Details of Drug Off-Target (DOT)

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

• DOT Name: Sphingosine-1-phosphate phosphatase 2 (SGPP2)
• Synonyms: SPPase2; Spp2; hSPP2; EC 3.1.3.-; Sphingosine-1-phosphatase 2
• Gene Name: SGPP2
• Related Disease:
  Colitis
  Endometriosis
  Inflammatory bowel disease
  Ulcerative colitis
  Advanced cancer
  Gastric cancer
  Neoplasm
  Stomach cancer
• UniProt ID: SGPP2_HUMAN
• EC Number: 3.1.3.-
• Pfam ID: PF01569
• Sequence:
  MAELLRSLQDSQLVARFQRRCGLFPAPDEGPRENGADPTERAARVPGVEHLPAANGKGGE
  APANGLRRAAAPEAYVQKYVVKNYFYYYLFQFSAALGQEVFYITFLPFTHWNIDPYLSRR
  LIIIWVLVMYIGQVAKDVLKWPRPSSPPVVKLEKRLIAEYGMPSTHAMAATAIAFTLLIS
  TMDRYQYPFVLGLVMAVVFSTLVCLSRLYTGMHTVLDVLGGVLITALLIVLTYPAWTFID
  CLDSASPLFPVCVIVVPFFLCYNYPVSDYYSPTRADTTTILAAGAGVTIGFWINHFFQLV
  SKPAESLPVIQNIPPLTTYMLVLGLTKFAVGIVLILLVRQLVQNLSLQVLYSWFKVVTRN
  KEARRRLEIEVPYKFVTYTSVGICATTFVPMLHRFLGLP
• Function: Has specific phosphohydrolase activity towards sphingoid base 1-phosphates. Has high phosphohydrolase activity against dihydrosphingosine-1-phosphate and sphingosine-1-phosphate (S1P) in vitro. Sphingosine-1-phosphate phosphatase activity is needed for efficient recycling of sphingosine into the sphingolipid synthesis pathway. May play a role in attenuating intracellular sphingosine 1-phosphate (S1P) signaling. May play a role in pro-inflammatory signaling. Plays a role in the regulation of pancreatic islet beta-cell endoplasmic reticulum stress and proliferation.
• Tissue Specificity: Expressed strongly in kidney and heart, followed by brain, colon, small intestine and lung. Not detected in skeletal muscle, thymus, spleen, liver, placenta, and peripheral blood leukocytes.
• KEGG Pathway:
  Sphingolipid metabolism (hsa00600)
  Metabolic pathways (hsa01100)
  Sphingolipid sig.ling pathway (hsa04071)
• Reactome Pathway: Sphingolipid metabolism (R-HSA-428157)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colitis	DISAF7DD	Strong	Altered Expression	[1]
Endometriosis	DISX1AG8	Strong	Altered Expression	[2]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[1]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[3]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[3]
Neoplasm	DISZKGEW	moderate	Biomarker	[3]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[3]

11 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 Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[10]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Sphingosine-1-phosphate phosphatase 2 (SGPP2).	[13]

References

• [1] Sphingosine-1-phosphate phosphatase 2 promotes disruption of mucosal integrity, and contributes to ulcerative colitis in mice and humans.FASEB J. 2016 Aug;30(8):2945-58. doi: 10.1096/fj.201600394R. Epub 2016 Apr 29.
• [2] Sphingosine pathway deregulation in endometriotic tissues.Fertil Steril. 2012 Apr;97(4):904-11. doi: 10.1016/j.fertnstert.2011.12.051. Epub 2012 Jan 24.
• [3] Tumor suppressor microRNA-31 inhibits gastric carcinogenesis by targeting Smad4 and SGPP2.Cancer Gene Ther. 2015 Dec;22(12):564-72. doi: 10.1038/cgt.2015.41. Epub 2015 Oct 23.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] 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.
• [9] 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.
• [10] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [11] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [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] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.