Details of Drug Off-Target (DOT)

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

• DOT Name: DNA repair protein RAD51 homolog 2 (RAD51B)
• Synonyms: R51H2; RAD51 homolog B; Rad51B; RAD51-like protein 1
• Gene Name: RAD51B
• Related Disease:
  Epithelial ovarian cancer
  Glioma
  Prostate cancer
  Prostate carcinoma
  Adult glioblastoma
  Age-related macular degeneration
  Breast neoplasm
  Cervical carcinoma
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Drug dependence
  Glioblastoma multiforme
  Hypothyroidism
  Lung adenocarcinoma
  Lung carcinoma
  Lung squamous cell carcinoma
  Male breast carcinoma
  Nasopharyngeal carcinoma
  Neoplasm
  Neovascular age-related macular degeneration
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Ovarian serous adenocarcinoma
  Primary biliary cholangitis
  Rheumatoid arthritis
  Substance abuse
  Substance dependence
  Advanced cancer
  Asthma
  Colon carcinoma
  Hereditary breast ovarian cancer syndrome
  Melanoma
  Acute myelogenous leukaemia
  Gastric cancer
  Hamartoma
  Stomach cancer
  Systemic lupus erythematosus
  Uterine fibroids
• UniProt ID: RA51B_HUMAN
• PDB ID: 8FAZ; 8GBJ; 8OUY; 8OUZ
• Pfam ID: PF08423
• Sequence:
  MGSKKLKRVGLSQELCDRLSRHQILTCQDFLCLSPLELMKVTGLSYRGVHELLCMVSRAC
  APKMQTAYGIKAQRSADFSPAFLSTTLSALDEALHGGVACGSLTEITGPPGCGKTQFCIM
  MSILATLPTNMGGLEGAVVYIDTESAFSAERLVEIAESRFPRYFNTEEKLLLTSSKVHLY
  RELTCDEVLQRIESLEEEIISKGIKLVILDSVASVVRKEFDAQLQGNLKERNKFLAREAS
  SLKYLAEEFSIPVILTNQITTHLSGALASQADLVSPADDLSLSEGTSGSSCVIAALGNTW
  SHSVNTRLILQYLDSERRQILIAKSPLAPFTSFVYTIKEEGLVLQETTFCSVTQAELNWA
  PEILPPQPPEQLGLQMCHHTQLIF
• Function: Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. May promote the assembly of presynaptic RAD51 nucleoprotein filaments. Binds single-stranded DNA and double-stranded DNA and has DNA-dependent ATPase activity. Part of the RAD51 paralog protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 binds predominantly to the intersection of the four duplex arms of the Holliday junction and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway.
• Tissue Specificity: Expressed in a wide range of tissues.
• KEGG Pathway: Homologous recombi.tion (hsa03440)
• Reactome Pathway:
  Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) (R-HSA-5693554)
  Resolution of D-loop Structures through Holliday Junction Intermediates (R-HSA-5693568)
  Homologous DNA Pairing and Strand Exchange (R-HSA-5693579)
  Presynaptic phase of homologous DNA pairing and strand exchange (R-HSA-5693616)
  Defective homologous recombination repair (HRR) due to BRCA1 loss of function (R-HSA-9701192)
  Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function (R-HSA-9704331)
  Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function (R-HSA-9704646)
  Impaired BRCA2 binding to PALB2 (R-HSA-9709603)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  HDR through Homologous Recombination (HRR) (R-HSA-5685942)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Definitive	Biomarker	[1]
Glioma	DIS5RPEH	Definitive	Genetic Variation	[2]
Prostate cancer	DISF190Y	Definitive	Genetic Variation	[3]
Prostate carcinoma	DISMJPLE	Definitive	Genetic Variation	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[8]
Colon cancer	DISVC52G	Strong	Genetic Variation	[9]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[10]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[10]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[10]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[10]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[10]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[10]
Drug dependence	DIS9IXRC	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[12]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[10]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[10]
Lung squamous cell carcinoma	DISXPIBD	Strong	Genetic Variation	[10]
Male breast carcinoma	DISUNQ2Q	Strong	Biomarker	[13]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[14]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[15]
Neovascular age-related macular degeneration	DIS5S9R7	Strong	Genetic Variation	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[1]
Ovarian serous adenocarcinoma	DISSU72Z	Strong	Genetic Variation	[10]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[18]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[19]
Substance abuse	DIS327VW	Strong	Biomarker	[11]
Substance dependence	DISDRAAR	Strong	Biomarker	[11]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[20]
Asthma	DISW9QNS	moderate	Genetic Variation	[21]
Colon carcinoma	DISJYKUO	moderate	Genetic Variation	[9]
Hereditary breast ovarian cancer syndrome	DISWDUGU	moderate	Genetic Variation	[22]
Melanoma	DIS1RRCY	moderate	Biomarker	[23]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[24]
Gastric cancer	DISXGOUK	Limited	Biomarker	[20]
Hamartoma	DIS0I87H	Limited	Biomarker	[25]
Stomach cancer	DISKIJSX	Limited	Biomarker	[20]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[26]
Uterine fibroids	DISBZRMJ	Limited	Altered Expression	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[31]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[32]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[33]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[35]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[38]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[39]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DNA repair protein RAD51 homolog 2 (RAD51B).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of DNA repair protein RAD51 homolog 2 (RAD51B).	[34]
Marinol	DM70IK5	Approved	Marinol increases the methylation of DNA repair protein RAD51 homolog 2 (RAD51B).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of DNA repair protein RAD51 homolog 2 (RAD51B).	[40]

References

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