Details of Drug Off-Target (DOT)

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

• DOT Name: Polycomb group RING finger protein 6 (PCGF6)
• Synonyms: Mel18 and Bmi1-like RING finger; RING finger protein 134
• Gene Name: PCGF6
• Related Disease: B-cell neoplasm
• UniProt ID: PCGF6_HUMAN
• PDB ID: 2DJB
• Pfam ID: PF16207 ; PF13923
• Sequence:
  MEGVAVVTAGSVGAAKTEGAAALPPPPPVSPPALTPAPAAGEEGPAPLSETGAPGCSGSR
  PPELEPERSLGRFRGRFEDEDEELEEEEELEEEEEEEEEDMSHFSLRLEGGRQDSEDEEE
  RLINLSELTPYILCSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQ
  PLYNIRLDRQLQDIVYKLVINLEEREKKQMHDFYKERGLEVPKPAVPQPVPSSKGRSKKV
  LESVFRIPPELDMSLLLEFIGANEGTGHFKPLEKKFVRVSGEATIGHVEKFLRRKMGLDP
  ACQVDIICGDHLLEQYQTLREIRRAIGDAAMQDGLLVLHYGLVVSPLKIT
• Function: Transcriptional repressor. May modulate the levels of histone H3K4Me3 by activating KDM5D histone demethylase. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Polycomb repressive complex (hsa03083)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway: Transcriptional Regulation by E2F6 (R-HSA-8953750)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Polycomb group RING finger protein 6 (PCGF6).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Polycomb group RING finger protein 6 (PCGF6).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Polycomb group RING finger protein 6 (PCGF6).	[4]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Polycomb group RING finger protein 6 (PCGF6).	[4]

References

• [1] Comparative genome profiling across subtypes of low-grade B-cell lymphoma identifies type-specific and common aberrations that target genes with a role in B-cell neoplasia.Haematologica. 2008 May;93(5):670-9. doi: 10.3324/haematol.12221. Epub 2008 Mar 26.
• [2] 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.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] 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.