Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU07O6U)

• DOT Name: RING finger protein 214 (RNF214)
• Gene Name: RNF214
• Related Disease: Cardiovascular disease
• UniProt ID: RN214_HUMAN
• Sequence:
  MAASEVAGVVANAPSPPESSSLCASKSDEGLPDGLSTKDSAQKQKNSPLLSVSSQTITKE
  NNRNVHLEHSEQNPGSSAGDTSAAHQVVLGENLIATALCLSGSGSQSDLKDVASTAGEEG
  DTSLRESLHPVTRSLKAGCHTKQLASRNCSEEKSPQTSILKEGNRDTSLDFRPVVSPANG
  VEGVRVDQDDDQDSSSLKLSQNIAVQTDFKTADSEVNTDQDIEKNLDKMMTERTLLKERY
  QEVLDKQRQVENQLQVQLKQLQQRREEEMKNHQEILKAIQDVTIKREETKKKIEKEKKEF
  LQKEQDLKAEIEKLCEKGRREVWEMELDRLKNQDGEINRNIMEETERAWKAEILSLESRK
  ELLVLKLEEAEKEAELHLTYLKSTPPTLETVRSKQEWETRLNGVRIMKKNVRDQFNSHIQ
  LVRNGAKLSSLPQIPTPTLPPPPSETDFMLQVFQPSPSLAPRMPFSIGQVTMPMVMPSAD
  PRSLSFPILNPALSQPSQPSSPLPGSHGRNSPGLGSLVSPHGPHMPPAASIPPPPGLGGV
  KASAETPRPQPVDKLEKILEKLLTRFPQCNKAQMTNILQQIKTARTTMAGLTMEELIQLV
  AARLAEHERVAASTQPLGRIRALFPAPLAQISTPMFLPSAQVSYPGRSSHAPATCKLCLM
  CQKLVQPSELHPMACTHVLHKECIKFWAQTNTNDTCPFCPTLK

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]

3 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 RING finger protein 214 (RNF214).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of RING finger protein 214 (RNF214).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of RING finger protein 214 (RNF214).	[7]

4 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 RING finger protein 214 (RNF214).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RING finger protein 214 (RNF214).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RING finger protein 214 (RNF214).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RING finger protein 214 (RNF214).	[6]

References

• [1] Genetic determinants of cardiovascular events among women with migraine: a genome-wide association study.PLoS One. 2011;6(7):e22106. doi: 10.1371/journal.pone.0022106. Epub 2011 Jul 14.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] 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.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.