General Information of Target

Target ID LDTP10637
Target Name Proton-coupled folate transporter (SLC46A1)
Gene Name SLC46A1
Gene ID 113235
Synonyms
G21; HCP1; PCFT; Proton-coupled folate transporter; HsPCFT; hPCFT; Heme carrier protein 1; PCFT/HCP1; Solute carrier family 46 member 1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MRTEAEAAGPPLEPGDFVQLPVPVIQQLYHWDCGLACSRMVLRYLGQLDDSEFERALQKL
QLTRSIWTIDLAYLMHHFGVRHRFCTQTLGVDKGYKNQSFYRKHFDTEETRVNQLFAQAK
ACKVLVEKCTVSVKDIQAHLAQGHVAIVLVNSGVLHCDLCSSPVKYCCFTPSGHHCFCRT
PDYQGHFIVLRGYNRATGCIFYNNPAYADPGMCSTSISNFEEARTSYGTDEDILFVYLDS
Target Type
Successful
Target Bioclass
Transporter and channel
Family
Major facilitator superfamily, SLC46A family
Subcellular location
Cell membrane
Function
Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force. Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus. Functions at acidic pH via alternate outward- and inward-open conformation states. Protonation of residues in the outward open state primes the protein for transport. Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate. Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases. Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes. Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine. Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells. Hence, participates in the trafficking of heme and increases intracellular iron content.; [Isoform 2]: Inactive isoform which is not able to mediate proton-coupled folate transport.
TTD ID
T19229
Uniprot ID
Q96NT5
DrugMap ID
TTY8Z2E
Ensemble ID
ENST00000612814.5
HGNC ID
HGNC:30521
ChEMBL ID
CHEMBL1795188

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C21(1.26)  LDD3313  [1]
BTD
 Probe Info 
C21(1.26)  LDD2136  [2]
IPM
 Probe Info 
N.A.  LDD0005  [3]
TFBX
 Probe Info 
N.A.  LDD0148  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0214  AC1 HEK-293T C21(1.04)  LDD1507  [5]
 LDCM0215  AC10 HEK-293T C21(1.06)  LDD1508  [5]
 LDCM0226  AC11 HEK-293T C21(0.92)  LDD1509  [5]
 LDCM0237  AC12 HEK-293T C21(0.95)  LDD1510  [5]
 LDCM0276  AC17 HEK-293T C21(1.04)  LDD1515  [5]
 LDCM0277  AC18 HEK-293T C21(0.96)  LDD1516  [5]
 LDCM0278  AC19 HEK-293T C21(1.04)  LDD1517  [5]
 LDCM0279  AC2 HEK-293T C21(0.89)  LDD1518  [5]
 LDCM0280  AC20 HEK-293T C21(0.96)  LDD1519  [5]
 LDCM0285  AC25 HEK-293T C21(1.04)  LDD1524  [5]
 LDCM0286  AC26 HEK-293T C21(0.96)  LDD1525  [5]
 LDCM0287  AC27 HEK-293T C21(1.01)  LDD1526  [5]
 LDCM0288  AC28 HEK-293T C21(1.08)  LDD1527  [5]
 LDCM0290  AC3 HEK-293T C21(0.96)  LDD1529  [5]
 LDCM0294  AC33 HEK-293T C21(1.07)  LDD1533  [5]
 LDCM0295  AC34 HEK-293T C21(0.97)  LDD1534  [5]
 LDCM0296  AC35 HEK-293T C21(1.07)  LDD1535  [5]
 LDCM0297  AC36 HEK-293T C21(1.03)  LDD1536  [5]
 LDCM0301  AC4 HEK-293T C21(1.06)  LDD1540  [5]
 LDCM0303  AC41 HEK-293T C21(1.04)  LDD1542  [5]
 LDCM0304  AC42 HEK-293T C21(0.96)  LDD1543  [5]
 LDCM0305  AC43 HEK-293T C21(1.02)  LDD1544  [5]
 LDCM0306  AC44 HEK-293T C21(0.98)  LDD1545  [5]
 LDCM0311  AC49 HEK-293T C21(1.02)  LDD1550  [5]
 LDCM0313  AC50 HEK-293T C21(0.94)  LDD1552  [5]
 LDCM0314  AC51 HEK-293T C21(0.90)  LDD1553  [5]
 LDCM0315  AC52 HEK-293T C21(0.99)  LDD1554  [5]
 LDCM0320  AC57 HEK-293T C21(1.06)  LDD1559  [5]
 LDCM0321  AC58 HEK-293T C21(0.99)  LDD1560  [5]
 LDCM0322  AC59 HEK-293T C21(0.98)  LDD1561  [5]
 LDCM0324  AC60 HEK-293T C21(1.12)  LDD1563  [5]
 LDCM0356  AKOS034007680 HEK-293T C21(1.07)  LDD1570  [5]
 LDCM0369  CL100 HEK-293T C21(0.97)  LDD1573  [5]
 LDCM0371  CL102 HEK-293T C21(1.05)  LDD1575  [5]
 LDCM0372  CL103 HEK-293T C21(0.93)  LDD1576  [5]
 LDCM0373  CL104 HEK-293T C21(0.97)  LDD1577  [5]
 LDCM0375  CL106 HEK-293T C21(1.01)  LDD1579  [5]
 LDCM0376  CL107 HEK-293T C21(0.95)  LDD1580  [5]
 LDCM0377  CL108 HEK-293T C21(0.94)  LDD1581  [5]
 LDCM0380  CL110 HEK-293T C21(1.08)  LDD1584  [5]
 LDCM0381  CL111 HEK-293T C21(0.96)  LDD1585  [5]
 LDCM0382  CL112 HEK-293T C21(1.00)  LDD1586  [5]
 LDCM0384  CL114 HEK-293T C21(1.26)  LDD1588  [5]
 LDCM0385  CL115 HEK-293T C21(0.96)  LDD1589  [5]
 LDCM0386  CL116 HEK-293T C21(1.05)  LDD1590  [5]
 LDCM0388  CL118 HEK-293T C21(1.16)  LDD1592  [5]
 LDCM0389  CL119 HEK-293T C21(0.92)  LDD1593  [5]
 LDCM0391  CL120 HEK-293T C21(1.05)  LDD1595  [5]
 LDCM0393  CL122 HEK-293T C21(1.07)  LDD1597  [5]
 LDCM0394  CL123 HEK-293T C21(1.08)  LDD1598  [5]
 LDCM0395  CL124 HEK-293T C21(1.02)  LDD1599  [5]
 LDCM0397  CL126 HEK-293T C21(1.09)  LDD1601  [5]
 LDCM0398  CL127 HEK-293T C21(0.94)  LDD1602  [5]
 LDCM0399  CL128 HEK-293T C21(1.01)  LDD1603  [5]
 LDCM0401  CL14 HEK-293T C21(0.99)  LDD1605  [5]
 LDCM0402  CL15 HEK-293T C21(1.05)  LDD1606  [5]
 LDCM0403  CL16 HEK-293T C21(1.07)  LDD1607  [5]
 LDCM0404  CL17 HEK-293T C21(1.12)  LDD1608  [5]
 LDCM0405  CL18 HEK-293T C21(1.02)  LDD1609  [5]
 LDCM0406  CL19 HEK-293T C21(0.90)  LDD1610  [5]
 LDCM0407  CL2 HEK-293T C21(1.01)  LDD1611  [5]
 LDCM0408  CL20 HEK-293T C21(0.96)  LDD1612  [5]
 LDCM0414  CL26 HEK-293T C21(1.06)  LDD1618  [5]
 LDCM0415  CL27 HEK-293T C21(0.94)  LDD1619  [5]
 LDCM0416  CL28 HEK-293T C21(1.00)  LDD1620  [5]
 LDCM0417  CL29 HEK-293T C21(0.95)  LDD1621  [5]
 LDCM0418  CL3 HEK-293T C21(0.90)  LDD1622  [5]
 LDCM0419  CL30 HEK-293T C21(1.00)  LDD1623  [5]
 LDCM0420  CL31 HEK-293T C21(1.05)  LDD1624  [5]
 LDCM0421  CL32 HEK-293T C21(1.01)  LDD1625  [5]
 LDCM0428  CL39 HEK-293T C21(0.96)  LDD1632  [5]
 LDCM0429  CL4 HEK-293T C21(0.99)  LDD1633  [5]
 LDCM0430  CL40 HEK-293T C21(0.98)  LDD1634  [5]
 LDCM0431  CL41 HEK-293T C21(0.97)  LDD1635  [5]
 LDCM0432  CL42 HEK-293T C21(0.91)  LDD1636  [5]
 LDCM0433  CL43 HEK-293T C21(0.98)  LDD1637  [5]
 LDCM0434  CL44 HEK-293T C21(1.10)  LDD1638  [5]
 LDCM0440  CL5 HEK-293T C21(1.05)  LDD1644  [5]
 LDCM0441  CL50 HEK-293T C21(1.08)  LDD1645  [5]
 LDCM0443  CL52 HEK-293T C21(1.00)  LDD1646  [5]
 LDCM0444  CL53 HEK-293T C21(1.08)  LDD1647  [5]
 LDCM0445  CL54 HEK-293T C21(1.14)  LDD1648  [5]
 LDCM0446  CL55 HEK-293T C21(0.95)  LDD1649  [5]
 LDCM0447  CL56 HEK-293T C21(1.10)  LDD1650  [5]
 LDCM0451  CL6 HEK-293T C21(1.08)  LDD1654  [5]
 LDCM0454  CL62 HEK-293T C21(1.15)  LDD1657  [5]
 LDCM0455  CL63 HEK-293T C21(0.89)  LDD1658  [5]
 LDCM0456  CL64 HEK-293T C21(0.96)  LDD1659  [5]
 LDCM0457  CL65 HEK-293T C21(1.02)  LDD1660  [5]
 LDCM0458  CL66 HEK-293T C21(0.98)  LDD1661  [5]
 LDCM0459  CL67 HEK-293T C21(0.91)  LDD1662  [5]
 LDCM0460  CL68 HEK-293T C21(1.01)  LDD1663  [5]
 LDCM0462  CL7 HEK-293T C21(0.90)  LDD1665  [5]
 LDCM0467  CL74 HEK-293T C21(1.10)  LDD1670  [5]
 LDCM0469  CL76 HEK-293T C21(0.91)  LDD1672  [5]
 LDCM0470  CL77 HEK-293T C21(1.07)  LDD1673  [5]
 LDCM0471  CL78 HEK-293T C21(0.97)  LDD1674  [5]
 LDCM0472  CL79 HEK-293T C21(0.91)  LDD1675  [5]
 LDCM0473  CL8 HEK-293T C21(1.73)  LDD1676  [5]
 LDCM0474  CL80 HEK-293T C21(1.09)  LDD1677  [5]
 LDCM0480  CL86 HEK-293T C21(1.20)  LDD1683  [5]
 LDCM0481  CL87 HEK-293T C21(0.99)  LDD1684  [5]
 LDCM0482  CL88 HEK-293T C21(1.06)  LDD1685  [5]
 LDCM0483  CL89 HEK-293T C21(1.01)  LDD1686  [5]
 LDCM0485  CL90 HEK-293T C21(1.15)  LDD1688  [5]
 LDCM0486  CL91 HEK-293T C21(1.04)  LDD1689  [5]
 LDCM0487  CL92 HEK-293T C21(1.08)  LDD1690  [5]
 LDCM0493  CL98 HEK-293T C21(1.02)  LDD1696  [5]
 LDCM0494  CL99 HEK-293T C21(1.01)  LDD1697  [5]
 LDCM0495  E2913 HEK-293T C21(0.82)  LDD1698  [5]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C21(2.29)  LDD1702  [2]
 LDCM0468  Fragment33 HEK-293T C21(0.93)  LDD1671  [5]
 LDCM0427  Fragment51 HEK-293T C21(1.01)  LDD1631  [5]
 LDCM0022  KB02 A2780 C21(1.68)  LDD2254  [1]
 LDCM0023  KB03 MDA-MB-231 C21(4.26)  LDD1701  [2]
 LDCM0024  KB05 Hs 936.T C21(1.26)  LDD3313  [1]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C21(1.26)  LDD2136  [2]
 LDCM0544  Nucleophilic fragment 39 MDA-MB-231 C21(0.79)  LDD2137  [2]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 6 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Folic Acid Small molecular drug D0Z0DW
Folic Acid Small molecular drug DB00158
Methotrexate Small molecular drug D0SV8E
Pemetrexed Small molecular drug DB00642
Pralatrexate Small molecular drug DB06813
Sulfasalazine Small molecular drug DB00795
Investigative
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Premetrexed Small molecular drug D0UZ9U
[3h]Folinic Acid Small molecular drug D0R4PS
[3h]N5-methylfolate Small molecular drug D0C2VP

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
3 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
4 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
5 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402