Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIUYAG5)

DOT Name Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1)
Synonyms Drosophila retinal degeneration B homolog; Phosphatidylinositol transfer protein, membrane-associated 1; PITPnm 1; Pyk2 N-terminal domain-interacting receptor 2; NIR-2
Gene Name PITPNM1
Related Disease
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Colorectal carcinoma ( )
Hepatitis C virus infection ( )
Neoplasm ( )
Psoriatic arthritis ( )
Schizophrenia ( )
Retinal degeneration ( )
UniProt ID
PITM1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF02862 ; PF02121
Sequence
MLIKEYHILLPMSLDEYQVAQLYMIQKKSREESSGEGSGVEILANRPYTDGPGGSGQYTH
KVYHVGSHIPGWFRALLPKAALQVEEESWNAYPYTRTRYTCPFVEKFSIEIETYYLPDGG
QQPNVFNLSGAERRQRILDTIDIVRDAVAPGEYKAEEDPRLYHSVKTGRGPLSDDWARTA
AQTGPLMCAYKLCKVEFRYWGMQAKIEQFIHDVGLRRVMLRAHRQAWCWQDEWTELSMAD
IRALEEETARMLAQRMAKCNTGSEGSEAQPPGKPSTEARSAASNTGTPDGPEAPPGPDAS
PDASFGKQWSSSSRSSYSSQHGGAVSPQSLSEWRMQNIARDSENSSEEEFFDAHEGFSDS
EEVFPKEMTKWNSNDFIDAFASPVEAEGTPEPGAEAAKGIEDGAQAPRDSEGLDGAGELG
AEACAVHALFLILHSGNILDSGPGDANSKQADVQTLSSAFEAVTRIHFPEALGHVALRLV
PCPPICAAAYALVSNLSPYSHDGDSLSRSQDHIPLAALPLLATSSSRYQGAVATVIARTN
QAYSAFLRSPEGAGFCGQVALIGDGVGGILGFDALCHSANAGTGSRGSSRRGSMNNELLS
PEFGPVRDPLADGVEGLGRGSPEPSALPPQRIPSDMASPEPEGSQNSLQAAPATTSSWEP
RRASTAFCPPAASSEAPDGPSSTARLDFKVSGFFLFGSPLGLVLALRKTVMPALEAAQMR
PACEQIYNLFHAADPCASRLEPLLAPKFQAIAPLTVPRYQKFPLGDGSSLLLADTLQTHS
SLFLEELEMLVPSTPTSTSGAFWKGSELATDPPAQPAAPSTTSEVVKILERWWGTKRIDY
SLYCPEALTAFPTVTLPHLFHASYWESADVVAFILRQVIEKERPQLAECEEPSIYSPAFP
REKWQRKRTQVKIRNVTSNHRASDTVVCEGRPQVLSGRFMYGPLDVVTLTGEKVDVYIMT
QPLSGKWIHFGTEVTNSSGRLTFPVPPERALGIGVYPVRMVVRGDHTYAECCLTVVARGT
EAVVFSIDGSFTASVSIMGSDPKVRAGAVDVVRHWQDSGYLIVYVTGRPDMQKHRVVAWL
SQHNFPHGVVSFCDGLTHDPLRQKAMFLQSLVQEVELNIVAGYGSPKDVAVYAALGLSPS
QTYIVGRAVRKLQAQCQFLSDGYVAHLGQLEAGSHSHASSGPPRAALGKSSYGVAAPVDF
LRKQSQLLRSRGPSQAEREGPGTPPTTLARGKARSISLKLDSEE
Function
Catalyzes the transfer of phosphatidylinositol (PI) between membranes. Binds PI, phosphatidylcholine (PC) and phosphatidic acid (PA) with the binding affinity order of PI > PA > PC. Regulates RHOA activity, and plays a role in cytoskeleton remodeling. Necessary for normal completion of cytokinesis. Plays a role in maintaining normal diacylglycerol levels in the Golgi apparatus. Necessary for maintaining the normal structure of the endoplasmic reticulum and the Golgi apparatus. Required for protein export from the endoplasmic reticulum and the Golgi. Binds calcium ions.
Tissue Specificity Ubiquitous.
Reactome Pathway
Synthesis of PI (R-HSA-1483226 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [4]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [5]
Neoplasm DISZKGEW Strong Biomarker [6]
Psoriatic arthritis DISLWTG2 Strong Biomarker [7]
Schizophrenia DISSRV2N Strong Biomarker [8]
Retinal degeneration DISM1JHQ Limited Genetic Variation [9]
------------------------------------------------------------------------------------
⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [10]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [20]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [21]
------------------------------------------------------------------------------------
10 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 Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [11]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [12]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [13]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [14]
Quercetin DM3NC4M Approved Quercetin increases the expression of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [15]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [16]
Selenium DM25CGV Approved Selenium increases the expression of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [17]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [18]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [19]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Membrane-associated phosphatidylinositol transfer protein 1 (PITPNM1). [22]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 Drug(s)

References

1 A nano-cocktail of an NIR-II emissive fluorophore and organoplatinum(ii) metallacycle for efficient cancer imaging and therapy.Chem Sci. 2019 Jun 13;10(29):7023-7028. doi: 10.1039/c9sc02466b. eCollection 2019 Aug 7.
2 The lipid-transfer protein Nir2 enhances epithelial-mesenchymal transition and facilitates breast cancer metastasis.J Cell Sci. 2014 Nov 1;127(Pt 21):4740-9. doi: 10.1242/jcs.155721. Epub 2014 Sep 1.
3 Correction: A bright NIR-II fluorescent probe for breast carcinoma imaging and image-guided surgery.Chem Commun (Camb). 2019 Dec 25;55(99):15005. doi: 10.1039/c9cc90519g. Epub 2019 Nov 28.
4 Hydrogen Sulfide-Activatable Second Near-Infrared Fluorescent Nanoassemblies for Targeted Photothermal Cancer Therapy.Nano Lett. 2018 Oct 10;18(10):6411-6416. doi: 10.1021/acs.nanolett.8b02767. Epub 2018 Sep 24.
5 Nir2 Is an Effector of VAPs Necessary for Efficient Hepatitis C Virus Replication and Phosphatidylinositol 4-Phosphate Enrichment at the Viral Replication Organelle.J Virol. 2019 Oct 29;93(22):e00742-19. doi: 10.1128/JVI.00742-19. Print 2019 Nov 15.
6 Pd@Au Bimetallic Nanoplates Decorated Mesoporous MnO(2) for Synergistic Nucleus-Targeted NIR-II Photothermal and Hypoxia-Relieved Photodynamic Therapy.Adv Healthc Mater. 2020 Jan;9(2):e1901528. doi: 10.1002/adhm.201901528. Epub 2019 Dec 10.
7 Hypoxia-triggered single molecule probe for high-contrast NIR II/PA tumor imaging and robust photothermal therapy.Theranostics. 2018 Nov 15;8(21):6025-6034. doi: 10.7150/thno.26607. eCollection 2018.
8 Exome sequencing supports a de novo mutational paradigm for schizophrenia.Nat Genet. 2011 Aug 7;43(9):864-8. doi: 10.1038/ng.902.
9 Targeting of Nir2 to lipid droplets is regulated by a specific threonine residue within its PI-transfer domain.Curr Biol. 2002 Sep 3;12(17):1513-8. doi: 10.1016/s0960-9822(02)01107-7.
10 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.
11 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
12 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.
13 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.
14 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.
15 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
16 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
17 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
18 Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol. 2008 May;28(4):491-508.
19 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.
20 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
21 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.
22 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.