Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPKUY50)

DOT Name Phosphatidylinositide phosphatase SAC2 (INPP5F)
Synonyms EC 3.1.3.25; Inositol polyphosphate 5-phosphatase F; Sac domain-containing inositol phosphatase 2; Sac domain-containing phosphoinositide 4-phosphatase 2; hSAC2
Gene Name INPP5F
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Neuralgia ( )
Hyperglycemia ( )
Hyperlipidemia ( )
Parkinson disease ( )
Type-1/2 diabetes ( )
UniProt ID
SAC2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4XUU
EC Number
3.1.3.25
Pfam ID
PF12456 ; PF02383
Sequence
MELFQAKDHYILQQGERALWCSRRDGGLQLRPATDLLLAWNPICLGLVEGVIGKIQLHSD
LPWWLILIRQKALVGKLPGDHEVCKVTKIAVLSLSEMEPQDLELELCKKHHFGINKPEKI
IPSPDDSKFLLKTFTHIKSNVSAPNKKKVKESKEKEKLERRLLEELLKMFMDSESFYYSL
TYDLTNSVQRQSTGERDGRPLWQKVDDRFFWNKYMIQDLTEIGTPDVDFWIIPMIQGFVQ
IEELVVNYTESSDDEKSSPETPPQESTCVDDIHPRFLVALISRRSRHRAGMRYKRRGVDK
NGNVANYVETEQLIHVHNHTLSFVQTRGSVPVFWSQVGYRYNPRPRLDRSEKETVAYFCA
HFEEQLNIYKKQVIINLVDQAGREKIIGDAYLKQVLLFNNSHLTYVSFDFHEHCRGMKFE
NVQTLTDAIYDIILDMKWCWVDEAGVICKQEGIFRVNCMDCLDRTNVVQAAIARVVMEQQ
LKKLGVMPPEQPLPVKCNRIYQIMWANNGDSISRQYAGTAALKGDFTRTGERKLAGVMKD
GVNSANRYYLNRFKDAYRQAVIDLMQGIPVTEDLYSIFTKEKEHEALHKENQRSHQELIS
QLLQSYMKLLLPDDEKFHGGWALIDCDPSLIDATHRDVDVLLLLSNSAYYVAYYDDEVDK
VNQYQRLSLENLEKIEIGPEPTLFGKPKFSCMRLHYRYKEASGYFHTLRAVMRNPEEDGK
DTLQCIAEMLQITKQAMGSDLPIIEKKLERKSSKPHEDIIGIRSQNQGSLAQGKNFLMSK
FSSLNQKVKQTKSNVNIGNLRKLGNFTKPEMKVNFLKPNLKVNLWKSDSSLETMENTGVM
DKVQAESDGDMSSDNDSYHSDEFLTNSKSDEDRQLANSLESVGPIDYVLPSCGIIASAPR
LGSRSQSLSSTDSSVHAPSEITVAHGSGLGKGQESPLKKSPSAGDVHILTGFAKPMDIYC
HRFVQDAQNKVTHLSETRSVSQQASQERNQMTNQVSNETQSESTEQTPSRPSQLDVSLSA
TGPQFLSVEPAHSVASQKTPTSASSMLELETGLHVTPSPSESSSSRAVSPFAKIRSSMVQ
VASITQAGLTHGINFAVSKVQKSPPEPEIINQVQQNELKKMFIQCQTRIIQI
Function
Inositol 4-phosphatase which mainly acts on phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, which converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol, for a sequential dephosphorylation of phosphatidylinositol 4,5-bisphosphate at the 5 and 4 position of inositol, thus playing an important role in the endocytic recycling. Regulator of TF:TFRC and integrins recycling pathway, is also involved in cell migration mechanisms. Modulates AKT/GSK3B pathway by decreasing AKT and GSK3B phosphorylation. Negatively regulates STAT3 signaling pathway through inhibition of STAT3 phosphorylation and translocation to the nucleus. Functionally important modulator of cardiac myocyte size and of the cardiac response to stress. May play a role as negative regulator of axon regeneration after central nervous system injuries.
Tissue Specificity Ubiquitous . Highly expressed in brain .
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Metabolic pathways (hsa01100 )
Phosphatidylinositol sig.ling system (hsa04070 )
Reactome Pathway
Synthesis of PIPs at the early endosome membrane (R-HSA-1660516 )
BioCyc Pathway
MetaCyc:HS12255-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Neuralgia DISWO58J Strong Biomarker [2]
Hyperglycemia DIS0BZB5 Limited Biomarker [3]
Hyperlipidemia DIS61J3S Limited Biomarker [3]
Parkinson disease DISQVHKL Limited Genetic Variation [4]
Type-1/2 diabetes DISIUHAP Limited Biomarker [3]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Phosphatidylinositide phosphatase SAC2 (INPP5F). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Phosphatidylinositide phosphatase SAC2 (INPP5F). [14]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Phosphatidylinositide phosphatase SAC2 (INPP5F). [16]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Phosphatidylinositide phosphatase SAC2 (INPP5F). [17]
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13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [8]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [9]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [10]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [11]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [12]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [12]
Rosiglitazone DMILWZR Approved Rosiglitazone increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [13]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [15]
PMID27336223-Compound-5 DM6E50A Patented PMID27336223-Compound-5 increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [13]
Scriptaid DM9JZ21 Preclinical Scriptaid increases the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [12]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Phosphatidylinositide phosphatase SAC2 (INPP5F). [18]
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⏷ Show the Full List of 13 Drug(s)

References

1 Coumarin-Fatty Acid Conjugates as Potential ER/AKT-1 Antagonists for ER Positive Breast Cancer.Anticancer Agents Med Chem. 2020;20(4):437-449. doi: 10.2174/1871520619666191028104339.
2 Pregabalin on Hdac2 and Inpp5f levels in rats with CCI-induced neuropathic pain.Exp Ther Med. 2019 Feb;17(2):1300-1305. doi: 10.3892/etm.2018.7037. Epub 2018 Nov 30.
3 Hyperglycemia and hyperlipidemia blunts the Insulin-Inpp5f negative feedback loop in the diabetic heart.Sci Rep. 2016 Feb 24;6:22068. doi: 10.1038/srep22068.
4 Association analyses of variants of SIPA1L2, MIR4697, GCH1, VPS13C, and DDRGK1 with Parkinson's disease in East Asians.Neurobiol Aging. 2018 Aug;68:159.e7-159.e14. doi: 10.1016/j.neurobiolaging.2018.03.005. Epub 2018 Mar 10.
5 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.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 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.
8 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.
9 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
10 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.
11 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
12 Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
13 PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
14 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.
15 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.
16 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.
17 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.
18 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.