Details of Drug Off-Target (DOT)

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

• DOT Name: Probable proton-coupled zinc antiporter SLC30A4 (SLC30A4)
• Synonyms: Solute carrier family 30 member 4; Zinc transporter 4; ZnT-4
• Gene Name: SLC30A4
• UniProt ID: ZNT4_HUMAN
• Pfam ID: PF01545
• Sequence:
  MAGSGAWKRLKSMLRKDDAPLFLNDTSAFDFSDEAGDEGLSRFNKLRVVVADDGSEAPER
  PVNGAHPTLQADDDSLLDQDLPLTNSQLSLKVDSCDNCSKQREILKQRKVKARLTIAAVL
  YLLFMIGELVGGYIANSLAIMTDALHMLTDLSAIILTLLALWLSSKSPTKRFTFGFHRLE
  VLSAMISVLLVYILMGFLLYEAVQRTIHMNYEINGDIMLITAAVGVAVNVIMGFLLNQSG
  HRHSHSHSLPSNSPTRGSGCERNHGQDSLAVRAAFVHALGDLVQSVGVLIAAYIIRFKPE
  YKIADPICTYVFSLLVAFTTFRIIWDTVVIILEGVPSHLNVDYIKEALMKIEDVYSVEDL
  NIWSLTSGKSTAIVHIQLIPGSSSKWEEVQSKANHLLLNTFGMYRCTIQLQSYRQEVDRT
  CANCQSSSP
• Function: Probable proton-coupled zinc ion antiporter mediating zinc import from cytoplasm potentially into the endocytic compartment. Controls zinc deposition in milk.

Molecular Interaction Atlas (MIA) of This DOT

1 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 Probable proton-coupled zinc antiporter SLC30A4 (SLC30A4).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable proton-coupled zinc antiporter SLC30A4 (SLC30A4).	[2]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Probable proton-coupled zinc antiporter SLC30A4 (SLC30A4).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Probable proton-coupled zinc antiporter SLC30A4 (SLC30A4).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Probable proton-coupled zinc antiporter SLC30A4 (SLC30A4).	[5]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Probable proton-coupled zinc antiporter SLC30A4 (SLC30A4).	[6]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Probable proton-coupled zinc antiporter SLC30A4 (SLC30A4).	[7]

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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] 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.
• [4] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [5] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [6] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [7] Induction of zinc transporters by forskolin in human trophoblast BeWo cells. Reprod Toxicol. 2006 Apr;21(3):285-91. doi: 10.1016/j.reprotox.2005.02.006. Epub 2005 Apr 18.