Human Gene SLC46A1 (ENST00000612814.5) from GENCODE V44
Description: Homo sapiens solute carrier family 46 member 1 (SLC46A1), transcript variant 1, mRNA. (from RefSeq NM_080669) RefSeq Summary (NM_080669): This gene encodes a transmembrane proton-coupled folate transporter protein that facilitates the movement of folate and antifolate substrates across cell membranes, optimally in acidic pH environments. This protein is also expressed in the brain and choroid plexus where it transports folates into the central nervous system. This protein further functions as a heme transporter in duodenal enterocytes, and potentially in other tissues like liver and kidney. Its localization to the apical membrane or cytoplasm of intestinal cells is modulated by dietary iron levels. Mutations in this gene are associated with autosomal recessive hereditary folate malabsorption disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2013]. Gencode Transcript: ENST00000612814.5 Gencode Gene: ENSG00000076351.13 Transcript (Including UTRs) Position: hg38 chr17:28,394,642-28,406,212 Size: 11,571 Total Exon Count: 5 Strand: - Coding Region Position: hg38 chr17:28,399,656-28,406,114 Size: 6,459 Coding Exon Count: 5
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
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). 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
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