Details of Drug Off-Target (DOT)

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

• DOT Name: RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMOC1)
• Synonyms: UPF0600 protein C5orf51
• Gene Name: RIMOC1
• UniProt ID: RIMC1_HUMAN
• Pfam ID: PF17716
• Sequence:
  MAAAVSSVVRRVEELGDLAQAHIQQLSEAAGEDDHFLIRASAALEKLKLLCGEEKECSNP
  SNLLELYTQAILDMTYFEENKLVDEDFPEDSSSQKVKELISFLSEPEILVKENNMHPKHC
  NLLGDELLECLSWRRGALLYMYCHSLTKRREWLLRKSSLLKKYLLDGISYLLQMLNYRCP
  IQLNEGVSFQDLDTAKLLSAGIFSDIHLLAMMYSGEMCYWGSKYCADQQPENHEVDTSVS
  GAGCTTYKEPLDFREVGEKILKKYVSVCEGPLKEQEWNTTNAKQILNFFHHRCN
• Function: Plays an important role in the removal of damaged mitochondria via mitophagy by controlling the stability and localization of RAB7A. Required for the recruitment of RAB7A and ATG9A vesicles to damaged mitochondria and promotes the stability of RAB7A by inhibiting its proteasomal degradation during mitophagy.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMOC1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMOC1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMOC1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMOC1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMOC1).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMOC1).	[5]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMOC1).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMOC1).	[8]

References

• [1] 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.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.