Details of Drug Off-Target (DOT)

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

• DOT Name: Interferon-stimulated gene 20 kDa protein (ISG20)
• Synonyms: EC 3.1.13.1; Estrogen-regulated transcript 45 protein; Promyelocytic leukemia nuclear body-associated protein ISG20
• Gene Name: ISG20
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Hashimoto thyroiditis
  Adult lymphoma
  Advanced cancer
  Allergic asthma
  Arthritis
  Autoimmune hepatitis
  Autoimmune thyroid disease
  Chronic hepatitis B virus infection
  Endometriosis
  Epithelial ovarian cancer
  Glioma
  Graft-versus-host disease
  Graves disease
  Hepatitis B virus infection
  Influenza
  Juvenile idiopathic arthritis
  Lymphoma
  Multiple sclerosis
  Nervous system inflammation
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Ovarian cancer
  Pediatric lymphoma
  Psoriasis
  Relapsing-remitting multiple sclerosis
  Rheumatoid arthritis
  Tuberculosis
  Type-1 diabetes
  Type-1/2 diabetes
  Breast carcinoma
  Lung cancer
  Lung carcinoma
  Prostate cancer
  Prostate carcinoma
  Small lymphocytic lymphoma
  Systemic mastocytosis
  Melanoma
  Acute lymphocytic leukaemia
  Asthma
  Breast cancer
  Colitis
  Crohn disease
  Inflammatory bowel disease
  Mastocytosis
  Myasthenia gravis
  Myelodysplastic syndrome
  Ulcerative colitis
• UniProt ID: ISG20_HUMAN
• PDB ID: 1WLJ; 7UGB
• EC Number: 3.1.13.1
• Pfam ID: PF00929
• Sequence:
  MAGSREVVAMDCEMVGLGPHRESGLARCSLVNVHGAVLYDKFIRPEGEITDYRTRVSGVT
  PQHMVGATPFAVARLEILQLLKGKLVVGHDLKHDFQALKEDMSGYTIYDTSTDRLLWREA
  KLDHCRRVSLRVLSERLLHKSIQNSLLGHSSVEDARATMELYQISQRIRARRGLPRLAVS
  D
• Function: Interferon-induced antiviral exoribonuclease that acts mainly on single-stranded RNA. Exhibits antiviral activity against RNA viruses including hepatitis C virus (HCV), hepatitis A virus (HAV) and yellow fever virus (YFV). Inhibition of several viruses such as chikungunya virus (CHIKV) does not involve the degradation of viral RNAs, but rather the inhibition of translation of viral proteins. Exerts a translational control over a large panel of non-self RNA substrates while sparing endogenous transcripts. This activity correlates with the protein's ability to localize in cytoplasmic processing bodies. May also act as master regulator of over hundred interferon stimulated genes leading to viral genome translation inhibition. May play additional roles in the maturation of snRNAs and rRNAs, and in ribosome biogenesis.
• Tissue Specificity: Highly expressed in peripheral blood leukocytes, spleen, thymus, colon and lung. Up regulated by E2 in estrogen receptor-positive breast cancer lines.
• Reactome Pathway: Interferon alpha/beta signaling (R-HSA-909733)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Definitive	Biomarker	[1]
Atherosclerosis	DISMN9J3	Definitive	Biomarker	[1]
Hashimoto thyroiditis	DIS77CDF	Definitive	Biomarker	[2]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Allergic asthma	DISHF0H3	Strong	Altered Expression	[5]
Arthritis	DIST1YEL	Strong	Biomarker	[6]
Autoimmune hepatitis	DISOX03Q	Strong	Biomarker	[7]
Autoimmune thyroid disease	DISIHC6A	Strong	Altered Expression	[8]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Biomarker	[9]
Endometriosis	DISX1AG8	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Graft-versus-host disease	DIS0QADF	Strong	Biomarker	[13]
Graves disease	DISU4KOQ	Strong	Biomarker	[8]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[14]
Influenza	DIS3PNU3	Strong	Altered Expression	[15]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Altered Expression	[16]
Lymphoma	DISN6V4S	Strong	Biomarker	[3]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[17]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[18]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[19]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[20]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[3]
Psoriasis	DIS59VMN	Strong	Biomarker	[21]
Relapsing-remitting multiple sclerosis	DISSXFCF	Strong	Biomarker	[22]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[23]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[24]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[25]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[26]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[27]
Lung cancer	DISCM4YA	moderate	Biomarker	[4]
Lung carcinoma	DISTR26C	moderate	Biomarker	[4]
Prostate cancer	DISF190Y	moderate	Altered Expression	[28]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[28]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[29]
Systemic mastocytosis	DISNQ2OY	moderate	Altered Expression	[30]
Melanoma	DIS1RRCY	Disputed	Biomarker	[31]
Acute lymphocytic leukaemia	DISPX75S	Limited	Biomarker	[32]
Asthma	DISW9QNS	Limited	Biomarker	[33]
Breast cancer	DIS7DPX1	Limited	Biomarker	[27]
Colitis	DISAF7DD	Limited	Biomarker	[34]
Crohn disease	DIS2C5Q8	Limited	Biomarker	[35]
Inflammatory bowel disease	DISGN23E	Limited	Altered Expression	[36]
Mastocytosis	DIS1TEE0	Limited	Altered Expression	[37]
Myasthenia gravis	DISELRCI	Limited	Biomarker	[38]
Myelodysplastic syndrome	DISYHNUI	Limited	Altered Expression	[39]
Ulcerative colitis	DIS8K27O	Limited	Biomarker	[40]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Interferon-stimulated gene 20 kDa protein (ISG20) affects the response to substance of Etoposide.	[65]
Mitoxantrone	DMM39BF	Approved	Interferon-stimulated gene 20 kDa protein (ISG20) affects the response to substance of Mitoxantrone.	[65]

29 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 Interferon-stimulated gene 20 kDa protein (ISG20).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[43]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[45]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[46]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[47]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[48]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[48]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[49]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[50]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[45]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[51]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[52]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[53]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[50]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[50]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[50]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[54]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[50]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[50]
Aripiprazole	DM3NUMH	Approved	Aripiprazole increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[55]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[56]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[57]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[58]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[59]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[60]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[62]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Interferon-stimulated gene 20 kDa protein (ISG20).	[63]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Interferon-stimulated gene 20 kDa protein (ISG20).	[61]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate increases the methylation of Interferon-stimulated gene 20 kDa protein (ISG20).	[64]

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