Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO9G2RZ)

• DOT Name: Signal transducer and activator of transcription 2 (STAT2)
• Synonyms: p113
• Gene Name: STAT2
• Related Disease:
  Adult glioblastoma
  Adult lymphoma
  Advanced cancer
  Breast carcinoma
  Cardiovascular disease
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Cytomegalovirus infection
  Esophageal squamous cell carcinoma
  Fibrosarcoma
  Glioblastoma multiforme
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Immunodeficiency 45
  Leukopenia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lymphoma
  Melanoma
  Multiple sclerosis
  Myeloid leukaemia
  Nasal polyp
  Nasopharyngeal carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Pediatric lymphoma
  Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection
  Promyelocytic leukaemia
  Pseudo-TORCH syndrome 3
  Psoriasis
  Rectal carcinoma
  Squamous cell carcinoma
  Status epilepticus seizure
  Systemic lupus erythematosus
  Type-1/2 diabetes
  Zika virus infection
  Chronic mucocutaneous candidiasis
  Influenza
  Pancreatic cancer
  Neuroblastoma
  Asthma
  Breast cancer
  Cutaneous squamous cell carcinoma
  Enterovirus infection
  Periodontitis
  Primary cutaneous T-cell lymphoma
  Skin cancer
• UniProt ID: STAT2_HUMAN
• PDB ID: 2KA4; 6UX2; 6WCZ
• Pfam ID: PF00017 ; PF12188 ; PF01017 ; PF02864 ; PF02865 ; PF21354
• Sequence:
  MAQWEMLQNLDSPFQDQLHQLYSHSLLPVDIRQYLAVWIEDQNWQEAALGSDDSKATMLF
  FHFLDQLNYECGRCSQDPESLLLQHNLRKFCRDIQPFSQDPTQLAEMIFNLLLEEKRILI
  QAQRAQLEQGEPVLETPVESQQHEIESRILDLRAMMEKLVKSISQLKDQQDVFCFRYKIQ
  AKGKTPSLDPHQTKEQKILQETLNELDKRRKEVLDASKALLGRLTTLIELLLPKLEEWKA
  QQQKACIRAPIDHGLEQLETWFTAGAKLLFHLRQLLKELKGLSCLVSYQDDPLTKGVDLR
  NAQVTELLQRLLHRAFVVETQPCMPQTPHRPLILKTGSKFTVRTRLLVRLQEGNESLTVE
  VSIDRNPPQLQGFRKFNILTSNQKTLTPEKGQSQGLIWDFGYLTLVEQRSGGSGKGSNKG
  PLGVTEELHIISFTVKYTYQGLKQELKTDTLPVVIISNMNQLSIAWASVLWFNLLSPNLQ
  NQQFFSNPPKAPWSLLGPALSWQFSSYVGRGLNSDQLSMLRNKLFGQNCRTEDPLLSWAD
  FTKRESPPGKLPFWTWLDKILELVHDHLKDLWNDGRIMGFVSRSQERRLLKKTMSGTFLL
  RFSESSEGGITCSWVEHQDDDKVLIYSVQPYTKEVLQSLPLTEIIRHYQLLTEENIPENP
  LRFLYPRIPRDEAFGCYYQEKVNLQERRKYLKHRLIVVSNRQVDELQQPLELKPEPELES
  LELELGLVPEPELSLDLEPLLKAGLDLGPELESVLESTLEPVIEPTLCMVSQTVPEPDQG
  PVSQPVPEPDLPCDLRHLNTEPMEIFRNCVKIEEIMPNGDPLLAGQNTVDEVYVSRPSHF
  YTDGPLMPSDF
• Function: Signal transducer and activator of transcription that mediates signaling by type I interferons (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state. In addition, has also a negative feedback regulatory role in the type I interferon signaling by recruiting USP18 to the type I IFN receptor subunit IFNAR2 thereby mitigating the response to type I IFNs. Acts as a regulator of mitochondrial fission by modulating the phosphorylation of DNM1L at 'Ser-616' and 'Ser-637' which activate and inactivate the GTPase activity of DNM1L respectively.
• KEGG Pathway:
  Chemokine sig.ling pathway (hsa04062)
  Necroptosis (hsa04217)
  Osteoclast differentiation (hsa04380)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  C-type lectin receptor sig.ling pathway (hsa04625)
  JAK-STAT sig.ling pathway (hsa04630)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Coro.virus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  Interferon alpha/beta signaling (R-HSA-909733)
  Regulation of IFNA/IFNB signaling (R-HSA-912694)
  Potential therapeutics for SARS (R-HSA-9679191)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Interleukin-20 family signaling (R-HSA-8854691)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Fibrosarcoma	DISWX7MU	Strong	Altered Expression	[9]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Immunodeficiency 45	DISUPB0X	Strong	GermlineCausalMutation	[12]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[13]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[14]
Lung cancer	DISCM4YA	Strong	Altered Expression	[15]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[15]
Lymphoma	DISN6V4S	Strong	Biomarker	[2]
Melanoma	DIS1RRCY	Strong	Biomarker	[16]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[17]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[18]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[19]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[20]
Neoplasm	DISZKGEW	Strong	Altered Expression	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[14]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	DIS0V8SJ	Strong	Autosomal recessive	[12]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[18]
Pseudo-TORCH syndrome 3	DISJO8W4	Strong	Autosomal recessive	[22]
Psoriasis	DIS59VMN	Strong	Biomarker	[23]
Rectal carcinoma	DIS8FRR7	Strong	Biomarker	[6]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[24]
Status epilepticus seizure	DISY3BIC	Strong	Altered Expression	[25]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[26]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[27]
Zika virus infection	DISQUCTY	Strong	Biomarker	[28]
Chronic mucocutaneous candidiasis	DISPSGYF	moderate	Biomarker	[29]
Influenza	DIS3PNU3	moderate	Biomarker	[30]
Pancreatic cancer	DISJC981	moderate	Biomarker	[31]
Neuroblastoma	DISVZBI4	Disputed	Altered Expression	[32]
Asthma	DISW9QNS	Limited	Genetic Variation	[33]
Breast cancer	DIS7DPX1	Limited	Biomarker	[4]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Altered Expression	[34]
Enterovirus infection	DISH2UDP	Limited	Altered Expression	[35]
Periodontitis	DISI9JOI	Limited	Biomarker	[36]
Primary cutaneous T-cell lymphoma	DIS35WVW	Limited	Biomarker	[37]
Skin cancer	DISTM18U	Limited	Altered Expression	[16]

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 Signal transducer and activator of transcription 2 (STAT2).	[38]
Interferon alfa-2B	DMWCQP4	Approved	Interferon alfa-2B increases the phosphorylation of Signal transducer and activator of transcription 2 (STAT2).	[51]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Signal transducer and activator of transcription 2 (STAT2).	[54]
Tetramethylbutylphenol	DMW9CH2	Investigative	Tetramethylbutylphenol increases the phosphorylation of Signal transducer and activator of transcription 2 (STAT2).	[61]

23 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 Signal transducer and activator of transcription 2 (STAT2).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Signal transducer and activator of transcription 2 (STAT2).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[43]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Signal transducer and activator of transcription 2 (STAT2).	[44]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Signal transducer and activator of transcription 2 (STAT2).	[45]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[46]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[47]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Signal transducer and activator of transcription 2 (STAT2).	[48]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[49]
Busulfan	DMXYJ9C	Approved	Busulfan decreases the expression of Signal transducer and activator of transcription 2 (STAT2).	[50]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone decreases the expression of Signal transducer and activator of transcription 2 (STAT2).	[50]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[52]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Signal transducer and activator of transcription 2 (STAT2).	[48]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Signal transducer and activator of transcription 2 (STAT2).	[53]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Signal transducer and activator of transcription 2 (STAT2).	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[56]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Signal transducer and activator of transcription 2 (STAT2).	[57]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[58]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[59]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[50]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Signal transducer and activator of transcription 2 (STAT2).	[60]

References

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