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Identification
HMDB Protein ID HMDBP03060
Secondary Accession Numbers
  • 8592
Name Proton-coupled folate transporter
Synonyms
  1. G21
  2. Heme carrier protein 1
  3. PCFT/HCP1
  4. Solute carrier family 46 member 1
Gene Name SLC46A1
Protein Type Transporter
Biological Properties
General Function Involved in transmembrane transport
Specific 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
Pathways
  • Folate malabsorption, hereditary
  • Folate Metabolism
  • Methotrexate Action Pathway
  • Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
transporter activity
Process
establishment of localization
transport
transmembrane transport
Cellular Location
  1. Cytoplasm
  2. Multi-pass membrane protein
  3. Apical cell membrane
Gene Properties
Chromosome Location Chromosome:1
Locus 17q11.2
SNPs SLC46A1
Gene Sequence
>1380 bp
ATGGAGGGGAGCGCGAGCCCCCCGGAAAAGCCCCGCGCCCGCCCTGCGGCTGCCGTGCTG
TGCCGGGGCCCGGTAGAGCCGCTGGTCTTCCTGGCCAACTTTGCCTTGGTCCTGCAGGGC
CCGCTCACCACGCAGTATCTGTGGCACCGCTTCAGCGCCGACCTCGGCTACAATGGCACC
CGCCAAAGGGGGGGCTGCAGCAACCGCAGCGCGGACCCCACCATGCAGGAAGTGGAGACC
CTTACCTCCCACTGGACCCTCTACATGAACGTGGGCGGCTTCCTGGTGGGGCTCTTCTCG
TCCACCCTGCTGGGAGCTTGGAGCGACAGTGTGGGCCGCCGCCCGCTGCTAGTGCTGGCC
TCGCTGGGCCTGCTGCTCCAGGCCCTAGTGTCCGTTTTTGTGGTGCAGCTGCAGCTCCAC
GTCGGCTACTTCGTGCTGGGTCGCATCCTTTGTGCCCTCCTCGGCGACTTCGGTGGCCTT
CTGGCTGCTAGCTTTGCGTCCGTGGCAGATGTCAGCTCCAGTCGCAGCCGCACCTTCCGG
ATGGCCCTGCTAGAAGCCAGCATCGGGGTGGCTGGGATGCTGGCAAGCCTCCTCGGGGGC
CACTGGCTCCGGGCCCAGGGTTATGCCAACCCCTTCTGGCTGGCCTTGGCCTTGCTGATA
GCCATGACTCTCTATGCAGCTTTCTGCTTTGGTGAGACCTTAAAGGAGCCAAAGTCCACC
CGGCTCTTCACGTTCCGTCACCACCGATCCATTGTCCAGCTCTATGTGGCTCCCGCCCCA
GAGAAGTCCAGGAAACATTTAGCCCTCTACTCACTGGCCATCTTCGTGGTGATCACTGTG
CACTTTGGGGCCCAGGACATCTTAACCCTTTATGAACTAAGCACACCCCTCTGCTGGGAC
TCCAAACTAATCGGCTATGGTTCTGCAGCTCAGCATCTCCCCTACCTCACCAGCCTGCTG
GCCCTGAAGCTCCTGCAGTACTGCCTGGCCGATGCCTGGGTAGCTGAGATCGGCCTGGCC
TTCAACATCCTGGGGATGGTGGTCTTTGCCTTTGCCACTATCACGCCTCTCATGTTCACA
GGATATGGGTTGCTTTTCCTGTCATTAGTCATCACACCTGTCATCCGGGCTAAACTCTCC
AAGCTGGTGAGAGAGACAGAGCAGGGTGCTCTCTTTTCTGCTGTGGCCTGTGTGAATAGC
CTGGCCATGCTGACGGCCTCCGGCATCTTCAACTCACTCTACCCAGCCACTCTGAACTTT
ATGAAGGGGTTCCCCTTCCTCCTGGGAGCTGGCCTCCTGCTCATCCCGGCTGTTCTGATT
GGGATGCTGGAAAAGGCTGATCCTCACCTCGAGTTCCAGCAGTTTCCCCAGAGCCCCTGA
Protein Properties
Number of Residues 459
Molecular Weight 49770.0
Theoretical pI 8.97
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 87-107
  • 115-135
  • 149-169
  • 183-203
  • 211-231
  • 267-287
  • 303-325
  • 337-357
  • 359-379
  • 390-410
  • 423-443
Protein Sequence
>Proton-coupled folate transporter
MEGSASPPEKPRARPAAAVLCRGPVEPLVFLANFALVLQGPLTTQYLWHRFSADLGYNGT
RQRGGCSNRSADPTMQEVETLTSHWTLYMNVGGFLVGLFSSTLLGAWSDSVGRRPLLVLA
SLGLLLQALVSVFVVQLQLHVGYFVLGRILCALLGDFGGLLAASFASVADVSSSRSRTFR
MALLEASIGVAGMLASLLGGHWLRAQGYANPFWLALALLIAMTLYAAFCFGETLKEPKST
RLFTFRHHRSIVQLYVAPAPEKSRKHLALYSLAIFVVITVHFGAQDILTLYELSTPLCWD
SKLIGYGSAAQHLPYLTSLLALKLLQYCLADAWVAEIGLAFNILGMVVFAFATITPLMFT
GYGLLFLSLVITPVIRAKLSKLVRETEQGALFSAVACVNSLAMLTASGIFNSLYPATLNF
MKGFPFLLGAGLLLIPAVLIGMLEKADPHLEFQQFPQSP
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q96NT5
UniProtKB/Swiss-Prot Entry Name PCFT_HUMAN
PDB IDs Not Available
GenBank Gene ID AK054669
GeneCard ID SLC46A1
GenAtlas ID SLC46A1
HGNC ID HGNC:30521
References
General References
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  4. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  5. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  6. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  7. Wang B, Malik R, Nigg EA, Korner R: Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal Chem. 2008 Dec 15;80(24):9526-33. doi: 10.1021/ac801708p. [PubMed:19007248 ]
  8. Shayeghi M, Latunde-Dada GO, Oakhill JS, Laftah AH, Takeuchi K, Halliday N, Khan Y, Warley A, McCann FE, Hider RC, Frazer DM, Anderson GJ, Vulpe CD, Simpson RJ, McKie AT: Identification of an intestinal heme transporter. Cell. 2005 Sep 9;122(5):789-801. [PubMed:16143108 ]
  9. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID: Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. 2006 Dec 1;127(5):917-28. [PubMed:17129779 ]
  10. Latunde-Dada GO, Takeuchi K, Simpson RJ, McKie AT: Haem carrier protein 1 (HCP1): Expression and functional studies in cultured cells. FEBS Lett. 2006 Dec 22;580(30):6865-70. Epub 2006 Nov 29. [PubMed:17156779 ]
  11. Zhao R, Min SH, Qiu A, Sakaris A, Goldberg GL, Sandoval C, Malatack JJ, Rosenblatt DS, Goldman ID: The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption. Blood. 2007 Aug 15;110(4):1147-52. Epub 2007 Apr 19. [PubMed:17446347 ]
  12. Sharma S, Dimasi D, Broer S, Kumar R, Della NG: Heme carrier protein 1 (HCP1) expression and functional analysis in the retina and retinal pigment epithelium. Exp Cell Res. 2007 Apr 1;313(6):1251-9. Epub 2007 Feb 6. [PubMed:17335806 ]
  13. Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, Yuasa H: Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther. 2007 Aug;322(2):469-76. Epub 2007 May 2. [PubMed:17475902 ]
  14. Lasry I, Berman B, Straussberg R, Sofer Y, Bessler H, Sharkia M, Glaser F, Jansen G, Drori S, Assaraf YG: A novel loss-of-function mutation in the proton-coupled folate transporter from a patient with hereditary folate malabsorption reveals that Arg 113 is crucial for function. Blood. 2008 Sep 1;112(5):2055-61. doi: 10.1182/blood-2008-04-150276. Epub 2008 Jun 17. [PubMed:18559978 ]