Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD50E5Y)

DOT Name Oxysterol-binding protein-related protein 8 (OSBPL8)
Synonyms ORP-8; OSBP-related protein 8
Gene Name OSBPL8
Related Disease
Non-insulin dependent diabetes ( )
Atherosclerosis ( )
Congenital contractural arachnodactyly ( )
Gastric cancer ( )
Neoplasm ( )
Stomach cancer ( )
UniProt ID
OSBL8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1V88; 5U77; 5U78; 8P7A
Pfam ID
PF01237 ; PF00169
Sequence
MEGGLADGEPDRTSLLGDSKDVLGPSTVVANSDESQLLTPGKMSQRQGKEAYPTPTKDLH
QPSLSPASPHSQGFERGKEDISQNKDESSLSMSKSKSESKLYNGSEKDSSTSSKLTKKES
LKVQKKNYREEKKRATKELLSTITDPSVIVMADWLKIRGTLKSWTKLWCVLKPGVLLIYK
TQKNGQWVGTVLLNACEIIERPSKKDGFCFKLFHPLEQSIWAVKGPKGEAVGSITQPLPS
SYLIIRATSESDGRCWMDALELALKCSSLLKRTMIREGKEHDLSVSSDSTHVTFYGLLRA
NNLHSGDNFQLNDSEIERQHFKDQDMYSDKSDKENDQEHDESDNEVMGKSEESDTDTSER
QDDSYIEPEPVEPLKETTYTEQSHEELGEAGEASQTETVSEENKSLIWTLLKQVRPGMDL
SKVVLPTFILEPRSFLDKLSDYYYHADFLSEAALEENPYFRLKKVVKWYLSGFYKKPKGL
KKPYNPILGETFRCLWIHPRTNSKTFYIAEQVSHHPPISAFYVSNRKDGFCLSGSILAKS
KFYGNSLSAILEGEARLTFLNRGEDYVMTMPYAHCKGILYGTMTLELGGTVNITCQKTGY
SAILEFKLKPFLGSSDCVNQISGKLKLGKEVLATLEGHWDSEVFITDKKTDNSEVFWNPT
PDIKQWRLIRHTVKFEEQGDFESEKLWQRVTRAINAKDQTEATQEKYVLEEAQRQAARDR
KTKNEEWSCKLFELDPLTGEWHYKFADTRPWDPLNDMIQFEKDGVIQTKVKHRTPMVSVP
KMKHKPTRQQKKVAKGYSSPEPDIQDSSGSEAQSVKPSTRRKKGIELGDIQSSIESIKQT
QEEIKRNIMALRNHLVSSTPATDYFLQQKDYFIIFLLILLQVIINFMFK
Function
Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner. Binds oxysterol, 25-hydroxycholesterol and cholesterol.
Tissue Specificity Widely expressed . Expressed at higher level in macrophages .
Reactome Pathway
Acyl chain remodelling of PS (R-HSA-1482801 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Non-insulin dependent diabetes DISK1O5Z Definitive Posttranslational Modification [1]
Atherosclerosis DISMN9J3 Strong Biomarker [2]
Congenital contractural arachnodactyly DISOM1K7 Strong Biomarker [3]
Gastric cancer DISXGOUK moderate Altered Expression [4]
Neoplasm DISZKGEW moderate Altered Expression [4]
Stomach cancer DISKIJSX moderate Altered Expression [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 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 Oxysterol-binding protein-related protein 8 (OSBPL8). [5]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [6]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [8]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [10]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [12]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [13]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [14]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [15]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [16]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [19]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Oxysterol-binding protein-related protein 8 (OSBPL8). [21]
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⏷ Show the Full List of 14 Drug(s)
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Oxysterol-binding protein-related protein 8 (OSBPL8). [17]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Oxysterol-binding protein-related protein 8 (OSBPL8). [18]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Oxysterol-binding protein-related protein 8 (OSBPL8). [20]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Oxysterol-binding protein-related protein 8 (OSBPL8). [18]
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References

1 A Novel Regulator of Type II Diabetes: MicroRNA-143.Trends Endocrinol Metab. 2018 Jun;29(6):380-388. doi: 10.1016/j.tem.2018.03.019. Epub 2018 Apr 18.
2 OSBP-related protein 8 (ORP8) suppresses ABCA1 expression and cholesterol efflux from macrophages.J Biol Chem. 2008 Jan 4;283(1):332-340. doi: 10.1074/jbc.M705313200. Epub 2007 Nov 8.
3 Expression of oxysterol binding protein isoforms in opisthorchiasis-associated cholangiocarcinoma: a potential molecular marker for tumor metastasis.Parasitol Int. 2012 Mar;61(1):136-9. doi: 10.1016/j.parint.2011.07.003. Epub 2011 Jul 8.
4 Oxysterol-Binding Protein-Related Protein 8 Inhibits Gastric Cancer Growth Through Induction of ER Stress, Inhibition of Wnt Signaling, and Activation of Apoptosis.Oncol Res. 2017 May 24;25(5):799-808. doi: 10.3727/096504016X14783691306605. Epub 2016 Nov 8.
5 The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
6 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
7 Toxicogenomics-based prediction of acetaminophen-induced liver injury using human hepatic cell systems. Toxicol Lett. 2016 Jan 5;240(1):50-9.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
10 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.
11 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.
12 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
13 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
14 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.
15 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
16 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
17 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.
18 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.
19 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
20 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.
21 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.