Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1IR6CD)

• DOT Name: AP-1 complex subunit mu-1 (AP1M1)
• Synonyms: AP-mu chain family member mu1A; Adaptor protein complex AP-1 subunit mu-1; Adaptor-related protein complex 1 subunit mu-1; Clathrin assembly protein complex 1 mu-1 medium chain 1; Clathrin coat assembly protein AP47; Clathrin coat-associated protein AP47; Golgi adaptor HA1/AP1 adaptin mu-1 subunit; Mu-adaptin 1; Mu1A-adaptin
• Gene Name: AP1M1
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Hepatitis B virus infection
  Liver cancer
• UniProt ID: AP1M1_HUMAN
• Pfam ID: PF00928 ; PF01217
• Sequence:
  MSASAVYVLDLKGKVLICRNYRGDVDMSEVEHFMPILMEKEEEGMLSPILAHGGVRFMWI
  KHNNLYLVATSKKNACVSLVFSFLYKVVQVFSEYFKELEEESIRDNFVIIYELLDELMDF
  GYPQTTDSKILQEYITQEGHKLETGAPRPPATVTNAVSWRSEGIKYRKNEVFLDVIESVN
  LLVSANGNVLRSEIVGSIKMRVFLSGMPELRLGLNDKVLFDNTGRGKSKSVELEDVKFHQ
  CVRLSRFENDRTISFIPPDGEFELMSYRLNTHVKPLIWIESVIEKHSHSRIEYMIKAKSQ
  FKRRSTANNVEIHIPVPNDADSPKFKTTVGSVKWVPENSEIVWSIKSFPGGKEYLMRAHF
  GLPSVEAEDKEGKPPISVKFEIPYFTTSGIQVRYLKIIEKSGYQALPWVRYITQNGDYQL
  RTQ
• 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)
  Neutrophil degranulation (R-HSA-6798695)
  Nef mediated downregulation of MHC class I complex cell surface expression (R-HSA-164940)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Biomarker	[1]
Hepatitis B virus infection	DISLQ2XY	Definitive	Biomarker	[1]
Liver cancer	DISDE4BI	Definitive	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of AP-1 complex subunit mu-1 (AP1M1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of AP-1 complex subunit mu-1 (AP1M1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of AP-1 complex subunit mu-1 (AP1M1).	[4]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of AP-1 complex subunit mu-1 (AP1M1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of AP-1 complex subunit mu-1 (AP1M1).	[6]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of AP-1 complex subunit mu-1 (AP1M1).	[9]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of AP-1 complex subunit mu-1 (AP1M1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of AP-1 complex subunit mu-1 (AP1M1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of AP-1 complex subunit mu-1 (AP1M1).	[8]

References

• [1] HBV upregulates AP-1 complex subunit mu-1 expression via the JNK pathway to promote proliferation of liver cancer cells.Oncol Lett. 2019 Jul;18(1):456-464. doi: 10.3892/ol.2019.10291. Epub 2019 Apr 30.
• [2] 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.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [7] 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.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [10] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.