Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI5UTF6)

• DOT Name: AP-3 complex subunit sigma-1 (AP3S1)
• Synonyms: AP-3 complex subunit sigma-3A; Adaptor-related protein complex 3 subunit sigma-1; Clathrin-associated/assembly/adaptor protein, small 3; Sigma-3A-adaptin; Sigma3A-adaptin; Sigma-adaptin 3a
• Gene Name: AP3S1
• Related Disease: Non-insulin dependent diabetes
• UniProt ID: AP3S1_HUMAN
• Pfam ID: PF01217
• Sequence:
  MIKAILIFNNHGKPRLSKFYQPYSEDTQQQIIRETFHLVSKRDENVCNFLEGGLLIGGSD
  NKLIYRHYATLYFVFCVDSSESELGILDLIQVFVETLDKCFENVCELDLIFHVDKVHNIL
  AEMVMGGMVLETNMNEIVTQIDAQNKLEKSEAGLAGAPARAVSAVKNMNLPEIPRNINIG
  DISIKVPNLPSFK
• 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)
• Reactome Pathway: Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of AP-3 complex subunit sigma-1 (AP3S1).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of AP-3 complex subunit sigma-1 (AP3S1).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of AP-3 complex subunit sigma-1 (AP3S1).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of AP-3 complex subunit sigma-1 (AP3S1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of AP-3 complex subunit sigma-1 (AP3S1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of AP-3 complex subunit sigma-1 (AP3S1).	[7]

References

• [1] Variants in KCNQ1, AP3S1, MAN2A1, and ALDH7A1 and the risk of type 2 diabetes in the Chinese Northern Han population: a case-control study and meta-analysis.Med Sci Monit. 2010 Jun;16(6):BR179-83.
• [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] 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.
• [4] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [5] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [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] 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.