Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ05YRP)

• DOT Name: 2'-5'-oligoadenylate synthase-like protein (OASL)
• Synonyms: 2'-5'-OAS-related protein; 2'-5'-OAS-RP; 59 kDa 2'-5'-oligoadenylate synthase-like protein; Thyroid receptor-interacting protein 14; TR-interacting protein 14; TRIP-14; p59 OASL; p59OASL
• Gene Name: OASL
• Related Disease:
  Influenza
  Lung cancer
  Lung carcinoma
  Lupus
  Multiple sclerosis
  Non-insulin dependent diabetes
  Systemic lupus erythematosus
  Systemic sclerosis
  Tuberculosis
  Hepatitis C virus infection
• UniProt ID: OASL_HUMAN
• PDB ID: 1WH3; 4XQ7
• Pfam ID: PF10421 ; PF00240
• Sequence:
  MALMQELYSTPASRLDSFVAQWLQPHREWKEEVLDAVRTVEEFLRQEHFQGKRGLDQDVR
  VLKVVKVGSFGNGTVLRSTREVELVAFLSCFHSFQEAAKHHKDVLRLIWKTMWQSQDLLD
  LGLEDLRMEQRVPDALVFTIQTRGTAEPITVTIVPAYRALGPSLPNSQPPPEVYVSLIKA
  CGGPGNFCPSFSELQRNFVKHRPTKLKSLLRLVKHWYQQYVKARSPRANLPPLYALELLT
  IYAWEMGTEEDENFMLDEGFTTVMDLLLEYEVICIYWTKYYTLHNAIIEDCVRKQLKKER
  PIILDPADPTLNVAEGYRWDIVAQRASQCLKQDCCYDNRENPISSWNVKRARDIHLTVEQ
  RGYPDFNLIVNPYEPIRKVKEKIRRTRGYSGLQRLSFQVPGSERQLLSSRCSLAKYGIFS
  HTHIYLLETIPSEIQVFVKNPDGGSYAYAINPNSFILGLKQQIEDQQGLPKKQQQLEFQG
  QVLQDWLGLGIYGIQDSDTLILSKKKGEALFPAS
• Function: Does not have 2'-5'-OAS activity, but can bind double-stranded RNA. Displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L.
• Tissue Specificity: Expressed in most tissues, with the highest levels in primary blood Leukocytes and other hematopoietic system tissues, colon, stomach and to some extent in testis.
• KEGG Pathway: Human papillomavirus infection (hsa05165)
• Reactome Pathway:
  OAS antiviral response (R-HSA-8983711)
  Interferon alpha/beta signaling (R-HSA-909733)
  Interferon gamma signaling (R-HSA-877300)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Influenza	DIS3PNU3	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Lupus	DISOKJWA	Strong	Biomarker	[3]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[5]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[6]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[7]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[8]
Hepatitis C virus infection	DISQ0M8R	Limited	Altered Expression	[9]

22 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 2'-5'-oligoadenylate synthase-like protein (OASL).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[18]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[19]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[20]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[21]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[20]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[22]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[22]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[23]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[24]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[28]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of 2'-5'-oligoadenylate synthase-like protein (OASL).	[29]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of 2'-5'-oligoadenylate synthase-like protein (OASL).	[15]

References

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• [9] 2',5'-Oligoadenylate synthetase-like gene highly induced by hepatitis C virus infection in human liver is inhibitory to viral replication in vitro.Biochem Biophys Res Commun. 2010 Feb 12;392(3):397-402. doi: 10.1016/j.bbrc.2010.01.034. Epub 2010 Jan 13.
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• [12] 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.
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• [18] 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.
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• [20] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [21] Differently expressed long noncoding RNAs and mRNAs in TK6 cells exposed to low dose hydroquinone. Oncotarget. 2017 Oct 4;8(56):95554-95567. doi: 10.18632/oncotarget.21481. eCollection 2017 Nov 10.
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• [27] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
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