Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF0FG5K)

• DOT Name: Proton-coupled zinc antiporter SLC30A8 (SLC30A8)
• Synonyms: Solute carrier family 30 member 8; Zinc transporter 8; ZnT-8
• Gene Name: SLC30A8
• UniProt ID: ZNT8_HUMAN
• PDB ID: 6XPD; 6XPE; 6XPF
• Pfam ID: PF01545
• Sequence:
  MEFLERTYLVNDKAAKMYAFTLESVELQQKPVNKDQCPRERPEELESGGMYHCHSGSKPT
  EKGANEYAYAKWKLCSASAICFIFMIAEVVGGHIAGSLAVVTDAAHLLIDLTSFLLSLFS
  LWLSSKPPSKRLTFGWHRAEILGALLSILCIWVVTGVLVYLACERLLYPDYQIQATVMII
  VSSCAVAANIVLTVVLHQRCLGHNHKEVQANASVRAAFVHALGDLFQSISVLISALIIYF
  KPEYKIADPICTFIFSILVLASTITILKDFSILLMEGVPKSLNYSGVKELILAVDGVLSV
  HSLHIWSLTMNQVILSAHVATAASRDSQVVRREIAKALSKSFTMHSLTIQMESPVDQDPD
  CLFCEDPCD
• Function: Proton-coupled zinc ion antiporter mediating the entry of zinc into the lumen of pancreatic beta cell secretory granules, thereby regulating insulin secretion.
• Tissue Specificity: In the endocrine pancreas, expressed in insulin-producing beta cells. Expressed at relatively high levels in subcutaneous fat tissue from lean persons; much lower levels in visceral fat, whether from lean or obese individuals, and in subcutaneous fat tissue from obese individuals. Expressed in peripheral blood mononuclear cells, including T-cells and B-cells, with great variation among individuals ranging from negative to strongly positive.
• Reactome Pathway:
  Zinc efflux and compartmentalization by the SLC30 family (R-HSA-435368)
  Insulin processing (R-HSA-264876)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
3-iodothyronamine	DM3L0F8	Investigative	Proton-coupled zinc antiporter SLC30A8 (SLC30A8) affects the uptake of 3-iodothyronamine.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Proton-coupled zinc antiporter SLC30A8 (SLC30A8).	[1]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Proton-coupled zinc antiporter SLC30A8 (SLC30A8).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Proton-coupled zinc antiporter SLC30A8 (SLC30A8).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Proton-coupled zinc antiporter SLC30A8 (SLC30A8).	[2]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Proton-coupled zinc antiporter SLC30A8 (SLC30A8).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Proton-coupled zinc antiporter SLC30A8 (SLC30A8).	[6]

References

• [1] 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.
• [2] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [3] 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.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [7] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.