Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPL0AI1)

• DOT Name: DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C)
• Synonyms: A3C; EC 3.5.4.38; APOBEC1-like; Phorbolin I
• Gene Name: APOBEC3C
• Related Disease:
  Asthma
  Anxiety
  Bloom syndrome
  Burkitt lymphoma
  Depression
  Hepatitis B virus infection
  Immunodeficiency
  Leukemia
  Psychotic disorder
  Skin disease
  Zika virus infection
  Rheumatoid arthritis
  Advanced cancer
  Anxiety disorder
  Invasive ductal breast carcinoma
• UniProt ID: ABC3C_HUMAN
• PDB ID: 3VM8; 3VOW
• EC Number: 3.5.4.38
• Pfam ID: PF18782
• Sequence:
  MNPQIRNPMKAMYPGTFYFQFKNLWEANDRNETWLCFTVEGIKRRSVVSWKTGVFRNQVD
  SETHCHAERCFLSWFCDDILSPNTKYQVTWYTSWSPCPDCAGEVAEFLARHSNVNLTIFT
  ARLYYFQYPCYQEGLRSLSQEGVAVEIMDYEDFKYCWENFVYNDNEPFKPWKGLKTNFRL
  LKRRLRESLQ
• Function: DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Exhibits antiviral activity against simian immunodeficiency virus (SIV), hepatitis B virus (HBV), herpes simplex virus 1 (HHV-1) and Epstein-Barr virus (EBV) and may inhibit the mobility of LTR and non-LTR retrotransposons. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.
• Tissue Specificity: Expressed in spleen, testes, peripherical blood lymphocytes, heart, thymus, prostate and ovary.
• KEGG Pathway:
  Viral life cycle - HIV-1 (hsa03250)
  Human immunodeficiency virus 1 infection (hsa05170)
• Reactome Pathway:
  Formation of the Editosome (R-HSA-75094)
  mRNA Editing (R-HSA-72200)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Anxiety	DISIJDBA	Strong	Genetic Variation	[2]
Bloom syndrome	DISKXQ7J	Strong	Genetic Variation	[3]
Burkitt lymphoma	DIS9D5XU	Strong	Genetic Variation	[3]
Depression	DIS3XJ69	Strong	Genetic Variation	[2]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[4]
Immunodeficiency	DIS093I0	Strong	Genetic Variation	[5]
Leukemia	DISNAKFL	Strong	Biomarker	[6]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[7]
Skin disease	DISDW8R6	Strong	Biomarker	[8]
Zika virus infection	DISQUCTY	Strong	Biomarker	[9]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[10]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[11]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[12]
Invasive ductal breast carcinoma	DIS43J58	Limited	Genetic Variation	[13]

This DOT Affected the Drug Response of 7 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) affects the response to substance of Doxorubicin.	[33]
Etoposide	DMNH3PG	Approved	DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) affects the response to substance of Etoposide.	[33]
Paclitaxel	DMLB81S	Approved	DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) affects the response to substance of Paclitaxel.	[33]
Mitomycin	DMH0ZJE	Approved	DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) affects the response to substance of Mitomycin.	[33]
Topotecan	DMP6G8T	Approved	DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) affects the response to substance of Topotecan.	[33]
Mitoxantrone	DMM39BF	Approved	DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) affects the response to substance of Mitoxantrone.	[33]
Vinblastine	DM5TVS3	Approved	DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) affects the response to substance of Vinblastine.	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[20]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[21]
Marinol	DM70IK5	Approved	Marinol increases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[22]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[23]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[24]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[25]
Artesunate	DMR27C8	Approved	Artesunate increases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[26]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[27]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C).	[24]

References

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