Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYGBP6G)

• DOT Name: ER membrane protein complex subunit 5 (MMGT1)
• Synonyms: Membrane magnesium transporter 1; Transmembrane protein 32
• Gene Name: MMGT1
• UniProt ID: EMC5_HUMAN
• PDB ID: 6WW7; 6Z3W; 7ADO; 7ADP; 8EOI; 8S9S
• Pfam ID: PF10270
• Sequence:
  MAPSLWKGLVGIGLFALAHAAFSAAQHRSYMRLTEKEDESLPIDIVLQTLLAFAVTCYGI
  VHIAGEFKDMDATSELKNKTFDTLRNHPSFYVFNHRGRVLFRPSDTANSSNQDALSSNTS
  LKLRKLESLRR
• 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. May be involved in Mg(2+) transport.
• Reactome Pathway: Miscellaneous transport and binding events (R-HSA-5223345)

Molecular Interaction Atlas (MIA) of This DOT

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 5 (MMGT1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ER membrane protein complex subunit 5 (MMGT1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ER membrane protein complex subunit 5 (MMGT1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ER membrane protein complex subunit 5 (MMGT1).	[4]

2 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 decreases the methylation of ER membrane protein complex subunit 5 (MMGT1).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of ER membrane protein complex subunit 5 (MMGT1).	[6]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] 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.
• [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] 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.
• [6] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.