Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUE5YLC)

• DOT Name: AP-1 complex subunit mu-2 (AP1M2)
• Synonyms: AP-mu chain family member mu1B; Adaptor protein complex AP-1 subunit mu-2; Adaptor-related protein complex 1 subunit mu-2; Clathrin assembly protein complex 1 mu-2 medium chain 2; Golgi adaptor HA1/AP1 adaptin mu-2 subunit; Mu-adaptin 2; Mu1B-adaptin
• Gene Name: AP1M2
• Related Disease: Renal cell carcinoma
• UniProt ID: AP1M2_HUMAN
• Pfam ID: PF00928 ; PF01217
• Sequence:
  MSASAVFILDVKGKPLISRNYKGDVAMSKIEHFMPLLVQREEEGALAPLLSHGQVHFLWI
  KHSNLYLVATTSKNANASLVYSFLYKTIEVFCEYFKELEEESIRDNFVIVYELLDELMDF
  GFPQTTDSKILQEYITQQSNKLETGKSRVPPTVTNAVSWRSEGIKYKKNEVFIDVIESVN
  LLVNANGSVLLSEIVGTIKLKVFLSGMPELRLGLNDRVLFELTGRSKNKSVELEDVKFHQ
  CVRLSRFDNDRTISFIPPDGDFELMSYRLSTQVKPLIWIESVIEKFSHSRVEIMVKAKGQ
  FKKQSVANGVEISVPVPSDADSPRFKTSVGSAKYVPERNVVIWSIKSFPGGKEYLMRAHF
  GLPSVEKEEVEGRPPIGVKFEIPYFTVSGIQVRYMKIIEKSGYQALPWVRYITQSGDYQL
  RTS
• Function: Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.
• KEGG Pathway:
  Lysosome (hsa04142)
  Human immunodeficiency virus 1 infection (hsa05170)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Lysosome Vesicle Biogenesis (R-HSA-432720)
  Golgi Associated Vesicle Biogenesis (R-HSA-432722)
  Nef mediated downregulation of MHC class I complex cell surface expression (R-HSA-164940)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[1]

15 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 AP-1 complex subunit mu-2 (AP1M2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of AP-1 complex subunit mu-2 (AP1M2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of AP-1 complex subunit mu-2 (AP1M2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of AP-1 complex subunit mu-2 (AP1M2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of AP-1 complex subunit mu-2 (AP1M2).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of AP-1 complex subunit mu-2 (AP1M2).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of AP-1 complex subunit mu-2 (AP1M2).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of AP-1 complex subunit mu-2 (AP1M2).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of AP-1 complex subunit mu-2 (AP1M2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of AP-1 complex subunit mu-2 (AP1M2).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of AP-1 complex subunit mu-2 (AP1M2).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of AP-1 complex subunit mu-2 (AP1M2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of AP-1 complex subunit mu-2 (AP1M2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of AP-1 complex subunit mu-2 (AP1M2).	[14]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of AP-1 complex subunit mu-2 (AP1M2).	[15]

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 AP-1 complex subunit mu-2 (AP1M2).	[12]

References

• [1] Gene expression profiling separates chromophobe renal cell carcinoma from oncocytoma and identifies vesicular transport and cell junction proteins as differentially expressed genes.Clin Cancer Res. 2006 Dec 1;12(23):6937-45. doi: 10.1158/1078-0432.CCR-06-1268.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] 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.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.