Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI1UJXT)

• DOT Name: Oxysterol-binding protein-related protein 5 (OSBPL5)
• Synonyms: ORP-5; OSBP-related protein 5; Oxysterol-binding protein homolog 1
• Gene Name: OSBPL5
• Related Disease:
  Advanced cancer
  Alcohol dependence
  Arthropathy
  Non-alcoholic fatty liver disease
  Pancreatic tumour
  Silver-Russell syndrome
  Pancreatic cancer
• UniProt ID: OSBL5_HUMAN
• Pfam ID: PF01237 ; PF00169
• Sequence:
  MKEEAFLRRRFSLCPPSSTPQKVDPRKLTRNLLLSGDNELYPLSPGKDMEPNGPSLPRDE
  GPPTPSSATKVPPAEYRLCNGSDKECVSPTARVTKKETLKAQKENYRQEKKRATRQLLSA
  LTDPSVVIMADSLKIRGTLKSWTKLWCVLKPGVLLIYKTPKVGQWVGTVLLHCCELIERP
  SKKDGFCFKLFHPLDQSVWAVKGPKGESVGSITQPLPSSYLIFRAASESDGRCWLDALEL
  ALRCSSLLRLGTCKPGRDGEPGTSPDASPSSLCGLPASATVHPDQDLFPLNGSSLENDAF
  SDKSERENPEESDTETQDHSRKTESGSDQSETPGAPVRRGTTYVEQVQEELGELGEASQV
  ETVSEENKSLMWTLLKQLRPGMDLSRVVLPTFVLEPRSFLNKLSDYYYHADLLSRAAVEE
  DAYSRMKLVLRWYLSGFYKKPKGIKKPYNPILGETFRCCWFHPQTDSRTFYIAEQVSHHP
  PVSAFHVSNRKDGFCISGSITAKSRFYGNSLSALLDGKATLTFLNRAEDYTLTMPYAHCK
  GILYGTMTLELGGKVTIECAKNNFQAQLEFKLKPFFGGSTSINQISGKITSGEEVLASLS
  GHWDRDVFIKEEGSGSSALFWTPSGEVRRQRLRQHTVPLEEQTELESERLWQHVTRAISK
  GDQHRATQEKFALEEAQRQRARERQESLMPWKPQLFHLDPITQEWHYRYEDHSPWDPLKD
  IAQFEQDGILRTLQQEAVARQTTFLGSPGPRHERSGPDQRLRKASDQPSGHSQATESSGS
  TPESCPELSDEEQDGDFVPGGESPCPRCRKEARRLQALHEAILSIREAQQELHRHLSAML
  SSTARAAQAPTPGLLQSPRSWFLLCVFLACQLFINHILK
• 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. May cooperate with NPC1 to mediate the exit of cholesterol from endosomes/lysosomes. Binds 25-hydroxycholesterol and cholesterol.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Cholesterol metabolism (hsa04979)
• Reactome Pathway: Acyl chain remodelling of PS (R-HSA-1482801)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[2]
Arthropathy	DISVEERK	Strong	Biomarker	[3]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[4]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[5]
Silver-Russell syndrome	DISSVJ1D	Strong	Biomarker	[6]
Pancreatic cancer	DISJC981	Limited	Biomarker	[7]

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 Oxysterol-binding protein-related protein 5 (OSBPL5).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Oxysterol-binding protein-related protein 5 (OSBPL5).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Oxysterol-binding protein-related protein 5 (OSBPL5).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Oxysterol-binding protein-related protein 5 (OSBPL5).	[18]

7 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 Oxysterol-binding protein-related protein 5 (OSBPL5).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Oxysterol-binding protein-related protein 5 (OSBPL5).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Oxysterol-binding protein-related protein 5 (OSBPL5).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Oxysterol-binding protein-related protein 5 (OSBPL5).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Oxysterol-binding protein-related protein 5 (OSBPL5).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Oxysterol-binding protein-related protein 5 (OSBPL5).	[15]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Oxysterol-binding protein-related protein 5 (OSBPL5).	[16]

References

• [1] Oxysterol-binding protein-related protein 5 (ORP5) promotes cell proliferation by activation of mTORC1 signaling.J Biol Chem. 2018 Mar 9;293(10):3806-3818. doi: 10.1074/jbc.RA117.001558. Epub 2018 Jan 22.
• [2] Genome-wide association study of alcohol dependence implicates a region on chromosome 11.Alcohol Clin Exp Res. 2010 May;34(5):840-52. doi: 10.1111/j.1530-0277.2010.01156.x. Epub 2010 Mar 1.
• [3] Epigenome-wide analysis of sperm cells identifies IL22 as a possible germ line risk locus for psoriatic arthritis.PLoS One. 2019 Feb 19;14(2):e0212043. doi: 10.1371/journal.pone.0212043. eCollection 2019.
• [4] GWAS and enrichment analyses of non-alcoholic fatty liver disease identify new trait-associated genes and pathways across eMERGE Network.BMC Med. 2019 Jul 17;17(1):135. doi: 10.1186/s12916-019-1364-z.
• [5] Oxysterol binding protein-related protein-5 is related to invasion and poor prognosis in pancreatic cancer.Cancer Sci. 2008 Dec;99(12):2387-94. doi: 10.1111/j.1349-7006.2008.00987.x. Epub 2008 Nov 20.
• [6] Genome-wide analysis of differential DNA methylation in Silver-Russell syndrome.Sci China Life Sci. 2017 Jul;60(7):692-699. doi: 10.1007/s11427-017-9079-7. Epub 2017 Jun 14.
• [7] The role of oxysterol binding protein-related protein 5 in pancreatic cancer.Cancer Sci. 2010 Apr;101(4):898-905. doi: 10.1111/j.1349-7006.2009.01475.x. Epub 2009 Dec 16.
• [8] 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.
• [9] 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.
• [10] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [11] 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.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [14] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [15] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [16] 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.
• [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] 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.