Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4YSBV5)

• DOT Name: Leucine-rich repeat-containing protein 41 (LRRC41)
• Synonyms: Protein Muf1
• Gene Name: LRRC41
• UniProt ID: LRC41_HUMAN
• Sequence:
  MAAPEAWRARSCWFCEVAAATTMEATSREAAPAKSSASGPNAPPALFELCGRAVSAHMGV
  LESGVWALPGPILQSILPLLNIYYLERIEETALKKGLSTQAIWRRLWDELMKTRPSSLES
  VTCWRAKFMEAFFSHVLRGTIDVSSDRRLCDQRFSPLLHSSRHVRQLTICNMLQGATELV
  AEPNRRVLETLASSLHTLKFRHLLFSDVAAQQSLRQLLHQLIHHGAVSQVSLYSWPVPES
  ALFILILTMSAGFWQPGPGGPPCRLCGEASRGRAPSRDEGSLLLGSRRPRRDAAERCAAA
  LMASRRKSEAKQMPRAAPATRVTRRSTQESLTAGGTDLKRELHPPATSHEAPGTKRSPSA
  PAATSSASSSTSSYKRAPASSAPQPKPLKRFKRAAGKKGARTRQGPGAESEDLYDFVFIV
  AGEKEDGEEMEIGEVACGALDGSDPSCLGLPALEASQRFRSISTLELFTVPLSTEAALTL
  CHLLSSWVSLESLTLSYNGLGSNIFRLLDSLRALSGQAGCRLRALHLSDLFSPLPILELT
  RAIVRALPLLRVLSIRVDHPSQRDNPGVPGNAGPPSHIIGDEEIPENCLEQLEMGFPRGA
  QPAPLLCSVLKASGSLQQLSLDSATFASPQDFGLVLQTLKEYNLALKRLSFHDMNLADCQ
  SEVLFLLQNLTLQEITFSFCRLFEKRPAQFLPEMVAAMKGNSTLKGLRLPGNRLGNAGLL
  ALADVFSEDSSSSLCQLDISSNCIKPDGLLEFAKRLERWGRGAFGHLRLFQNWLDQDAVT
  AREAIRRLRATCHVVSDSWDSSQAFADYVSTM
• Function: Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
• Reactome Pathway:
  RHOBTB3 ATPase cycle (R-HSA-9706019)
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Leucine-rich repeat-containing protein 41 (LRRC41).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Leucine-rich repeat-containing protein 41 (LRRC41).	[2]
Selenium	DM25CGV	Approved	Selenium increases the expression of Leucine-rich repeat-containing protein 41 (LRRC41).	[4]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Leucine-rich repeat-containing protein 41 (LRRC41).	[5]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Leucine-rich repeat-containing protein 41 (LRRC41).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Leucine-rich repeat-containing protein 41 (LRRC41).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Leucine-rich repeat-containing protein 41 (LRRC41).	[8]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Leucine-rich repeat-containing protein 41 (LRRC41).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Leucine-rich repeat-containing protein 41 (LRRC41).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Leucine-rich repeat-containing protein 41 (LRRC41).	[3]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [3] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [4] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [7] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.