Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUQYY8Z)

• DOT Name: Endoplasmic reticulum membrane protein complex subunit 7 (EMC7)
• Synonyms: ER membrane protein complex subunit 7
• Gene Name: EMC7
• Related Disease: Cardiomyopathy
• UniProt ID: EMC7_HUMAN
• PDB ID: 1B0G; 1LP9; 2J8U; 2JCC; 2UWE; 6WW7; 6Z3W; 7ADO; 8EOI; 8S9S
• Pfam ID: PF09430
• Sequence:
  MAAALWGFFPVLLLLLLSGDVQSSEVPGAAAEGSGGSGVGIGDRFKIEGRAVVPGVKPQD
  WISAARVLVDGEEHVGFLKTDGSFVVHDIPSGSYVVEVVSPAYRFDPVRVDITSKGKMRA
  RYVNYIKTSEVVRLPYPLQMKSSGPPSYFIKRESWGWTDFLMNPMVMMMVLPLLIFVLLP
  KVVNTSDPDMRREMEQSMNMLNSNHELPDVSEFMTRLFSSKSSGKSSSGSSKTGKSGAGK
  RR
• 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).

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiomyopathy	DISUPZRG	Strong	Altered Expression	[1]

6 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 Endoplasmic reticulum membrane protein complex subunit 7 (EMC7).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endoplasmic reticulum membrane protein complex subunit 7 (EMC7).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Endoplasmic reticulum membrane protein complex subunit 7 (EMC7).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Endoplasmic reticulum membrane protein complex subunit 7 (EMC7).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Endoplasmic reticulum membrane protein complex subunit 7 (EMC7).	[6]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Endoplasmic reticulum membrane protein complex subunit 7 (EMC7).	[7]

References

• [1] [Familial hypertrophic cardiomyopathy--a case report].Kardiol Pol. 2006 Nov;64(11):1287-91.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [5] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [7] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.