Details of Drug Off-Target (DOT)

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

• DOT Name: E3 ubiquitin-protein ligase RNF167 (RNF167)
• Synonyms: EC 2.3.2.27; RING finger protein 167
• Gene Name: RNF167
• Related Disease: Neoplasm
• UniProt ID: RN167_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF02225 ; PF13639
• Sequence:
  MHPAAFPLPVVVAAVLWGAAPTRGLIRATSDHNASMDFADLPALFGATLSQEGLQGFLVE
  AHPDNACSPIAPPPPAPVNGSVFIALLRRFDCNFDLKVLNAQKAGYGAAVVHNVNSNELL
  NMVWNSEEIQQQIWIPSVFIGERSSEYLRALFVYEKGARVLLVPDNTFPLGYYLIPFTGI
  VGLLVLAMGAVMIARCIQHRKRLQRNRLTKEQLKQIPTHDYQKGDQYDVCAICLDEYEDG
  DKLRVLPCAHAYHSRCVDPWLTQTRKTCPICKQPVHRGPGDEDQEEETQGQEEGDEGEPR
  DHPASERTPLLGSSPTLPTSFGSLAPAPLVFPGPSTDPPLSPPSSPVILV
• Function: E3 ubiquitin-protein ligase that acts as a regulator of the TORC1 signaling pathway. Positively regulates the TORC1 signaling pathway independently of arginine levels: acts by catalyzing 'Lys-29'-polyubiquitination and degradation of CASTOR1, releasing the GATOR2 complex from CASTOR1. Also negatively regulates the TORC1 signaling pathway in response to leucine deprivation: acts by mediating 'Lys-63'-linked polyubiquitination of SESN2, promoting SESN2-interaction with the GATOR2 complex. Also involved in protein trafficking and localization. Acts as a regulator of synaptic transmission by mediating ubiquitination and degradation of AMPAR receptor GluA2/GRIA2. Does not catalyze ubiquitination of GluA1/GRIA1. Also acts as a regulator of the recycling endosome pathway by mediating ubiquitination of VAMP3. Regulates lysosome positioning by catalyzing ubiquitination and degradation of ARL8B. Plays a role in growth regulation involved in G1/S transition by mediating, possibly by mediating ubiquitination of SLC22A18. Acts with a limited set of E2 enzymes, such as UBE2D1 and UBE2N.
• Tissue Specificity: Widely expressed . Strongly expressed in the kidney, pancreas, testis and liver (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Disputed	Biomarker	[1]

1 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 RNF167 (RNF167).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of E3 ubiquitin-protein ligase RNF167 (RNF167).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of E3 ubiquitin-protein ligase RNF167 (RNF167).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of E3 ubiquitin-protein ligase RNF167 (RNF167).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of E3 ubiquitin-protein ligase RNF167 (RNF167).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of E3 ubiquitin-protein ligase RNF167 (RNF167).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of E3 ubiquitin-protein ligase RNF167 (RNF167).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase RNF167 (RNF167).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of E3 ubiquitin-protein ligase RNF167 (RNF167).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of E3 ubiquitin-protein ligase RNF167 (RNF167).	[11]

References

• [1] Tumor suppressor candidate TSSC5 is regulated by UbcH6 and a novel ubiquitin ligase RING105.Oncogene. 2006 Mar 2;25(9):1330-9. doi: 10.1038/sj.onc.1209167.
• [2] 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.
• [3] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [4] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [9] 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.
• [10] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.