Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT704QRC)

• DOT Name: Solute carrier family 45 member 4 (SLC45A4)
• Gene Name: SLC45A4
• UniProt ID: S45A4_HUMAN
• Pfam ID: PF07690
• Sequence:
  MKMAPQNADPESMQVQELSVPLPDPQKAGGAEAENCETISEGSIDRIPMRLWVMHGAVMF
  GREFCYAMETALVTPILLQIGLPEQYYSLTWFLSPILGLIFTPLIGSASDRCTLSWGRRR
  PFILALCVGVLFGVALFLNGSAIGLALGDVPNRQPIGIVLTVLGVVVLDFSADATEGPIR
  AYLLDVVDSEEQDMALNIHAFSAGLGGAIGYVLGGLDWTQTFLGSWFRTQNQVLFFFAAI
  IFTVSVALHLFSIDEEQYSPQQERSAEEPGALDGGEPHGVPAFPDEVQSEHELALDYPDV
  DIMRSKSDSALHVPDTALDLEPELLFLHDIEPSIFHDASYPATPRSTSQELAKTKLPRLA
  TFLKEAAKEDETLLDNHLNEAKVPNGSGSPTKDALGGYTRVDTKPSATSSSMRRRRHAFR
  RQASSTFSYYGKLGSHCYRYRRANAVVLIKPSRSMSDLYDMQKRQRQHRHRNQSGATTSS
  GDTESEEGEGETTVRLLWLSMLKMPRELMRLCLCHLLTWFSVIAEAVFYTDFMGQVIFEG
  DPKAPSNSTAWQAYNAGVKMGCWGLVIYAATGAICSALLQKYLDNYDLSVRVIYVLGTLG
  FSVGTAVMAMFPNVYVAMVTISTMGIVSMSISYCPYALLGQYHDIKQYIHHSPGNSKRGF
  GIDCAILSCQVYISQILVASALGGVVDAVGTVRVIPMVASVGSFLGFLTATFLVIYPNVS
  EEAKEEQKGLSSPLAGEGRAGGNSEKPTVLKLTRKEGLQGPVETESVV
• Function: Proton-associated sucrose transporter. May be able to transport also glucose and fructose.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paraquat	DMR8O3X	Investigative	Solute carrier family 45 member 4 (SLC45A4) increases the response to substance of Paraquat.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
3-iodothyronamine	DM3L0F8	Investigative	Solute carrier family 45 member 4 (SLC45A4) affects the uptake of 3-iodothyronamine.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Solute carrier family 45 member 4 (SLC45A4).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Solute carrier family 45 member 4 (SLC45A4).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Solute carrier family 45 member 4 (SLC45A4).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Solute carrier family 45 member 4 (SLC45A4).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Solute carrier family 45 member 4 (SLC45A4).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Solute carrier family 45 member 4 (SLC45A4).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Solute carrier family 45 member 4 (SLC45A4).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Solute carrier family 45 member 4 (SLC45A4).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors. Toxicol In Vitro. 2015 Sep;29(6):1231-9. doi: 10.1016/j.tiv.2014.10.012. Epub 2014 Oct 24.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] 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.
• [6] Gene expression profiling of A549 cells exposed to Milan PM2.5. Toxicol Lett. 2012 Mar 7;209(2):136-45.
• [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.
• [8] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [9] A CRISPR screen identifies a pathway required for paraquat-induced cell death. Nat Chem Biol. 2017 Dec;13(12):1274-1279. doi: 10.1038/nchembio.2499. Epub 2017 Oct 23.
• [10] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.