Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEEQS43)

• DOT Name: DNA ligase 1 (LIG1)
• Synonyms: EC 6.5.1.1; DNA ligase I; Polydeoxyribonucleotide synthase 1
• Gene Name: LIG1
• Related Disease:
  Glioma
  Advanced cancer
  Alzheimer disease
  Ataxia-telangiectasia
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Cerebellar ataxia
  Immunodeficiency
  Immunodeficiency 96
  Neoplasm
  Neuroblastoma
  Non-small-cell lung cancer
  Renal cell carcinoma
  Trichohepatoenteric syndrome
  Urinary bladder cancer
  Urinary bladder neoplasm
  Cervical cancer
  Cervical carcinoma
• UniProt ID: DNLI1_HUMAN
• PDB ID: 1X9N; 5YY9; 6P09; 6P0A; 6P0B; 6P0C; 6P0D; 6P0E; 6Q1V; 7KR3; 7KR4; 7L34; 7L35; 7QNZ; 7QO1; 7SUM; 7SX5; 7SXE; 8B8T
• EC Number: 6.5.1.1
• Pfam ID: PF04679 ; PF01068 ; PF04675
• Sequence:
  MQRSIMSFFHPKKEGKAKKPEKEASNSSRETEPPPKAALKEWNGVVSESDSPVKRPGRKA
  ARVLGSEGEEEDEALSPAKGQKPALDCSQVSPPRPATSPENNASLSDTSPMDSSPSGIPK
  RRTARKQLPKRTIQEVLEEQSEDEDREAKRKKEEEEEETPKESLTEAEVATEKEGEDGDQ
  PTTPPKPLKTSKAETPTESVSEPEVATKQELQEEEEQTKPPRRAPKTLSSFFTPRKPAVK
  KEVKEEEPGAPGKEGAAEGPLDPSGYNPAKNNYHPVEDACWKPGQKVPYLAVARTFEKIE
  EVSARLRMVETLSNLLRSVVALSPPDLLPVLYLSLNHLGPPQQGLELGVGDGVLLKAVAQ
  ATGRQLESVRAEAAEKGDVGLVAENSRSTQRLMLPPPPLTASGVFSKFRDIARLTGSAST
  AKKIDIIKGLFVACRHSEARFIARSLSGRLRLGLAEQSVLAALSQAVSLTPPGQEFPPAM
  VDAGKGKTAEARKTWLEEQGMILKQTFCEVPDLDRIIPVLLEHGLERLPEHCKLSPGIPL
  KPMLAHPTRGISEVLKRFEEAAFTCEYKYDGQRAQIHALEGGEVKIFSRNQEDNTGKYPD
  IISRIPKIKLPSVTSFILDTEAVAWDREKKQIQPFQVLTTRKRKEVDASEIQVQVCLYAF
  DLIYLNGESLVREPLSRRRQLLRENFVETEGEFVFATSLDTKDIEQIAEFLEQSVKDSCE
  GLMVKTLDVDATYEIAKRSHNWLKLKKDYLDGVGDTLDLVVIGAYLGRGKRAGRYGGFLL
  ASYDEDSEELQAICKLGTGFSDEELEEHHQSLKALVLPSPRPYVRIDGAVIPDHWLDPSA
  VWEVKCADLSLSPIYPAARGLVDSDKGISLRFPRFIRVREDKQPEQATTSAQVACLYRKQ
  SQIQNQQGEDSGSDPEDTY
• Function: DNA ligase that seals nicks in double-stranded during DNA repair. Also involved in DNA replication and DNA recombination.
• KEGG Pathway:
  D. replication (hsa03030)
  Base excision repair (hsa03410)
  Nucleotide excision repair (hsa03420)
  Mismatch repair (hsa03430)
• Reactome Pathway:
  Early Phase of HIV Life Cycle (R-HSA-162594)
  Processive synthesis on the C-strand of the telomere (R-HSA-174414)
  Mismatch repair (MMR) directed by MSH2 (R-HSA-5358565)
  Mismatch repair (MMR) directed by MSH2 (R-HSA-5358606)
  PCNA-Dependent Long Patch Base Excision Repair (R-HSA-5651801)
  Gap-filling DNA repair synthesis and ligation in GG-NER (R-HSA-5696397)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  Processive synthesis on the lagging strand (R-HSA-69183)
  POLB-Dependent Long Patch Base Excision Repair (R-HSA-110362)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[7]
Immunodeficiency	DIS093I0	Strong	Biomarker	[8]
Immunodeficiency 96	DISFWBT9	Strong	Autosomal recessive	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[11]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[12]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[13]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[5]
Cervical cancer	DISFSHPF	Limited	Altered Expression	[14]
Cervical carcinoma	DIST4S00	Limited	Altered Expression	[14]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	DNA ligase 1 (LIG1) affects the response to substance of Fluorouracil.	[38]

6 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 ligase 1 (LIG1).	[15]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of DNA ligase 1 (LIG1).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of DNA ligase 1 (LIG1).	[32]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of DNA ligase 1 (LIG1).	[34]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of DNA ligase 1 (LIG1).	[34]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of DNA ligase 1 (LIG1).	[37]

19 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 ligase 1 (LIG1).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA ligase 1 (LIG1).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA ligase 1 (LIG1).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA ligase 1 (LIG1).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA ligase 1 (LIG1).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA ligase 1 (LIG1).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA ligase 1 (LIG1).	[22]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA ligase 1 (LIG1).	[24]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA ligase 1 (LIG1).	[24]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DNA ligase 1 (LIG1).	[25]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DNA ligase 1 (LIG1).	[26]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of DNA ligase 1 (LIG1).	[27]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA ligase 1 (LIG1).	[28]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of DNA ligase 1 (LIG1).	[29]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of DNA ligase 1 (LIG1).	[30]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of DNA ligase 1 (LIG1).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA ligase 1 (LIG1).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA ligase 1 (LIG1).	[35]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA ligase 1 (LIG1).	[36]

References

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