Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYMU9G1)

• DOT Name: DNA repair protein RAD50 (RAD50)
• Synonyms: hRAD50; EC 3.6.-.-
• Gene Name: RAD50
• Related Disease:
  Prostate cancer
  Allergic asthma
  Ataxia-telangiectasia
  Atopic dermatitis
  Childhood acute lymphoblastic leukemia
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Endometrial cancer
  Epithelial ovarian cancer
  Fanconi anemia complementation group A
  Fanconi's anemia
  Glioma
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Hereditary breast ovarian cancer syndrome
  leukaemia
  Lung cancer
  Lung carcinoma
  Lymphoma, non-Hodgkin, familial
  Narcolepsy
  Nijmegen breakage syndrome-like disorder
  Non-hodgkin lymphoma
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Polycystic ovarian syndrome
  Prostate carcinoma
  Allergic rhinitis
  B-cell lymphoma
  Crohn disease
  Hereditary neoplastic syndrome
  Uterine fibroids
  Adenocarcinoma
  Adenoma
  Breast neoplasm
  Carcinoma
  Colorectal neoplasm
  Endometrial carcinoma
  Kaposi sarcoma
  Liver cirrhosis
  Myocardial infarction
  Nasopharyngeal carcinoma
  Nijmegen breakage syndrome
  Plasma cell myeloma
  Psoriasis
  Familial ovarian cancer
  Hereditary breast carcinoma
• UniProt ID: RAD50_HUMAN
• PDB ID: 5GOX
• EC Number: 3.6.-.-
• Pfam ID: PF13476 ; PF04423 ; PF13558
• Sequence:
  MSRIEKMSILGVRSFGIEDKDKQIITFFSPLTILVGPNGAGKTTIIECLKYICTGDFPPG
  TKGNTFVHDPKVAQETDVRAQIRLQFRDVNGELIAVQRSMVCTQKSKKTEFKTLEGVITR
  TKHGEKVSLSSKCAEIDREMISSLGVSKAVLNNVIFCHQEDSNWPLSEGKALKQKFDEIF
  SATRYIKALETLRQVRQTQGQKVKEYQMELKYLKQYKEKACEIRDQITSKEAQLTSSKEI
  VKSYENELDPLKNRLKEIEHNLSKIMKLDNEIKALDSRKKQMEKDNSELEEKMEKVFQGT
  DEQLNDLYHNHQRTVREKERKLVDCHRELEKLNKESRLLNQEKSELLVEQGRLQLQADRH
  QEHIRARDSLIQSLATQLELDGFERGPFSERQIKNFHKLVRERQEGEAKTANQLMNDFAE
  KETLKQKQIDEIRDKKTGLGRIIELKSEILSKKQNELKNVKYELQQLEGSSDRILELDQE
  LIKAERELSKAEKNSNVETLKMEVISLQNEKADLDRTLRKLDQEMEQLNHHTTTRTQMEM
  LTKDKADKDEQIRKIKSRHSDELTSLLGYFPNKKQLEDWLHSKSKEINQTRDRLAKLNKE
  LASSEQNKNHINNELKRKEEQLSSYEDKLFDVCGSQDFESDLDRLKEEIEKSSKQRAMLA
  GATAVYSQFITQLTDENQSCCPVCQRVFQTEAELQEVISDLQSKLRLAPDKLKSTESELK
  KKEKRRDEMLGLVPMRQSIIDLKEKEIPELRNKLQNVNRDIQRLKNDIEEQETLLGTIMP
  EEESAKVCLTDVTIMERFQMELKDVERKIAQQAAKLQGIDLDRTVQQVNQEKQEKQHKLD
  TVSSKIELNRKLIQDQQEQIQHLKSTTNELKSEKLQISTNLQRRQQLEEQTVELSTEVQS
  LYREIKDAKEQVSPLETTLEKFQQEKEELINKKNTSNKIAQDKLNDIKEKVKNIHGYMKD
  IENYIQDGKDDYKKQKETELNKVIAQLSECEKHKEKINEDMRLMRQDIDTQKIQERWLQD
  NLTLRKRNEELKEVEEERKQHLKEMGQMQVLQMKSEHQKLEENIDNIKRNHNLALGRQKG
  YEEEIIHFKKELREPQFRDAEEKYREMMIVMRTTELVNKDLDIYYKTLDQAIMKFHSMKM
  EEINKIIRDLWRSTYRGQDIEYIEIRSDADENVSASDKRRNYNYRVVMLKGDTALDMRGR
  CSAGQKVLASLIIRLALAETFCLNCGIIALDEPTTNLDRENIESLAHALVEIIKSRSQQR
  NFQLLVITHDEDFVELLGRSEYVEKFYRIKKNIDQCSEIVKCSVSSLGFNVH
• Function: Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11 to prevent nucleolytic degradation past a given point. The complex may also be required for DNA damage signaling via activation of the ATM kinase. In telomeres the MRN complex may modulate t-loop formation.
• Tissue Specificity: Expressed at very low level in most tissues, except in testis where it is expressed at higher level. Expressed in fibroblasts.
• KEGG Pathway:
  Homologous recombi.tion (hsa03440)
  Non-homologous end-joining (hsa03450)
  Cellular senescence (hsa04218)
• Reactome Pathway:
  HDR through Single Strand Annealing (SSA) (R-HSA-5685938)
  HDR through MMEJ (alt-NHEJ) (R-HSA-5685939)
  HDR through Homologous Recombination (HRR) (R-HSA-5685942)
  Sensing of DNA Double Strand Breaks (R-HSA-5693548)
  Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) (R-HSA-5693554)
  Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565)
  Resolution of D-loop Structures through Holliday Junction Intermediates (R-HSA-5693568)
  Nonhomologous End-Joining (NHEJ) (R-HSA-5693571)
  Homologous DNA Pairing and Strand Exchange (R-HSA-5693579)
  Processing of DNA double-strand break ends (R-HSA-5693607)
  Presynaptic phase of homologous DNA pairing and strand exchange (R-HSA-5693616)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  G2/M DNA damage checkpoint (R-HSA-69473)
  Meiotic recombination (R-HSA-912446)
  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 RAD51 (R-HSA-9709570)
  Impaired BRCA2 binding to PALB2 (R-HSA-9709603)
  DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Definitive	Biomarker	[1]
Allergic asthma	DISHF0H3	Strong	Genetic Variation	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[3]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[9]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[10]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[10]
Glioma	DIS5RPEH	Strong	Biomarker	[11]
Head and neck cancer	DISBPSQZ	Strong	Genetic Variation	[12]
Head and neck carcinoma	DISOU1DS	Strong	Genetic Variation	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[13]
Hereditary breast ovarian cancer syndrome	DISWDUGU	Strong	Genetic Variation	[14]
leukaemia	DISS7D1V	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[15]
Lung carcinoma	DISTR26C	Strong	Biomarker	[15]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Genetic Variation	[16]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[17]
Nijmegen breakage syndrome-like disorder	DISQF01Z	Strong	Autosomal recessive	[18]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[9]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[9]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[20]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[21]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]
Allergic rhinitis	DIS3U9HN	moderate	Genetic Variation	[22]
B-cell lymphoma	DISIH1YQ	moderate	Biomarker	[16]
Crohn disease	DIS2C5Q8	Disputed	Genetic Variation	[23]
Hereditary neoplastic syndrome	DISGXLG5	Disputed	CausalMutation	[24]
Uterine fibroids	DISBZRMJ	Disputed	Altered Expression	[25]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[26]
Adenoma	DIS78ZEV	Limited	Altered Expression	[26]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[27]
Carcinoma	DISH9F1N	Limited	Genetic Variation	[28]
Colorectal neoplasm	DISR1UCN	Limited	Biomarker	[29]
Endometrial carcinoma	DISXR5CY	Limited	Genetic Variation	[8]
Kaposi sarcoma	DISC1H1Z	Limited	Biomarker	[30]
Liver cirrhosis	DIS4G1GX	Limited	Therapeutic	[31]
Myocardial infarction	DIS655KI	Limited	Therapeutic	[32]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[33]
Nijmegen breakage syndrome	DIS98HVL	Limited	Biomarker	[34]
Plasma cell myeloma	DIS0DFZ0	Limited	Altered Expression	[35]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[36]
Familial ovarian cancer	DISGLR2C	Refuted	Autosomal dominant	[37]
Hereditary breast carcinoma	DISAEZT5	Refuted	Autosomal dominant	[37]

26 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 repair protein RAD50 (RAD50).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DNA repair protein RAD50 (RAD50).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA repair protein RAD50 (RAD50).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DNA repair protein RAD50 (RAD50).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA repair protein RAD50 (RAD50).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA repair protein RAD50 (RAD50).	[43]
Arsenic	DMTL2Y1	Approved	Arsenic increases the mutagenesis of DNA repair protein RAD50 (RAD50).	[44]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of DNA repair protein RAD50 (RAD50).	[45]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of DNA repair protein RAD50 (RAD50).	[46]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of DNA repair protein RAD50 (RAD50).	[47]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of DNA repair protein RAD50 (RAD50).	[48]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DNA repair protein RAD50 (RAD50).	[49]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of DNA repair protein RAD50 (RAD50).	[50]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of DNA repair protein RAD50 (RAD50).	[51]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of DNA repair protein RAD50 (RAD50).	[49]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of DNA repair protein RAD50 (RAD50).	[52]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of DNA repair protein RAD50 (RAD50).	[53]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of DNA repair protein RAD50 (RAD50).	[54]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of DNA repair protein RAD50 (RAD50).	[40]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of DNA repair protein RAD50 (RAD50).	[55]
NVP-LAQ824	DM8JWNA	Phase 3	NVP-LAQ824 decreases the expression of DNA repair protein RAD50 (RAD50).	[56]
Arecoline	DMFJZK3	Phase 1	Arecoline increases the expression of DNA repair protein RAD50 (RAD50).	[59]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of DNA repair protein RAD50 (RAD50).	[61]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of DNA repair protein RAD50 (RAD50).	[62]
Flavone	DMEQH6J	Investigative	Flavone increases the expression of DNA repair protein RAD50 (RAD50).	[45]
Dimethylformamide	DML6O4N	Investigative	Dimethylformamide increases the expression of DNA repair protein RAD50 (RAD50).	[63]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of DNA repair protein RAD50 (RAD50).	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of DNA repair protein RAD50 (RAD50).	[58]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of DNA repair protein RAD50 (RAD50).	[60]

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