Target Information
| Target General Information | Top | |||||
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| Target ID |
T35465
(Former ID: TTDI03511)
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| Target Name |
Solute carrier family 19 member 1 (SLC19A1)
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| Synonyms |
Reduced folate carrier protein; RFC1; RFC; Placental folate transporter; Intestinal folate carrier 1; IFC-1; Folate transporter 1; FOLT; FLOT1
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| Gene Name |
SLC19A1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Folate deficiency anaemia [ICD-11: 3A02] | |||||
| 2 | Leukaemia [ICD-11: 2A60-2B33] | |||||
| 3 | Nutritional deficiency [ICD-11: 5B50-5B71] | |||||
| Function |
Transporter for the intake of folate. Uptake of folate in human placental choriocarcinoma cells occurs by a novel mechanism called potocytosis which functionally couples three components, namely the folate receptor, the folate transporter, and a V-type H(+)-pump.
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| UniProt ID | ||||||
| Sequence |
MVPSSPAVEKQVPVEPGPDPELRSWRHLVCYLCFYGFMAQIRPGESFITPYLLGPDKNFT
REQVTNEITPVLSYSYLAVLVPVFLLTDYLRYTPVLLLQGLSFVSVWLLLLLGHSVAHMQ LMELFYSVTMAARIAYSSYIFSLVRPARYQRVAGYSRAAVLLGVFTSSVLGQLLVTVGRV SFSTLNYISLAFLTFSVVLALFLKRPKRSLFFNRDDRGRCETSASELERMNPGPGGKLGH ALRVACGDSVLARMLRELGDSLRRPQLRLWSLWWVFNSAGYYLVVYYVHILWNEVDPTTN SARVYNGAADAASTLLGAITSFAAGFVKIRWARWSKLLIAGVTATQAGLVFLLAHTRHPS SIWLCYAAFVLFRGSYQFLVPIATFQIASSLSKELCALVFGVNTFFATIVKTIITFIVSD VRGLGLPVRKQFQLYSVYFLILSIIYFLGAMLDGLRHCQRGHHPRQPPAQGLRSAAEEKA AQALSVQDKGLGGLQPAQSPPLSPEDSLGAVGPASLEQRQSDPYLAQAPAPQAAEFLSPV TTPSPCTLCSAQASGPEAADETCPQLAVHPPGVSKLGLQCLPSDGVQNVNQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Folic Acid | Drug Info | Approved | Vitamin deficiency | [2], [3], [4] | |
| 2 | Methotrexate | Drug Info | Approved | leukaemia | [5] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Folic Acid | Drug Info | [1] | |||
| 2 | Methotrexate | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Pemetrexed | Ligand Info | |||||
| Structure Description | Structure of hSLC19A1+PMX | PDB:8GOF | ||||
| Method | Electron microscopy | Resolution | 3.00 Å | Mutation | No | [6] |
| PDB Sequence |
DPELRSWRHL
28 VCYLCFYGFM38 AQIRPGESFI48 TPYLLGPDKN58 FTREQVTNEI68 TPVLSYSYLA 78 VLVPVFLLTD88 YLRYTPVLLL98 QGLSFVSVWL108 LLLLGHSVAH118 MQLMELFYSV 128 TMAARIAYSS138 YIFSLVRPAR148 YQRVAGYSRA158 AVLLGVFTSS168 VLGQLLVTVG 178 RVSFSTLNYI188 SLAFLTFSVV198 LALFLKRPKR208 SLFFNRDDSV250 LARMLRELGD 260 SLRRPQLRLW270 SLWWVFNSAG280 YYLVVYYVHI290 LWNEVDPTTN300 SARVYNGAAD 310 AASTLLGAIT320 SFAAGFVKIR330 WARWSKLLIA340 GVTATQAGLV350 FLLAHTRHPS 360 SIWLCYAAFV370 LFRGSYQFLV380 PIATFQIASS390 LSKELCALVF400 GVNTFFATIV 410 KTIITFIVSD420 VRGLGLPVRK430 QFQLYSVYFL440 ILSIIYFLGA450 MLDGLRH |
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GLU45
4.894
ILE48
3.681
THR49
2.695
LEU52
3.356
VAL64
3.826
ILE68
4.477
THR69
4.140
LEU72
3.413
MET122
3.756
GLU123
2.704
TYR126
3.216
MET130
3.562
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| Ligand Name: Methotrexate | Ligand Info | |||||
| Structure Description | Cryo-EM structure of the human reduced folate carrier in complex with methotrexate | PDB:7TX6 | ||||
| Method | Electron microscopy | Resolution | 3.30 Å | Mutation | Yes | [7] |
| PDB Sequence |
RSWRHLVCYL
32 CFYGFMAQIR42 PGESFITPYL52 LGPDKNFTRE62 QVTNEITPVL72 SYSYLAVLVP 82 VFLLTDYLRY92 TPVLLLQGLS102 FVSVWLLLLL112 GHSVAHMQLM122 ELFYSVTMAA 132 RIAYSSYIFS142 LVRPARYQRV152 AGYSRAAVLL162 GVFTSSVLGQ172 LLVTVGRVSF 182 STLNYISLAF192 LTFSVVLALF202 LKRPKRSLFL251 ARMLRELGDS261 LRRPQLRLWS 271 LWWVFNSAGY281 YLVVYYVHIL291 WNEVDPTTNS301 ARVYNGAADA311 ASTLLGAITS 321 FAAGFVKIRW331 ARWSKLLIAG341 VTATQAGLVF351 LLAHTRHPSS361 IWLCYAAFVL 371 FRGSYQFLVP381 IATFQIASSL391 SKELCALVFG401 VNTFFATIVK411 TIITFIVSDV 421 RGLGLPVRKQ431 FQLYSVYFLI441 LSIIYFLGAM451 LDGLRHCQ
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GLU45
4.322
ILE48
3.518
THR49
3.114
LEU52
3.828
VAL64
4.211
ILE68
4.387
THR69
3.598
LEU72
3.565
TYR76
3.093
MET122
4.278
GLU123
2.860
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Pathway Affiliation
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Vitamin digestion and absorption | hsa04977 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Profiles in Patients | Top | |||||
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| Drug Resistance Mutation (DRM) | ||||||
| References | Top | |||||
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| REF 1 | Increased activity of a novel low pH folate transporter associated with lipophilic antifolate resistance in chinese hamster ovary cells. J Biol Chem. 1998 Apr 3;273(14):8106-11. | |||||
| REF 2 | 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. (Ligand id: 4563). | |||||
| REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040514. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for ... Trials. 2015 Mar 4;16:77. | |||||
| REF 6 | Recognition of cyclic dinucleotides and folates by human SLC19A1. Nature. 2022 Dec;612(7938):170-176. | |||||
| REF 7 | Methotrexate recognition by the human reduced folate carrier SLC19A1. Nature. 2022 Sep;609(7929):1056-1062. | |||||
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