Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7EM0F7)

• DOT Name: Lysine-rich nucleolar protein 1 (KNOP1)
• Synonyms: Protein FAM191A; Testis-specific gene 118 protein
• Gene Name: KNOP1
• UniProt ID: KNOP1_HUMAN
• Pfam ID: PF15477
• Sequence:
  MITKTHKVDLGLPEKKKKKKVVKEPETRYSVLNNDDYFADVSPLRATSPSKSVAHGQAPE
  MPLVKKKKKKKKGVSTLCEEHVEPETTLPARRTEKSPSLRKQVFGHLEFLSGEKKNKKSP
  LAMSHASGVKTSPDPRQGEEETRVGKKLKKHKKEKKGAQDPTAFSVQDPWFCEAREARDV
  GDTCSVGKKDEEQAALGQKRKRKSPREHNGKVKKKKKIHQEGDALPGHSKPSRSMESSPR
  KGSKKKPVKVEAPEYIPISDDPKASAKKKMKSKKKVEQPVIEEPALKRKKKKKRKESGVA
  GDPWKEETDTDLEVVLEKKGNMDEAHIDQVRRKALQEEIDRESGKTEASETRKWTGTQFG
  QWDTAGFENEDQKLKFLRLMGGFKNLSPSFSRPASTIARPNMALGKKAADSLQQNLQRDY
  DRAMSWKYSRGAGLGFSTAPNKIFYIDRNASKSVKLED

Molecular Interaction Atlas (MIA) of This DOT

9 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 Lysine-rich nucleolar protein 1 (KNOP1).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lysine-rich nucleolar protein 1 (KNOP1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Lysine-rich nucleolar protein 1 (KNOP1).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Lysine-rich nucleolar protein 1 (KNOP1).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Lysine-rich nucleolar protein 1 (KNOP1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lysine-rich nucleolar protein 1 (KNOP1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Lysine-rich nucleolar protein 1 (KNOP1).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Lysine-rich nucleolar protein 1 (KNOP1).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Lysine-rich nucleolar protein 1 (KNOP1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Lysine-rich nucleolar protein 1 (KNOP1).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Lysine-rich nucleolar protein 1 (KNOP1).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Lysine-rich nucleolar protein 1 (KNOP1).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [6] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] 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.
• [9] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [10] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.