Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSQDJ5A)

DOT Name Folate receptor beta (FOLR2)
Synonyms FR-beta; Folate receptor 2; Folate receptor, fetal/placental; Placental folate-binding protein; FBP
Gene Name FOLR2
UniProt ID
FOLR2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4KMY; 4KMZ; 4KN0; 4KN1; 4KN2
Pfam ID
PF03024
Sequence
MVWKWMPLLLLLVCVATMCSAQDRTDLLNVCMDAKHHKTKPGPEDKLHDQCSPWKKNACC
TASTSQELHKDTSRLYNFNWDHCGKMEPACKRHFIQDTCLYECSPNLGPWIQQVNQSWRK
ERFLDVPLCKEDCQRWWEDCHTSHTCKSNWHRGWDWTSGVNKCPAGALCRTFESYFPTPA
ALCEGLWSHSYKVSNYSRGSGRCIQMWFDSAQGNPNEEVARFYAAAMHVNAGEMLHGTGG
LLLSLALMLQLWLLG
Function
Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release.
Tissue Specificity Expressed in placenta and hematopoietic cells. Expression is increased in malignant tissues.
KEGG Pathway
Antifolate resistance (hsa01523 )
Endocytosis (hsa04144 )
Reactome Pathway
Metabolism of folate and pterines (R-HSA-196757 )
Post-translational modification (R-HSA-163125 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Folate receptor beta (FOLR2) decreases the response to substance of Cisplatin. [3]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Folate receptor beta (FOLR2). [1]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Folate receptor beta (FOLR2). [2]
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References

1 Synergistic induction of folate receptor beta by all-trans retinoic acid and histone deacetylase inhibitors in acute myelogenous leukemia cells: mechanism and utility in enhancing selective growth inhibition by antifolates. Cancer Res. 2006 Jun 1;66(11):5875-82. doi: 10.1158/0008-5472.CAN-05-4048.
2 Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells. Am J Clin Nutr. 2007 Jul;86(1):159-66. doi: 10.1093/ajcn/86.1.159.
3 HDAC4-regulated STAT1 activation mediates platinum resistance in ovarian cancer. Cancer Res. 2011 Jul 1;71(13):4412-22. doi: 10.1158/0008-5472.CAN-10-4111. Epub 2011 May 13.