Details of Drug Off-Target (DOT)

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

• DOT Name: RecQ-like DNA helicase BLM (BLM)
• Synonyms: EC 5.6.2.4; Bloom syndrome protein; DNA 3'-5' helicase BLM; DNA helicase, RecQ-like type 2; RecQ2; RecQ protein-like 3
• Gene Name: BLM
• Related Disease:
  Bloom syndrome
  Digestive system neoplasm
  Acute lymphocytic leukaemia
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Adenoma
  Alzheimer disease
  Arteriosclerosis
  Ataxia-telangiectasia
  Atherosclerosis
  Bladder cancer
  Carcinoma
  Cataract
  Chromosomal disorder
  Colon cancer
  Colorectal carcinoma
  Colorectal neoplasm
  Endometrial cancer
  Endometrial carcinoma
  Familial adenomatous polyposis
  Hereditary neoplastic syndrome
  Immunodeficiency
  Leukemia
  Lung neoplasm
  Lymphoma
  Metastatic malignant neoplasm
  Myelodysplastic syndrome
  Premature aging syndrome
  Promyelocytic leukaemia
  Prostate cancer
  Prostate carcinoma
  Pulmonary fibrosis
  Rothmund-Thomson syndrome
  Small-cell lung cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Werner syndrome
  Nasopharyngeal carcinoma
  Osteosarcoma
  Breast cancer
  Fanconi anemia complementation group A
  Melanoma
  Adult lymphoma
  Fanconi's anemia
  Hereditary breast carcinoma
  Nervous system disease
  Neuroblastoma
  Pediatric lymphoma
  Systemic sclerosis
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: BLM_HUMAN
• PDB ID: 2KV2; 2MH9; 2RRD; 3WE2; 3WE3; 4CDG; 4CGZ; 4O3M; 5LUP; 5MK5; 5U6K; 7AUC; 7AUD; 7XUW; 7XV0
• EC Number: 5.6.2.4
• Pfam ID: PF08072 ; PF16204 ; PF16202 ; PF00270 ; PF00271 ; PF00570 ; PF16124 ; PF09382
• Sequence:
  MAAVPQNNLQEQLERHSARTLNNKLSLSKPKFSGFTFKKKTSSDNNVSVTNVSVAKTPVL
  RNKDVNVTEDFSFSEPLPNTTNQQRVKDFFKNAPAGQETQRGGSKSLLPDFLQTPKEVVC
  TTQNTPTVKKSRDTALKKLEFSSSPDSLSTINDWDDMDDFDTSETSKSFVTPPQSHFVRV
  STAQKSKKGKRNFFKAQLYTTNTVKTDLPPPSSESEQIDLTEEQKDDSEWLSSDVICIDD
  GPIAEVHINEDAQESDSLKTHLEDERDNSEKKKNLEEAELHSTEKVPCIEFDDDDYDTDF
  VPPSPEEIISASSSSSKCLSTLKDLDTSDRKEDVLSTSKDLLSKPEKMSMQELNPETSTD
  CDARQISLQQQLIHVMEHICKLIDTIPDDKLKLLDCGNELLQQRNIRRKLLTEVDFNKSD
  ASLLGSLWRYRPDSLDGPMEGDSCPTGNSMKELNFSHLPSNSVSPGDCLLTTTLGKTGFS
  ATRKNLFERPLFNTHLQKSFVSSNWAETPRLGKKNESSYFPGNVLTSTAVKDQNKHTASI
  NDLERETQPSYDIDNFDIDDFDDDDDWEDIMHNLAASKSSTAAYQPIKEGRPIKSVSERL
  SSAKTDCLPVSSTAQNINFSESIQNYTDKSAQNLASRNLKHERFQSLSFPHTKEMMKIFH
  KKFGLHNFRTNQLEAINAALLGEDCFILMPTGGGKSLCYQLPACVSPGVTVVISPLRSLI
  VDQVQKLTSLDIPATYLTGDKTDSEATNIYLQLSKKDPIIKLLYVTPEKICASNRLISTL
  ENLYERKLLARFVIDEAHCVSQWGHDFRQDYKRMNMLRQKFPSVPVMALTATANPRVQKD
  ILTQLKILRPQVFSMSFNRHNLKYYVLPKKPKKVAFDCLEWIRKHHPYDSGIIYCLSRRE
  CDTMADTLQRDGLAALAYHAGLSDSARDEVQQKWINQDGCQVICATIAFGMGIDKPDVRF
  VIHASLPKSVEGYYQESGRAGRDGEISHCLLFYTYHDVTRLKRLIMMEKDGNHHTRETHF
  NNLYSMVHYCENITECRRIQLLAYFGENGFNPDFCKKHPDVSCDNCCKTKDYKTRDVTDD
  VKSIVRFVQEHSSSQGMRNIKHVGPSGRFTMNMLVDIFLGSKSAKIQSGIFGKGSAYSRH
  NAERLFKKLILDKILDEDLYINANDQAIAYVMLGNKAQTVLNGNLKVDFMETENSSSVKK
  QKALVAKVSQREEMVKKCLGELTEVCKSLGKVFGVHYFNIFNTVTLKKLAESLSSDPEVL
  LQIDGVTEDKLEKYGAEVISVLQKYSEWTSPAEDSSPGISLSSSRGPGRSAAEELDEEIP
  VSSHYFASKTRNERKRKKMPASQRSKRRKTASSGSKAKGGSATCRKISSKTKSSSIIGSS
  SASHTSQATSGANSKLGIMAPPKPINRPFLKPSYAFS
• Function: ATP-dependent DNA helicase that unwinds single- and double-stranded DNA in a 3'-5' direction. Participates in DNA replication and repair. Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA. Negatively regulates sister chromatid exchange (SCE). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution. Binds single-stranded DNA (ssDNA), forked duplex DNA and DNA Holliday junction. Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks; (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby suppressing immune sensing and proviral hyper-integration.
• KEGG Pathway:
  Homologous recombi.tion (hsa03440)
  Fanconi anemia pathway (hsa03460)
• Reactome Pathway:
  SUMOylation of DNA damage response and repair proteins (R-HSA-3108214)
  HDR through Single Strand Annealing (SSA) (R-HSA-5685938)
  HDR through Homologous Recombination (HRR) (R-HSA-5685942)
  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)
  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)
  Processive synthesis on the C-strand of the telomere (R-HSA-174414)

Molecular Interaction Atlas (MIA) of This DOT

51 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bloom syndrome	DISKXQ7J	Definitive	Autosomal recessive	[1]
Digestive system neoplasm	DISPOJCT	Definitive	Genetic Variation	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[3]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adenoma	DIS78ZEV	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[6]
Ataxia-telangiectasia	DISP3EVR	Strong	Altered Expression	[7]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[9]
Cataract	DISUD7SL	Strong	Biomarker	[10]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[11]
Colon cancer	DISVC52G	Strong	Biomarker	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[13]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[14]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[14]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[4]
Hereditary neoplastic syndrome	DISGXLG5	Strong	CausalMutation	[15]
Immunodeficiency	DIS093I0	Strong	Biomarker	[16]
Leukemia	DISNAKFL	Strong	Biomarker	[3]
Lung neoplasm	DISVARNB	Strong	Biomarker	[17]
Lymphoma	DISN6V4S	Strong	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[18]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[3]
Premature aging syndrome	DIS51AGT	Strong	Genetic Variation	[19]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[20]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[21]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[21]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[22]
Rothmund-Thomson syndrome	DISGVBCV	Strong	Biomarker	[23]
Small-cell lung cancer	DISK3LZD	Strong	Genetic Variation	[24]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[8]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[8]
Werner syndrome	DISZY45W	Strong	Genetic Variation	[25]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Genetic Variation	[26]
Osteosarcoma	DISLQ7E2	Moderate	Autosomal recessive	[27]
Breast cancer	DIS7DPX1	Disputed	Autosomal dominant	[28]
Fanconi anemia complementation group A	DIS8PZLI	Disputed	Biomarker	[29]
Melanoma	DIS1RRCY	Disputed	Altered Expression	[30]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[31]
Fanconi's anemia	DISGW6Q8	Limited	Biomarker	[29]
Hereditary breast carcinoma	DISAEZT5	Limited	Biomarker	[32]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[33]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[34]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[31]
Systemic sclerosis	DISF44L6	Limited	Biomarker	[35]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[36]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[36]

28 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 RecQ-like DNA helicase BLM (BLM).	[37]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RecQ-like DNA helicase BLM (BLM).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RecQ-like DNA helicase BLM (BLM).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RecQ-like DNA helicase BLM (BLM).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RecQ-like DNA helicase BLM (BLM).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RecQ-like DNA helicase BLM (BLM).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RecQ-like DNA helicase BLM (BLM).	[43]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of RecQ-like DNA helicase BLM (BLM).	[44]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of RecQ-like DNA helicase BLM (BLM).	[45]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of RecQ-like DNA helicase BLM (BLM).	[46]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RecQ-like DNA helicase BLM (BLM).	[47]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of RecQ-like DNA helicase BLM (BLM).	[48]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of RecQ-like DNA helicase BLM (BLM).	[48]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of RecQ-like DNA helicase BLM (BLM).	[49]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of RecQ-like DNA helicase BLM (BLM).	[50]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of RecQ-like DNA helicase BLM (BLM).	[51]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of RecQ-like DNA helicase BLM (BLM).	[43]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of RecQ-like DNA helicase BLM (BLM).	[43]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of RecQ-like DNA helicase BLM (BLM).	[52]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of RecQ-like DNA helicase BLM (BLM).	[43]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of RecQ-like DNA helicase BLM (BLM).	[43]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of RecQ-like DNA helicase BLM (BLM).	[43]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of RecQ-like DNA helicase BLM (BLM).	[53]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of RecQ-like DNA helicase BLM (BLM).	[54]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of RecQ-like DNA helicase BLM (BLM).	[55]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of RecQ-like DNA helicase BLM (BLM).	[57]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of RecQ-like DNA helicase BLM (BLM).	[60]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of RecQ-like DNA helicase BLM (BLM).	[61]

3 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 RecQ-like DNA helicase BLM (BLM).	[56]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of RecQ-like DNA helicase BLM (BLM).	[58]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of RecQ-like DNA helicase BLM (BLM).	[59]

References

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