Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHLNI51)

• DOT Name: DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B)
• Synonyms: A3B; EC 3.5.4.38; Phorbolin-1-related protein; Phorbolin-2/3
• Gene Name: APOBEC3B
• Related Disease:
  Asthma
  Hepatitis B virus infection
  Adenocarcinoma
  Autoimmune disease
  Benign neoplasm
  Bladder cancer
  Carcinoma of liver and intrahepatic biliary tract
  Cervical carcinoma
  Clear cell renal carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Estrogen-receptor positive breast cancer
  Gastric cancer
  Glioma
  Head-neck squamous cell carcinoma
  Hepatitis C virus infection
  Human papillomavirus infection
  leukaemia
  Leukemia
  Liver cancer
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Renal cell carcinoma
  Squamous cell carcinoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Xeroderma pigmentosum group D
  Carcinoma
  Melanoma
  Neuroblastoma
  Plasma cell myeloma
  Acute myelogenous leukaemia
  Cervical cancer
  Head and neck cancer
  Head and neck neoplasm
  Lung adenocarcinoma
  Lymphoma
  Metastatic malignant neoplasm
  Prostate cancer
  Prostate carcinoma
  Uterine cervix neoplasm
• UniProt ID: ABC3B_HUMAN
• PDB ID: 2NBQ; 5CQD; 5CQH; 5CQI; 5CQK; 5SXG; 5SXH; 5TD5; 5TKM; 6NFK; 6NFL; 6NFM; 7RW6
• EC Number: 3.5.4.38
• Pfam ID: PF18782
• Sequence:
  MNPQIRNPMERMYRDTFYDNFENEPILYGRSYTWLCYEVKIKRGRSNLLWDTGVFRGQVY
  FKPQYHAEMCFLSWFCGNQLPAYKCFQITWFVSWTPCPDCVAKLAEFLSEHPNVTLTISA
  ARLYYYWERDYRRALCRLSQAGARVTIMDYEEFAYCWENFVYNEGQQFMPWYKFDENYAF
  LHRTLKEILRYLMDPDTFTFNFNNDPLVLRRRQTYLCYEVERLDNGTWVLMDQHMGFLCN
  EAKNLLCGFYGRHAELRFLDLVPSLQLDPAQIYRVTWFISWSPCFSWGCAGEVRAFLQEN
  THVRLRIFAARIYDYDPLYKEALQMLRDAGAQVSIMTYDEFEYCWDTFVYRQGCPFQPWD
  GLEEHSQALSGRLRAILQNQGN
• 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) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons.
• Tissue Specificity: Expressed at high and moderate levels in peripheral blood leukocytes, spleen, testes, heart, thymus, prostate and ovary. Also expressed at low levels in several other tissues.
• 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

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Hepatitis B virus infection	DISLQ2XY	Definitive	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[4]
Benign neoplasm	DISDUXAD	Strong	Biomarker	[5]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[6]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Genetic Variation	[7]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[11]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Altered Expression	[12]
Gastric cancer	DISXGOUK	Strong	Biomarker	[13]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[15]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[16]
Human papillomavirus infection	DISX61LX	Strong	Genetic Variation	[17]
leukaemia	DISS7D1V	Strong	Genetic Variation	[18]
Leukemia	DISNAKFL	Strong	Genetic Variation	[18]
Liver cancer	DISDE4BI	Strong	Genetic Variation	[7]
Lung cancer	DISCM4YA	Strong	Biomarker	[19]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[20]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[10]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[10]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[21]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[3]
Stomach cancer	DISKIJSX	Strong	Biomarker	[13]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[6]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[6]
Xeroderma pigmentosum group D	DISFFE93	Strong	Genetic Variation	[22]
Carcinoma	DISH9F1N	moderate	Genetic Variation	[23]
Melanoma	DIS1RRCY	moderate	Biomarker	[24]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[25]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[26]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[27]
Cervical cancer	DISFSHPF	Limited	Biomarker	[8]
Head and neck cancer	DISBPSQZ	Limited	Biomarker	[15]
Head and neck neoplasm	DIS1OB2G	Limited	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	Limited	Biomarker	[28]
Lymphoma	DISN6V4S	Limited	Biomarker	[29]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[30]
Prostate cancer	DISF190Y	Limited	Altered Expression	[31]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[31]
Uterine cervix neoplasm	DIS0BYVV	Limited	Biomarker	[15]

2 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 DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[32]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[37]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[39]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[41]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[42]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[44]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[44]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[45]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[46]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[47]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[48]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[49]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[50]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[51]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[52]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[53]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[54]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[55]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[56]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[57]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[58]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[59]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[60]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B).	[61]

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