ID:PCFT_HUMAN DESCRIPTION: RecName: Full=Proton-coupled folate transporter; AltName: Full=G21; AltName: Full=Heme carrier protein 1; AltName: Full=PCFT/HCP1; AltName: Full=Solute carrier family 46 member 1; FUNCTION: Has 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. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.3 uM for folic acid (at pH 5.5); KM=1.5 uM for folic acid (at pH 6.0); KM=2.7 uM for folic acid (at pH 6.5); KM=6.0 uM for folic acid (at pH 7.0); KM=56.2 uM for folic acid (at pH 7.5); pH dependence: Optimum pH is 4.0-5.5. Activity decreases above pH 5.5 and reaches negligible levels at neutral pH and above; SUBCELLULAR LOCATION: Apical cell membrane; Multi-pass membrane protein. Cytoplasm (By similarity). 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). TISSUE SPECIFICITY: Expressed 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. DISEASE: Defects in SLC46A1 are the cause of hereditary folate malabsorption (HFM) [MIM:229050]. HFM is a 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. SIMILARITY: Belongs to the major facilitator superfamily. SLC46A family. WEB RESOURCE: Name=Mendelian genes solute carrier family 46 (folate transporter), member 1 (SLC46A1); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/SLC46A1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF07690 - Major Facilitator Superfamily
SCOP Domains: 103473 - MFS general substrate transporter
ModBase Predicted Comparative 3D Structure on Q96NT5
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC065365 - Homo sapiens cDNA clone IMAGE:5922370, partial cds. AL832613 - Homo sapiens mRNA; cDNA DKFZp451K1917 (from clone DKFZp451K1917). JD231963 - Sequence 212987 from Patent EP1572962. AK074161 - Homo sapiens mRNA for FLJ00234 protein. BC022100 - Homo sapiens solute carrier family 46 (folate transporter), member 1, mRNA (cDNA clone IMAGE:4869412), with apparent retained intron. BC010691 - Homo sapiens solute carrier family 46 (folate transporter), member 1, mRNA (cDNA clone MGC:9564 IMAGE:3872267), complete cds. AK054669 - Homo sapiens cDNA FLJ30107 fis, clone BNGH41000198, weakly similar to TETRACYCLINE RESISTANCE PROTEIN, CLASS E. AK097194 - Homo sapiens cDNA FLJ39875 fis, clone SPLEN2015890. JD253683 - Sequence 234707 from Patent EP1572962. JD214636 - Sequence 195660 from Patent EP1572962. JD104259 - Sequence 85283 from Patent EP1572962. JD383369 - Sequence 364393 from Patent EP1572962. JD454780 - Sequence 435804 from Patent EP1572962. JD452229 - Sequence 433253 from Patent EP1572962. JD340519 - Sequence 321543 from Patent EP1572962. JD209891 - Sequence 190915 from Patent EP1572962. JD114710 - Sequence 95734 from Patent EP1572962. JD507039 - Sequence 488063 from Patent EP1572962. JD516135 - Sequence 497159 from Patent EP1572962. JD122524 - Sequence 103548 from Patent EP1572962. JD473188 - Sequence 454212 from Patent EP1572962. JD400438 - Sequence 381462 from Patent EP1572962. JD194117 - Sequence 175141 from Patent EP1572962. JF432839 - Synthetic construct Homo sapiens clone IMAGE:100074159 solute carrier family 46 (folate transporter), member 1 (SLC46A1) gene, encodes complete protein. KJ904957 - Synthetic construct Homo sapiens clone ccsbBroadEn_14351 SLC46A1 gene, encodes complete protein. AF086363 - Homo sapiens full length insert cDNA clone ZD66C06. AK295883 - Homo sapiens cDNA FLJ58315 complete cds, highly similar to Heme carrier protein 1.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q96NT5 (Reactome details) participates in the following event(s):
R-HSA-200646 Cytosolic folate export across the plasma membrane R-HSA-200729 Extracellular folate import across the plasma membrane R-HSA-917870 SLC46A1 transports FeHM from extracellular region to cytosol R-HSA-196757 Metabolism of folate and pterines R-HSA-917937 Iron uptake and transport R-HSA-196849 Metabolism of water-soluble vitamins and cofactors R-HSA-382551 Transport of small molecules R-HSA-196854 Metabolism of vitamins and cofactors R-HSA-1430728 Metabolism
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
