Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIUTHS1)

• DOT Name: ER membrane protein complex subunit 8 (EMC8)
• Synonyms: Neighbor of COX4; Protein FAM158B
• Gene Name: EMC8
• Related Disease: Myocardial infarction
• UniProt ID: EMC8_HUMAN
• PDB ID: 6WW7; 7ADO; 7ADP; 8EOI; 8S9S
• Pfam ID: PF03665
• Sequence:
  MPGVKLTTQAYCKMVLHGAKYPHCAVNGLLVAEKQKPRKEHLPLGGPGAHHTLFVDCIPL
  FHGTLALAPMLEVALTLIDSWCKDHSYVIAGYYQANERVKDASPNQVAEKVASRIAEGFS
  DTALIMVDNTKFTMDCVAPTIHVYEHHENRWRCRDPHHDYCEDWPEAQRISASLLDSRSY
  ETLVDFDNHLDDIRNDWTNPEINKAVLHLC
• Function: Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable).
• Tissue Specificity: Expressed in liver, pancreas, heart, lung, kidney, brain, skeletal muscle, and placenta. Expression levels are highest in pancreas and moderate in heart, skeletal muscle, and placenta.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[1]

9 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 ER membrane protein complex subunit 8 (EMC8).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ER membrane protein complex subunit 8 (EMC8).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of ER membrane protein complex subunit 8 (EMC8).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of ER membrane protein complex subunit 8 (EMC8).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ER membrane protein complex subunit 8 (EMC8).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of ER membrane protein complex subunit 8 (EMC8).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of ER membrane protein complex subunit 8 (EMC8).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ER membrane protein complex subunit 8 (EMC8).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ER membrane protein complex subunit 8 (EMC8).	[9]

References

• [1] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [4] 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.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [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] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.