F1NJ67 · PCFT_CHICK

  • 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:34040256).
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:34040256).
Functions at acidic pH via alternate outward- and inward-open conformation states (PubMed:34040256).
Protonation of residues in the outward open state primes the protein for transport (PubMed:34040256).
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 (PubMed:34040256).
Also able to transport antifolate drugs, such as methotrexate and pemetrexed (PubMed:34040256).
Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine (By similarity).
Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells (By similarity).

Catalytic activity

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
2 μMfolic acid

pH Dependence

Optimum pH is 5.0-5.5.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site98pemetrexed (UniProtKB | ChEBI)
Binding site164H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport
Binding site193H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport
Binding site193pemetrexed (UniProtKB | ChEBI)
Binding site289H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport
Binding site323pemetrexed (UniProtKB | ChEBI)
Binding site407pemetrexed (UniProtKB | ChEBI)
Binding site411pemetrexed (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentendosome
Cellular Componentendosome membrane
Cellular Componentplasma membrane
Molecular Functionfolic acid binding
Molecular Functionfolic acid:proton symporter activity
Molecular Functionmethotrexate transmembrane transporter activity
Molecular Functiontransmembrane transporter activity
Biological Processfolate import across plasma membrane
Biological Processtransmembrane transport

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Proton-coupled folate transporter
  • Alternative names
    • Solute carrier family 46 member 1

Gene names

    • Name
      SLC46A1
    • Synonyms
      PCFT

Organism names

  • Taxonomic identifier
  • Strain
    • Red jungle fowl
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Archelosauria > Archosauria > Dinosauria > Saurischia > Theropoda > Coelurosauria > Aves > Neognathae > Galloanserae > Galliformes > Phasianidae > Phasianinae > Gallus

Accessions

  • Primary accession
    F1NJ67
  • Secondary accessions
    • E6Y8U5

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: Localizes to the apical membrane of intestinal cells in iron-deficient cells, while it resides in the cytoplasm in iron-replete cells (By similarity).
Localizes to the basolateral membrane of choroid plexus (By similarity).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-29Cytoplasmic
Transmembrane30-48Helical; Name=TM1
Topological domain49-90Extracellular
Transmembrane91-116Helical; Name=TM2
Topological domain117-120Cytoplasmic
Transmembrane121-143Helical; Name=TM3
Topological domain144-148Extracellular
Transmembrane149-162Helical; Name=TM4
Topological domain163-185Cytoplasmic
Transmembrane186-211Helical; Name=TM5
Topological domain212-216Extracellular
Transmembrane217-235Helical; Name=TM6
Topological domain236-274Cytoplasmic
Transmembrane275-297Helical; Name=TM7
Topological domain298-310Extracellular
Transmembrane311-333Helical; Name=TM8
Topological domain334-339Cytoplasmic
Transmembrane340-359Helical; Name=TM9
Topological domain360-363Extracellular
Transmembrane364-384Helical; Name=TM10
Topological domain385-396Cytoplasmic
Transmembrane397-422Helical; Name=TM11
Topological domain423-430Extracellular
Transmembrane431-449Helical; Name=TM12
Topological domain450-473Cytoplasmic

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis164Strongly reduced proton-coupled folate transport.
Mutagenesis193Abolished proton-coupled folate transport.
Mutagenesis193Strong proton-coupled folate transport at pH 7.5.

PTM/Processing

Features

Showing features for chain, glycosylation, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_00004553801-473Proton-coupled folate transporter
Glycosylation65N-linked (GlcNAc...) asparagine
Disulfide bond72↔306
Glycosylation74N-linked (GlcNAc...) asparagine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed, including brain, aorta, liver, kidney, spleen, small intestine, pancreas, ovary and testis.

Gene expression databases

Interaction

Subunit

Monomer.

Protein-protein interaction databases

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region1-21Disordered

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    473
  • Mass (Da)
    50,465
  • Last updated
    2013-06-26 v2
  • Checksum
    794BE71E3B571BEA
MAAPSDPPTAATPPAPPPPARRCLLAPSVEPLLFLATLALGLQVPLATQYLWDRLGAERGYVGPNASSPHGCGNGSGAVDPLREEVEALVAHWNLCINLGGFFVGLFSVTLFGPWSDSVGRRPVLVLPAVGMAVQAAVYLLVMYLRLHVAYLLLGRIISGLLGDYNLILAGCFASVADSSNQRTRTFRVAILEACLGVAGMVASVGGGQWRKAEGYINPFWLVLAASLAAALYAALCLQETVKQRRAAKLLTLQHYKAVYKLYTAPEDLSSRRKLALYSLAFFLLVTVHFGTKDLYVLYELGSPLCWASDLIGYGSAASYLAYLSSLGGLRLLQLCLEDTWVAEIGLISNIAGLVVISLATTTPLMFTGYGIMFLSMAATPVIRAKLSKLVGETEQGALFASVACVEGLCSLVATGVFNSLYPSTLHFMRGFPFLFGAILLLIPAAIMGWIEIQDSNLQYSHFSDASSSPADG

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict25in Ref. 1; ACV70072
Sequence conflict392in Ref. 1; ACV70072

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
FJ655775
EMBL· GenBank· DDBJ
ACV70072.1
EMBL· GenBank· DDBJ
mRNA
AADN05000057
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.

Genome annotation databases

Similar Proteins

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