Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAX91ES)

• DOT Name: E3 ubiquitin-protein ligase RNF217 (RNF217)
• Synonyms: EC 2.3.2.31; IBR domain-containing protein 1; Opposite STL; RING finger protein 217
• Gene Name: RNF217
• Related Disease: Small lymphocytic lymphoma
• UniProt ID: RN217_HUMAN
• EC Number: 2.3.2.31
• Pfam ID: PF01485
• Sequence:
  MGEEQSTVSGGGGPQESQTLASGTAGHPEPPRPQGDSARAPPLRAASAEPSGGGCGSDWG
  CADTSAPEPARSLGPPGWSKSRAPAQPAGLALTGPLNPQTLPLQLELEEEEEEAGDRKEG
  GDEQQEAPPGEELEPRTRVGAADGLVLDVLGQRRPSLAKRQVFCSVYCVESDLPEAPASE
  QLSPPASPPGAPPVLNPPSTRSSFPSPRLSLPTDSLSPDGGSIELEFYLAPEPFSMPSLL
  GAPPYSGLGGVGDPYVPLMVLMCRVCLEDKPIKPLPCCKKAVCEECLKVYLSAQVQLGQV
  EIKCPITECFEFLEETTVVYNLTHEDSIKYKYFLELGRIDSSTKPCPQCKHFTTFKKKGH
  IPTPSRSESKYKIQCPTCQFVWCFKCHSPWHEGVNCKEYKKGDKLLRHWASEIEHGQRNA
  QKCPKCKIHIQRTEGCDHMTCSQCNTNFCYRCGERYRQLRFFGDHTSNLSIFGCKYRYLP
  ERPHLRRLVRGSVCAGKLFIAPLIMVLGLALGAIAVVIGLFVFPIYCLCKKQRKRSRTGM
  HW
• Function: E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates the degradation of the iron exporter ferroportin/SLC40A1 and thus regulates iron homeostasis.
• Tissue Specificity: Mainly expressed in testis and skeletal muscle.
• Reactome Pathway: Antigen processing (R-HSA-983168)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Small lymphocytic lymphoma	DIS30POX	moderate	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of E3 ubiquitin-protein ligase RNF217 (RNF217).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of E3 ubiquitin-protein ligase RNF217 (RNF217).	[3]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of E3 ubiquitin-protein ligase RNF217 (RNF217).	[4]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of E3 ubiquitin-protein ligase RNF217 (RNF217).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase RNF217 (RNF217).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of E3 ubiquitin-protein ligase RNF217 (RNF217).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of E3 ubiquitin-protein ligase RNF217 (RNF217).	[8]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of E3 ubiquitin-protein ligase RNF217 (RNF217).	[9]

1 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 increases the methylation of E3 ubiquitin-protein ligase RNF217 (RNF217).	[5]

References

• [1] Identification and characterization of OSTL (RNF217) encoding a RING-IBR-RING protein adjacent to a translocation breakpoint involving ETV6 in childhood ALL.Sci Rep. 2014 Oct 9;4:6565. doi: 10.1038/srep06565.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [5] 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.
• [6] 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.
• [7] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [9] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.