Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPJIL05)

DOT Name	DNA polymerase beta (POLB)
Synonyms	EC 2.7.7.7; 5'-deoxyribose-phosphate lyase; 5'-dRP lyase; EC 4.2.99.-; AP lyase; EC 4.2.99.18
Gene Name	POLB
UniProt ID	DPOLB_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1BPX ; 1BPY ; 1BPZ ; 1MQ2 ; 1MQ3 ; 1TV9 ; 1TVA ; 1ZJM ; 1ZJN ; 1ZQA ; 1ZQB ; 1ZQC ; 1ZQD ; 1ZQE ; 1ZQF ; 1ZQG ; 1ZQH ; 1ZQI ; 1ZQJ ; 1ZQK ; 1ZQL ; 1ZQM ; 1ZQN ; 1ZQO ; 1ZQP ; 1ZQQ ; 1ZQR ; 1ZQS ; 1ZQT ; 2FMP ; 2FMQ ; 2FMS ; 2I9G ; 2ISO ; 2ISP ; 2P66 ; 2PXI ; 3C2K ; 3C2L ; 3C2M ; 3GDX ; 3ISB ; 3ISC ; 3ISD ; 3JPN ; 3JPO ; 3JPP ; 3JPQ ; 3JPR ; 3JPS ; 3JPT ; 3LK9 ; 3MBY ; 3OGU ; 3RH4 ; 3RH5 ; 3RH6 ; 3RJE ; 3RJF ; 3RJG ; 3RJH ; 3RJI ; 3RJJ ; 3RJK ; 3TFR ; 3TFS ; 4DO9 ; 4DOA ; 4DOB ; 4DOC ; 4F5N ; 4F5O ; 4F5P ; 4F5Q ; 4F5R ; 4GXI ; 4GXJ ; 4GXK ; 4JWM ; 4JWN ; 4KLD ; 4KLE ; 4KLF ; 4KLG ; 4KLH ; 4KLI ; 4KLJ ; 4KLL ; 4KLM ; 4KLO ; 4KLQ ; 4KLS ; 4KLT ; 4KLU ; 4LVS ; 4M2Y ; 4M47 ; 4M9G ; 4M9H ; 4M9J ; 4M9L ; 4M9N ; 4MF2 ; 4MF8 ; 4MFA ; 4MFC ; 4MFF ; 4NLK ; 4NLN ; 4NLZ ; 4NM1 ; 4NM2 ; 4NXZ ; 4NY8 ; 4O5C ; 4O5E ; 4O5K ; 4O9M ; 4P2H ; 4PGQ ; 4PGX ; 4PGY ; 4PH5 ; 4PHA ; 4PHD ; 4PHE ; 4PHP ; 4PPX ; 4R63 ; 4R64 ; 4R65 ; 4R66 ; 4RPX ; 4RPY ; 4RPZ ; 4RQ0 ; 4RQ1 ; 4RQ2 ; 4RQ3 ; 4RQ4 ; 4RQ5 ; 4RQ6 ; 4RQ7 ; 4RQ8 ; 4RT2 ; 4RT3 ; 4TUP ; 4TUQ ; 4TUR ; 4TUS ; 4UAW ; 4UAY ; 4UAZ ; 4UB1 ; 4UB2 ; 4UB3 ; 4UB4 ; 4UB5 ; 4UBB ; 4UBC ; 4YMM ; 4YMN ; 4YMO ; 4YN4 ; 4Z6C ; 4Z6D ; 4Z6E ; 4Z6F ; 5BOL ; 5BOM ; 5BPC ; 5DB6 ; 5DB7 ; 5DB8 ; 5DB9 ; 5DBA ; 5DBB ; 5DBC ; 5EOZ ; 5HHH ; 5HHI ; 5J0O ; 5J0P ; 5J0Q ; 5J0R ; 5J0S ; 5J0T ; 5J0U ; 5J0W ; 5J0X ; 5J0Y ; 5J29 ; 5J2A ; 5J2B ; 5J2C ; 5J2D ; 5J2E ; 5J2F ; 5J2G ; 5J2H ; 5J2I ; 5J2J ; 5J2K ; 5TB8 ; 5TB9 ; 5TBA ; 5TBB ; 5TBC ; 5TZV ; 5U2R ; 5U2S ; 5U2T ; 5U8G ; 5U8H ; 5U8I ; 5U9H ; 5UGN ; 5UGO ; 5UGP ; 5V1F ; 5V1G ; 5V1H ; 5V1I ; 5V1J ; 5V1N ; 5V1O ; 5V1P ; 5V1R ; 5VEZ ; 5VRW ; 5VRX ; 5VRY ; 5VRZ ; 5VS0 ; 5VS1 ; 5VS2 ; 5VS3 ; 5VS4 ; 5WNX ; 5WNY ; 5WNZ ; 5WO0 ; 6BEL ; 6BEM ; 6BTE ; 6BTF ; 6CLY ; 6CPQ ; 6CR3 ; 6CR4 ; 6CR5 ; 6CR6 ; 6CR7 ; 6CR8 ; 6CR9 ; 6CRB ; 6CRC ; 6CRH ; 6CTI ; 6CTJ ; 6CTK ; 6CTL ; 6CTM ; 6CTN ; 6CTO ; 6CTP ; 6CTQ ; 6CTR ; 6CTT ; 6CTU ; 6CTV ; 6CTW ; 6CTX ; 6CU9 ; 6CUA ; 6CUB ; 6DIA ; 6DIC ; 6E3R ; 6E3V ; 6E3W ; 6E3X ; 6G2Q ; 6MR7 ; 6MR8 ; 6N2R ; 6N2S ; 6N2T ; 6NKR ; 6NKS ; 6NKT ; 6NKU ; 6NKV ; 6NKW ; 6NKX ; 6NKY ; 6NKZ ; 6NL0 ; 6PH5 ; 6PH6 ; 6PKZ ; 6U2O ; 6U6B ; 6UOK ; 6UOL ; 6UOM ; 6W2M ; 7ICE ; 7ICF ; 7ICG ; 7ICH ; 7ICI ; 7ICJ ; 7ICK ; 7ICL ; 7ICM ; 7ICN ; 7ICO ; 7ICP ; 7ICQ ; 7ICR ; 7ICS ; 7ICT ; 7ICU ; 7ICV ; 7K96 ; 7K97 ; 7MZ0 ; 7MZ1 ; 7MZ2 ; 7MZ3 ; 7MZ4 ; 7MZ8 ; 7RBE ; 7RBF ; 7RBG ; 7RBH ; 7RBI ; 7RBJ ; 7RBK ; 7RBL ; 7RBM ; 7RBN ; 7RBO ; 7S9J ; 7S9K ; 7S9L ; 7S9M ; 7S9N ; 7S9O ; 7S9P ; 7S9Q ; 8ICA ; 8ICB ; 8ICC ; 8ICE ; 8ICF ; 8ICG ; 8ICH ; 8ICI ; 8ICJ ; 8ICK ; 8ICL ; 8ICM ; 8ICN ; 8ICO ; 8ICP ; 8ICQ ; 8ICR ; 8ICS ; 8ICT ; 8ICU ; 8ICV ; 8ICW ; 8ICX ; 8ICY ; 8ICZ ; 9ICA ; 9ICB ; 9ICC ; 9ICE ; 9ICF ; 9ICG ; 9ICH ; 9ICI ; 9ICJ ; 9ICK ; 9ICL ; 9ICM ; 9ICN ; 9ICO ; 9ICP ; 9ICQ ; 9ICR ; 9ICS ; 9ICT ; 9ICU ; 9ICV ; 9ICW ; 9ICX ; 9ICY
EC Number	2.7.7.7; 4.2.99.-; 4.2.99.18
Pfam ID	PF14792 ; PF14791 ; PF10391 ; PF14716
Sequence	MSKRKAPQETLNGGITDMLTELANFEKNVSQAIHKYNAYRKAASVIAKYPHKIKSGAEAK KLPGVGTKIAEKIDEFLATGKLRKLEKIRQDDTSSSINFLTRVSGIGPSAARKFVDEGIK TLEDLRKNEDKLNHHQRIGLKYFGDFEKRIPREEMLQMQDIVLNEVKKVDSEYIATVCGS FRRGAESSGDMDVLLTHPSFTSESTKQPKLLHQVVEQLQKVHFITDTLSKGETKFMGVCQ LPSKNDEKEYPHRRIDIRLIPKDQYYCGVLYFTGSDIFNKNMRAHALEKGFTINEYTIRP LGVTGVAGEPLPVDSEKDIFDYIQWKYREPKDRSE
Function	Repair polymerase that plays a key role in base-excision repair. During this process, the damaged base is excised by specific DNA glycosylases, the DNA backbone is nicked at the abasic site by an apurinic/apyrimidic (AP) endonuclease, and POLB removes 5'-deoxyribose-phosphate from the preincised AP site acting as a 5'-deoxyribose-phosphate lyase (5'-dRP lyase); through its DNA polymerase activity, it adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases. It is also able to cleave sugar-phosphate bonds 3' to an intact AP site, acting as an AP lyase.
KEGG Pathway	Base excision repair (hsa03410 ) Human T-cell leukemia virus 1 infection (hsa05166 ) Viral carcinogenesis (hsa05203 )
Reactome Pathway	Resolution of AP sites via the multiple-nucleotide patch replacement pathway (R-HSA-110373 ) Resolution of AP sites via the single-nucleotide replacement pathway (R-HSA-110381 ) APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway (R-HSA-5649702 ) PCNA-Dependent Long Patch Base Excision Repair (R-HSA-5651801 ) Ub-specific processing proteases (R-HSA-5689880 ) Abasic sugar-phosphate removal via the single-nucleotide replacement pathway (R-HSA-73930 ) POLB-Dependent Long Patch Base Excision Repair (R-HSA-110362 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	DNA polymerase beta (POLB) decreases the response to substance of Temozolomide.	[14]
Colistin	DMMD9QE	Approved	DNA polymerase beta (POLB) increases the Nephropathy toxic ADR of Colistin.	[15]
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13 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 polymerase beta (POLB).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA polymerase beta (POLB).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA polymerase beta (POLB).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of DNA polymerase beta (POLB).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of DNA polymerase beta (POLB).	[5]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of DNA polymerase beta (POLB).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA polymerase beta (POLB).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DNA polymerase beta (POLB).	[8]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of DNA polymerase beta (POLB).	[9]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of DNA polymerase beta (POLB).	[10]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of DNA polymerase beta (POLB).	[11]
Taurine	DMVW7N3	Investigative	Taurine increases the expression of DNA polymerase beta (POLB).	[12]
HONOKIOL	DMJWT3X	Investigative	HONOKIOL decreases the activity of DNA polymerase beta (POLB).	[13]
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⏷ Show the Full List of 13 Drug(s)

References

1	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2	Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
3	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
4	Curcumin prevents DNA damage and enhances the repair potential in a chronically arsenic-exposed human population in West Bengal, India. Eur J Cancer Prev. 2011 Mar;20(2):123-31. doi: 10.1097/cej.0b013e328341017a.
5	Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
6	Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells. Br J Cancer. 2009 May 5;100(9):1425-33. doi: 10.1038/sj.bjc.6605039.
7	Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
8	A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
9	JWA antagonizes paraquat-induced neurotoxicity via activation of Nrf2. Toxicol Lett. 2017 Aug 5;277:32-40. doi: 10.1016/j.toxlet.2017.04.011. Epub 2017 Apr 18.
10	Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
11	APE1 modulates cellular responses to organophosphate pesticide-induced oxidative damage in non-small cell lung carcinoma A549 cells. Mol Cell Biochem. 2018 Apr;441(1-2):201-216.
12	Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.
13	Honokiol Inhibits DNA Polymerases and and Increases Bleomycin Sensitivity of Human Cancer Cells. Chem Res Toxicol. 2017 Feb 20;30(2):715-725. doi: 10.1021/acs.chemrestox.6b00451. Epub 2017 Jan 19.
14	The role of base excision repair in the sensitivity and resistance to temozolomide-mediated cell death. Cancer Res. 2005 Jul 15;65(14):6394-400. doi: 10.1158/0008-5472.CAN-05-0715.
15	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.