Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTECBF4R)

• DOT Name: RCC1 and BTB domain-containing protein 2 (RCBTB2)
• Synonyms: Chromosome condensation 1-like; CHC1-L; RCC1-like G exchanging factor; Regulator of chromosome condensation and BTB domain-containing protein 2
• Gene Name: RCBTB2
• Related Disease:
  Leukemia
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Neuroblastoma
  Plasma cell myeloma
• UniProt ID: RCBT2_HUMAN
• Pfam ID: PF00651 ; PF00415
• Sequence:
  MEEELPLFSGDSGKPVQATLSSLKMLDVGKWPIFSLCSEEELQLIRQACVFGSAGNEVLY
  TTVNDEIFVLGTNCCGCLGLGDVQSTIEPRRLDSLNGKKIACLSYGSGPHIVLATTEGEV
  FTWGHNAYSQLGNGTTNHGLVPCHISTNLSNKQVIEVACGSYHSLVLTSDGEVFAWGYNN
  SGQVGSGSTVNQPIPRRVTGCLQNKVVVTIACGQMCCMAVVDTGEVYVWGYNGNGQLGLG
  NSGNQPTPCRVAALQGIRVQRVACGYAHTLVLTDEGQVYAWGANSYGQLGTGNKSNQSYP
  TPVTVEKDRIIEIAACHSTHTSAAKTQGGHVYMWGQCRGQSVILPHLTHFSCTDDVFACF
  ATPAVTWRLLSVEPDDHLTVAESLKREFDNPDTADLKFLVDGKYIYAHKVLLKIRCEHFR
  SSLEDNEDDIVEMSEFSYPVYRAFLEYLYTDSISLSPEEAVGLLDLATFYRENRLKKLCQ
  QTIKQGICEENAIALLSAAVKYDAQDLEEFCFRFCINHLTVVTQTSGFAEMDHDLLKNFI
  SKASRVGAFKN

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leukemia	DISNAKFL	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[2]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[3]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[4]

10 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 RCC1 and BTB domain-containing protein 2 (RCBTB2).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RCC1 and BTB domain-containing protein 2 (RCBTB2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RCC1 and BTB domain-containing protein 2 (RCBTB2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RCC1 and BTB domain-containing protein 2 (RCBTB2).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of RCC1 and BTB domain-containing protein 2 (RCBTB2).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of RCC1 and BTB domain-containing protein 2 (RCBTB2).	[10]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial decreases the expression of RCC1 and BTB domain-containing protein 2 (RCBTB2).	[11]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium decreases the expression of RCC1 and BTB domain-containing protein 2 (RCBTB2).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of RCC1 and BTB domain-containing protein 2 (RCBTB2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RCC1 and BTB domain-containing protein 2 (RCBTB2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of RCC1 and BTB domain-containing protein 2 (RCBTB2).	[14]

References

• [1] Low expression of ZHX2, but not RCBTB2 or RAN, is associated with poor outcome in multiple myeloma.Br J Haematol. 2008 Apr;141(2):212-5. doi: 10.1111/j.1365-2141.2007.06956.x.
• [2] CHC1-L, a candidate gene for prostate carcinogenesis at 13q14.2, is frequently affected by loss of heterozygosity and underexpressed in human prostate cancer.Int J Cancer. 2002 Jun 10;99(5):689-96. doi: 10.1002/ijc.10393.
• [3] A culture device demonstrates that hydrostatic pressure increases mRNA of RGS5 in neuroblastoma and CHC1-L in lymphocytic cells.Cells Tissues Organs. 2003;174(4):155-61. doi: 10.1159/000072718.
• [4] Expression of RAN, ZHX-2, and CHC1L genes in multiple myeloma patients and in myeloma cell lines treated with HDAC and Dnmts inhibitors.Neoplasma. 2010;57(5):482-7. doi: 10.4149/neo_2010_05_482.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression. Cancer Res. 2005 Sep 1;65(17):7856-65. doi: 10.1158/0008-5472.CAN-05-1056.
• [8] 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.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [11] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] 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.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.