Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5L56A1)

• DOT Name: Kinetochore-associated protein NSL1 homolog (NSL1)
• Gene Name: NSL1
• UniProt ID: NSL1_HUMAN
• PDB ID: 4NF9; 5LSI; 5LSJ; 5LSK
• Pfam ID: PF08641
• Sequence:
  MAGSPELVVLDPPWDKELAAGTESQALVSATPREDFRVRCTSKRAVTEMLQLCGRFVQKL
  GDALPEEIREPALRDAQWTFESAVQENISINGQAWQEASDNCFMDSDIKVLEDQFDEIIV
  DIATKRKQYPRKILECVIKTIKAKQEILKQYHPVVHPLDLKYDPDPAPHMENLKCRGETV
  AKEISEAMKSLPALIEQGEGFSQVLRMQPVIHLQRIHQEVFSSCHRKPDAKPENFITQIE
  TTPTETASRKTSDMVLKRKQTKDCPQRKWYPLRPKKINLDT
• Function: Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis.
• Reactome Pathway:
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

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 increases the expression of Kinetochore-associated protein NSL1 homolog (NSL1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Kinetochore-associated protein NSL1 homolog (NSL1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Kinetochore-associated protein NSL1 homolog (NSL1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Kinetochore-associated protein NSL1 homolog (NSL1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Kinetochore-associated protein NSL1 homolog (NSL1).	[5]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Kinetochore-associated protein NSL1 homolog (NSL1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Kinetochore-associated protein NSL1 homolog (NSL1).	[7]

1 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 Kinetochore-associated protein NSL1 homolog (NSL1).	[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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [6] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.