}: . World Wide Web URL: https://omim.org/</ref>
 +
 
 +
== Function ==
 +
The encoded protein is a high-affinity transporter [[Chemical_specificity#Enzyme_specificity|specific]] to the intake of thiamine.<ref name=":0" /><ref name=":3" /> Thiamine transport is not [[Competitive inhibition|inhibited]] by other organic cations nor affected by [[Sodium#Biological_role|sodium ion]] concentration; it is stimulated by a [[Chemiosmosis#The_proton-motive_force|proton gradient]] directed outward, with an optimal [[pH]] between 8.0 and 8.5.<ref name=":1" /> TC1 is [[Intracellular transport|transported]] to the cell membrane by intracellular [[Vesicle_(biology_and_chemistry)|vesicles]] via [[microtubule]]s.<ref name=":2" /><ref name=":4" />
  
 
== Clinical significance ==
 
== 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. [[Age_of_onset|Onset]] is typically between [[Infant|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 neuropathy|optic atrophy]], [[Congenital heart defect|congenital heart defects]], short stature, and [[stroke]].<ref name=":0" /><ref name=":3" />
  
Mutations in this gene cause thiamin-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disorder characterized by [[diabetes mellitus]], [[megaloblastic anemia]] and sensorineural deafness.<ref name="pmid20835854">{{cite journal |author1=Bay A |author2=Keskin M |author3=Hizli S |author4=Uygun H |author5=Dai A |author6=Gumruk F | title = Thiamine-responsive megaloblastic anemia syndrome | journal = Int. J. Hematol. | volume = 92 | issue = 3 | pages = 524–6 |date=October 2010 | pmid = 20835854 | doi = 10.1007/s12185-010-0681-y | url = | issn = }}</ref>
+
A 3.8 kb [[Primary transcript|transcript]] is [[gene expression|expressed]] variably in most tissues, highest in [[skeletal muscle|skeletal]] and [[cardiac muscle]], followed by medium expression [[placenta]], [[heart]], [[liver]], [[kidney]] cells and low expression in [[lung]] cells. In [[Melanocyte|melanocytic cells]] ''SLC19A2'' [[gene expression]] may be [[Regulation of gene expression|regulated]] by [[Microphthalmia-associated transcription factor|MITF]].<ref name="pmid19067971">{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell & Melanoma Research | volume = 21 | issue = 6 | pages = 665–76 | date = December 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x }}</ref>  
  
==References==
+
== Interactions ==
{{reflist}}
+
This protein [[protein-protein interactions|interacts]] with [[Ceramide synthase 2|CERS2]].<ref>{{Cite web|url=https://www.ebi.ac.uk/intact/interactors/id:O60779*#|title=https://www.ebi.ac.uk/intact/interactors/id:O60779*#|last=IntAct|website=www.ebi.ac.uk|language=en|access-date=2018-08-23}}</ref>
  
==Further reading==
+
== References ==
{{refbegin|35em}}
+
{{reflist|32em}}
*{{cite journal   |vauthors=Guerrini I, Thomson AD, Cook CC, etal |title=Direct genomic PCR sequencing of the high affinity thiamine transporter (SLC19A2) gene identifies three genetic variants in Wernicke Korsakoff syndrome (WKS). |journal=Am. J. Med. Genet. B Neuropsychiatr. Genet. |volume=137B |issue= 1 |pages= 17–9 |year= 2005 |pmid= 16015585 |doi= 10.1002/ajmg.b.30194 }}
+
 
*{{cite journal   |vauthors=Subramanian VS, Mohammed ZM, Molina A, etal |title=Vitamin B1 (thiamine) uptake by human retinal pigment epithelial (ARPE-19) cells: mechanism and regulation. |journal=J. Physiol. |volume=582 |issue= Pt 1 |pages= 73–85 |year= 2007 |pmid= 17463047  |pmc=2075275 |doi= 10.1113/jphysiol.2007.128843 }}
+
== Further reading ==
*{{cite journal |author1=Ashokkumar B |author2=Vaziri ND |author3=Said HM |title=Thiamin uptake by the human-derived renal epithelial (HEK-293) cells: cellular and molecular mechanisms. |journal=Am. J. Physiol. Renal Physiol. |volume=291 |issue= 4 |pages= F796–805 |year= 2006 |pmid= 16705148 |doi= 10.1152/ajprenal.00078.2006 }}
+
{{refbegin|32em}}
*{{cite journal |author1=Nabokina SM |author2=Reidling JC |author3=Said HM |title=Differentiation-dependent up-regulation of intestinal thiamin uptake: cellular and molecular mechanisms. |journal=J. Biol. Chem. |volume=280 |issue= 38 |pages= 32676–82 |year= 2005 |pmid= 16055442 |doi= 10.1074/jbc.M505243200 }}
+
* {{cite journal | vauthors = Scharfe C, Hauschild M, Klopstock T, Janssen AJ, Heidemann PH, Meitinger T, Jaksch M | title = A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I | journal = Journal of Medical Genetics | volume = 37 | issue = 9 | pages = 669–73 | date = September 2000 | pmid = 10978358 }}
*{{cite journal   |vauthors=Gregory SG, Barlow KF, McLay KE, etal |title=The DNA sequence and biological annotation of human chromosome 1. |journal=Nature |volume=441 |issue= 7091 |pages= 315–21 |year= 2006 |pmid= 16710414 |doi= 10.1038/nature04727 }}
+
* {{cite journal | vauthors = Guerrini I, Thomson AD, Cook CC, McQuillin A, Sharma V, Kopelman M, Reynolds G, Jauhar P, Harper C, Gurling HM | title = Direct genomic PCR sequencing of the high affinity thiamine transporter (SLC19A2) gene identifies three genetic variants in Wernicke Korsakoff syndrome (WKS) | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 137B | issue = 1 | pages = 17–9 | date = August 2005 | pmid = 16015585 | doi = 10.1002/ajmg.b.30194 }}
*{{cite journal   |vauthors=Barbe L, Lundberg E, Oksvold P, etal |title=Toward a confocal subcellular atlas of the human proteome. |journal=Mol. Cell. Proteomics |volume=7 |issue= 3 |pages= 499–508 |year= 2008 |pmid= 18029348 |doi= 10.1074/mcp.M700325-MCP200 }}
+
* {{cite journal | vauthors = Subramanian VS, Mohammed ZM, Molina A, Marchant JS, Vaziri ND, Said HM | title = Vitamin B1 (thiamine) uptake by human retinal pigment epithelial (ARPE-19) cells: mechanism and regulation | journal = The Journal of Physiology | volume = 582 | issue = Pt 1 | pages = 73–85 | date = July 2007 | pmid = 17463047 | pmc = 2075275 | doi = 10.1113/jphysiol.2007.128843 }}
*{{cite journal   |vauthors=Ehret GB, O'Connor AA, Weder A, etal |title=Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study. |journal=Eur. J. Hum. Genet. |volume=17 |issue= 12 |pages= 1650–7 |year= 2009 |pmid= 19536175 |pmc=2783544 |doi= 10.1038/ejhg.2009.94 }}
+
* {{cite journal | vauthors = Ashokkumar B, Vaziri ND, Said HM | title = Thiamin uptake by the human-derived renal epithelial (HEK-293) cells: cellular and molecular mechanisms | journal = American Journal of Physiology. Renal Physiology | volume = 291 | issue = 4 | pages = F796-805 | date = October 2006 | pmid = 16705148 | doi = 10.1152/ajprenal.00078.2006 }}
*{{cite journal   |vauthors=Talmud PJ, Drenos F, Shah S, etal |title=Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. |journal=Am. J. Hum. Genet. |volume=85 |issue= 5 |pages= 628–42 |year= 2009 |pmid= 19913121  |pmc=2775832 |doi= 10.1016/j.ajhg.2009.10.014 }}
+
* {{cite journal | vauthors = Nabokina SM, Reidling JC, Said HM | title = Differentiation-dependent up-regulation of intestinal thiamin uptake: cellular and molecular mechanisms | journal = The Journal of Biological Chemistry | volume = 280 | issue = 38 | pages = 32676–82 | date = September 2005 | pmid = 16055442 | doi = 10.1074/jbc.M505243200 }}
*{{cite journal |author1=Olsen BS |author2=Hahnemann JM |author3=Schwartz M |author4=Østergaard E |title=Thiamine-responsive megaloblastic anaemia: a cause of syndromic diabetes in childhood. |journal=Pediatr Diabetes |volume=8 |issue= 4 |pages= 239–41 |year= 2007 |pmid= 17659067 |doi= 10.1111/j.1399-5448.2007.00251.x }}
+
* {{cite journal | vauthors = Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H | title = Toward a confocal subcellular atlas of the human proteome | journal = Molecular & Cellular Proteomics | volume = 7 | issue = 3 | pages = 499–508 | date = March 2008 | pmid = 18029348 | doi = 10.1074/mcp.M700325-MCP200 }}
*{{cite journal |author1=Subramanian VS |author2=Marchant JS |author3=Said HM |title=Targeting and intracellular trafficking of clinically relevant hTHTR1 mutations in human cell lines. |journal=Clin. Sci. |volume=113 |issue= 2 |pages= 93–102 |year= 2007 |pmid= 17331069 |doi= 10.1042/CS20060331 }}
+
* {{cite journal | vauthors = Ehret GB, O'Connor AA, Weder A, Cooper RS, Chakravarti A | title = Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study | journal = European Journal of Human Genetics | volume = 17 | issue = 12 | pages = 1650–7 | date = December 2009 | pmid = 19536175 | pmc = 2783544 | doi = 10.1038/ejhg.2009.94 }}
*{{cite journal   |vauthors=Pei LJ, Zhu HP, Li ZW, etal |title=Interaction between maternal periconceptional supplementation of folic acid and reduced folate carrier gene polymorphism of neural tube defects. |journal=Zhonghua Yi Xue Yi Chuan Xue Za Zhi |volume=22 |issue= 3 |pages= 284–7 |year= 2005 |pmid= 15952116 |doi= }}
+
* {{cite journal | vauthors = Olsen BS, Hahnemann JM, Schwartz M, Østergaard E | title = Thiamine-responsive megaloblastic anaemia: a cause of syndromic diabetes in childhood | journal = Pediatric Diabetes | volume = 8 | issue = 4 | pages = 239–41 | date = August 2007 | pmid = 17659067 | doi = 10.1111/j.1399-5448.2007.00251.x }}
*{{cite journal |author=Haas RH |title=Thiamin and the brain. |journal=Annu. Rev. Nutr. |volume=8 |issue= |pages= 483–515 |year= 1988 |pmid= 3060175 |doi= 10.1146/annurev.nu.08.070188.002411 }}
+
* {{cite journal | vauthors = Subramanian VS, Marchant JS, Said HM | title = Targeting and intracellular trafficking of clinically relevant hTHTR1 mutations in human cell lines | journal = Clinical Science | volume = 113 | issue = 2 | pages = 93–102 | date = July 2007 | pmid = 17331069 | doi = 10.1042/CS20060331 }}
*{{cite journal   |vauthors=Ricketts CJ, Minton JA, Samuel J, etal |title=Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families. |journal=Acta Paediatr. |volume=95 |issue= 1 |pages= 99–104 |year= 2006 |pmid= 16373304 |doi= 10.1080/08035250500323715 }}
+
* {{cite journal | vauthors = Pei LJ, Zhu HP, Li ZW, Zhang W, Ren AG, Zhu JH, Li Z | title = Interaction between maternal periconceptional supplementation of folic acid and reduced folate carrier gene polymorphism of neural tube defects | journal = Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics | volume = 22 | issue = 3 | pages = 284–7 | date = June 2005 | pmid = 15952116 | doi = }}
*{{cite journal |author1=Lagarde WH |author2=Underwood LE |author3=Moats-Staats BM |author4=Calikoglu AS |title=Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome. |journal=Am. J. Med. Genet. A |volume=125A |issue= 3 |pages= 299–305 |year= 2004 |pmid= 14994241 |doi= 10.1002/ajmg.a.20506 }}
+
* {{cite journal | vauthors = Haas RH | title = Thiamin and the brain | journal = Annual Review of Nutrition | volume = 8 | issue = | pages = 483–515 | year = 1988 | pmid = 3060175 | doi = 10.1146/annurev.nu.08.070188.002411 }}
*{{cite journal   |vauthors=Ashton LJ, Gifford AJ, Kwan E, etal |title=Reduced folate carrier and methylenetetrahydrofolate reductase gene polymorphisms: associations with clinical outcome in childhood acute lymphoblastic leukemia. |journal=Leukemia |volume=23 |issue= 7 |pages= 1348–51 |year= 2009 |pmid= 19340000 |doi= 10.1038/leu.2009.67 }}
+
* {{cite journal | vauthors = Ricketts CJ, Minton JA, Samuel J, Ariyawansa I, Wales JK, Lo IF, Barrett TG | title = Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families | journal = Acta Paediatrica | volume = 95 | issue = 1 | pages = 99–104 | date = January 2006 | pmid = 16373304 | doi = 10.1080/08035250500323715 }}
*{{cite journal   |vauthors=Bergmann AK, Campagna DR, McLoughlin EM, etal |title=Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations. |journal=Pediatr Blood Cancer |volume=54 |issue= 2 |pages= 273–8 |year= 2010 |pmid= 19731322  |pmc=2843911 |doi= 10.1002/pbc.22244 }}
+
* {{cite journal | vauthors = Lagarde WH, Underwood LE, Moats-Staats BM, Calikoglu AS | title = Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome | journal = American Journal of Medical Genetics. Part A | volume = 125A | issue = 3 | pages = 299–305 | date = March 2004 | pmid = 14994241 | doi = 10.1002/ajmg.a.20506 }}
*{{cite journal |author1=Subramanian VS |author2=Marchant JS |author3=Said HM |title=Targeting and trafficking of the human thiamine transporter-2 in epithelial cells. |journal=J. Biol. Chem. |volume=281 |issue= 8 |pages= 5233–45 |year= 2006 |pmid= 16371350 |doi= 10.1074/jbc.M512765200 }}
+
* {{cite journal | vauthors = Ashton LJ, Gifford AJ, Kwan E, Lingwood A, Lau DT, Marshall GM, Haber M, Norris MD | title = Reduced folate carrier and methylenetetrahydrofolate reductase gene polymorphisms: associations with clinical outcome in childhood acute lymphoblastic leukemia | journal = Leukemia | volume = 23 | issue = 7 | pages = 1348–51 | date = July 2009 | pmid = 19340000 | doi = 10.1038/leu.2009.67 }}
*{{cite journal   |vauthors=Mee L, Nabokina SM, Sekar VT, etal |title=Pancreatic beta cells and islets take up thiamin by a regulated carrier-mediated process: studies using mice and human pancreatic preparations. |journal=Am. J. Physiol. Gastrointest. Liver Physiol. |volume=297 |issue= 1 |pages= G197–206 |year= 2009 |pmid= 19423748  |pmc=2711754 |doi= 10.1152/ajpgi.00092.2009 }}
+
* {{cite journal | vauthors = Bergmann AK, Campagna DR, McLoughlin EM, Agarwal S, Fleming MD, Bottomley SS, Neufeld EJ | title = Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations | journal = Pediatric Blood & Cancer | volume = 54 | issue = 2 | pages = 273–8 | date = February 2010 | pmid = 19731322 | pmc = 2843911 | doi = 10.1002/pbc.22244 }}
*{{cite journal   |vauthors=Cheung CL, Chan BY, Chan V, etal |title=Pre-B-cell leukemia homeobox 1 (PBX1) shows functional and possible genetic association with bone mineral density variation. |journal=Hum. Mol. Genet. |volume=18 |issue= 4 |pages= 679–87 |year= 2009 |pmid= 19064610 |doi= 10.1093/hmg/ddn397 }}
+
* {{cite journal | vauthors = Subramanian VS, Marchant JS, Said HM | title = Targeting and trafficking of the human thiamine transporter-2 in epithelial cells | journal = The Journal of Biological Chemistry | volume = 281 | issue = 8 | pages = 5233–45 | date = February 2006 | pmid = 16371350 | doi = 10.1074/jbc.M512765200 }}
*{{cite journal  |vauthors=Bailey SD, Xie C, Do R, etal |title=Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. |journal=Diabetes Care |volume=33 |issue= 10 |pages= 2250–3 |year= 2010 |pmid= 20628086 |pmc=2945168 |doi= 10.2337/dc10-0452 }}
+
* {{cite journal | vauthors = Mee L, Nabokina SM, Sekar VT, Subramanian VS, Maedler K, Said HM | title = Pancreatic beta cells and islets take up thiamin by a regulated carrier-mediated process: studies using mice and human pancreatic preparations | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 297 | issue = 1 | pages = G197-206 | date = July 2009 | pmid = 19423748 | pmc = 2711754 | doi = 10.1152/ajpgi.00092.2009 }}
 +
* {{cite journal | vauthors = Cheung CL, Chan BY, Chan V, Ikegawa S, Kou I, Ngai H, Smith D, Luk KD, Huang QY, Mori S, Sham PC, Kung AW | title = Pre-B-cell leukemia homeobox 1 (PBX1) shows functional and possible genetic association with bone mineral density variation | journal = Human Molecular Genetics | volume = 18 | issue = 4 | pages = 679–87 | date = February 2009 | pmid = 19064610 | doi = 10.1093/hmg/ddn397 }}
 +
* {{cite journal | vauthors = Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, Keavney B, Yusuf S, Gerstein HC, Engert JC, Anand S | title = Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study | journal = Diabetes Care | volume = 33 | issue = 10 | pages = 2250–3 | date = October 2010 | pmid = 20628086 | pmc = 2945168 | doi = 10.2337/dc10-0452 }}
 
{{refend}}
 
{{refend}}
  
==External links==
+
== External links ==
 
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=trma  GeneReviews/NIH/NCBI/UW entry on Thiamine-Responsive Megaloblastic Anemia or Rogers Syndrome]
 
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=trma  GeneReviews/NIH/NCBI/UW entry on Thiamine-Responsive Megaloblastic Anemia or Rogers Syndrome]
 
* {{MeshName|SLC19A2+protein,+human}}
 
* {{MeshName|SLC19A2+protein,+human}}
  
 
{{Membrane transport proteins}}
 
{{Membrane transport proteins}}
 
+
{{NLM content}}
 +
{{Portal bar|Mitochondria|Gene Wiki}}
 
[[Category:Solute carrier family]]
 
[[Category:Solute carrier family]]
 
 
{{membrane-protein-stub}}
 

Latest revision as of 12:52, 23 August 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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. 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.
  2. 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.
  3. 3.0 3.1 "Entrez Gene: solute carrier family 19 (thiamine transporter)". This article incorporates text from this source, which is in the public domain.
  4. 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.
  5. 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.
  6. "SLC19A2 - Thiamine transporter 1". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  7. 7.0 7.1 7.2 "SLC19A2 - Thiamine transporter 1 - Homo sapiens (Human) - SLC19A2 gene & protein". www.uniprot.org. Retrieved 2018-08-21.80px 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. PMC 5210571. PMID 27899622.
  9. 9.0 9.1 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. PMID 10542220.
  10. 10.0 10.1 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.
  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. 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.
  13. IntAct. "https://www.ebi.ac.uk/intact/interactors/id:O60779*#". www.ebi.ac.uk. Retrieved 2018-08-23. External link in |title= (help)

Further reading

External links

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


Linked-in.jpg