Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8M7KWA)

• DOT Name: Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J)
• Synonyms: EC 3.1.3.36; Inositol polyphosphate 5-phosphatase J; Phosphatidylinositol 1,3,4,5-tetrakisphosphate 5-phosphatase; EC 3.1.3.56; Phosphatidylinositol 1,4,5-trisphosphate 5-phosphatase; EC 3.1.3.56
• Gene Name: INPP5J
• Related Disease:
  Breast cancer
  Breast carcinoma
  Advanced cancer
• UniProt ID: PI5PA_HUMAN
• EC Number: 3.1.3.36; 3.1.3.56
• Pfam ID: PF17751
• Sequence:
  MEGQSSRGSRRPGTRAGLGSLPMPQGVAQTGAPSKVDSSFQLPAKKNAALGPSEPRLALA
  PVGPRAAMSASSEGPRLALASPRPILAPLCTPEGQKTATAHRSSSLAPTSVGQLVMSASA
  GPKPPPATTGSVLAPTSLGLVMPASAGPRSPPVTLGPNLAPTSRDQKQEPPASVGPKPTL
  AASGLSLALASEEQPPELPSTPSPVPSPVLSPTQEQALAPASTASGAASVGQTSARKRDA
  PAPRPLPASEGHLQPPAQTSGPTGSPPCIQTSPDPRLSPSFRARPEALHSSPEDPVLPRP
  PQTLPLDVGQGPSEPGTHSPGLLSPTFRPGAPSGQTVPPPLPKPPRSPSRSPSHSPNRSP
  CVPPAPDMALPRLGTQSTGPGRCLSPNLQAQEAPAPVTTSSSTSTLSSSPWSAQPTWKSD
  PGFRITVVTWNVGTAMPPDDVTSLLHLGGGDDSDGADMIAIGLQEVNSMLNKRLKDALFT
  DQWSELFMDALGPFNFVLVSSVRMQGVILLLFAKYYHLPFLRDVQTDCTRTGLGGYWGNK
  GGVSVRLAAFGHMLCFLNCHLPAHMDKAEQRKDNFQTILSLQQFQGPGAQGILDHDLVFW
  FGDLNFRIESYDLHFVKFAIDSDQLHQLWEKDQLNMAKNTWPILKGFQEGPLNFAPTFKF
  DVGTNKYDTSAKKRKPAWTDRILWKVKAPGGGPSPSGRKSHRLQVTQHSYRSHMEYTVSD
  HKPVAAQFLLQFAFRDDMPLVRLEVADEWVRPEQAVVRYRMETVFARSSWDWIGLYRVGF
  RHCKDYVAYVWAKHEDVDGNTYQVTFSEESLPKGHGDFILGYYSHNHSILIGITEPFQIS
  LPSSELASSSTDSSGTSSEGEDDSTLELLAPKSRSPSPGKSKRHRSRSPGLARFPGLALR
  PSSRERRGASRSPSPQSRRLSRVAPDRSSNGSSRGSSEEGPSGLPGPWAFPPAVPRSLGL
  LPALRLETVDPGGGGSWGPDREALAPNSLSPSPQGHRGLEEGGLGP
• Function: Inositol 5-phosphatase, which converts inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate. Also converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate and inositol 1,3,4,5-tetrakisphosphate to inositol 1,3,4-trisphosphate in vitro. May be involved in modulation of the function of inositol and phosphatidylinositol polyphosphate-binding proteins that are present at membranes ruffles.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Synthesis of IP2, IP, and Ins in the cytosol (R-HSA-1855183)
  Synthesis of IP3 and IP4 in the cytosol (R-HSA-1855204)
  Synthesis of PIPs at the plasma membrane (R-HSA-1660499)
• BioCyc Pathway: MetaCyc:HS11950-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J).	[10]

References

• [1] The Inositol Polyphosphate 5-Phosphatase PIPP Regulates AKT1-Dependent Breast Cancer Growth and Metastasis.Cancer Cell. 2015 Aug 10;28(2):155-69. doi: 10.1016/j.ccell.2015.07.003.
• [2] Oncogenic Roles of the PI3K/AKT/mTOR Axis.Curr Top Microbiol Immunol. 2017;407:153-189. doi: 10.1007/82_2017_6.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] 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.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] 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.