Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXTN1HP)

• DOT Name: E3 ubiquitin-protein ligase RNF187 (RNF187)
• Synonyms: EC 2.3.2.27; RING domain AP1 coactivator 1; RACO-1; RING finger protein 187; RING-type E3 ubiquitin transferase RNF187
• Gene Name: RNF187
• Related Disease:
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Liver cancer
  Liver cirrhosis
  Non-small-cell lung cancer
  Acute myelogenous leukaemia
  Neoplasm
• UniProt ID: RN187_HUMAN
• PDB ID: 7OW2
• EC Number: 2.3.2.27
• Pfam ID: PF15227
• Sequence:
  MALPAGPAEAACALCQRAPREPVRADCGHRFCRACVVRFWAEEDGPFPCPECADDCWQRA
  VEPGRPPLSRRLLALEEAAAAPARDGPASEAALQLLCRADAGPLCAACRMAAGPEPPEWE
  PRWRKALRGKENKGSVEIMRKDLNDARDLHGQAESAAAVWKGHVMDRRKKALTDYKKLRA
  FFVEEEEHFLQEAEKEEGLPEDELADPTERFRSLLQAVSELEKKHRNLGLSMLLQ
• Function: E3 ubiquitin-protein ligase that acts as a coactivator of JUN-mediated gene activation in response to growth factor signaling via the MAP3K1 pathway, independently from MAPK8.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[2]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Liver cancer	DISDE4BI	Strong	Altered Expression	[2]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[4]
Neoplasm	DISZKGEW	Limited	Altered Expression	[3]

2 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 E3 ubiquitin-protein ligase RNF187 (RNF187).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of E3 ubiquitin-protein ligase RNF187 (RNF187).	[9]

6 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 E3 ubiquitin-protein ligase RNF187 (RNF187).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of E3 ubiquitin-protein ligase RNF187 (RNF187).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of E3 ubiquitin-protein ligase RNF187 (RNF187).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of E3 ubiquitin-protein ligase RNF187 (RNF187).	[10]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of E3 ubiquitin-protein ligase RNF187 (RNF187).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase RNF187 (RNF187).	[12]

3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28460551-Compound-3	DMA1FRM	Patented	PMID28460551-Compound-3 decreases the stability of E3 ubiquitin-protein ligase RNF187 (RNF187).	[11]
U0126	DM31OGF	Investigative	U0126 decreases the stability of E3 ubiquitin-protein ligase RNF187 (RNF187).	[11]
H-89	DM4RVGO	Investigative	H-89 decreases the stability of E3 ubiquitin-protein ligase RNF187 (RNF187).	[11]

References

• [1] An essential role of RNF187 in Notch1 mediated metastasis of hepatocellular carcinoma.J Exp Clin Cancer Res. 2019 Sep 2;38(1):384. doi: 10.1186/s13046-019-1382-x.
• [2] Prognostic value of increased expression of RACO-1 in patients with hepatitis B-related hepatocellular carcinoma.Ther Clin Risk Manag. 2017 Feb 15;13:191-200. doi: 10.2147/TCRM.S125331. eCollection 2017.
• [3] Overexpression of RNF187 induces cell EMT and apoptosis resistance in NSCLC.J Cell Physiol. 2019 Aug;234(8):14161-14169. doi: 10.1002/jcp.28111. Epub 2019 Jan 9.
• [4] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [5] 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.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [11] The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling. Nat Commun. 2015 Apr 8;6:6782. doi: 10.1038/ncomms7782.
• [12] 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.