Q6PEM8 · PCFT_MOUSE

  • Protein
    Proton-coupled folate transporter
  • Gene
    Slc46a1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Proton-coupled folate symporter that mediates folate absorption using an H+ gradient as a driving force (PubMed:17962486).
Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus (PubMed:17962486).
Functions at acidic pH via alternate outward- and inward-open conformation states (By similarity).
Protonation of residues in the outward open state primes the protein for transport (By similarity).
Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate (By similarity).
Also able to transport antifolate drugs, such as methotrexate and pemetrexed (PubMed:17962486).
Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes (By similarity).
Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine (PubMed:16143108).
Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells (PubMed:22058337).
Hence, participates in the trafficking of heme and increases intracellular iron content (By similarity).

Catalytic activity

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site156H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport
Binding site185H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport
Binding site281H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentbrush border membrane
Cellular Componentcytoplasm
Cellular Componentendosome membrane
Molecular Functionfolic acid binding
Molecular Functionfolic acid transmembrane transporter activity
Molecular Functionfolic acid:proton symporter activity
Molecular Functionheme transmembrane transporter activity
Molecular Functionmethotrexate transmembrane transporter activity
Biological Processfolate import across plasma membrane
Biological Processfolic acid transport
Biological Processheme transport

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Proton-coupled folate transporter
  • Alternative names
    • Heme carrier protein 1
    • PCFT/HCP1
    • Solute carrier family 46 member 1

Gene names

    • Name
      Slc46a1
    • Synonyms
      D11Ertd18e
      , Hcp1
      , Pcft

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • NOD
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q6PEM8
  • Secondary accessions
    • Q571I8
    • Q5SYG0
    • Q8R1H7
    • Q9D1P1

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Apical cell membrane
; Multi-pass membrane protein
Basolateral cell membrane
; Multi-pass membrane protein
Endosome membrane
; Multi-pass membrane protein
Cytoplasm
Note: Shifts from the apical membrane of intestinal cells iron-deficient cells to the cytoplasm in response to increased in iron stores (PubMed:16143108).
Localizes to the basolateral membrane of choroid plexus (PubMed:19074442).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-25Cytoplasmic
Transmembrane26-44Helical; Name=TM1
Topological domain45-82Extracellular
Transmembrane83-108Helical; Name=TM2
Topological domain109-112Cytoplasmic
Transmembrane113-135Helical; Name=TM3
Topological domain136-140Extracellular
Transmembrane141-154Helical; Name=TM4
Topological domain155-177Cytoplasmic
Transmembrane178-203Helical; Name=TM5
Topological domain204-208Extracellular
Transmembrane209-227Helical; Name=TM6
Topological domain228-266Cytoplasmic
Transmembrane267-289Helical; Name=TM7
Topological domain290-302Extracellular
Transmembrane303-325Helical; Name=TM8
Topological domain326-331Cytoplasmic
Transmembrane332-351Helical; Name=TM9
Topological domain352-355Extracellular
Transmembrane356-376Helical; Name=TM10
Topological domain377-388Cytoplasmic
Transmembrane389-414Helical; Name=TM11
Topological domain415-422Extracellular
Transmembrane423-441Helical; Name=TM12
Topological domain442-459Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Deletion mutant mice develop severe macrocytic normochromic anemia and ineffective erythropoiesis (PubMed:21346251).
More than 90% of mice die by 10 to 12 weeks of age (PubMed:21346251).

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 30 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for modified residue, chain, glycosylation, disulfide bond.

TypeIDPosition(s)Description
Modified residue1N-acetylmethionine
ChainPRO_00000848521-459Proton-coupled folate transporter
Modified residue6Phosphoserine
Glycosylation58N-linked (GlcNAc...) asparagine
Disulfide bond66↔298
Glycosylation68N-linked (GlcNAc...) asparagine
Modified residue458Phosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Highly expressed in duodenum, especially in duodenal mucosa, the main site of intestinal heme absorption (PubMed:16143108).
Expressed in the retina and retinal pigment epithelium (PubMed:17962486, PubMed:22058337).
Weakly expressed in the kidney (PubMed:16143108).
Not expressed in duodenum before weaning or in placenta (PubMed:16143108).
Weakly or not expressed in brain, heart, lung, skeletal muscle, testis and neonatal liver (PubMed:16143108).

Induction

Up-regulated in response to hypoxia, it is however unclear whether such up-regulation is direct or not (PubMed:16143108).
Not induced in the duodenum of iron-deficient mice (PubMed:16143108).

Gene expression databases

Interaction

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    459
  • Mass (Da)
    50,089
  • Last updated
    2004-07-05 v1
  • Checksum
    A251124B3B9846AF
MEGRVSSVGSPHSFLNAPVLFRGPVEPLVFLANFALVLQGPLTTQYLWHRFSTELGYNGTRHRENCGNQSADPLMKEVETLTSHWTLYMNVGGFLVGLFWSTLLGAWSDRVGRRPLLVLASLGLLLQAVVSIFVVQLELHVGFFVLGRALCALLGDFNGLLAASFASVADVSSNHSRTFRMALLEACIGVAGTLASLLGGHWLRAQGYANPFWLALALLIVMALYAAFCFGETVKEPKSTRLFTLRHHRSIARLYVVPAPEKSRMHLALYSLAIFVVVTVHFGAQDILTLYELSAPLCWDSKLIGYGSAAQHLPYLTSLLGLRLLQFCLADTWVAEIGLAFNILGMVVFAFATITPLMFTGYGLLFLSLVTTPVIRAKLSKLVSESEQGALFSAVACVNSLAMLMASGIFNSIYPATLNFMKGFPFLLGAGLLFIPAILIGVLEKVNPHPEFQQFPQSP

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
F6QD87F6QD87_MOUSESlc46a198

Sequence caution

The sequence BAD90126.1 differs from that shown. Reason: Erroneous initiation
The sequence CAI25543.1 differs from that shown. Reason: Erroneous gene model prediction

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict402in Ref. 1; BAB22685

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK003278
EMBL· GenBank· DDBJ
BAB22685.1
EMBL· GenBank· DDBJ
mRNA
AK170505
EMBL· GenBank· DDBJ
BAE41843.1
EMBL· GenBank· DDBJ
mRNA
AK220201
EMBL· GenBank· DDBJ
BAD90126.1
EMBL· GenBank· DDBJ
mRNA Different initiation
AL591177
EMBL· GenBank· DDBJ
CAI25542.1
EMBL· GenBank· DDBJ
Genomic DNA
AL591177
EMBL· GenBank· DDBJ
CAI25543.1
EMBL· GenBank· DDBJ
Genomic DNA Sequence problems.
BC024522
EMBL· GenBank· DDBJ
AAH24522.1
EMBL· GenBank· DDBJ
mRNA
BC057976
EMBL· GenBank· DDBJ
AAH57976.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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