Q9BZV2 (S19A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thiamine transporter 2
Short name=ThTr-2
Short name=ThTr2

Alternative name(s):
Solute carrier family 19 member 3

Gene names

Name:

SLC19A3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	496 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates high affinity thiamine uptake, propably via a proton anti-port mechanism. Has no folate transport activity. Ref.5
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Widely expressed but most abundant in placenta, kidney and liver. Ref.1 Ref.8
Involvement in disease	Thiamine metabolism dysfunction syndrome 2, biotin- or thiamine-responsive type (THMD2) [MIM:607483]: An autosomal recessive metabolic disorder characterized by episodic encephalopathy, often triggered by febrile illness, presenting as confusion, seizures, external ophthalmoplegia, dysphagia, and sometimes coma and death. If untreated, encephalopathies can result in permanent dystonia. Brain imaging may show characteristic bilateral lesions of the basal ganglia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8
Sequence similarities	Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family. [View classification]

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	thiamine-containing compound metabolic process Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	folic acid binding Inferred from electronic annotation. Source: InterPro reduced folate carrier activity Inferred from electronic annotation. Source: InterPro thiamine uptake transmembrane transporter activity Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 496	496	Thiamine transporter 2		PRO_0000232656
Regions
	Topological domain	1 – 7	7	Cytoplasmic Potential
	Transmembrane	8 – 28	21	Helical; Potential
	Topological domain	29 – 53	25	Extracellular Potential
	Transmembrane	54 – 74	21	Helical; Potential
	Topological domain	75 – 81	7	Cytoplasmic Potential
	Transmembrane	82 – 102	21	Helical; Potential
	Topological domain	103 – 110	8	Extracellular Potential
	Transmembrane	111 – 131	21	Helical; Potential
	Topological domain	132 – 144	13	Cytoplasmic Potential
	Transmembrane	145 – 165	21	Helical; Potential
	Topological domain	166 – 169	4	Extracellular Potential
	Transmembrane	170 – 190	21	Helical; Potential
	Topological domain	191 – 282	92	Cytoplasmic Potential
	Transmembrane	283 – 303	21	Helical; Potential
	Topological domain	304 – 316	13	Extracellular Potential
	Transmembrane	317 – 337	21	Helical; Potential
	Topological domain	338 – 342	5	Cytoplasmic Potential
	Transmembrane	343 – 363	21	Helical; Potential
	Topological domain	364 – 375	12	Extracellular Potential
	Transmembrane	376 – 396	21	Helical; Potential
	Topological domain	397 – 405	9	Cytoplasmic Potential
	Transmembrane	406 – 426	21	Helical; Potential
	Topological domain	427 – 434	8	Extracellular Potential
	Transmembrane	435 – 455	21	Helical; Potential
	Topological domain	456 – 496	41	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	45	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	166	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	23	1	G → V in THMD2. Ref.8		VAR_025992
	Natural variant	174	1	V → I. Corresponds to variant rs59736804 [ dbSNP | Ensembl ].		VAR_061864
	Natural variant	350	1	V → A. Corresponds to variant rs34507036 [ dbSNP | Ensembl ].		VAR_052405
	Natural variant	422	1	T → A in THMD2. Ref.8		VAR_025993

Sequences

	Sequence		Length	Mass (Da)
	Q9BZV2 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: B102651C205F0F16	FASTA	496	55,665
	10 20 30 40 50 60 MDCYRTSLSS SWIYPTVILC LFGFFSMMRP SEPFLIPYLS GPDKNLTSAE ITNEIFPVWT 70 80 90 100 110 120 YSYLVLLLPV FVLTDYVRYK PVIILQGISF IITWLLLLFG QGVKTMQVVE FFYGMVTAAE 130 140 150 160 170 180 VAYYAYIYSV VSPEHYQRVS GYCRSVTLAA YTAGSVLAQL LVSLANMSYF YLNVISLASV 190 200 210 220 230 240 SVAFLFSLFL PMPKKSMFFH AKPSREIKKS SSVNPVLEET HEGEAPGCEE QKPTSEILST 250 260 270 280 290 300 SGKLNKGQLN SLKPSNVTVD VFVQWFQDLK ECYSSKRLFY WSLWWAFATA GFNQVLNYVQ 310 320 330 340 350 360 ILWDYKAPSQ DSSIYNGAVE AIATFGGAVA AFAVGYVKVN WDLLGELALV VFSVVNAGSL 370 380 390 400 410 420 FLMHYTANIW ACYAGYLIFK SSYMLLITIA VFQIAVNLNV ERYALVFGIN TFIALVIQTI 430 440 450 460 470 480 MTVIVVDQRG LNLPVSIQFL VYGSYFAVIA GIFLMRSMYI TYSTKSQKDV QSPAPSENPD 490 VSHPEEESNI IMSTKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of the human and mouse SLC19A3 gene: a novel member of the reduced folate family of micronutrient transporter genes." Eudy J.D., Spiegelstein O., Barber R.C., Wlodarczyk B.J., Talbot J., Finnell R.H. Mol. Genet. Metab. 71:581-590(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Placenta.
[2]	"Molecular cloning of an orphan transporter: a new member of the folate transporter gene family." Wang H., Huang W., Srinivas S.R., Sugawara M., Devoe L.D., Leibach F.H., Ganapathy V., Prasad P.D. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"SLC19A3 encodes a second thiamine transporter ThTr2." Rajgopal A., Edmondnson A., Goldman I.D., Zhao R. Biochim. Biophys. Acta 1537:175-178(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"SLC19: the folate/thiamine transporter family." Ganapathy V., Smith S.B., Prasad P.D. Pflugers Arch. 447:641-646(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[7]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-45, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3." Zeng W.-Q., Al-Yamani E., Acierno J.S. Jr., Slaugenhaupt S.A., Gillis T., MacDonald M.E., Ozand P.T., Gusella J.F. Am. J. Hum. Genet. 77:16-26(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THMD2 VAL-23 AND ALA-422, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF271633 mRNA. Translation: AAG53879.1. AF283317 mRNA. Translation: AAK69539.1. AC064853 Genomic DNA. Translation: AAX93157.1. BC032014 mRNA. Translation: AAH32014.1.
IPI	IPI00019278.
RefSeq	NP_079519.1. NM_025243.3.
UniGene	Hs.221597.
3D structure databases
ProteinModelPortal	Q9BZV2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BZV2. 3 interactions.
STRING	9606.ENSP00000258403.
Polymorphism databases
DMDM	74733486.
Proteomic databases
PaxDb	Q9BZV2.
PRIDE	Q9BZV2.
Protocols and materials databases
DNASU	80704.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258403; ENSP00000258403; ENSG00000135917. ENST00000425817; ENSP00000397393; ENSG00000135917.
GeneID	80704.
KEGG	hsa:80704.
UCSC	uc002vpi.3. human.
Organism-specific databases
CTD	80704.
GeneCards	GC02M228513.
HGNC	HGNC:16266. SLC19A3.
HPA	HPA038898.
MIM	606152. gene. 607483. phenotype.
neXtProt	NX_Q9BZV2.
Orphanet	65284. Biotin-responsive basal ganglia disease. 263410. Infantile spams - psychomotor retardation - progressive brain atrophy - basal ganglia disease. 199348. Thiamine-responsive encephalopathy.
PharmGKB	PA38397.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG241030.
HOGENOM	HOG000001583.
HOVERGEN	HBG054198.
InParanoid	Q9BZV2.
KO	K14610.
OMA	ANLSYFY.
OrthoDB	EOG4N04F7.
PhylomeDB	Q9BZV2.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9BZV2.
Bgee	Q9BZV2.
CleanEx	HS_SLC19A3.
Genevestigator	Q9BZV2.
GermOnline	ENSG00000135917. Homo sapiens.
Family and domain databases
InterPro	IPR002666. Folate_carrier. IPR016196. MFS_dom_general_subst_transpt. [Graphical view]
PANTHER	PTHR10686. PTHR10686. 1 hit.
Pfam	PF01770. Folate_carrier. 1 hit. [Graphical view]
PIRSF	PIRSF028739. Folate_carrier. 1 hit.
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
TIGRFAMs	TIGR00806. rfc. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	SLC19A3. human.
DrugBank	DB00151. L-Cysteine.
GenomeRNAi	80704.
NextBio	70999.
SOURCE	Search...

Entry information

Entry name

S19A3_HUMAN

Accession

Primary (citable) accession number: Q9BZV2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 18, 2006
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.