Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3S2TWF)

• DOT Name: ER membrane protein complex subunit 2 (EMC2)
• Synonyms: Tetratricopeptide repeat protein 35; TPR repeat protein 35
• Gene Name: EMC2
• Related Disease:
  Androgenetic alopecia
  Baldness, male pattern
• UniProt ID: EMC2_HUMAN
• PDB ID: 6WW7; 6Y4L; 6Z3W; 7ADO; 7ADP; 8EOI; 8S9S
• Pfam ID: PF14559
• Sequence:
  MAKVSELYDVTWEEMRDKMRKWREENSRNSEQIVEVGEELINEYASKLGDDIWIIYEQVM
  IAALDYGRDDLALFCLQELRRQFPGSHRVKRLTGMRFEAMERYDDAIQLYDRILQEDPTN
  TAARKRKIAIRKAQGKNVEAIRELNEYLEQFVGDQEAWHELAELYINEHDYAKAAFCLEE
  LMMTNPHNHLYCQQYAEVKYTQGGLENLELSRKYFAQALKLNNRNMRALFGLYMSASHIA
  SNPKASAKTKKDNMKYASWAASQINRAYQFAGRSKKETKYSLKAVEDMLETLQITQS
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Androgenetic alopecia	DISSJR1P	Limited	Genetic Variation	[1]
Baldness, male pattern	DIS9C9RO	Limited	Genetic Variation	[1]

1 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 ER membrane protein complex subunit 2 (EMC2).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ER membrane protein complex subunit 2 (EMC2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ER membrane protein complex subunit 2 (EMC2).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of ER membrane protein complex subunit 2 (EMC2).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ER membrane protein complex subunit 2 (EMC2).	[6]

References

• [1] GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] 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.