Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7I3U0G)

DOT Name Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D)
Synonyms
EC 3.1.3.86; Inositol polyphosphate-5-phosphatase D; EC 3.1.3.56; Inositol polyphosphate-5-phosphatase of 145 kDa; SIP-145; Phosphatidylinositol 4,5-bisphosphate 5-phosphatase; EC 3.1.3.36; SH2 domain-containing inositol 5'-phosphatase 1; SH2 domain-containing inositol phosphatase 1; SHIP-1; p150Ship; hp51CN
Gene Name INPP5D
UniProt ID
SHIP1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2YSX ; 5RW2 ; 5RW3 ; 5RW4 ; 5RW5 ; 5RW6 ; 5RW7 ; 5RW8 ; 5RW9 ; 5RWA ; 5RWB ; 5RWC ; 5RWD ; 5RWE ; 5RWF ; 5RWG ; 5RWH ; 5RWI ; 5RWJ ; 5RWK ; 5RWL ; 5RWM ; 5RWN ; 5RWO ; 5RWP ; 5RWQ ; 5RWR ; 5RWS ; 5RWT ; 5RWU ; 5RWV ; 5RWW ; 5RWX ; 5RWY ; 5RWZ ; 5RX0 ; 5RX1 ; 5RX2 ; 5RX3 ; 5RX4 ; 5RX5 ; 5RX6 ; 5RX7 ; 5RX8 ; 5RX9 ; 5RXA ; 5RXB ; 5RXC ; 5RXD ; 5RXE ; 5RXF ; 5RXG ; 5RXH ; 5RXI ; 5RXJ ; 5RXK ; 5RXL ; 5RXM ; 5RXO ; 5RXP ; 5RXQ ; 5RXR ; 5RXS ; 5RXT ; 5RXU ; 5RXV ; 5RXW ; 5RXX ; 5RXY ; 5RXZ ; 5RY0 ; 5RY1 ; 5RY2 ; 5RY3 ; 5RY4 ; 5RY5 ; 5RY6 ; 5RY7 ; 5RY8 ; 5RY9 ; 5RYA ; 5RYB ; 5RYC ; 5RYD ; 5RYE ; 5RYF ; 5RYG ; 5RYH ; 5RYI ; 5RYJ ; 5RYK ; 5RYL ; 6IBD ; 6XY7 ; 8PDG ; 8PDH ; 8PDI ; 8PDJ
EC Number
3.1.3.36; 3.1.3.56; 3.1.3.86
Pfam ID
PF00017
Sequence
MVPCWNHGNITRSKAEELLSRTGKDGSFLVRASESISRAYALCVLYRNCVYTYRILPNED
DKFTVQASEGVSMRFFTKLDQLIEFYKKENMGLVTHLQYPVPLEEEDTGDDPEEDTVESV
VSPPELPPRNIPLTASSCEAKEVPFSNENPRATETSRPSLSETLFQRLQSMDTSGLPEEH
LKAIQDYLSTQLAQDSEFVKTGSSSLPHLKKLTTLLCKELYGEVIRTLPSLESLQRLFDQ
QLSPGLRPRPQVPGEANPINMVSKLSQLTSLLSSIEDKVKALLHEGPESPHRPSLIPPVT
FEVKAESLGIPQKMQLKVDVESGKLIIKKSKDGSEDKFYSHKKILQLIKSQKFLNKLVIL
VETEKEKILRKEYVFADSKKREGFCQLLQQMKNKHSEQPEPDMITIFIGTWNMGNAPPPK
KITSWFLSKGQGKTRDDSADYIPHDIYVIGTQEDPLSEKEWLEILKHSLQEITSVTFKTV
AIHTLWNIRIVVLAKPEHENRISHICTDNVKTGIANTLGNKGAVGVSFMFNGTSLGFVNS
HLTSGSEKKLRRNQNYMNILRFLALGDKKLSPFNITHRFTHLFWFGDLNYRVDLPTWEAE
TIIQKIKQQQYADLLSHDQLLTERREQKVFLHFEEEEITFAPTYRFERLTRDKYAYTKQK
ATGMKYNLPSWCDRVLWKSYPLVHVVCQSYGSTSDIMTSDHSPVFATFEAGVTSQFVSKN
GPGTVDSQGQIEFLRCYATLKTKSQTKFYLEFHSSCLESFVKSQEGENEEGSEGELVVKF
GETLPKLKPIISDPEYLLDQHILISIKSSDSDESYGEGCIALRLEATETQLPIYTPLTHH
GELTGHFQGEIKLQTSQGKTREKLYDFVKTERDESSGPKTLKSLTSHDPMKQWEVTSRAP
PCSGSSITEIINPNYMGVGPFGPPMPLHVKQTLSPDQQPTAWSYDQPPKDSPLGPCRGES
PPTPPGQPPISPKKFLPSTANRGLPPRTQESRPSDLGKNAGDTLPQEDLPLTKPEMFENP
LYGSLSSFPKPAPRKDQESPKMPRKEPPPCPEPGILSPSIVLTKAQEADRGEGPGKQVPA
PRLRSFTCSSSAEGRAAGGDKSQGKPKTPVSSQAPVPAKRPIKPSRSEINQQTPPTPTPR
PPLPVKSPAVLHLQHSKGRDYRDNTELPHHGKHRPEEGPPGPLGRTAMQ
Function
Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Able also to hydrolyzes the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression.
Tissue Specificity
Specifically expressed in immune and hematopoietic cells. Expressed in bone marrow and blood cells. Levels vary considerably within this compartment. Present in at least 74% of immature CD34+ cells, whereas within the more mature population of CD33+ cells, it is present in only 10% of cells. Present in the majority of T-cells, while it is present in a minority of B-cells (at protein level).
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Metabolic pathways (hsa01100 )
Phosphatidylinositol sig.ling system (hsa04070 )
B cell receptor sig.ling pathway (hsa04662 )
Fc epsilon RI sig.ling pathway (hsa04664 )
Fc gamma R-mediated phagocytosis (hsa04666 )
Reactome Pathway
Synthesis of IP3 and IP4 in the cytosol (R-HSA-1855204 )
Downstream TCR signaling (R-HSA-202424 )
PECAM1 interactions (R-HSA-210990 )
Interleukin receptor SHC signaling (R-HSA-912526 )
Signaling by CSF1 (M-CSF) in myeloid cells (R-HSA-9680350 )
Synthesis of PIPs at the plasma membrane (R-HSA-1660499 )
BioCyc Pathway
MetaCyc:HS09849-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [1]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [14]
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18 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [2]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [4]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [5]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [6]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [7]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [8]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [9]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [11]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [13]
UNC0379 DMD1E4J Preclinical UNC0379 increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [15]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [16]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [17]
Phencyclidine DMQBEYX Investigative Phencyclidine increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [18]
QUERCITRIN DM1DH96 Investigative QUERCITRIN affects the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [19]
ELLAGIC ACID DMX8BS5 Investigative ELLAGIC ACID increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D). [20]
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⏷ Show the Full List of 18 Drug(s)

References

1 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.
2 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
3 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.
4 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
6 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
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 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 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.
11 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
12 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
13 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.
14 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.
15 Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
16 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.
17 Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
18 Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.
19 Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
20 Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.