S19A3_HUMAN
ID S19A3_HUMAN Reviewed; 496 AA.
AC Q9BZV2;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Thiamine transporter 2;
DE Short=ThTr-2;
DE Short=ThTr2;
DE AltName: Full=Solute carrier family 19 member 3;
GN Name=SLC19A3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=11136550; DOI=10.1006/mgme.2000.3112;
RA Eudy J.D., Spiegelstein O., Barber R.C., Wlodarczyk B.J., Talbot J.,
RA Finnell R.H.;
RT "Identification and characterization of the human and mouse SLC19A3 gene: a
RT novel member of the reduced folate family of micronutrient transporter
RT genes.";
RL Mol. Genet. Metab. 71:581-590(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RA Wang H., Huang W., Srinivas S.R., Sugawara M., Devoe L.D., Leibach F.H.,
RA Ganapathy V., Prasad P.D.;
RT "Molecular cloning of an orphan transporter: a new member of the folate
RT transporter gene family.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11731220; DOI=10.1016/s0925-4439(01)00073-4;
RA Rajgopal A., Edmondnson A., Goldman I.D., Zhao R.;
RT "SLC19A3 encodes a second thiamine transporter ThTr2.";
RL Biochim. Biophys. Acta 1537:175-178(2001).
RN [6]
RP REVIEW.
RX PubMed=14770311; DOI=10.1007/s00424-003-1068-1;
RA Ganapathy V., Smith S.B., Prasad P.D.;
RT "SLC19: the folate/thiamine transporter family.";
RL Pflugers Arch. 447:641-646(2004).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-45.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP VARIANTS THMD2 VAL-23 AND ALA-422, AND TISSUE SPECIFICITY.
RX PubMed=15871139; DOI=10.1086/431216;
RA Zeng W.-Q., Al-Yamani E., Acierno J.S. Jr., Slaugenhaupt S.A., Gillis T.,
RA MacDonald M.E., Ozand P.T., Gusella J.F.;
RT "Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to
RT mutations in SLC19A3.";
RL Am. J. Hum. Genet. 77:16-26(2005).
CC -!- FUNCTION: Mediates high affinity thiamine uptake, probably via a proton
CC anti-port mechanism. Has no folate transport activity.
CC {ECO:0000269|PubMed:11731220}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) + thiamine(out) = H(+)(out) + thiamine(in);
CC Xref=Rhea:RHEA:71271, ChEBI:CHEBI:15378, ChEBI:CHEBI:18385;
CC Evidence={ECO:0000269|PubMed:11731220};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:11731220};
CC -!- INTERACTION:
CC Q9BZV2; Q8WVX3-2: C4orf3; NbExp=3; IntAct=EBI-3923779, EBI-12003442;
CC Q9BZV2; P49447: CYB561; NbExp=3; IntAct=EBI-3923779, EBI-8646596;
CC Q9BZV2; P78329: CYP4F2; NbExp=3; IntAct=EBI-3923779, EBI-1752413;
CC Q9BZV2; O00258: GET1; NbExp=3; IntAct=EBI-3923779, EBI-18908258;
CC Q9BZV2; O43561-2: LAT; NbExp=3; IntAct=EBI-3923779, EBI-8070286;
CC Q9BZV2; Q96GM1: PLPPR2; NbExp=3; IntAct=EBI-3923779, EBI-12955265;
CC Q9BZV2; P07204: THBD; NbExp=3; IntAct=EBI-3923779, EBI-941422;
CC Q9BZV2; Q9Y6G1: TMEM14A; NbExp=3; IntAct=EBI-3923779, EBI-2800360;
CC Q9BZV2; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-3923779, EBI-8638294;
CC Q9BZV2; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-3923779, EBI-10315004;
CC Q9BZV2; O95159: ZFPL1; NbExp=3; IntAct=EBI-3923779, EBI-718439;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Widely expressed but most abundant in placenta,
CC kidney and liver. {ECO:0000269|PubMed:11136550,
CC ECO:0000269|PubMed:15871139}.
CC -!- DISEASE: Thiamine metabolism dysfunction syndrome 2, biotin- or
CC thiamine-responsive type (THMD2) [MIM:607483]: An autosomal recessive
CC metabolic disorder characterized by episodic encephalopathy, often
CC triggered by febrile illness, presenting as confusion, seizures,
CC external ophthalmoplegia, dysphagia, and sometimes coma and death. If
CC untreated, encephalopathies can result in permanent dystonia. Brain
CC imaging may show characteristic bilateral lesions of the basal ganglia.
CC {ECO:0000269|PubMed:15871139}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the reduced folate carrier (RFC) transporter (TC
CC 2.A.48) family. {ECO:0000305}.
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DR EMBL; AF271633; AAG53879.1; -; mRNA.
DR EMBL; AF283317; AAK69539.1; -; mRNA.
DR EMBL; AC064853; AAX93157.1; -; Genomic_DNA.
DR EMBL; BC032014; AAH32014.1; -; mRNA.
DR CCDS; CCDS2468.1; -.
DR RefSeq; NP_079519.1; NM_025243.3.
DR RefSeq; XP_011510234.1; XM_011511932.1.
DR RefSeq; XP_011510235.1; XM_011511933.1.
DR AlphaFoldDB; Q9BZV2; -.
DR BioGRID; 123266; 19.
DR IntAct; Q9BZV2; 16.
DR MINT; Q9BZV2; -.
DR STRING; 9606.ENSP00000258403; -.
DR DrugBank; DB00152; Thiamine.
DR TCDB; 2.A.48.1.4; the reduced folate carrier (rfc) family.
DR GlyGen; Q9BZV2; 2 sites.
DR iPTMnet; Q9BZV2; -.
DR PhosphoSitePlus; Q9BZV2; -.
DR BioMuta; SLC19A3; -.
DR DMDM; 74733486; -.
DR EPD; Q9BZV2; -.
DR jPOST; Q9BZV2; -.
DR MassIVE; Q9BZV2; -.
DR MaxQB; Q9BZV2; -.
DR PaxDb; Q9BZV2; -.
DR PeptideAtlas; Q9BZV2; -.
DR PRIDE; Q9BZV2; -.
DR ProteomicsDB; 79906; -.
DR Antibodypedia; 34387; 133 antibodies from 25 providers.
DR DNASU; 80704; -.
DR Ensembl; ENST00000258403.8; ENSP00000258403.3; ENSG00000135917.16.
DR Ensembl; ENST00000644224.2; ENSP00000495385.1; ENSG00000135917.16.
DR GeneID; 80704; -.
DR KEGG; hsa:80704; -.
DR MANE-Select; ENST00000644224.2; ENSP00000495385.1; NM_025243.4; NP_079519.1.
DR UCSC; uc002vpi.4; human.
DR CTD; 80704; -.
DR DisGeNET; 80704; -.
DR GeneCards; SLC19A3; -.
DR GeneReviews; SLC19A3; -.
DR HGNC; HGNC:16266; SLC19A3.
DR HPA; ENSG00000135917; Tissue enhanced (adipose tissue, breast, placenta).
DR MalaCards; SLC19A3; -.
DR MIM; 606152; gene.
DR MIM; 607483; phenotype.
DR neXtProt; NX_Q9BZV2; -.
DR OpenTargets; ENSG00000135917; -.
DR Orphanet; 65284; Biotin-thiamine-responsive basal ganglia disease.
DR Orphanet; 263410; Infantile spasms-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR Orphanet; 199348; Thiamine-responsive encephalopathy.
DR PharmGKB; PA38397; -.
DR VEuPathDB; HostDB:ENSG00000135917; -.
DR eggNOG; KOG3810; Eukaryota.
DR GeneTree; ENSGT00950000183022; -.
DR HOGENOM; CLU_036909_0_1_1; -.
DR InParanoid; Q9BZV2; -.
DR OMA; QDVYPFG; -.
DR OrthoDB; 795242at2759; -.
DR PhylomeDB; Q9BZV2; -.
DR TreeFam; TF313684; -.
DR PathwayCommons; Q9BZV2; -.
DR Reactome; R-HSA-196819; Vitamin B1 (thiamin) metabolism.
DR SignaLink; Q9BZV2; -.
DR SIGNOR; Q9BZV2; -.
DR BioGRID-ORCS; 80704; 6 hits in 1069 CRISPR screens.
DR ChiTaRS; SLC19A3; human.
DR GeneWiki; SLC19A3; -.
DR GenomeRNAi; 80704; -.
DR Pharos; Q9BZV2; Tbio.
DR PRO; PR:Q9BZV2; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9BZV2; protein.
DR Bgee; ENSG00000135917; Expressed in subcutaneous adipose tissue and 113 other tissues.
DR ExpressionAtlas; Q9BZV2; baseline and differential.
DR Genevisible; Q9BZV2; HS.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015234; F:thiamine transmembrane transporter activity; ISS:BHF-UCL.
DR GO; GO:0071934; P:thiamine transmembrane transport; ISS:BHF-UCL.
DR GO; GO:0015888; P:thiamine transport; IDA:UniProtKB.
DR GO; GO:0042723; P:thiamine-containing compound metabolic process; TAS:Reactome.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR002666; Folate_carrier.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR028337; ThTr-2.
DR PANTHER; PTHR10686; PTHR10686; 1.
DR Pfam; PF01770; Folate_carrier; 1.
DR PIRSF; PIRSF028739; Folate_carrier; 1.
DR PIRSF; PIRSF500795; Thiamine_transporter_2; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00806; rfc; 1.
PE 1: Evidence at protein level;
KW Disease variant; Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..496
FT /note="Thiamine transporter 2"
FT /id="PRO_0000232656"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..53
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 54..74
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 75..81
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 103..110
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 132..144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..169
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..282
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 283..303
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 304..316
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 317..337
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 338..342
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 343..363
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 364..375
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 376..396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 397..405
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 406..426
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 427..434
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 435..455
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 456..496
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 468..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 23
FT /note="G -> V (in THMD2; dbSNP:rs121917882)"
FT /evidence="ECO:0000269|PubMed:15871139"
FT /id="VAR_025992"
FT VARIANT 174
FT /note="V -> I (in dbSNP:rs59736804)"
FT /id="VAR_061864"
FT VARIANT 350
FT /note="V -> A (in dbSNP:rs34507036)"
FT /id="VAR_052405"
FT VARIANT 422
FT /note="T -> A (in THMD2; dbSNP:rs121917884)"
FT /evidence="ECO:0000269|PubMed:15871139"
FT /id="VAR_025993"
SQ SEQUENCE 496 AA; 55665 MW; B102651C205F0F16 CRC64;
MDCYRTSLSS SWIYPTVILC LFGFFSMMRP SEPFLIPYLS GPDKNLTSAE ITNEIFPVWT
YSYLVLLLPV FVLTDYVRYK PVIILQGISF IITWLLLLFG QGVKTMQVVE FFYGMVTAAE
VAYYAYIYSV VSPEHYQRVS GYCRSVTLAA YTAGSVLAQL LVSLANMSYF YLNVISLASV
SVAFLFSLFL PMPKKSMFFH AKPSREIKKS SSVNPVLEET HEGEAPGCEE QKPTSEILST
SGKLNKGQLN SLKPSNVTVD VFVQWFQDLK ECYSSKRLFY WSLWWAFATA GFNQVLNYVQ
ILWDYKAPSQ DSSIYNGAVE AIATFGGAVA AFAVGYVKVN WDLLGELALV VFSVVNAGSL
FLMHYTANIW ACYAGYLIFK SSYMLLITIA VFQIAVNLNV ERYALVFGIN TFIALVIQTI
MTVIVVDQRG LNLPVSIQFL VYGSYFAVIA GIFLMRSMYI TYSTKSQKDV QSPAPSENPD
VSHPEEESNI IMSTKL
