Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT54Y9TN)

• DOT Name: Major facilitator superfamily domain-containing protein 12 (MFSD12)
• Gene Name: MFSD12
• Related Disease:
  Advanced cancer
  Melanoma
  Neoplasm
  Neuroblastoma
• UniProt ID: MFS12_HUMAN
• Pfam ID: PF13347
• Sequence:
  MGPGPPAAGAAPSPRPLSLVARLSYAVGHFLNDLCASMWFTYLLLYLHSVRAYSSRGAGL
  LLLLGQVADGLCTPLVGYEADRAASCCARYGPRKAWHLVGTVCVLLSFPFIFSPCLGCGA
  ATPEWAALLYYGPFIVIFQFGWASTQISHLSLIPELVTNDHEKVELTALRYAFTVVANIT
  VYGAAWLLLHLQGSSRVEPTQDISISDQLGGQDVPVFRNLSLLVVGVGAVFSLLFHLGTR
  ERRRPHAEEPGEHTPLLAPATAQPLLLWKHWLREPAFYQVGILYMTTRLIVNLSQTYMAM
  YLTYSLHLPKKFIATIPLVMYLSGFLSSFLMKPINKCIGRNMTYFSGLLVILAFAAWVAL
  AEGLGVAVYAAAVLLGAGCATILVTSLAMTADLIGPHTNSGAFVYGSMSFLDKVANGLAV
  MAIQSLHPCPSELCCRACVSFYHWAMVAVTGGVGVAAALCLCSLLLWPTRLRRWDRDARP
• Function: Transporter that mediates the import of cysteine into melanosomes, thereby regulating skin pigmentation. In melanosomes, cysteine import is required both for normal levels of cystine, the oxidized dimer of cysteine, and provide cysteine for the production of the cysteinyldopas used in pheomelanin synthesis, thereby regulating skin pigmentation. Also catalyzes import of cysteine into lysosomes in non-pigmented cells, regulating lysosomal cystine and cysteine storage, which is essnetial for redox homeostasis.
• Tissue Specificity: Widely expressed, with high expression in primary melanocytes.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Melanoma	DIS1RRCY	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[1]

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 Major facilitator superfamily domain-containing protein 12 (MFSD12).	[3]

9 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 Major facilitator superfamily domain-containing protein 12 (MFSD12).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Major facilitator superfamily domain-containing protein 12 (MFSD12).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Major facilitator superfamily domain-containing protein 12 (MFSD12).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Major facilitator superfamily domain-containing protein 12 (MFSD12).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Major facilitator superfamily domain-containing protein 12 (MFSD12).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Major facilitator superfamily domain-containing protein 12 (MFSD12).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Major facilitator superfamily domain-containing protein 12 (MFSD12).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Major facilitator superfamily domain-containing protein 12 (MFSD12).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Major facilitator superfamily domain-containing protein 12 (MFSD12).	[12]

References

• [1] Novel protein pp3501 mediates the inhibitory effect of sodium butyrate on SH-SY5Y cell proliferation.J Cell Biochem. 2012 Aug;113(8):2696-703. doi: 10.1002/jcb.24145.
• [2] Bioinformatics-based analysis reveals elevated MFSD12 as a key promoter of cell proliferation and a potential therapeutic target in melanoma.Oncogene. 2019 Mar;38(11):1876-1891. doi: 10.1038/s41388-018-0531-6. Epub 2018 Nov 1.
• [3] 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.
• [4] 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.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] 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.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.