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Protein

Folate transporter 1

Gene

SLC19A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • folic acid binding Source: GO_Central
  • folic acid transporter activity Source: BHF-UCL
  • methotrexate transporter activity Source: ProtInc
  • reduced folate carrier activity Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Transport

Keywords - Ligandi

Folate-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000173638-MONOMER.
ReactomeiR-HSA-196757. Metabolism of folate and pterines.

Protein family/group databases

TCDBi2.A.48.1.1. the reduced folate carrier (rfc) family.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:SLC19A1
Synonyms:FLOT1, RFC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:10937. SLC19A1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 23Cytoplasmic1 PublicationAdd BLAST23
Transmembranei24 – 44HelicalCuratedAdd BLAST21
Topological domaini45 – 70Extracellular1 PublicationAdd BLAST26
Transmembranei71 – 89HelicalCuratedAdd BLAST19
Topological domaini90 – 95Cytoplasmic1 Publication6
Transmembranei96 – 116HelicalCuratedAdd BLAST21
Topological domaini117 – 123Extracellular1 Publication7
Transmembranei124 – 144HelicalCuratedAdd BLAST21
Topological domaini145 – 159Cytoplasmic1 PublicationAdd BLAST15
Transmembranei160 – 177HelicalCuratedAdd BLAST18
Topological domaini178 – 186Extracellular1 Publication9
Transmembranei187 – 203HelicalCuratedAdd BLAST17
Topological domaini204 – 259Cytoplasmic1 PublicationAdd BLAST56
Transmembranei260 – 287HelicalCuratedAdd BLAST28
Topological domaini288 – 309Extracellular1 PublicationAdd BLAST22
Transmembranei310 – 327HelicalCuratedAdd BLAST18
Topological domaini328 – 333Cytoplasmic1 Publication6
Transmembranei334 – 354HelicalCuratedAdd BLAST21
Topological domaini355 – 360Extracellular1 Publication6
Transmembranei361 – 378HelicalCuratedAdd BLAST18
Topological domaini379 – 394Cytoplasmic1 PublicationAdd BLAST16
Transmembranei395 – 419HelicalCuratedAdd BLAST25
Topological domaini420 – 433Extracellular1 PublicationAdd BLAST14
Transmembranei434 – 454HelicalCuratedAdd BLAST21
Topological domaini455 – 591Cytoplasmic1 PublicationAdd BLAST137

GO - Cellular componenti

  • apical plasma membrane Source: BHF-UCL
  • basolateral plasma membrane Source: BHF-UCL
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi6573.
MalaCardsiSLC19A1.
OpenTargetsiENSG00000173638.
Orphaneti306574. Methotrexate dose selection.
PharmGKBiPA327.

Chemistry databases

ChEMBLiCHEMBL4833.
DrugBankiDB00563. Methotrexate.
DB06813. Pralatrexate.
GuidetoPHARMACOLOGYi1014.

Polymorphism and mutation databases

BioMutaiSLC19A1.
DMDMi12643280.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001786601 – 591Folate transporter 1Add BLAST591

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei5PhosphoserineCombined sources1
Glycosylationi58N-linked (GlcNAc...)Sequence analysis1
Modified residuei225PhosphoserineCombined sources1
Modified residuei474PhosphoserineBy similarity1
Modified residuei485PhosphoserineBy similarity1
Modified residuei499PhosphoserineCombined sources1
Modified residuei503PhosphoserineCombined sources1

Post-translational modificationi

Heavily glycosylated.

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP41440.
MaxQBiP41440.
PaxDbiP41440.
PeptideAtlasiP41440.
PRIDEiP41440.

PTM databases

iPTMnetiP41440.
PhosphoSitePlusiP41440.
SwissPalmiP41440.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000173638.
CleanExiHS_FLOT1.
HS_RFC1.
HS_SLC19A1.
ExpressionAtlasiP41440. baseline and differential.
GenevisibleiP41440. HS.

Organism-specific databases

HPAiHPA024802.

Interactioni

Protein-protein interaction databases

BioGridi112461. 3 interactors.
IntActiP41440. 2 interactors.
STRINGi9606.ENSP00000308895.

Chemistry databases

BindingDBiP41440.

Structurei

3D structure databases

ProteinModelPortaliP41440.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3810. Eukaryota.
ENOG410XT34. LUCA.
GeneTreeiENSGT00510000046382.
HOGENOMiHOG000001583.
HOVERGENiHBG054198.
InParanoidiP41440.
KOiK14609.
OMAiTSSIWLC.
OrthoDBiEOG091G0BSJ.
PhylomeDBiP41440.
TreeFamiTF313684.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR002666. Folate_carrier.
IPR020846. MFS_dom.
IPR028339. RFC.
[Graphical view]
PANTHERiPTHR10686. PTHR10686. 1 hit.
PTHR10686:SF12. PTHR10686:SF12. 1 hit.
PfamiPF01770. Folate_carrier. 1 hit.
[Graphical view]
PIRSFiPIRSF028739. Folate_carrier. 1 hit.
PIRSF500793. Folate_transporter_1. 1 hit.
SUPFAMiSSF103473. SSF103473. 2 hits.
TIGRFAMsiTIGR00806. rfc. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P41440-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVPSSPAVEK QVPVEPGPDP ELRSWRHLVC YLCFYGFMAQ IRPGESFITP
60 70 80 90 100
YLLGPDKNFT REQVTNEITP VLSYSYLAVL VPVFLLTDYL RYTPVLLLQG
110 120 130 140 150
LSFVSVWLLL LLGHSVAHMQ LMELFYSVTM AARIAYSSYI FSLVRPARYQ
160 170 180 190 200
RVAGYSRAAV LLGVFTSSVL GQLLVTVGRV SFSTLNYISL AFLTFSVVLA
210 220 230 240 250
LFLKRPKRSL FFNRDDRGRC ETSASELERM NPGPGGKLGH ALRVACGDSV
260 270 280 290 300
LARMLRELGD SLRRPQLRLW SLWWVFNSAG YYLVVYYVHI LWNEVDPTTN
310 320 330 340 350
SARVYNGAAD AASTLLGAIT SFAAGFVKIR WARWSKLLIA GVTATQAGLV
360 370 380 390 400
FLLAHTRHPS SIWLCYAAFV LFRGSYQFLV PIATFQIASS LSKELCALVF
410 420 430 440 450
GVNTFFATIV KTIITFIVSD VRGLGLPVRK QFQLYSVYFL ILSIIYFLGA
460 470 480 490 500
MLDGLRHCQR GHHPRQPPAQ GLRSAAEEKA AQALSVQDKG LGGLQPAQSP
510 520 530 540 550
PLSPEDSLGA VGPASLEQRQ SDPYLAQAPA PQAAEFLSPV TTPSPCTLCS
560 570 580 590
AQASGPEAAD ETCPQLAVHP PGVSKLGLQC LPSDGVQNVN Q
Length:591
Mass (Da):64,868
Last modified:December 1, 2000 - v3
Checksum:i0437B1615F5517EB
GO
Isoform 2 (identifier: P41440-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-63: MVPSSPAVEK...GPDKNFTREQ → MRPQPAEPAPGGRGNEACSIHSE

Note: No experimental confirmation available.
Show »
Length:551
Mass (Da):60,034
Checksum:i491A0402C6E9A05F
GO
Isoform 3 (identifier: P41440-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     432-591: FQLYSVYFLI...PSDGVQNVNQ → NEELHVASLS...PVCPSEVCPS

Note: No experimental confirmation available.
Show »
Length:489
Mass (Da):54,262
Checksum:i64D568ECA8030F70
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti62 – 63EQ → DE (PubMed:7826387).Curated2
Sequence conflicti62 – 63EQ → DE (PubMed:7641195).Curated2
Sequence conflicti268R → P in AAA98442 (PubMed:7826387).Curated1
Sequence conflicti457H → D in AAB35058 (PubMed:7641195).Curated1
Sequence conflicti483A → R in AAB35058 (PubMed:7641195).Curated1
Sequence conflicti549C → S (PubMed:7826387).Curated1
Sequence conflicti549C → S (PubMed:7641195).Curated1
Sequence conflicti549C → S (PubMed:7852378).Curated1
Sequence conflicti549C → S (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02021027H → R.5 PublicationsCorresponds to variant rs1051266dbSNPEnsembl.1
Natural variantiVAR_052404558A → V.Corresponds to variant rs35786590dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0428911 – 63MVPSS…FTREQ → MRPQPAEPAPGGRGNEACSI HSE in isoform 2. 1 PublicationAdd BLAST63
Alternative sequenceiVSP_044497432 – 591FQLYS…QNVNQ → NEELHVASLSLWKSHLRLAA DTLSSEGSSGSGPRSWFLSP TLRAALHGPVCPSEVCPS in isoform 3. 1 PublicationAdd BLAST160

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U15939 mRNA. Translation: AAA98442.1.
U19720 mRNA. Translation: AAC50180.1.
S78996 mRNA. Translation: AAB35058.1.
U17566 mRNA. Translation: AAA74914.1.
U92873
, 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.
CCDSiCCDS13725.1. [P41440-1]
CCDS56217.1. [P41440-2]
CCDS56218.1. [P41440-3]
PIRiI38924.
I52728.
RefSeqiNP_001192135.1. NM_001205206.1. [P41440-3]
NP_001192136.1. NM_001205207.1. [P41440-2]
NP_919231.1. NM_194255.2. [P41440-1]
XP_011528002.1. XM_011529700.2. [P41440-1]
XP_011528003.1. XM_011529701.2. [P41440-1]
XP_011528004.1. XM_011529702.2. [P41440-1]
XP_011528005.1. XM_011529703.2. [P41440-1]
XP_011528006.1. XM_011529704.2. [P41440-1]
XP_016883935.1. XM_017028446.1. [P41440-3]
UniGeneiHs.736903.
Hs.84190.

Genome annotation databases

EnsembliENST00000311124; ENSP00000308895; ENSG00000173638. [P41440-1]
ENST00000380010; ENSP00000369347; ENSG00000173638. [P41440-3]
ENST00000485649; ENSP00000441772; ENSG00000173638. [P41440-2]
GeneIDi6573.
KEGGihsa:6573.
UCSCiuc002zhl.3. human. [P41440-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U15939 mRNA. Translation: AAA98442.1.
U19720 mRNA. Translation: AAC50180.1.
S78996 mRNA. Translation: AAB35058.1.
U17566 mRNA. Translation: AAA74914.1.
U92873
, 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.
CCDSiCCDS13725.1. [P41440-1]
CCDS56217.1. [P41440-2]
CCDS56218.1. [P41440-3]
PIRiI38924.
I52728.
RefSeqiNP_001192135.1. NM_001205206.1. [P41440-3]
NP_001192136.1. NM_001205207.1. [P41440-2]
NP_919231.1. NM_194255.2. [P41440-1]
XP_011528002.1. XM_011529700.2. [P41440-1]
XP_011528003.1. XM_011529701.2. [P41440-1]
XP_011528004.1. XM_011529702.2. [P41440-1]
XP_011528005.1. XM_011529703.2. [P41440-1]
XP_011528006.1. XM_011529704.2. [P41440-1]
XP_016883935.1. XM_017028446.1. [P41440-3]
UniGeneiHs.736903.
Hs.84190.

3D structure databases

ProteinModelPortaliP41440.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112461. 3 interactors.
IntActiP41440. 2 interactors.
STRINGi9606.ENSP00000308895.

Chemistry databases

BindingDBiP41440.
ChEMBLiCHEMBL4833.
DrugBankiDB00563. Methotrexate.
DB06813. Pralatrexate.
GuidetoPHARMACOLOGYi1014.

Protein family/group databases

TCDBi2.A.48.1.1. the reduced folate carrier (rfc) family.

PTM databases

iPTMnetiP41440.
PhosphoSitePlusiP41440.
SwissPalmiP41440.

Polymorphism and mutation databases

BioMutaiSLC19A1.
DMDMi12643280.

Proteomic databases

EPDiP41440.
MaxQBiP41440.
PaxDbiP41440.
PeptideAtlasiP41440.
PRIDEiP41440.

Protocols and materials databases

DNASUi6573.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000311124; ENSP00000308895; ENSG00000173638. [P41440-1]
ENST00000380010; ENSP00000369347; ENSG00000173638. [P41440-3]
ENST00000485649; ENSP00000441772; ENSG00000173638. [P41440-2]
GeneIDi6573.
KEGGihsa:6573.
UCSCiuc002zhl.3. human. [P41440-1]

Organism-specific databases

CTDi6573.
DisGeNETi6573.
GeneCardsiSLC19A1.
HGNCiHGNC:10937. SLC19A1.
HPAiHPA024802.
MalaCardsiSLC19A1.
MIMi600424. gene.
neXtProtiNX_P41440.
OpenTargetsiENSG00000173638.
Orphaneti306574. Methotrexate dose selection.
PharmGKBiPA327.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3810. Eukaryota.
ENOG410XT34. LUCA.
GeneTreeiENSGT00510000046382.
HOGENOMiHOG000001583.
HOVERGENiHBG054198.
InParanoidiP41440.
KOiK14609.
OMAiTSSIWLC.
OrthoDBiEOG091G0BSJ.
PhylomeDBiP41440.
TreeFamiTF313684.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000173638-MONOMER.
ReactomeiR-HSA-196757. Metabolism of folate and pterines.

Miscellaneous databases

GeneWikiiSLC19A1.
GenomeRNAii6573.
PROiP41440.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173638.
CleanExiHS_FLOT1.
HS_RFC1.
HS_SLC19A1.
ExpressionAtlasiP41440. baseline and differential.
GenevisibleiP41440. HS.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR002666. Folate_carrier.
IPR020846. MFS_dom.
IPR028339. RFC.
[Graphical view]
PANTHERiPTHR10686. PTHR10686. 1 hit.
PTHR10686:SF12. PTHR10686:SF12. 1 hit.
PfamiPF01770. Folate_carrier. 1 hit.
[Graphical view]
PIRSFiPIRSF028739. Folate_carrier. 1 hit.
PIRSF500793. Folate_transporter_1. 1 hit.
SUPFAMiSSF103473. SSF103473. 2 hits.
TIGRFAMsiTIGR00806. rfc. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiS19A1_HUMAN
AccessioniPrimary (citable) accession number: P41440
Secondary accession number(s): B2R7U8
, B7Z8C3, E9PFY4, O00553, O60227, Q13026, Q9BTX8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 1, 2000
Last modified: November 2, 2016
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.