Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN8P9OE)

• DOT Name: AP-3 complex subunit sigma-2 (AP3S2)
• Synonyms: AP-3 complex subunit sigma-3B; Adaptor-related protein complex 3 subunit sigma-2; Sigma-3B-adaptin; Sigma3B-adaptin; Sigma-adaptin 3b
• Gene Name: AP3S2
• Related Disease:
  Obesity
  Non-insulin dependent diabetes
• UniProt ID: AP3S2_HUMAN
• Pfam ID: PF01217
• Sequence:
  MIQAILVFNNHGKPRLVRFYQRFPEEIQQQIVRETFHLVLKRDDNICNFLEGGSLIGGSD
  YKLIYRHYATLYFVFCVDSSESELGILDLIQVFVETLDKCFENVCELDLIFHMDKVHYIL
  QEVVMGGMVLETNMNEIVAQIEAQNRLEKSEGGLSAAPARAVSAVKNINLPEIPRNINIG
  DLNIKVPNLSQFV
• Function: Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.
• Tissue Specificity: Present in all adult tissues examined.
• KEGG Pathway: Lysosome (hsa04142)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obesity	DIS47Y1K	Strong	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of AP-3 complex subunit sigma-2 (AP3S2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of AP-3 complex subunit sigma-2 (AP3S2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of AP-3 complex subunit sigma-2 (AP3S2).	[4]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of AP-3 complex subunit sigma-2 (AP3S2).	[5]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of AP-3 complex subunit sigma-2 (AP3S2).	[6]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of AP-3 complex subunit sigma-2 (AP3S2).	[7]

References

• [1] Physical Interactions and Expression Quantitative Traits Loci Identify Regulatory Connections for Obesity and Type 2 Diabetes Associated SNPs.Front Genet. 2017 Oct 13;8:150. doi: 10.3389/fgene.2017.00150. eCollection 2017.
• [2] Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.Nat Genet. 2019 Mar;51(3):379-386. doi: 10.1038/s41588-018-0332-4. Epub 2019 Feb 4.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [6] 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.
• [7] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [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.