Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3N73QR)

• DOT Name: Major centromere autoantigen B (CENPB)
• Synonyms: Centromere protein B; CENP-B
• Gene Name: CENPB
• Related Disease:
  Sjogren syndrome
  Systemic sclerosis
• UniProt ID: CENPB_HUMAN
• PDB ID: 1BW6; 1HLV; 1UFI; 6KDR
• Pfam ID: PF09026 ; PF04218 ; PF03184 ; PF03221
• Sequence:
  MGPKRRQLTFREKSRIIQEVEENPDLRKGEIARRFNIPPSTLSTILKNKRAILASERKYG
  VASTCRKTNKLSPYDKLEGLLIAWFQQIRAAGLPVKGIILKEKALRIAEELGMDDFTASN
  GWLDRFRRRHGVVSCSGVARARARNAAPRTPAAPASPAAVPSEGSGGSTTGWRAREEQPP
  SVAEGYASQDVFSATETSLWYDFLPDQAAGLCGGDGRPRQATQRLSVLLCANADGSEKLP
  PLVAGKSAKPRAGQAGLPCDYTANSKGGVTTQALAKYLKALDTRMAAESRRVLLLAGRLA
  AQSLDTSGLRHVQLAFFPPGTVHPLERGVVQQVKGHYRQAMLLKAMAALEGQDPSGLQLG
  LTEALHFVAAAWQAVEPSDIAACFREAGFGGGPNATITTSLKSEGEEEEEEEEEEEEEEG
  EGEEEEEEGEEEEEEGGEGEELGEEEEVEEEGDVDSDEEEEEDEESSSEGLEAEDWAQGV
  VEAGGSFGAYGAQEEAQCPTLHFLEGGEDSDSDSEEEDDEEEDDEDEDDDDDEEDGDEVP
  VPSFGEAMAYFAMVKRYLTSFPIDDRVQSHILHLEHDLVHVTRKNHARQAGVRGLGHQS
• Function: Interacts with centromeric heterochromatin in chromosomes and binds to a specific 17 bp subset of alphoid satellite DNA, called the CENP-B box. May organize arrays of centromere satellite DNA into a higher-order structure which then directs centromere formation and kinetochore assembly in mammalian chromosomes (Probable).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[1]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[2]

4 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 Major centromere autoantigen B (CENPB).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Major centromere autoantigen B (CENPB).	[7]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Major centromere autoantigen B (CENPB).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Major centromere autoantigen B (CENPB).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Major centromere autoantigen B (CENPB).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Major centromere autoantigen B (CENPB).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Major centromere autoantigen B (CENPB).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Major centromere autoantigen B (CENPB).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Major centromere autoantigen B (CENPB).	[11]

References

• [1] Reproducibility of fluid-phase measurements in PBS-treated sputum supernatant of healthy and stable COPD subjects.Int J Chron Obstruct Pulmon Dis. 2019 Apr 11;14:835-852. doi: 10.2147/COPD.S187661. eCollection 2019.
• [2] Evaluation of a commercial immunoassay for autoantibodies in Chinese Han systemic sclerosis population.Clin Chim Acta. 2019 Apr;491:121-125. doi: 10.1016/j.cca.2019.01.020. Epub 2019 Jan 24.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [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.
• [9] 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.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.