Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2GKIKE)

DOT Name	E3 ubiquitin-protein ligase RNF180 (RNF180)
Synonyms	EC 2.3.2.27; RING finger protein 180; RING-type E3 ubiquitin transferase RNF180
Gene Name	RNF180
Related Disease	Advanced cancer ( ) Gastric cancer ( ) Neoplasm ( ) Stomach cancer ( ) Type-1 diabetes ( )
UniProt ID	RN180_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.3.2.27
Pfam ID	PF19332 ; PF00097
Sequence	MKRSKELITKNHSQEETSILRCWKCRKCIASSGCFMEYLENQVIKDKDDSVDAQNICHVW HMNVEALPEWISCLIQKAQWTVGKLNCPFCGARLGGFNFVSTPKCSCGQLAAVHLSKSRT DYQPTQAGRLMRPSVKYLSHPRVQSGCDKEALLTGGGSENRNHRLLNMARNNNDPGRLTE ALCLEVRPTYFEMKNEKLLSKASEPKYQLFVPQLVTGRCATRAFHRKSHSLDLNISEKLT LLPTLYEIHSKTTAYSRLNETQPIDLSGLPLQSSKNSYSFQNPSSFDPSMLLQRFSVAPH ETQTQRGGEFQCGLEAASVYSDHTNTNNLTFLMDLPSAGRSMPEASDQEEHLSPLDFLHS ANFSLGSINQRLNKRERSKLKNLRRKQRRRERWLQKQGKYSGVGLLDHMTLNNEMSTDED NEYAEEKDSYICAVCLDVYFNPYMCYPCHHIFCEPCLRTLAKDNPSSTPCPLCRTIISRV FFQTELNNATKTFFTKEYLKIKQSFQKSNSAKWPLPSCRKAFHLFGGFRRHAAPVTRRQF PHGAHRMDYLHFEDDSRGWWFDMDMVIIYIYSVNWVIGFIVFCFLCYFFFPF
Function	E3 ubiquitin-protein ligase which promotes polyubiquitination and degradation by the proteasome pathway of ZIC2.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Limited	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]
Stomach cancer	DISKIJSX	Limited	Biomarker	[2]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[3]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of E3 ubiquitin-protein ligase RNF180 (RNF180).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of E3 ubiquitin-protein ligase RNF180 (RNF180).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of E3 ubiquitin-protein ligase RNF180 (RNF180).	[10]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of E3 ubiquitin-protein ligase RNF180 (RNF180).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of E3 ubiquitin-protein ligase RNF180 (RNF180).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of E3 ubiquitin-protein ligase RNF180 (RNF180).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of E3 ubiquitin-protein ligase RNF180 (RNF180).	[9]
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References

1	Characterization of the gene structure, functional significance, and clinical application of RNF180, a novel gene in gastric cancer.Cancer. 2012 Feb 15;118(4):947-59. doi: 10.1002/cncr.26189. Epub 2011 Jun 29.
2	Promoter methylation of RNF180 is associated with H.pylori infection and serves as a marker for gastric cancer and atrophic gastritis.Oncotarget. 2016 Apr 26;7(17):24800-9. doi: 10.18632/oncotarget.8523.
3	HTR1A a novel type 1 diabetes susceptibility gene on chromosome 5p13-q13.PLoS One. 2012;7(5):e35439. doi: 10.1371/journal.pone.0035439. Epub 2012 May 1.
4	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.
5	Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
6	Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
7	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.
8	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
9	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.
10	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.