Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBEMB2M)

• DOT Name: ER membrane protein complex subunit 9 (EMC9)
• Synonyms: Protein FAM158A
• Gene Name: EMC9
• UniProt ID: EMC9_HUMAN
• PDB ID: 6Y4L; 6Z3W
• Pfam ID: PF03665
• Sequence:
  MGEVEISALAYVKMCLHAARYPHAAVNGLFLAPAPRSGECLCLTDCVPLFHSHLALSVML
  EVALNQVDVWGAQAGLVVAGYYHANAAVNDQSPGPLALKIAGRIAEFFPDAVLIMLDNQK
  LVPQPRVPPVIVLENQGLRWVPKDKNLVMWRDWEESRQMVGALLEDRAHQHLVDFDCHLD
  DIRQDWTNQRLNTQITQWVGPTNGNGNA
• 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

7 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 ER membrane protein complex subunit 9 (EMC9).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ER membrane protein complex subunit 9 (EMC9).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of ER membrane protein complex subunit 9 (EMC9).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ER membrane protein complex subunit 9 (EMC9).	[4]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of ER membrane protein complex subunit 9 (EMC9).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ER membrane protein complex subunit 9 (EMC9).	[6]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of ER membrane protein complex subunit 9 (EMC9).	[4]

References

• [1] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.