F1NJ67 · PCFT_CHICK
- ProteinProton-coupled folate transporter
- GeneSLC46A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids473 (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: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).
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
- 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)
- H+(in) + methotrexate(in) = H+(out) + methotrexate(out)
- H+(in) + pemetrexed(in) = H+(out) + pemetrexed(out)
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
2 μM | folic acid |
pH Dependence
Optimum pH is 5.0-5.5.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 98 | pemetrexed (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 164 | H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport | ||||
Sequence: D | ||||||
Binding site | 193 | H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport | ||||
Sequence: E | ||||||
Binding site | 193 | pemetrexed (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 289 | H+ (UniProtKB | ChEBI); reversibly protonated residue during proton transport | ||||
Sequence: H | ||||||
Binding site | 323 | pemetrexed (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 407 | pemetrexed (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 411 | pemetrexed (UniProtKB | ChEBI) | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | basolateral plasma membrane | |
Cellular Component | endosome | |
Cellular Component | endosome membrane | |
Cellular Component | plasma membrane | |
Molecular Function | folic acid binding | |
Molecular Function | folic acid:proton symporter activity | |
Molecular Function | methotrexate transmembrane transporter activity | |
Molecular Function | transmembrane transporter activity | |
Biological Process | folate import across plasma membrane | |
Biological Process | transmembrane 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
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Archelosauria > Archosauria > Dinosauria > Saurischia > Theropoda > Coelurosauria > Aves > Neognathae > Galloanserae > Galliformes > Phasianidae > Phasianinae > Gallus
Accessions
- Primary accessionF1NJ67
- 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
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).
Localizes to the basolateral membrane of choroid plexus (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-29 | Cytoplasmic | ||||
Sequence: MAAPSDPPTAATPPAPPPPARRCLLAPSV | ||||||
Transmembrane | 30-48 | Helical; Name=TM1 | ||||
Sequence: EPLLFLATLALGLQVPLAT | ||||||
Topological domain | 49-90 | Extracellular | ||||
Sequence: QYLWDRLGAERGYVGPNASSPHGCGNGSGAVDPLREEVEALV | ||||||
Transmembrane | 91-116 | Helical; Name=TM2 | ||||
Sequence: AHWNLCINLGGFFVGLFSVTLFGPWS | ||||||
Topological domain | 117-120 | Cytoplasmic | ||||
Sequence: DSVG | ||||||
Transmembrane | 121-143 | Helical; Name=TM3 | ||||
Sequence: RRPVLVLPAVGMAVQAAVYLLVM | ||||||
Topological domain | 144-148 | Extracellular | ||||
Sequence: YLRLH | ||||||
Transmembrane | 149-162 | Helical; Name=TM4 | ||||
Sequence: VAYLLLGRIISGLL | ||||||
Topological domain | 163-185 | Cytoplasmic | ||||
Sequence: GDYNLILAGCFASVADSSNQRTR | ||||||
Transmembrane | 186-211 | Helical; Name=TM5 | ||||
Sequence: TFRVAILEACLGVAGMVASVGGGQWR | ||||||
Topological domain | 212-216 | Extracellular | ||||
Sequence: KAEGY | ||||||
Transmembrane | 217-235 | Helical; Name=TM6 | ||||
Sequence: INPFWLVLAASLAAALYAA | ||||||
Topological domain | 236-274 | Cytoplasmic | ||||
Sequence: LCLQETVKQRRAAKLLTLQHYKAVYKLYTAPEDLSSRRK | ||||||
Transmembrane | 275-297 | Helical; Name=TM7 | ||||
Sequence: LALYSLAFFLLVTVHFGTKDLYV | ||||||
Topological domain | 298-310 | Extracellular | ||||
Sequence: LYELGSPLCWASD | ||||||
Transmembrane | 311-333 | Helical; Name=TM8 | ||||
Sequence: LIGYGSAASYLAYLSSLGGLRLL | ||||||
Topological domain | 334-339 | Cytoplasmic | ||||
Sequence: QLCLED | ||||||
Transmembrane | 340-359 | Helical; Name=TM9 | ||||
Sequence: TWVAEIGLISNIAGLVVISL | ||||||
Topological domain | 360-363 | Extracellular | ||||
Sequence: ATTT | ||||||
Transmembrane | 364-384 | Helical; Name=TM10 | ||||
Sequence: PLMFTGYGIMFLSMAATPVIR | ||||||
Topological domain | 385-396 | Cytoplasmic | ||||
Sequence: AKLSKLVGETEQ | ||||||
Transmembrane | 397-422 | Helical; Name=TM11 | ||||
Sequence: GALFASVACVEGLCSLVATGVFNSLY | ||||||
Topological domain | 423-430 | Extracellular | ||||
Sequence: PSTLHFMR | ||||||
Transmembrane | 431-449 | Helical; Name=TM12 | ||||
Sequence: GFPFLFGAILLLIPAAIMG | ||||||
Topological domain | 450-473 | Cytoplasmic | ||||
Sequence: WIEIQDSNLQYSHFSDASSSPADG |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 164 | Strongly reduced proton-coupled folate transport. | ||||
Sequence: D → N | ||||||
Mutagenesis | 193 | Abolished proton-coupled folate transport. | ||||
Sequence: E → A | ||||||
Mutagenesis | 193 | Strong proton-coupled folate transport at pH 7.5. | ||||
Sequence: E → N |
PTM/Processing
Features
Showing features for chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000455380 | 1-473 | Proton-coupled folate transporter | |||
Sequence: MAAPSDPPTAATPPAPPPPARRCLLAPSVEPLLFLATLALGLQVPLATQYLWDRLGAERGYVGPNASSPHGCGNGSGAVDPLREEVEALVAHWNLCINLGGFFVGLFSVTLFGPWSDSVGRRPVLVLPAVGMAVQAAVYLLVMYLRLHVAYLLLGRIISGLLGDYNLILAGCFASVADSSNQRTRTFRVAILEACLGVAGMVASVGGGQWRKAEGYINPFWLVLAASLAAALYAALCLQETVKQRRAAKLLTLQHYKAVYKLYTAPEDLSSRRKLALYSLAFFLLVTVHFGTKDLYVLYELGSPLCWASDLIGYGSAASYLAYLSSLGGLRLLQLCLEDTWVAEIGLISNIAGLVVISLATTTPLMFTGYGIMFLSMAATPVIRAKLSKLVGETEQGALFASVACVEGLCSLVATGVFNSLYPSTLHFMRGFPFLFGAILLLIPAAIMGWIEIQDSNLQYSHFSDASSSPADG | ||||||
Glycosylation | 65 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 72↔306 | |||||
Sequence: CGNGSGAVDPLREEVEALVAHWNLCINLGGFFVGLFSVTLFGPWSDSVGRRPVLVLPAVGMAVQAAVYLLVMYLRLHVAYLLLGRIISGLLGDYNLILAGCFASVADSSNQRTRTFRVAILEACLGVAGMVASVGGGQWRKAEGYINPFWLVLAASLAAALYAALCLQETVKQRRAAKLLTLQHYKAVYKLYTAPEDLSSRRKLALYSLAFFLLVTVHFGTKDLYVLYELGSPLC | ||||||
Glycosylation | 74 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
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
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-21 | Disordered | ||||
Sequence: MAAPSDPPTAATPPAPPPPAR |
Sequence similarities
Belongs to the major facilitator superfamily. SLC46A family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length473
- Mass (Da)50,465
- Last updated2013-06-26 v2
- Checksum794BE71E3B571BEA
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 25 | in Ref. 1; ACV70072 | ||||
Sequence: L → P | ||||||
Sequence conflict | 392 | in Ref. 1; ACV70072 | ||||
Sequence: G → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
FJ655775 EMBL· GenBank· DDBJ | ACV70072.1 EMBL· GenBank· DDBJ | mRNA | ||
AADN05000057 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |