Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDF0E27)

• DOT Name: Charged multivesicular body protein 7 (CHMP7)
• Synonyms: Chromatin-modifying protein 7
• Gene Name: CHMP7
• UniProt ID: CHMP7_HUMAN
• Pfam ID: PF03357
• Sequence:
  MWSPEREAEAPAGGDPAGLLPPEWEEDEERMSFLFSAFKRSREVNSTDWDSKMGFWAPLV
  LSHSRRQGVVRLRLRDLQEAFQRKGSVPLGLATVLQDLLRRGELQRESDFMASVDSSWIS
  WGVGVFLLKPLKWTLSNMLGDNKVPAEEVLVAVELLKEKAEEVYRLYQNSPLSSHPVVAL
  SELSTLCANSCPDERTFYLVLLQLQKEKRVTVLEQNGEKIVKFARGPRAKVSPVNDVDVG
  VYQLMQSEQLLSRKVESLSQEAERCKEEARRACRAGKKQLALRSLKAKQRTEKRIEALHA
  KLDTVQGILDRIYASQTDQMVFNAYQAGVGALKLSMKDVTVEKAESLVDQIQELCDTQDE
  VSQTLAGGVTNGLDFDSEELEKELDILLQDTTKEPLDLPDNPRNRHFTNSVPNPRISDAE
  LEAELEKLSLSEGGLVPSSKSPKRQLEPTLKPL
• Function: ESCRT-III-like protein required to recruit the ESCRT-III complex to the nuclear envelope (NE) during late anaphase. Together with SPAST, the ESCRT-III complex promotes NE sealing and mitotic spindle disassembly during late anaphase. Recruited to the reforming NE during anaphase by LEMD2. Plays a role in the endosomal sorting pathway.
• KEGG Pathway:
  Endocytosis (hsa04144)
  Necroptosis (hsa04217)
• Reactome Pathway:
  Macroautophagy (R-HSA-1632852)
  Pyroptosis (R-HSA-5620971)
  Endosomal Sorting Complex Required For Transport (ESCRT) (R-HSA-917729)
  HCMV Late Events (R-HSA-9610379)
  Late endosomal microautophagy (R-HSA-9615710)
  Sealing of the nuclear envelope (NE) by ESCRT-III (R-HSA-9668328)
  Translation of Replicase and Assembly of the Replication Transcription Complex (R-HSA-9679504)
  Translation of Replicase and Assembly of the Replication Transcription Complex (R-HSA-9694676)
  Budding and maturation of HIV virion (R-HSA-162588)

Molecular Interaction Atlas (MIA) of This DOT

4 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 Charged multivesicular body protein 7 (CHMP7).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Charged multivesicular body protein 7 (CHMP7).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Charged multivesicular body protein 7 (CHMP7).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Charged multivesicular body protein 7 (CHMP7).	[6]

3 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 decreases the methylation of Charged multivesicular body protein 7 (CHMP7).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Charged multivesicular body protein 7 (CHMP7).	[5]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the acetylation of Charged multivesicular body protein 7 (CHMP7).	[7]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [7] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.