Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWR9YXE)

• DOT Name: Methyl-CpG-binding domain protein 4 (MBD4)
• Synonyms: EC 3.2.2.-; Methyl-CpG-binding endonuclease 1; Methyl-CpG-binding protein MBD4; Mismatch-specific DNA N-glycosylase
• Gene Name: MBD4
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Esophageal squamous cell carcinoma
  Uveal Melanoma
  Abdominal aortic aneurysm
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Adenoma
  Advanced cancer
  Aortic aneurysm
  Autism
  Autoimmune thrombocytopenia
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Colorectal neoplasm
  Endometrial cancer
  Endometrial carcinoma
  Gastric cancer
  Hantavirus infection
  Hepatocellular carcinoma
  Hyperplastic polyposis syndrome
  Immune thrombocytopenia
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Marinesco-Sjogren syndrome
  Red-green color blindness
  Subacute cutaneous lupus erythematosus
  Systemic lupus erythematosus
  Systemic sclerosis
  Tumor predisposition syndrome 2
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adenocarcinoma
  Glioma
  Mismatch repair cancer syndrome
  Non-small-cell lung cancer
  Osteomyelitis
• UniProt ID: MBD4_HUMAN
• PDB ID: 2MOE; 3IHO; 4DK9; 4E9E; 4E9F; 4E9G; 4E9H; 4EA4; 4EA5; 4LG7; 4OFA; 4OFE; 4OFH; 5CHZ; 6VJW; 7KZ0; 7KZ1; 7KZG
• EC Number: 3.2.2.-
• Pfam ID: PF01429
• Sequence:
  MGTTGLESLSLGDRGAAPTVTSSERLVPDPPNDLRKEDVAMELERVGEDEEQMMIKRSSE
  CNPLLQEPIASAQFGATAGTECRKSVPCGWERVVKQRLFGKTAGRFDVYFISPQGLKFRS
  KSSLANYLHKNGETSLKPEDFDFTVLSKRGIKSRYKDCSMAALTSHLQNQSNNSNWNLRT
  RSKCKKDVFMPPSSSSELQESRGLSNFTSTHLLLKEDEGVDDVNFRKVRKPKGKVTILKG
  IPIKKTKKGCRKSCSGFVQSDSKRESVCNKADAESEPVAQKSQLDRTVCISDAGACGETL
  SVTSEENSLVKKKERSLSSGSNFCSEQKTSGIINKFCSAKDSEHNEKYEDTFLESEEIGT
  KVEVVERKEHLHTDILKRGSEMDNNCSPTRKDFTGEKIFQEDTIPRTQIERRKTSLYFSS
  KYNKEALSPPRRKAFKKWTPPRSPFNLVQETLFHDPWKLLIATIFLNRTSGKMAIPVLWK
  FLEKYPSAEVARTADWRDVSELLKPLGLYDLRAKTIVKFSDEYLTKQWKYPIELHGIGKY
  GNDSYRIFCVNEWKQVHPEDHKLNKYHDWLWENHEKLSLS
• Function: Mismatch-specific DNA N-glycosylase involved in DNA repair. Has thymine glycosylase activity and is specific for G:T mismatches within methylated and unmethylated CpG sites. Can also remove uracil or 5-fluorouracil in G:U mismatches. Has no lyase activity. Was first identified as methyl-CpG-binding protein.
• 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

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Definitive	Genetic Variation	[1]
Cervical carcinoma	DIST4S00	Definitive	Genetic Variation	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Genetic Variation	[2]
Uveal Melanoma	DISA7ZGL	Definitive	Biomarker	[3]
Abdominal aortic aneurysm	DISD06OF	Strong	Biomarker	[4]
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[5]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[5]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[6]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[7]
Aortic aneurysm	DISQ5KRA	Strong	Biomarker	[4]
Autism	DISV4V1Z	Strong	Biomarker	[8]
Autoimmune thrombocytopenia	DISNF0OI	Strong	Altered Expression	[9]
Bladder cancer	DISUHNM0	Strong	Biomarker	[10]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[11]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[11]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[12]
Colon cancer	DISVC52G	Strong	Biomarker	[13]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[13]
Colonic neoplasm	DISSZ04P	Strong	Genetic Variation	[14]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[15]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[16]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[16]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[17]
Hantavirus infection	DISZFTMH	Strong	Genetic Variation	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[18]
Hyperplastic polyposis syndrome	DISVLOYP	Strong	Biomarker	[6]
Immune thrombocytopenia	DISVCBNS	Strong	Altered Expression	[9]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[19]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[19]
Lung neoplasm	DISVARNB	Strong	Genetic Variation	[20]
Marinesco-Sjogren syndrome	DISKEU0B	Strong	Genetic Variation	[21]
Red-green color blindness	DISV3ZVU	Strong	Biomarker	[22]
Subacute cutaneous lupus erythematosus	DIS6XDK0	Strong	Altered Expression	[23]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[24]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[25]
Tumor predisposition syndrome 2	DIS56CEM	Strong	Autosomal recessive	[26]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[10]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[10]
Adenocarcinoma	DIS3IHTY	moderate	Genetic Variation	[27]
Glioma	DIS5RPEH	Limited	Altered Expression	[28]
Mismatch repair cancer syndrome	DISIXHJ2	Limited	Biomarker	[29]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[30]
Osteomyelitis	DIS0VUZL	Limited	Biomarker	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Methyl-CpG-binding domain protein 4 (MBD4) affects the response to substance of Topotecan.	[52]

4 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 Methyl-CpG-binding domain protein 4 (MBD4).	[32]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Methyl-CpG-binding domain protein 4 (MBD4).	[48]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Methyl-CpG-binding domain protein 4 (MBD4).	[49]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Methyl-CpG-binding domain protein 4 (MBD4).	[49]

18 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 Methyl-CpG-binding domain protein 4 (MBD4).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[37]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[38]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[39]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[42]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[43]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[44]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[45]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[46]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[43]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[47]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[50]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Methyl-CpG-binding domain protein 4 (MBD4).	[51]

References

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