Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF7Y6M7)

• DOT Name: E3 ubiquitin-protein ligase RNF10 (RNF10)
• Synonyms: EC 2.3.2.27; RING finger protein 10
• Gene Name: RNF10
• Related Disease:
  Hyperglycemia
  Type-1/2 diabetes
  Cardiovascular disease
  Non-insulin dependent diabetes
• UniProt ID: RNF10_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF13445
• Sequence:
  MPLSSPNAAATASDMDKNSGSNSSSASSGSSKGQQPPRSASAGPAGESKPKSDGKNSSGS
  KRYNRKRELSYPKNESFNNQSRRSSSQKSKTFNKMPPQRGGGSSKLFSSSFNGGRRDEVA
  EAQRAEFSPAQFSGPKKINLNHLLNFTFEPRGQTGHFEGSGHGSWGKRNKWGHKPFNKEL
  FLQANCQFVVSEDQDYTAHFADPDTLVNWDFVEQVRICSHEVPSCPICLYPPTAAKITRC
  GHIFCWACILHYLSLSEKTWSKCPICYSSVHKKDLKSVVATESHQYVVGDTITMQLMKRE
  KGVLVALPKSKWMNVDHPIHLGDEQHSQYSKLLLASKEQVLHRVVLEEKVALEQQLAEEK
  HTPESCFIEAAIQELKTREEALSGLAGSRREVTGVVAALEQLVLMAPLAKESVFQPRKGV
  LEYLSAFDEETTEVCSLDTPSRPLALPLVEEEEAVSEPEPEGLPEACDDLELADDNLKEG
  TICTESSQQEPITKSGFTRLSSSPCYYFYQAEDGQHMFLHPVNVRCLVREYGSLERSPEK
  ISATVVEIAGYSMSEDVRQRHRYLSHLPLTCEFSICELALQPPVVSKETLEMFSDDIEKR
  KRQRQKKAREERRRERRIEIEENKKQGKYPEVHIPLENLQQFPAFNSYTCSSDSALGPTS
  TEGHGALSISPLSRSPGSHADFLLTPLSPTASQGSPSFCVGSLEEDSPFPSFAQMLRVGK
  AKADVWPKTAPKKDENSLVPPAPVDSDGESDNSDRVPVPSFQNSFSQAIEAAFMKLDTPA
  TSDPLSEEKGGKKRKKQKQKLLFSTSVVHTK
• Function: E3 ubiquitin-protein ligase that catalyzes monoubiquitination of 40S ribosomal proteins RPS2/us5 and RPS3/us3 in response to ribosome stalling. Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): RNF10 acts by mediating monoubiquitination of RPS2/us5 and RPS3/us3, promoting their degradation by the proteasome. Also promotes ubiquitination of 40S ribosomal proteins in response to ribosome stalling during translation elongation. The action of RNF10 in iRQC is counteracted by USP10. May also act as a transcriptional factor involved in the regulation of MAG (Myelin-associated glycoprotein) expression. Acts as a regulator of Schwann cell differentiation and myelination.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[1]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol increases the expression of E3 ubiquitin-protein ligase RNF10 (RNF10).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of E3 ubiquitin-protein ligase RNF10 (RNF10).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of E3 ubiquitin-protein ligase RNF10 (RNF10).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of E3 ubiquitin-protein ligase RNF10 (RNF10).	[7]

References

• [1] RING finger protein10 is a potential drug target for diabetic vascular complications.Mol Med Rep. 2019 Aug;20(2):931-938. doi: 10.3892/mmr.2019.10358. Epub 2019 Jun 6.
• [2] RING finger protein 10 attenuates vascular restenosis by inhibiting vascular smooth muscle cell hyperproliferation in vivo and vitro.IUBMB Life. 2019 May;71(5):632-642. doi: 10.1002/iub.1995. Epub 2018 Dec 30.
• [3] Whole exome sequencing identifies variation in CYB5A and RNF10 associated with adiposity and type 2 diabetes.Obesity (Silver Spring). 2014 Apr;22(4):984-8. doi: 10.1002/oby.20647. Epub 2013 Dec 5.
• [4] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [7] 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.