Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2YIOCQ)

DOT Name	Single-strand selective monofunctional uracil DNA glycosylase (SMUG1)
Synonyms	EC 3.2.2.-
Gene Name	SMUG1
Related Disease	Differentiated thyroid carcinoma ( ) Tuberculosis ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Bladder cancer ( ) Brain neoplasm ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Cardiovascular disease ( ) Cervical cancer ( ) Cervical carcinoma ( ) Clear cell renal carcinoma ( ) Endometrial cancer ( ) Epithelial ovarian cancer ( ) Glioblastoma multiforme ( ) Glioma ( ) Head and neck cancer ( ) Head and neck carcinoma ( ) Head-neck squamous cell carcinoma ( ) Invasive ductal breast carcinoma ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) MALT lymphoma ( ) Mantle cell lymphoma ( ) Melanoma ( ) Nasopharyngeal carcinoma ( ) Non-hodgkin lymphoma ( ) Pancreatic cancer ( ) Parkinson disease ( ) Renal cell carcinoma ( ) Sarcoidosis ( ) Squamous cell carcinoma ( ) Vasculitis ( ) B-cell lymphoma ( ) Colorectal carcinoma ( ) Neuroendocrine neoplasm ( ) Small-cell lung cancer ( ) Adenocarcinoma ( ) Endometrial carcinoma ( ) Esophageal squamous cell carcinoma ( ) Lewy body dementia ( ) Prostate cancer ( ) Prostate carcinoma ( )
UniProt ID	SMUG1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.2.2.-
Pfam ID	PF03167
Sequence	MPQAFLLGSIHEPAGALMEPQPCPGSLAESFLEEELRLNAELSQLQFSEPVGIIYNPVEY AWEPHRNYVTRYCQGPKEVLFLGMNPGPFGMAQTGVPFGEVSMVRDWLGIVGPVLTPPQE HPKRPVLGLECPQSEVSGARFWGFFRNLCGQPEVFFHHCFVHNLCPLLFLAPSGRNLTPA ELPAKQREQLLGICDAALCRQVQLLGVRLVVGVGRLAEQRARRALAGLMPEVQVEGLLHP SPRNPQANKGWEAVAKERLNELGLLPLLLK
Function	Recognizes base lesions in the genome and initiates base excision DNA repair. Acts as a monofunctional DNA glycosylase specific for uracil (U) residues in DNA with a preference for single-stranded DNA substrates. The activity is greater toward mismatches (U/G) compared to matches (U/A). Excises uracil (U), 5-formyluracil (fU) and uracil derivatives bearing an oxidized group at C5 [5-hydroxyuracil (hoU) and 5-hydroxymethyluracil (hmU)] in ssDNA and dsDNA, but not analogous cytosine derivatives (5-hydroxycytosine and 5-formylcytosine), nor other oxidized bases. The activity is damage-specific and salt-dependent. The substrate preference is the following: ssDNA > dsDNA (G pair) = dsDNA (A pair) at low salt concentration, and dsDNA (G pair) > dsDNA (A pair) > ssDNA at high salt concentration.
KEGG Pathway	Base excision repair (hsa03410 )
Reactome Pathway	Cleavage of the damaged pyrimidine (R-HSA-110329 ) Displacement of DNA glycosylase by APEX1 (R-HSA-110357 ) Recognition and association of DNA glycosylase with site containing an affected pyrimidine (R-HSA-110328 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Differentiated thyroid carcinoma	DIS1V20Y	Definitive	Biomarker	[1]
Tuberculosis	DIS2YIMD	Definitive	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[10]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[13]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[15]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[15]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[16]
Invasive ductal breast carcinoma	DIS43J58	Strong	Biomarker	[17]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[18]
Lung cancer	DISCM4YA	Strong	Biomarker	[19]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
MALT lymphoma	DIS1AVVE	Strong	Biomarker	[20]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[21]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[22]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[23]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[24]
Pancreatic cancer	DISJC981	Strong	Biomarker	[25]
Parkinson disease	DISQVHKL	Strong	Biomarker	[26]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[10]
Sarcoidosis	DISE5B8Z	Strong	Biomarker	[27]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[28]
Vasculitis	DISQRKDX	Strong	Biomarker	[29]
B-cell lymphoma	DISIH1YQ	moderate	Biomarker	[30]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[31]
Neuroendocrine neoplasm	DISNPLOO	moderate	Biomarker	[32]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[33]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[34]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[11]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Genetic Variation	[35]
Lewy body dementia	DISAE66J	Limited	Biomarker	[36]
Prostate cancer	DISF190Y	Limited	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[18]
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⏷ Show the Full List of 45 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Single-strand selective monofunctional uracil DNA glycosylase (SMUG1).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Single-strand selective monofunctional uracil DNA glycosylase (SMUG1).	[45]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Single-strand selective monofunctional uracil DNA glycosylase (SMUG1).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Single-strand selective monofunctional uracil DNA glycosylase (SMUG1).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Single-strand selective monofunctional uracil DNA glycosylase (SMUG1).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Single-strand selective monofunctional uracil DNA glycosylase (SMUG1).	[41]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Single-strand selective monofunctional uracil DNA glycosylase (SMUG1).	[42]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Single-strand selective monofunctional uracil DNA glycosylase (SMUG1).	[43]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Single-strand selective monofunctional uracil DNA glycosylase (SMUG1).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Single-strand selective monofunctional uracil DNA glycosylase (SMUG1).	[46]
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⏷ Show the Full List of 8 Drug(s)

References

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