Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6E5FYS)

• DOT Name: 2'-5'-oligoadenylate synthase 3 (OAS3)
• Synonyms: (2-5')oligo(A) synthase 3; 2-5A synthase 3; EC 2.7.7.84; p100 OAS; p100OAS
• Gene Name: OAS3
• Related Disease:
  Non-insulin dependent diabetes
  OPTN-related open angle glaucoma
  Small lymphocytic lymphoma
  Adult respiratory distress syndrome
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Alphavirus infectious disease
  Alzheimer disease
  B-cell lymphoma
  Bipolar disorder
  Bone disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Chikungunya virus infection
  Colitis
  Colon cancer
  Hepatitis B virus infection
  Hepatitis C virus infection
  Influenza
  Lung cancer
  Lung carcinoma
  Multiple sclerosis
  Myelitis
  Neoplasm
  Neuromyelitis optica
  Open-angle glaucoma
  Plasma cell myeloma
  Pneumonia
  Pneumonitis
  T-cell leukaemia
  Zika virus infection
  Acute myelogenous leukaemia
  Type-1 diabetes
  Adult lymphoma
  Anxiety
  Anxiety disorder
  Enterovirus infection
  Lymphoma
  Meningitis
  Optic neuritis
  Pediatric lymphoma
  Phenylketonuria
  Primary cutaneous T-cell lymphoma
  Type-1/2 diabetes
• UniProt ID: OAS3_HUMAN
• PDB ID: 4S3N
• EC Number: 2.7.7.84
• Pfam ID: PF01909 ; PF10421
• Sequence:
  MDLYSTPAAALDRFVARRLQPRKEFVEKARRALGALAAALRERGGRLGAAAPRVLKTVKG
  GSSGRGTALKGGCDSELVIFLDCFKSYVDQRARRAEILSEMRASLESWWQNPVPGLRLTF
  PEQSVPGALQFRLTSVDLEDWMDVSLVPAFNVLGQAGSGVKPKPQVYSTLLNSGCQGGEH
  AACFTELRRNFVNIRPAKLKNLILLVKHWYHQVCLQGLWKETLPPVYALELLTIFAWEQG
  CKKDAFSLAEGLRTVLGLIQQHQHLCVFWTVNYGFEDPAVGQFLQRQLKRPRPVILDPAD
  PTWDLGNGAAWHWDLLAQEAASCYDHPCFLRGMGDPVQSWKGPGLPRAGCSGLGHPIQLD
  PNQKTPENSKSLNAVYPRAGSKPPSCPAPGPTGAASIVPSVPGMALDLSQIPTKELDRFI
  QDHLKPSPQFQEQVKKAIDIILRCLHENCVHKASRVSKGGSFGRGTDLRDGCDVELIIFL
  NCFTDYKDQGPRRAEILDEMRAQLESWWQDQVPSLSLQFPEQNVPEALQFQLVSTALKSW
  TDVSLLPAFDAVGQLSSGTKPNPQVYSRLLTSGCQEGEHKACFAELRRNFMNIRPVKLKN
  LILLVKHWYRQVAAQNKGKGPAPASLPPAYALELLTIFAWEQGCRQDCFNMAQGFRTVLG
  LVQQHQQLCVYWTVNYSTEDPAMRMHLLGQLRKPRPLVLDPADPTWNVGHGSWELLAQEA
  AALGMQACFLSRDGTSVQPWDVMPALLYQTPAGDLDKFISEFLQPNRQFLAQVNKAVDTI
  CSFLKENCFRNSPIKVIKVVKGGSSAKGTALRGRSDADLVVFLSCFSQFTEQGNKRAEII
  SEIRAQLEACQQERQFEVKFEVSKWENPRVLSFSLTSQTMLDQSVDFDVLPAFDALGQLV
  SGSRPSSQVYVDLIHSYSNAGEYSTCFTELQRDFIISRPTKLKSLIRLVKHWYQQCTKIS
  KGRGSLPPQHGLELLTVYAWEQGGKDSQFNMAEGFRTVLELVTQYRQLCIYWTINYNAKD
  KTVGDFLKQQLQKPRPIILDPADPTGNLGHNARWDLLAKEAAACTSALCCMGRNGIPIQP
  WPVKAAV
• Function: Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes preferentially dimers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L 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 RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. Displays antiviral activity against Chikungunya virus (CHIKV), Dengue virus, Sindbis virus (SINV) and Semliki forest virus (SFV).
• Tissue Specificity: Present at high level in placenta trophoblast.
• 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:ENSG00000111331-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[1]
OPTN-related open angle glaucoma	DISDR98A	Definitive	Biomarker	[2]
Small lymphocytic lymphoma	DIS30POX	Definitive	Genetic Variation	[3]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[4]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alphavirus infectious disease	DISZGSCJ	Strong	Genetic Variation	[7]
Alzheimer disease	DISF8S70	Strong	Biomarker	[8]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[9]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[10]
Bone disease	DISE1F82	Strong	Biomarker	[11]
Breast cancer	DIS7DPX1	Strong	Biomarker	[12]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[12]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[12]
Chikungunya virus infection	DISDXEHY	Strong	Genetic Variation	[13]
Colitis	DISAF7DD	Strong	Genetic Variation	[14]
Colon cancer	DISVC52G	Strong	Altered Expression	[15]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[16]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[17]
Influenza	DIS3PNU3	Strong	Biomarker	[18]
Lung cancer	DISCM4YA	Strong	Altered Expression	[19]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[19]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[20]
Myelitis	DIS1KV65	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Neuromyelitis optica	DISBFGKL	Strong	Biomarker	[22]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[23]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[24]
Pneumonia	DIS8EF3M	Strong	Altered Expression	[25]
Pneumonitis	DIS88E0K	Strong	Altered Expression	[25]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[5]
Zika virus infection	DISQUCTY	Strong	Altered Expression	[26]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[27]
Type-1 diabetes	DIS7HLUB	Disputed	Biomarker	[28]
Adult lymphoma	DISK8IZR	Limited	Genetic Variation	[29]
Anxiety	DISIJDBA	Limited	Biomarker	[30]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[30]
Enterovirus infection	DISH2UDP	Limited	Genetic Variation	[31]
Lymphoma	DISN6V4S	Limited	Genetic Variation	[29]
Meningitis	DISQABAA	Limited	Genetic Variation	[32]
Optic neuritis	DISDYCHC	Limited	Biomarker	[22]
Pediatric lymphoma	DIS51BK2	Limited	Genetic Variation	[29]
Phenylketonuria	DISCU56J	Limited	Biomarker	[33]
Primary cutaneous T-cell lymphoma	DIS35WVW	Limited	Genetic Variation	[29]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[34]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	2'-5'-oligoadenylate synthase 3 (OAS3) affects the response to substance of Ethanol.	[54]

21 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[43]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[44]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[45]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[46]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[46]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[47]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[47]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[48]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[50]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[52]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of 2'-5'-oligoadenylate synthase 3 (OAS3).	[53]

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