Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO8HVVB)

• DOT Name: DNA damage-binding protein 2 (DDB2)
• Synonyms: DDB p48 subunit; DDBb; Damage-specific DNA-binding protein 2; UV-damaged DNA-binding protein 2; UV-DDB 2
• Gene Name: DDB2
• Related Disease:
  Xeroderma pigmentosum group E
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Chromosomal disorder
  Colonic neoplasm
  Colorectal adenoma
  Epithelial ovarian cancer
  Gastric cancer
  Glioblastoma multiforme
  Hepatitis B virus infection
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Mood disorder
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Skin neoplasm
  Stomach cancer
  Triple negative breast cancer
  Vascular disease
  Colorectal carcinoma
  Melanoma
  Skin cancer
  Xeroderma pigmentosum
  Advanced cancer
  Colon adenocarcinoma
  Colon cancer
  Colon carcinoma
  Head-neck squamous cell carcinoma
  Malignant pleural mesothelioma
• UniProt ID: DDB2_HUMAN
• PDB ID: 3EI4; 3I7L; 4E54; 4E5Z; 6R8Y; 6R8Z; 6R90; 6R91; 6R92
• Pfam ID: PF00400
• Sequence:
  MAPKKRPETQKTSEIVLRPRNKRSRSPLELEPEAKKLCAKGSGPSRRCDSDCLWVGLAGP
  QILPPCRSIVRTLHQHKLGRASWPSVQQGLQQSFLHTLDSYRILQKAAPFDRRATSLAWH
  PTHPSTVAVGSKGGDIMLWNFGIKDKPTFIKGIGAGGSITGLKFNPLNTNQFYASSMEGT
  TRLQDFKGNILRVFASSDTINIWFCSLDVSASSRMVVTGDNVGNVILLNMDGKELWNLRM
  HKKKVTHVALNPCCDWFLATASVDQTVKIWDLRQVRGKASFLYSLPHRHPVNAACFSPDG
  ARLLTTDQKSEIRVYSASQWDCPLGLIPHPHRHFQHLTPIKAAWHPRYNLIVVGRYPDPN
  FKSCTPYELRTIDVFDGNSGKMMCQLYDPESSGISSLNEFNPMGDTLASAMGYHILIWSQ
  EEARTRK
• Function: Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively. Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also functions as the substrate recognition module for the DCX (DDB2-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB2-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB2-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. The DDB2-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. The DDB2-CUL4-ROC1 complex also ubiquitinates KAT7/HBO1 in response to DNA damage, leading to its degradation: recognizes KAT7/HBO1 following phosphorylation by ATR ; [Isoform D1]: Inhibits UV-damaged DNA repair; [Isoform D2]: Inhibits UV-damaged DNA repair.
• Tissue Specificity: Ubiquitously expressed; with highest levels in corneal endothelium and lowest levels in brain. Isoform D1 is highly expressed in brain and heart. Isoform D2, isoform D3 and isoform D4 are weakly expressed.
• KEGG Pathway:
  Nucleotide excision repair (hsa03420)
  p53 sig.ling pathway (hsa04115)
  Ubiquitin mediated proteolysis (hsa04120)
  Hepatitis B (hsa05161)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Colorectal cancer (hsa05210)
  Pancreatic cancer (hsa05212)
  Endometrial cancer (hsa05213)
  Glioma (hsa05214)
  Thyroid cancer (hsa05216)
  Basal cell carcinoma (hsa05217)
  Melanoma (hsa05218)
  Chronic myeloid leukemia (hsa05220)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  DNA Damage Recognition in GG-NER (R-HSA-5696394)
  Formation of Incision Complex in GG-NER (R-HSA-5696395)
  Dual Incision in GG-NER (R-HSA-5696400)
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  Neddylation (R-HSA-8951664)
  Ub-specific processing proteases (R-HSA-5689880)

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Xeroderma pigmentosum group E	DIS9Q3CA	Definitive	Autosomal recessive	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Chromosomal disorder	DISM5BB5	Strong	Altered Expression	[4]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[5]
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[7]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[8]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[9]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[10]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[11]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[11]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[12]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[12]
Neoplasm	DISZKGEW	Strong	Altered Expression	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[14]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[7]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[7]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[15]
Prostate cancer	DISF190Y	Strong	Biomarker	[16]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[16]
Skin neoplasm	DIS16DDV	Strong	Altered Expression	[17]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[8]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[18]
Vascular disease	DISVS67S	Strong	Genetic Variation	[19]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[20]
Melanoma	DIS1RRCY	moderate	Biomarker	[21]
Skin cancer	DISTM18U	moderate	Genetic Variation	[22]
Xeroderma pigmentosum	DISQ9H19	Supportive	Autosomal recessive	[23]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[24]
Colon adenocarcinoma	DISDRE0J	Limited	Biomarker	[25]
Colon cancer	DISVC52G	Limited	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[6]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Biomarker	[25]
Malignant pleural mesothelioma	DIST2R60	Limited	Biomarker	[26]

37 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 DNA damage-binding protein 2 (DDB2).	[27]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA damage-binding protein 2 (DDB2).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA damage-binding protein 2 (DDB2).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of DNA damage-binding protein 2 (DDB2).	[30]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA damage-binding protein 2 (DDB2).	[31]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA damage-binding protein 2 (DDB2).	[32]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA damage-binding protein 2 (DDB2).	[33]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA damage-binding protein 2 (DDB2).	[34]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of DNA damage-binding protein 2 (DDB2).	[35]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of DNA damage-binding protein 2 (DDB2).	[28]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the expression of DNA damage-binding protein 2 (DDB2).	[36]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of DNA damage-binding protein 2 (DDB2).	[37]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA damage-binding protein 2 (DDB2).	[38]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA damage-binding protein 2 (DDB2).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of DNA damage-binding protein 2 (DDB2).	[39]
Marinol	DM70IK5	Approved	Marinol decreases the expression of DNA damage-binding protein 2 (DDB2).	[40]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DNA damage-binding protein 2 (DDB2).	[41]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of DNA damage-binding protein 2 (DDB2).	[42]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of DNA damage-binding protein 2 (DDB2).	[43]
Mitomycin	DMH0ZJE	Approved	Mitomycin increases the expression of DNA damage-binding protein 2 (DDB2).	[44]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of DNA damage-binding protein 2 (DDB2).	[45]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of DNA damage-binding protein 2 (DDB2).	[45]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of DNA damage-binding protein 2 (DDB2).	[44]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of DNA damage-binding protein 2 (DDB2).	[45]
Morphine	DMRMS0L	Approved	Morphine increases the expression of DNA damage-binding protein 2 (DDB2).	[46]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DNA damage-binding protein 2 (DDB2).	[47]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of DNA damage-binding protein 2 (DDB2).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA damage-binding protein 2 (DDB2).	[49]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of DNA damage-binding protein 2 (DDB2).	[50]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of DNA damage-binding protein 2 (DDB2).	[52]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of DNA damage-binding protein 2 (DDB2).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA damage-binding protein 2 (DDB2).	[54]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DNA damage-binding protein 2 (DDB2).	[55]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of DNA damage-binding protein 2 (DDB2).	[56]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA damage-binding protein 2 (DDB2).	[57]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of DNA damage-binding protein 2 (DDB2).	[58]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of DNA damage-binding protein 2 (DDB2).	[59]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of DNA damage-binding protein 2 (DDB2).	[51]

References

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