Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9IHH51)

• DOT Name: ER membrane protein complex subunit 6 (EMC6)
• Synonyms: Transmembrane protein 93
• Gene Name: EMC6
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Cervical Intraepithelial neoplasia
  Gastric adenocarcinoma
  Adult glioblastoma
  Glioblastoma multiforme
  Neoplasm
• UniProt ID: EMC6_HUMAN
• PDB ID: 6WW7; 6Z3W; 7ADO; 7ADP; 8EOI; 8S9S
• Pfam ID: PF07019
• Sequence:
  MAAVVAKREGPPFISEAAVRGNAAVLDYCRTSVSALSGATAGILGLTGLYGFIFYLLASV
  LLSLLLILKAGRRWNKYFKSRRPLFTGGLIGGLFTYVLFWTFLYGMVHVY
• 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 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Strong	Biomarker	[1]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[1]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Biomarker	[1]
Gastric adenocarcinoma	DISWWLTC	Strong	Altered Expression	[2]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[3]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]

5 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 6 (EMC6).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ER membrane protein complex subunit 6 (EMC6).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ER membrane protein complex subunit 6 (EMC6).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of ER membrane protein complex subunit 6 (EMC6).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ER membrane protein complex subunit 6 (EMC6).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of ER membrane protein complex subunit 6 (EMC6).	[8]

References

• [1] Expression levels and roles of EMC-6, Beclin1, and Rab5a in the cervical cancer.Eur Rev Med Pharmacol Sci. 2017 Jul;21(13):3038-3046.
• [2] ER membrane protein complex subunit 6 (EMC6) is a novel tumor suppressor in gastric cancer.BMB Rep. 2017 Aug;50(8):411-416. doi: 10.5483/bmbrep.2017.50.8.065.
• [3] EMC6/TMEM93 suppresses glioblastoma proliferation by modulating autophagy.Cell Death Dis. 2016 Jan 14;7(1):e2043. doi: 10.1038/cddis.2015.408.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.