Details of Drug Off-Target (DOT)

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

• DOT Name: Heme transporter HRG1 (SLC48A1)
• Synonyms: Heme-responsive gene 1 protein homolog; HRG-1; hHRG-1; Solute carrier family 48 member 1
• Gene Name: SLC48A1
• UniProt ID: HRG1_HUMAN
• Pfam ID: PF16954
• Sequence:
  MAPSRLQLGLRAAYSGISSVAGFSIFLVWTVVYRQPGTAAMGGLAGVLALWVLVTHVMYM
  QDYWRTWLKGLRGFFFVGVLFSAVSIAAFCTFLVLAITRHQSLTDPTSYYLSSVWSFISF
  KWAFLLSLYAHRYRADFADISILSDF
• Function: Heme transporter that regulates intracellular heme availability through the endosomal or lysosomal compartment. In macrophages of the reticuloendothelial system, is the heme transporter for heme-iron recycling. Essential for macrophage iron homeostasis, transports heme from the phagolysosome to the cytoplasm during erythrophagocytosis (EP).
• Tissue Specificity: Highly expressed in the brain, kidney, heart and skeletal muscle. Moderately expressed in the liver, lung, placenta and small intestine. Strongly expressed in macrophages of the reticuloendothelial system .

Molecular Interaction Atlas (MIA) of This DOT

16 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 Heme transporter HRG1 (SLC48A1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Heme transporter HRG1 (SLC48A1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Heme transporter HRG1 (SLC48A1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heme transporter HRG1 (SLC48A1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Heme transporter HRG1 (SLC48A1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Heme transporter HRG1 (SLC48A1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Heme transporter HRG1 (SLC48A1).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heme transporter HRG1 (SLC48A1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Heme transporter HRG1 (SLC48A1).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Heme transporter HRG1 (SLC48A1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Heme transporter HRG1 (SLC48A1).	[11]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Heme transporter HRG1 (SLC48A1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Heme transporter HRG1 (SLC48A1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Heme transporter HRG1 (SLC48A1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Heme transporter HRG1 (SLC48A1).	[15]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Heme transporter HRG1 (SLC48A1).	[16]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol. 2005 Mar;128(5):636-44.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [13] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [14] 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.
• [15] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [16] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.