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MGP006334

UniProt Annotations

Entry Information
Gene Namesolute carrier family 46 (folate transporter), member 1
Protein EntryPCFT_HUMAN
UniProt IDQ96NT5
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q96NT5-1; Sequence=Displayed; Name=2; IsoId=Q96NT5-2; Sequence=VSP_016053; Note=Inactive isoform which results in impaired folate absorption, giving rise to hereditary folate malabsorption (HFM).;
Biophysicochemical PropertiesKinetic parameters: KM=1.3 uM for folic acid (at pH 5.5) {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17475902}; KM=1.5 uM for folic acid (at pH 6.0) {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17475902}; KM=2.7 uM for folic acid (at pH 6.5) {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17475902}; KM=6.0 uM for folic acid (at pH 7.0) {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17475902}; KM=56.2 uM for folic acid (at pH 7.5) {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17475902}; pH dependence: Optimum pH is 4.0-5.5. Activity decreases above pH 5.5 and reaches negligible levels at neutral pH and above. {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17475902};
DiseaseHereditary folate malabsorption (HFM) [MIM:229050]: Rare autosomal recessive disorder characterized by impaired intestinal folate absorption with folate deficiency resulting in anemia, hypoimmunoglobulinemia with recurrent infections, and recurrent or chronic diarrhea. In many patients, neurological abnormalities such as seizures or mental retardation become apparent during early childhood, attributed to impaired transport of folates into the central nervous system. When diagnosed early, the disorder can be treated by administration of folate. If untreated, it can be fatal and, if treatment is delayed, the neurological defects can become permanent. {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17446347, ECO:0000269|PubMed:18559978, ECO:0000269|PubMed:20686069, ECO:0000269|PubMed:20805364, ECO:0000269|PubMed:21333572}. Note=The disease is caused by mutations affecting the gene represented in this entry.
FunctionHas been shown to act both as an intestinal proton- coupled high-affinity folate transporter and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithelial cells. The iron is then released from heme and may be transported into the bloodstream. Dietary heme iron is an important nutritional source of iron. Shows a higher affinity for folate than heme. {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17156779, ECO:0000269|PubMed:17446347, ECO:0000269|PubMed:17475902}.
SimilarityBelongs to the major facilitator superfamily. SLC46A family. {ECO:0000305}.
Subcellular LocationApical cell membrane; Multi-pass membrane protein. Cytoplasm {ECO:0000250}. Note=Localizes to the apical membrane of intestinal cells in iron-deficient cells, while it resides in the cytoplasm in iron-replete cells. {ECO:0000250}.
SubunitMonomer. {ECO:0000269|PubMed:23601781}.
Tissue SpecificityExpressed in kidney, liver, placenta, small intestine, spleen, retina and retinal pigment epithelium. Lower levels found in colon and testis. Very low levels in brain, lung, stomach, heart and muscle. In intestine, expressed in duodenum with lower levels in jejunum, ileum, cecum, rectum and segments of the colon. {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17335806}.
Web ResourceName=Mendelian genes solute carrier family 46 (folate transporter), member 1 (SLC46A1); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/SLC46A1";
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