Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG4FVQB)

• DOT Name: Solute carrier family 53 member 1
• Synonyms: Phosphate exporter SLC53A1; Protein SYG1 homolog; Xenotropic and polytropic murine leukemia virus receptor X3; X-receptor; Xenotropic and polytropic retrovirus receptor 1
• Gene Name: XPR1
• Related Disease:
  Basal ganglia calcification, idiopathic, 6
  Bilateral striopallidodentate calcinosis
• UniProt ID: S53A1_HUMAN
• PDB ID: 5IJH
• Pfam ID: PF03124 ; PF03105
• Sequence:
  MKFAEHLSAHITPEWRKQYIQYEAFKDMLYSAQDQAPSVEVTDEDTVKRYFAKFEEKFFQ
  TCEKELAKINTFYSEKLAEAQRRFATLQNELQSSLDAQKESTGVTTLRQRRKPVFHLSHE
  ERVQHRNIKDLKLAFSEFYLSLILLQNYQNLNFTGFRKILKKHDKILETSRGADWRVAHV
  EVAPFYTCKKINQLISETEAVVTNELEDGDRQKAMKRLRVPPLGAAQPAPAWTTFRVGLF
  CGIFIVLNITLVLAAVFKLETDRSIWPLIRIYRGGFLLIEFLFLLGINTYGWRQAGVNHV
  LIFELNPRSNLSHQHLFEIAGFLGILWCLSLLACFFAPISVIPTYVYPLALYGFMVFFLI
  NPTKTFYYKSRFWLLKLLFRVFTAPFHKVGFADFWLADQLNSLSVILMDLEYMICFYSLE
  LKWDESKGLLPNNSEESGICHKYTYGVRAIVQCIPAWLRFIQCLRRYRDTKRAFPHLVNA
  GKYSTTFFMVTFAALYSTHKERGHSDTMVFFYLWIVFYIISSCYTLIWDLKMDWGLFDKN
  AGENTFLREEIVYPQKAYYYCAIIEDVILRFAWTIQISITSTTLLPHSGDIIATVFAPLE
  VFRRFVWNFFRLENEHLNNCGEFRAVRDISVAPLNADDQTLLEQMMDQDDGVRNRQKNRS
  WKYNQSISLRRPRLASQSKARDTKVLIEDTDDEANT
• Function: Inorganic ion transporter that mediates phosphate ion export across plasma membrane. Plays a major role in phosphate homeostasis, preventing intracellular phosphate accumulation and possible calcium phosphate precipitation, ultimately preserving calcium signaling. The molecular mechanism of phosphate transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated. Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), important intracellular signaling molecules involved in regulation of phosphate flux.
• Tissue Specificity: Widely expressed. Detected in spleen, lymph node, thymus, leukocytes, bone marrow, heart, kidney, pancreas and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Basal ganglia calcification, idiopathic, 6	DIS8PLFS	Strong	Autosomal dominant	[1]
Bilateral striopallidodentate calcinosis	DISNZJTB	Supportive	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Phosphate	DMUXQG7	Approved	Solute carrier family 53 member 1 affects the export of Phosphate.	[1]

12 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 53 member 1.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Solute carrier family 53 member 1.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Solute carrier family 53 member 1.	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Solute carrier family 53 member 1.	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Solute carrier family 53 member 1.	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Solute carrier family 53 member 1.	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Solute carrier family 53 member 1.	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Solute carrier family 53 member 1.	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Solute carrier family 53 member 1.	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Solute carrier family 53 member 1.	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Solute carrier family 53 member 1.	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Solute carrier family 53 member 1.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Solute carrier family 53 member 1.	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Solute carrier family 53 member 1.	[11]

References

• [1] Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet. 2015 Jun;47(6):579-81. doi: 10.1038/ng.3289. Epub 2015 May 4.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [9] 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.
• [10] 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.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet. 2015 Jun;47(6):579-81. doi: 10.1038/ng.3289. Epub 2015 May 4.