Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCCS9DB)

• DOT Name: Nuclear cap-binding protein subunit 3 (NCBP3)
• Synonyms: Protein ELG
• Gene Name: NCBP3
• UniProt ID: NCBP3_HUMAN
• Pfam ID: PF10309
• Sequence:
  MAAVRGLRVSVKAEAPAGPALGLPSPEAESGVDRGEPEPMEVEEGELEIVPVRRSLKELI
  PDTSRRYENKAGSFITGIDVTSKEAIEKKEQRAKRFHFRSEVNLAQRNVALDRDMMKKAI
  PKVRLETIYICGVDEMSTQDVFSYFKEYPPAHIEWLDDTSCNVVWLDEMTATRALINMSS
  LPAQDKIRSRDASEDKSAEKRKKDKQEDSSDDDEAEEGEVEDENSSDVELDTLSQVEEES
  LLRNDLRPANKLAKGNRLFMRFATKDDKKELGAARRSQYYMKYGNPNYGGMKGILSNSWK
  RRYHSRRIQRDVIKKRALIGDDVGLTSYKHRHSGLVNVPEEPIEEEEEEEEEEEEEEEED
  QDMDADDRVVVEYHEELPALKQPRERSASRRSSASSSDSDEMDYDLELKMISTPSPKKSM
  KMTMYADEVESQLKNIRNSMRADSVSSSNIKNRIGNKLPPEKFADVRHLLDEKRQHSRPR
  PPVSSTKSDIRQRLGKRPHSPEKAFSSNPVVRREPSSDVHSRLGVPRQDSKGLYADTREK
  KSGNLWTRLGSAPKTKEKNTKKVDHRAPGAEEDDSELQRAWGALIKEKEQSRQKKSRLDN
  LPSLQIEVSRESSSGSEAES
• Function: Associates with NCBP1/CBP80 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export. NCBP3 serves as adapter protein linking the capped RNAs (m7GpppG-capped RNA) to NCBP1/CBP80. Unlike the conventional CBC with NCBP2 which binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus, the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role in only mRNA export. The alternative CBC is particularly important in cellular stress situations such as virus infections and the NCBP3 activity is critical to inhibit virus growth.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Nuclear cap-binding protein subunit 3 (NCBP3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nuclear cap-binding protein subunit 3 (NCBP3).	[4]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Nuclear cap-binding protein subunit 3 (NCBP3).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Nuclear cap-binding protein subunit 3 (NCBP3).	[6]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Nuclear cap-binding protein subunit 3 (NCBP3).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nuclear cap-binding protein subunit 3 (NCBP3).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nuclear cap-binding protein subunit 3 (NCBP3).	[3]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [5] 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.
• [6] 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.