Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5V72D3)

• DOT Name: G2/mitotic-specific cyclin-B3 (CCNB3)
• Gene Name: CCNB3
• Related Disease:
  Osteosarcoma
  Bone sarcoma
  Desmoplastic small round cell tumor
  Ewing sarcoma
  Neoplasm
  Advanced cancer
  Soft tissue sarcoma
  Synovial sarcoma
• UniProt ID: CCNB3_HUMAN
• Pfam ID: PF02984 ; PF00134
• Sequence:
  MLLPLPPQSSKPVPKKSQSSKIVPSHHDPSEKTGENCQTKISPSSLQESPSSLQGALKKR
  SAFEDLTNASQCQPVQPKKEANKEFVKVVSKKINRNTHALGLAKKNKRNLKWHKLEVTPV
  VASTTVVPNIMEKPLILDISTTSKTPNTEEASLFRKPLVLKEEPTIEDETLINKSLSLKK
  CSNHEEVSLLEKLQPLQEESDSDDAFVIEPMTFKKTHKTEEAAITKKTLSLKKKMCASQR
  KQSCQEESLAVQDVNMEEDSFFMESMSFKKKPKTEESIPTHKLSSLKKKCTIYGKICHFR
  KPPVLQTTICGAMSSIKKPTTEKETLFQELSVLQEKHTTEHEMSILKKSLALQKTNFKED
  SLVKESLAFKKKPSTEEAIMMPVILKEQCMTEGKRSRLKPLVLQEITSGEKSLIMKPLSI
  KEKPSTEKESFSQEPSALQKKHTTQEEVSILKEPSSLLKSPTEESPFDEALAFTKKCTIE
  EAPPTKKPLILKRKHATQGTMSHLKKPLILQTTSGEKSLIKEPLPFKEEKVSLKKKCTTQ
  EMMSICPELLDFQDMIGEDKNSFFMEPMSFRKNPTTEETVLTKTSLSLQEKKITQGKMSH
  LKKPLVLQKITSEEESFYKKLLPFKMKSTTEEKFLSQEPSALKEKHTTLQEVSLSKESLA
  IQEKATTEEEFSQELFSLHVKHTNKSGSLFQEALVLQEKTDAEEDSLKNLLALQEKSTME
  EESLINKLLALKEELSAEAATNIQTQLSLKKKSTSHGKVFFLKKQLALNETINEEEFLNK
  QPLALEGYPSIAEGETLFKKLLAMQEEPSIEKEAVLKEPTIDTEAHFKEPLALQEEPSTE
  KEAVLKEPSVDTEAHFKETLALQEKPSIEQEALFKRHSALWEKPSTEKETIFKESLDLQE
  KPSIKKETLLKKPLALKMSTINEAVLFEDMIALNEKPTTGKELSFKEPLALQESPTYKED
  TFLKTLLVPQVGTSPNVSSTAPESITSKSSIATMTSVGKSGTINEAFLFEDMITLNEKPT
  TGKELSFKEPLALQESPTCKEDTFLETFLIPQIGTSPYVFSTTPESITEKSSIATMTSVG
  KSRTTTESSACESASDKPVSPQAKGTPKEITPREDIDEDSSDPSFNPMYAKEIFSYMKER
  EEQFILTDYMNRQIEITSDMRAILVDWLVEVQVSFEMTHETLYLAVKLVDLYLMKAVCKK
  DKLQLLGATAFMIAAKFEEHNSPRVDDFVYICDDNYQRSEVLSMEINILNVLKCDINIPI
  AYHFLRRYARCIHTNMKTLTLSRYICEMTLQEYHYVQEKASKLAAASLLLALYMKKLGYW
  VPFLEHYSGYSISELHPLVRQLNKLLTFSSYDSLKAVYYKYSHPVFFEVAKIPALDMLKL
  EEILNCDCEAQGLVL
• Function: Cyclins are positive regulatory subunits of the cyclin-dependent kinases (CDKs), and thereby play an essential role in the control of the cell cycle, notably via their destruction during cell division. Its tissue specificity suggest that it may be required during early meiotic prophase I.
• Tissue Specificity: Testis specific. In testis, it is expressed in developing germ cells, but not in Leydig cells. Weakly or not expressed in other tissues.
• KEGG Pathway:
  FoxO sig.ling pathway (hsa04068)
  Cell cycle (hsa04110)
  Cellular senescence (hsa04218)
  Progesterone-mediated oocyte maturation (hsa04914)
  Human immunodeficiency virus 1 infection (hsa05170)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Bone sarcoma	DIS95A0A	Strong	Biomarker	[1]
Desmoplastic small round cell tumor	DISLI2ME	Strong	Genetic Variation	[2]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]
Soft tissue sarcoma	DISSN8XB	Limited	Biomarker	[5]
Synovial sarcoma	DISEZJS7	Limited	Biomarker	[5]

5 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 G2/mitotic-specific cyclin-B3 (CCNB3).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of G2/mitotic-specific cyclin-B3 (CCNB3).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of G2/mitotic-specific cyclin-B3 (CCNB3).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of G2/mitotic-specific cyclin-B3 (CCNB3).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of G2/mitotic-specific cyclin-B3 (CCNB3).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of G2/mitotic-specific cyclin-B3 (CCNB3).	[9]

References

• [1] Clear cell sarcomas of the kidney are characterised by BCOR gene abnormalities, including exon 15 internal tandem duplications and BCOR-CCNB3 gene fusion.Histopathology. 2018 Jan;72(2):320-329. doi: 10.1111/his.13366. Epub 2017 Oct 30.
• [2] PAX7 immunohistochemical evaluation of Ewing sarcoma and other small round cell tumours.Histopathology. 2018 Oct;73(4):645-652. doi: 10.1111/his.13689. Epub 2018 Aug 2.
• [3] An undifferentiated sarcoma with BCOR-CCNB3 fusion transcript - pathological and clinical retrospective study.Neoplasma. 2018;65(4):630-636. doi: 10.4149/neo_2018_171107N716.
• [4] Clinicopathologic Diversity of Undifferentiated Sarcoma With BCOR-CCNB3 Fusion: Analysis of 11 Cases With a Reappraisal of the Utility of Immunohistochemistry for BCOR and CCNB3.Am J Surg Pathol. 2017 Dec;41(12):1713-1721. doi: 10.1097/PAS.0000000000000934.
• [5] BCOR-CCNB3-positive soft tissue sarcoma with round-cell and spindle-cell histology: a series of four cases highlighting the pitfall of mimicking poorly differentiated synovial sarcoma.Histopathology. 2016 Nov;69(5):792-801. doi: 10.1111/his.13001. Epub 2016 Jul 15.
• [6] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [7] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [8] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [9] 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.
• [10] 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.
• [11] Impact of Environmentally Relevant Concentrations of Bisphenol A (BPA) on the Gene Expression Profile in an In Vitro Model of the Normal Human Ovary. Int J Mol Sci. 2022 May 10;23(10):5334. doi: 10.3390/ijms23105334.