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P41440 (S19A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Folate transporter 1

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

Protein attributes

Sequence length591 AA.
Sequence statusComplete.
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]

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P41440-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P41440-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-63: MVPSSPAVEK...GPDKNFTREQ → MRPQPAEPAPGGRGNEACSIHSE
Note: No experimental confirmation available.
Isoform 3 (identifier: P41440-3)

The sequence of this isoform differs from the canonical sequence as follows:
     432-591: FQLYSVYFLI...PSDGVQNVNQ → NEELHVASLS...PVCPSEVCPS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 591591Folate transporter 1
PRO_0000178660

Regions

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

Amino acid modifications

Modified residue11N-acetylmethionine Ref.16
Modified residue4741Phosphoserine By similarity
Modified residue4851Phosphoserine By similarity
Modified residue4991Phosphoserine Ref.15
Modified residue5031Phosphoserine Ref.15
Glycosylation581N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 6363MVPSS…FTREQ → MRPQPAEPAPGGRGNEACSI HSE in isoform 2.
VSP_042891
Alternative sequence432 – 591160FQLYS…QNVNQ → NEELHVASLSLWKSHLRLAA DTLSSEGSSGSGPRSWFLSP TLRAALHGPVCPSEVCPS in isoform 3.
VSP_044497
Natural variant271H → R. Ref.1 Ref.3 Ref.4 Ref.6 Ref.11
Corresponds to variant rs1051266 [ dbSNP | Ensembl ].
VAR_020210
Natural variant5581A → V.
Corresponds to variant rs35786590 [ dbSNP | Ensembl ].
VAR_052404

Experimental info

Sequence conflict62 – 632EQ → DE Ref.1
Sequence conflict62 – 632EQ → DE 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
Sequence conflict5491C → S Ref.4
Sequence conflict5491C → S Ref.5
Sequence conflict5491C → S Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 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

Isoform 2 [UniParc].

Checksum: 491A0402C6E9A05F
Show »

FASTA55160,034
Isoform 3 [UniParc].

Checksum: 64D568ECA8030F70
Show »

FASTA48954,262

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 [GENOMIC DNA], 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Small intestine.
[8]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Thymus and Tongue.
[9]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]"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] (ISOFORM 3), VARIANT ARG-27.
Tissue: Brain.
[12]"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] [Europe PMC] [Abstract]
Cited for: TOPOLOGY.
[13]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-499 AND SER-503, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
AK303168 mRNA. Translation: BAH13909.1.
AK313125 mRNA. Translation: BAG35945.1.
AL163302 Genomic DNA. Translation: CAB90483.1. Sequence problems.
BX322561 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09331.1.
BC003068 mRNA. Translation: AAH03068.1.
PIRI38924.
I52728.
RefSeqNP_001192135.1. NM_001205206.1.
NP_001192136.1. NM_001205207.1.
NP_919231.1. NM_194255.2.
UniGeneHs.736903.
Hs.84190.

3D structure databases

ProteinModelPortalP41440.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112461. 1 interaction.
STRING9606.ENSP00000308895.

Chemistry

BindingDBP41440.
ChEMBLCHEMBL4833.
GuidetoPHARMACOLOGY1014.

Protein family/group databases

TCDB2.A.48.1.1. the reduced folate carrier (rfc) family.

PTM databases

PhosphoSiteP41440.

Polymorphism databases

DMDM12643280.

Proteomic databases

PaxDbP41440.
PRIDEP41440.

Protocols and materials databases

DNASU6573.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000311124; ENSP00000308895; ENSG00000173638. [P41440-1]
ENST00000380010; ENSP00000369347; ENSG00000173638. [P41440-3]
ENST00000485649; ENSP00000441772; ENSG00000173638. [P41440-2]
GeneID6573.
KEGGhsa:6573.
UCSCuc002zhl.2. human. [P41440-1]
uc002zhm.2. human. [P41440-3]
uc011aft.2. human. [P41440-2]

Organism-specific databases

CTD6573.
GeneCardsGC21M046913.
HGNCHGNC:10937. SLC19A1.
HPAHPA024802.
MIM600424. gene.
neXtProtNX_P41440.
Orphanet306574. Methotrexate dose selection.
PharmGKBPA327.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG241030.
HOVERGENHBG054198.
InParanoidP41440.
KOK14609.
OMAHILWNVV.
PhylomeDBP41440.
TreeFamTF313684.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

ArrayExpressP41440.
BgeeP41440.
CleanExHS_FLOT1.
HS_RFC1.
HS_SLC19A1.
GenevestigatorP41440.

Family and domain databases

InterProIPR002666. Folate_carrier.
IPR016196. MFS_dom_general_subst_transpt.
IPR028339. RFC.
[Graphical view]
PANTHERPTHR10686. PTHR10686. 1 hit.
PfamPF01770. Folate_carrier. 1 hit.
[Graphical view]
PIRSFPIRSF028739. Folate_carrier. 1 hit.
PIRSF500793. Folate_transporter_1. 1 hit.
SUPFAMSSF103473. SSF103473. 2 hits.
TIGRFAMsTIGR00806. rfc. 1 hit.
ProtoNetSearch...

Other

GeneWikiSLC19A1.
GenomeRNAi6573.
NextBio25575.
PROP41440.
SOURCESearch...

Entry information

Entry nameS19A1_HUMAN
AccessionPrimary (citable) accession number: P41440
Secondary accession number(s): B2R7U8 expand/collapse secondary AC list , B7Z8C3, E9PFY4, O00553, O60227, Q13026, Q9BTX8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 1, 2000
Last modified: April 16, 2014
This is version 120 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

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