Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA0YMLW)

• DOT Name: E3 ubiquitin ligase RNF121 (RNF121)
• Synonyms: EC 2.3.2.27; RING finger protein 121
• Gene Name: RNF121
• Related Disease:
  Advanced cancer
  Barrett esophagus
  Clear cell renal carcinoma
  Renal cell carcinoma
• UniProt ID: RN121_HUMAN
• EC Number: 2.3.2.27
• Sequence:
  MAAVVEVEVGGGAAGERELDEVDMSDLSPEEQWRVEHARMHAKHRGHEAMHAEMVLILIA
  TLVVAQLLLVQWKQRHPRSYNMVTLFQMWVVPLYFTVKLHWWRFLVIWILFSAVTAFVTF
  RATRKPLVQTTPRLVYKWFLLIYKISYATGIVGYMAVMFTLFGLNLLFKIKPEDAMDFGI
  SLLFYGLYYGVLERDFAEMCADYMASTIGFYSESGMPTKHLSDSVCAVCGQQIFVDVSEE
  GIIENTYRLSCNHVFHEFCIRGWCIVGKKQTCPYCKEKVDLKRMFSNPWERPHVMYGQLL
  DWLRYLVAWQPVIIGVVQGINYILGLE
• Function: E3 ubiquitin ligase which accepts ubiquitin and transfers it to substrates thereby promoting their degradation by the endoplasmic reticulum-associated degradation (ERAD) pathway which is a pathway involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. May regulate the unfolded protein response to reduce endoplasmic reticulum stress.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Barrett esophagus	DIS416Y7	Strong	Altered Expression	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[1]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[1]

2 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 ligase RNF121 (RNF121).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of E3 ubiquitin ligase RNF121 (RNF121).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of E3 ubiquitin ligase RNF121 (RNF121).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of E3 ubiquitin ligase RNF121 (RNF121).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of E3 ubiquitin ligase RNF121 (RNF121).	[4]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of E3 ubiquitin ligase RNF121 (RNF121).	[4]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of E3 ubiquitin ligase RNF121 (RNF121).	[4]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of E3 ubiquitin ligase RNF121 (RNF121).	[7]

References

• [1] Really interesting new gene finger protein 121 is a tumor suppressor of renal cell carcinoma.Gene. 2018 Nov 15;676:322-328. doi: 10.1016/j.gene.2018.08.067. Epub 2018 Aug 25.
• [2] RING finger proteins are involved in the progression of barrett esophagus to esophageal adenocarcinoma: a preliminary study.Gut Liver. 2014 Sep;8(5):487-94. doi: 10.5009/gnl13133. Epub 2014 Feb 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] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] 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.
• [7] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.