Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT64CCTM)

• DOT Name: 2'-5'-oligoadenylate synthase 2 (OAS2)
• Synonyms: (2-5')oligo(A) synthase 2; 2-5A synthase 2; EC 2.7.7.84; p69 OAS / p71 OAS; p69OAS / p71OAS
• Gene Name: OAS2
• Related Disease:
  Hepatocellular carcinoma
  Atopic dermatitis
  Chikungunya virus infection
  Chronic fatigue syndrome
  Colorectal carcinoma
  Dengue
  Depression
  Hepatitis C virus infection
  Influenza
  Major depressive disorder
  Psoriasis
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Systemic sclerosis
  Prostate cancer
  Prostate carcinoma
  Advanced cancer
  Asthma
  Encephalitis
  Enterovirus infection
  Meningitis
  Oral cancer
• UniProt ID: OAS2_HUMAN
• EC Number: 2.7.7.84
• Pfam ID: PF01909 ; PF10421
• Sequence:
  MGNGESQLSSVPAQKLGWFIQEYLKPYEECQTLIDEMVNTICDVLQEPEQFPLVQGVAIG
  GSYGRKTVLRGNSDGTLVLFFSDLKQFQDQKRSQRDILDKTGDKLKFCLFTKWLKNNFEI
  QKSLDGFTIQVFTKNQRISFEVLAAFNALSLNDNPSPWIYRELKRSLDKTNASPGEFAVC
  FTELQQKFFDNRPGKLKDLILLIKHWHQQCQKKIKDLPSLSPYALELLTVYAWEQGCRKD
  NFDIAEGVRTVLELIKCQEKLCIYWMVNYNFEDETIRNILLHQLQSARPVILDPVDPTNN
  VSGDKICWQWLKKEAQTWLTSPNLDNELPAPSWNVLPAPLFTTPGHLLDKFIKEFLQPNK
  CFLEQIDSAVNIIRTFLKENCFRQSTAKIQIVRGGSTAKGTALKTGSDADLVVFHNSLKS
  YTSQKNERHKIVKEIHEQLKAFWREKEEELEVSFEPPKWKAPRVLSFSLKSKVLNESVSF
  DVLPAFNALGQLSSGSTPSPEVYAGLIDLYKSSDLPGGEFSTCFTVLQRNFIRSRPTKLK
  DLIRLVKHWYKECERKLKPKGSLPPKYALELLTIYAWEQGSGVPDFDTAEGFRTVLELVT
  QYQQLCIFWKVNYNFEDETVRKFLLSQLQKTRPVILDPAEPTGDVGGGDRWCWHLLAKEA
  KEWLSSPCFKDGTGNPIPPWKVPTMQTPGSCGARIHPIVNEMFSSRSHRILNNNSKRNF
• Function: Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. Activated by detection of double stranded RNA (dsRNA): polymerizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNASEL) leading to its dimerization and subsequent activation. Activation of RNASEL leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNASEL-dependent pathway or an alternative antiviral pathway independent of RNASEL. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. May act as a negative regulator of lactation, stopping lactation in virally infected mammary gland lobules, thereby preventing transmission of viruses to neonates. Non-infected lobules would not be affected, allowing efficient pup feeding during infection.
• KEGG Pathway:
  NOD-like receptor sig.ling pathway (hsa04621)
  Hepatitis C (hsa05160)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  OAS antiviral response (R-HSA-8983711)
  Interferon alpha/beta signaling (R-HSA-909733)
  Interferon gamma signaling (R-HSA-877300)
• BioCyc Pathway: MetaCyc:ENSG00000111335-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[1]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[2]
Chikungunya virus infection	DISDXEHY	Strong	Genetic Variation	[3]
Chronic fatigue syndrome	DIS34WJ5	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Dengue	DISKH221	Strong	Genetic Variation	[6]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[1]
Influenza	DIS3PNU3	Strong	Biomarker	[7]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[4]
Psoriasis	DIS59VMN	Strong	Altered Expression	[8]
Squamous cell carcinoma	DISQVIFL	Strong	Posttranslational Modification	[8]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[9]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[10]
Prostate cancer	DISF190Y	moderate	Genetic Variation	[11]
Prostate carcinoma	DISMJPLE	moderate	Genetic Variation	[11]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[12]
Asthma	DISW9QNS	Limited	Genetic Variation	[13]
Encephalitis	DISLD1RL	Limited	Genetic Variation	[14]
Enterovirus infection	DISH2UDP	Limited	Genetic Variation	[14]
Meningitis	DISQABAA	Limited	Genetic Variation	[15]
Oral cancer	DISLD42D	Limited	Altered Expression	[12]

19 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 2'-5'-oligoadenylate synthase 2 (OAS2).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[19]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[21]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[22]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[23]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[24]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[25]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[26]
Amantadine	DMS3YE9	Approved	Amantadine increases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[27]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[28]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[31]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[32]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of 2'-5'-oligoadenylate synthase 2 (OAS2).	[33]

References

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• [25] 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.
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• [33] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.