Q6PEM8 · PCFT_MOUSE
- ProteinProton-coupled folate transporter
- GeneSlc46a1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids459 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
- folate(in) + H+(in) = folate(out) + H+(out)
- (6S)-5-methyl-5,6,7,8-tetrahydrofolate(in) + H+(in) = (6S)-5-methyl-5,6,7,8-tetrahydrofolate(out) + H+(out)
- methotrexate(in) + H+(in) = methotrexate(out) + H+(out)
- pemetrexed(in) + H+(in) = pemetrexed(out) + H+(out)
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 156 | H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport | ||||
Sequence: D | ||||||
Binding site | 185 | H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport | ||||
Sequence: E | ||||||
Binding site | 281 | H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | basolateral plasma membrane | |
Cellular Component | brush border membrane | |
Cellular Component | cytoplasm | |
Cellular Component | endosome membrane | |
Molecular Function | folic acid binding | |
Molecular Function | folic acid transmembrane transporter activity | |
Molecular Function | folic acid:proton symporter activity | |
Molecular Function | heme transmembrane transporter activity | |
Molecular Function | methotrexate transmembrane transporter activity | |
Biological Process | folate import across plasma membrane | |
Biological Process | folic acid transport | |
Biological Process | heme transport |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProton-coupled folate transporter
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ6PEM8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-25 | Cytoplasmic | ||||
Sequence: MEGRVSSVGSPHSFLNAPVLFRGPV | ||||||
Transmembrane | 26-44 | Helical; Name=TM1 | ||||
Sequence: EPLVFLANFALVLQGPLTT | ||||||
Topological domain | 45-82 | Extracellular | ||||
Sequence: QYLWHRFSTELGYNGTRHRENCGNQSADPLMKEVETLT | ||||||
Transmembrane | 83-108 | Helical; Name=TM2 | ||||
Sequence: SHWTLYMNVGGFLVGLFWSTLLGAWS | ||||||
Topological domain | 109-112 | Cytoplasmic | ||||
Sequence: DRVG | ||||||
Transmembrane | 113-135 | Helical; Name=TM3 | ||||
Sequence: RRPLLVLASLGLLLQAVVSIFVV | ||||||
Topological domain | 136-140 | Extracellular | ||||
Sequence: QLELH | ||||||
Transmembrane | 141-154 | Helical; Name=TM4 | ||||
Sequence: VGFFVLGRALCALL | ||||||
Topological domain | 155-177 | Cytoplasmic | ||||
Sequence: GDFNGLLAASFASVADVSSNHSR | ||||||
Transmembrane | 178-203 | Helical; Name=TM5 | ||||
Sequence: TFRMALLEACIGVAGTLASLLGGHWL | ||||||
Topological domain | 204-208 | Extracellular | ||||
Sequence: RAQGY | ||||||
Transmembrane | 209-227 | Helical; Name=TM6 | ||||
Sequence: ANPFWLALALLIVMALYAA | ||||||
Topological domain | 228-266 | Cytoplasmic | ||||
Sequence: FCFGETVKEPKSTRLFTLRHHRSIARLYVVPAPEKSRMH | ||||||
Transmembrane | 267-289 | Helical; Name=TM7 | ||||
Sequence: LALYSLAIFVVVTVHFGAQDILT | ||||||
Topological domain | 290-302 | Extracellular | ||||
Sequence: LYELSAPLCWDSK | ||||||
Transmembrane | 303-325 | Helical; Name=TM8 | ||||
Sequence: LIGYGSAAQHLPYLTSLLGLRLL | ||||||
Topological domain | 326-331 | Cytoplasmic | ||||
Sequence: QFCLAD | ||||||
Transmembrane | 332-351 | Helical; Name=TM9 | ||||
Sequence: TWVAEIGLAFNILGMVVFAF | ||||||
Topological domain | 352-355 | Extracellular | ||||
Sequence: ATIT | ||||||
Transmembrane | 356-376 | Helical; Name=TM10 | ||||
Sequence: PLMFTGYGLLFLSLVTTPVIR | ||||||
Topological domain | 377-388 | Cytoplasmic | ||||
Sequence: AKLSKLVSESEQ | ||||||
Transmembrane | 389-414 | Helical; Name=TM11 | ||||
Sequence: GALFSAVACVNSLAMLMASGIFNSIY | ||||||
Topological domain | 415-422 | Extracellular | ||||
Sequence: PATLNFMK | ||||||
Transmembrane | 423-441 | Helical; Name=TM12 | ||||
Sequence: GFPFLLGAGLLFIPAILIG | ||||||
Topological domain | 442-459 | Cytoplasmic | ||||
Sequence: VLEKVNPHPEFQQFPQSP |
Keywords
- Cellular component
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).
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.
PTM/Processing
Features
Showing features for modified residue, chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000084852 | 1-459 | Proton-coupled folate transporter | |||
Sequence: MEGRVSSVGSPHSFLNAPVLFRGPVEPLVFLANFALVLQGPLTTQYLWHRFSTELGYNGTRHRENCGNQSADPLMKEVETLTSHWTLYMNVGGFLVGLFWSTLLGAWSDRVGRRPLLVLASLGLLLQAVVSIFVVQLELHVGFFVLGRALCALLGDFNGLLAASFASVADVSSNHSRTFRMALLEACIGVAGTLASLLGGHWLRAQGYANPFWLALALLIVMALYAAFCFGETVKEPKSTRLFTLRHHRSIARLYVVPAPEKSRMHLALYSLAIFVVVTVHFGAQDILTLYELSAPLCWDSKLIGYGSAAQHLPYLTSLLGLRLLQFCLADTWVAEIGLAFNILGMVVFAFATITPLMFTGYGLLFLSLVTTPVIRAKLSKLVSESEQGALFSAVACVNSLAMLMASGIFNSIYPATLNFMKGFPFLLGAGLLFIPAILIGVLEKVNPHPEFQQFPQSP | ||||||
Modified residue | 6 | Phosphoserine | ||||
Sequence: S | ||||||
Glycosylation | 58 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 66↔298 | |||||
Sequence: CGNQSADPLMKEVETLTSHWTLYMNVGGFLVGLFWSTLLGAWSDRVGRRPLLVLASLGLLLQAVVSIFVVQLELHVGFFVLGRALCALLGDFNGLLAASFASVADVSSNHSRTFRMALLEACIGVAGTLASLLGGHWLRAQGYANPFWLALALLIVMALYAAFCFGETVKEPKSTRLFTLRHHRSIARLYVVPAPEKSRMHLALYSLAIFVVVTVHFGAQDILTLYELSAPLC | ||||||
Glycosylation | 68 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 458 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
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).
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).
Not induced in the duodenum of iron-deficient mice (PubMed:16143108).
Gene expression databases
Structure
Sequence
- Sequence statusComplete
- Length459
- Mass (Da)50,089
- Last updated2004-07-05 v1
- ChecksumA251124B3B9846AF
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F6QD87 | F6QD87_MOUSE | Slc46a1 | 98 |
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 402 | in Ref. 1; BAB22685 | ||||
Sequence: A → V |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |