Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTY8Z2E)

• DTT Name: Proton-coupled folate transporter (SLC46A1)
• Synonyms: Solute carrier family 46 member 1; PCFT/HCP1; PCFT; Heme carrier protein 1; HCP1; G21
• Gene Name: SLC46A1
• DTT Type: Successful target; [1]
• Related Disease:
  Folate deficiency anaemia [ICD-11: 3A02]
  Leukaemia [ICD-11: 2A60-2B33]
  Nutritional deficiency [ICD-11: 5B50-5B71]
• UniProt ID: PCFT_HUMAN
• TTD ID: T19229
• Sequence:
  MEGSASPPEKPRARPAAAVLCRGPVEPLVFLANFALVLQGPLTTQYLWHRFSADLGYNGT
  RQRGGCSNRSADPTMQEVETLTSHWTLYMNVGGFLVGLFSSTLLGAWSDSVGRRPLLVLA
  SLGLLLQALVSVFVVQLQLHVGYFVLGRILCALLGDFGGLLAASFASVADVSSSRSRTFR
  MALLEASIGVAGMLASLLGGHWLRAQGYANPFWLALALLIAMTLYAAFCFGETLKEPKST
  RLFTFRHHRSIVQLYVAPAPEKSRKHLALYSLAIFVVITVHFGAQDILTLYELSTPLCWD
  SKLIGYGSAAQHLPYLTSLLALKLLQYCLADAWVAEIGLAFNILGMVVFAFATITPLMFT
  GYGLLFLSLVITPVIRAKLSKLVRETEQGALFSAVACVNSLAMLTASGIFNSLYPATLNF
  MKGFPFLLGAGLLLIPAVLIGMLEKADPHLEFQQFPQSP
• 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.
• KEGG Pathway:
  Antifolate resistance (hsa01523)
  Vitamin digestion and absorption (hsa04977)
  Mineral absorption (hsa04978)
• Reactome Pathway:
  Iron uptake and transport (R-HSA-917937)
  Heme signaling (R-HSA-9707616)
  Metabolism of folate and pterines (R-HSA-196757)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[1]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[1]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PREMETREXED	DMVOGT4	Discovery agent	N.A.	Investigative	[1]
[3H]folinic acid	DME0XHN	Discovery agent	N.A.	Investigative	[1]
[3H]N5-methylfolate	DM0THB9	Discovery agent	N.A.	Investigative	[1]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Proton-coupled folate transporter (SLC46A1) DTP Info
• Gene Name: SLC46A1

4 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[2]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[3]
Pemetrexed	DMMX2E6	Malignant pleural mesothelioma	2C26.0	Approved	[4]
Pralatrexate	DMAO80I	Breast cancer	2C60-2C65	Approved	[5]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1213).
• [2] Characterization of uptake of folates by rat and human blood-brain barrier endothelial cells. Biofactors. 2010 May-Jun;36(3):201-9.
• [3] Site-specific contribution of proton-coupled folate transporter/haem carrier protein 1 in the intestinal absorption of methotrexate in rats. J Pharm Pharmacol. 2009 Jul;61(7):911-8.
• [4] The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier. Mol Pharmacol. 2008 Sep;74(3):854-62.
• [5] Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.