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Reviewed, UniProtKB/Swiss-Prot P41440 (S19A1_HUMAN)

Last modified November 25, 2008. Version 67. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Folate transporter 1
      Short name=FOLT
Alternative name(s):
    Reduced folate carrier protein
      Short name=RFC
    Intestinal folate carrier
    IFC-1
    Placental folate transporter
    Solute carrier family 19 member 1
Gene names
Name: SLC19A1
Synonyms: FLOT1, RFC1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length591 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Transporter for the intake of folate. Uptake of folate in human placental choriocarcinoma cells occurs by a novel mechanism called potocytosis which functionally couples three components, namely the folate receptor, the folate transporter, and a V-type H(+)-pump.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Placenta, liver, and to a much smaller extent, in lung.

Post-translational modification

Heavily glycosylated.

Sequence similarities

Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family. [View classification]

Ontologies

Keywords

   Biological processTransport
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
   LigandFolate-binding
   PTMGlycoprotein
Phosphoprotein

Gene Ontology (GO)

   Biological processfolic acid transport Ref.1

Traceable author statement. Source: ProtInc

   Cellular componentintegral to plasma membrane Ref.1

Traceable author statement. Source: ProtInc

membrane fraction

Traceable author statement. Source: ProtInc

   Molecular functionfolic acid binding

Inferred from electronic annotation. Source: InterPro

folic acid transporter activity Ref.1

Traceable author statement. Source: ProtInc

methotrexate transporter activity

Traceable author statement. Source: ProtInc

reduced folate carrier activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 591591Folate transporter 1
PRO_0000178660

Regions

Topological domain1 – 2323Cytoplasmic Probable
Transmembrane24 – 4421 Probable
Topological domain45 – 7026Extracellular Probable
Transmembrane71 – 8919 Probable
Topological domain90 – 956Cytoplasmic Probable
Transmembrane96 – 11621 Probable
Topological domain117 – 1237Extracellular Probable
Transmembrane124 – 14421 Probable
Topological domain145 – 15915Cytoplasmic Probable
Transmembrane160 – 17718 Probable
Topological domain178 – 1869Extracellular Probable
Transmembrane187 – 20317 Probable
Topological domain204 – 25956Cytoplasmic Probable
Transmembrane260 – 28728 Probable
Topological domain288 – 30922Extracellular Probable
Transmembrane310 – 32718 Probable
Topological domain328 – 3336Cytoplasmic Probable
Transmembrane334 – 35421 Probable
Topological domain355 – 3606Extracellular Probable
Transmembrane361 – 37818 Probable
Topological domain379 – 39416Cytoplasmic Probable
Transmembrane395 – 41925 Probable
Topological domain420 – 43314Extracellular Probable
Transmembrane434 – 45421 Probable
Topological domain455 – 591137Cytoplasmic Probable

Amino acid modifications

Modified residue5831Phosphoserine
Glycosylation581N-linked (GlcNAc...) Potential

Natural variations

Natural variant271H → R: dbSNP rs1051266.
VAR_020210

Experimental info

Sequence conflict62 – 632EQ → DE Ref.1 Ref.4
Sequence conflict2681R → P in AAA98442. Ref.1
Sequence conflict4571H → D in AAB35058. Ref.4
Sequence conflict4831A → R in AAB35058. Ref.4
Sequence conflict5491C → S Ref.1 Ref.4 Ref.5 Ref.6

Sequences

Sequence LengthMass (Da)Tools
P41440-1 [UniParc].

Last modified December 1, 2000. Version 3.
Checksum: 0437B1615F5517EB

FASTA59164,868
        10         20         30         40         50         60 
MVPSSPAVEK QVPVEPGPDP ELRSWRHLVC YLCFYGFMAQ IRPGESFITP YLLGPDKNFT 

        70         80         90        100        110        120 
REQVTNEITP VLSYSYLAVL VPVFLLTDYL RYTPVLLLQG LSFVSVWLLL LLGHSVAHMQ 

       130        140        150        160        170        180 
LMELFYSVTM AARIAYSSYI FSLVRPARYQ RVAGYSRAAV LLGVFTSSVL GQLLVTVGRV 

       190        200        210        220        230        240 
SFSTLNYISL AFLTFSVVLA LFLKRPKRSL FFNRDDRGRC ETSASELERM NPGPGGKLGH 

       250        260        270        280        290        300 
ALRVACGDSV LARMLRELGD SLRRPQLRLW SLWWVFNSAG YYLVVYYVHI LWNEVDPTTN 

       310        320        330        340        350        360 
SARVYNGAAD AASTLLGAIT SFAAGFVKIR WARWSKLLIA GVTATQAGLV FLLAHTRHPS 

       370        380        390        400        410        420 
SIWLCYAAFV LFRGSYQFLV PIATFQIASS LSKELCALVF GVNTFFATIV KTIITFIVSD 

       430        440        450        460        470        480 
VRGLGLPVRK QFQLYSVYFL ILSIIYFLGA MLDGLRHCQR GHHPRQPPAQ GLRSAAEEKA 

       490        500        510        520        530        540 
AQALSVQDKG LGGLQPAQSP PLSPEDSLGA VGPASLEQRQ SDPYLAQAPA PQAAEFLSPV 

       550        560        570        580        590 
TTPSPCTLCS AQASGPEAAD ETCPQLAVHP PGVSKLGLQC LPSDGVQNVN Q 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of the human placental folate transporter."
Prasad P.D., Ramamoorthy S., Leibach F.H., Ganapathy V.
Biochem. Biophys. Res. Commun. 206:681-687(1995) [PubMed: 7826387] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-27.
Tissue: Placenta.
[2]Prasad P.D.
Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 490-527.
[3]"Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-defective Chinese hamster ovary cells."
Wong S.C., Proefke A., Bhushan A., Matherly L.H.
J. Biol. Chem. 270:17468-17475(1995) [PubMed: 7615551] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-27.
[4]"Isolation of a gene encoding a human reduced folate carrier (RFC1) and analysis of its expression in transport-deficient, methotrexate-resistant human breast cancer cells."
Moscow J.A., Gong M., He R., Sgagias M.K., Dixon K.H., Anzick S.L., Meltzer P.S., Cowan K.H.
Cancer Res. 55:3790-3794(1995) [PubMed: 7641195] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-27.
Tissue: Testis.
[5]"Isolation of a human cDNA that complements a mutant hamster cell defective in methotrexate uptake."
Williams F.M., Flintoff W.F.
J. Biol. Chem. 270:2987-2992(1995) [PubMed: 7852378] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lymphoma.
[6]"Structural analysis of the human RFC1 gene encoding a folate transporter and alternatively spliced transcripts with 5' end heterogeneity."
Tolner B.M., Roy K., Sirotnak F.M.
Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE, VARIANT ARG-27.
Tissue: Liver.
[7]"Human intestinal folate transport: cloning, expression, and distribution of complementary RNA."
Nguyen T.T., Dyer D.L., Dunning D.D., Rubin S.A., Grant K.E., Said H.M.
Gastroenterology 112:783-791(1997) [PubMed: 9041240] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Small intestine.
[8]"The DNA sequence of human chromosome 21."
Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed: 10830953] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"Topological and functional analysis of the human reduced folate carrier by hemagglutinin epitope insertion."
Ferguson P.L., Flintoff W.F.
J. Biol. Chem. 274:16269-16278(1999) [PubMed: 10347183] [Abstract]
Cited for: TOPOLOGY.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-583, MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

U15939 mRNA. Translation: AAA98442.1.
U19720 mRNA. Translation: AAC50180.1.
S78996 mRNA. Translation: AAB35058.1.
U17566 mRNA. Translation: AAA74914.1.
U92873 expand/collapse EMBL AC list , U92869, U92870, U92871, U92872 Genomic DNA. Translation: AAC26162.1.
AF004354 mRNA. Translation: AAB61417.1.
AL163302 Genomic DNA. Translation: CAB90483.1. Sequence problems.
PIRI38924.
I52728.
RefSeqNP_919231.1.
UniGeneHs.84190

3D structure databases

ModBaseSearch...

PTM databases

PhosphoSiteP41440.

Genome annotation databases

EnsemblENSG00000173638. Homo sapiens. [Contig view]
GeneID6573.
KEGGhsa:6573.

Organism-specific databases

H-InvDBHIX0016185.
HGNCHGNC:10937. SLC19A1.
MIM600424. gene.
PharmGKBPA327.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOVERGENP41440.

Enzyme and pathway databases

ReactomeREACT_11127. Metabolism of vitamins and cofactors.

Gene expression databases

ArrayExpressP41440.
CleanExHS_FLOT1.
HS_RFC1.
HS_SLC19A1.
GermOnlineENSG00000173638. Homo sapiens.

Family and domain databases

InterProIPR002666. Folate_carrier.
[Graphical view]
PANTHERPTHR10686. Folate_carrier. 1 hit.
PfamPF01770. Folate_carrier. 1 hit.
[Graphical view]
PIRSFPIRSF028739. Folate_carrier. 1 hit.
TIGRFAMsTIGR00806. rfc. 1 hit.
ProtoNetSearch...

Other Resources

NextBio25575.
SOURCESearch...

Entry information

Entry nameS19A1_HUMAN
AccessionPrimary (citable) accession number: P41440
Secondary accession number(s): O00553, O60227, Q13026
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 1, 2000
Last modified: November 25, 2008
This is version 67 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents