Details of Drug Off-Target (DOT)

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

• DOT Name: Myb-binding protein 1A (MYBBP1A)
• Gene Name: MYBBP1A
• Related Disease:
  Hepatocellular carcinoma
  Androgen insensitivity syndrome
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Glucocorticoid resistance
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Kidney cancer
  Neoplasm
  Non-small-cell lung cancer
  Oropharyngeal squamous cell carcinoma
  Pancreatitis
  Prostate neoplasm
  Pulmonary tuberculosis
  Renal carcinoma
  Rheumatoid arthritis
  Cervical carcinoma
  Metastatic malignant neoplasm
  Prostate carcinoma
  Tuberculosis
  Prostate cancer
• UniProt ID: MBB1A_HUMAN
• Pfam ID: PF04931
• Sequence:
  MESRDPAQPMSPGEATQSGARPADRYGLLKHSREFLDFFWDIAKPEQETRLAATEKLLEY
  LRGRPKGSEMKYALKRLITGLGVGRETARPCYSLALAQLLQSFEDLPLCSILQQIQEKYD
  LHQVKKAMLRPALFANLFGVLALFQSGRLVKDQEALMKSVKLLQALAQYQNHLQEQPRKA
  LVDILSEVSKATLQEILPEVLKADLNIILSSPEQLELFLLAQQKVPSKLKKLVGSVNLFS
  DENVPRLVNVLKMAASSVKKDRKLPAIALDLLRLALKEDKFPRFWKEVVEQGLLKMQFWP
  ASYLCFRLLGAALPLLTKEQLHLVMQGDVIRHYGEHVCTAKLPKQFKFAPEMDDYVGTFL
  EGCQDDPERQLAVLVAFSSVTNQGLPVTPTFWRVVRFLSPPALQGYVAWLRAMFLQPDLD
  SLVDFSTNNQKKAQDSSLHMPERAVFRLRKWIIFRLVSIVDSLHLEMEEALTEQVARFCL
  FHSFFVTKKPTSQIPETKHPFSFPLENQAREAVSSAFFSLLQTLSTQFKQAPGQTQGGQP
  WTYHLVQFADLLLNHSHNVTTVTPFTAQQRQAWDRMLQTLKELEAHSAEARAAAFQHLLL
  LVGIHLLKSPAESCDLLGDIQTCIRKSLGEKPRRSRTKTIDPQEPPWVEVLVEILLALLA
  QPSHLMRQVARSVFGHICSHLTPRALQLILDVLNPETSEDENDRVVVTDDSDERRLKGAE
  DKSEEGEDNRSSESEEESEGEESEEEERDGDVDQGFREQLMTVLQAGKALGGEDSENEEE
  LGDEAMMALDQSLASLFAEQKLRIQARRDEKNKLQKEKALRRDFQIRVLDLVEVLVTKQP
  ENALVLELLEPLLSIIRRSLRSSSSKQEQDLLHKTARIFTHHLCRARRYCHDLGERAGAL
  HAQVERLVQQAGRQPDSPTALYHFNASLYLLRVLKGNTAEGCVHETQEKQKAGTDPSHMP
  TGPQAASCLDLNLVTRVYSTALSSFLTKRNSPLTVPMFLSLFSRHPVLCQSLLPILVQHI
  TGPVRPRHQACLLLQKTLSMREVRSCFEDPEWKQLMGQVLAKVTENLRVLGEAQTKAQHQ
  QALSSLELLNVLFRTCKHEKLTLDLTVLLGVLQGQQQSLQQGAHSTGSSRLHDLYWQAMK
  TLGVQRPKLEKKDAKEIPSATQSPISKKRKKKGFLPETKKRKKRKSEDGTPAEDGTPAAT
  GGSQPPSMGRKKRNRTKAKVPAQANGTPTTKSPAPGAPTRSPSTPAKSPKLQKKNQKPSQ
  VNGAPGSPTEPAGQKQHQKALPKKGVLGKSPLSALARKKARLSLVIRSPSLLQSGAKKKA
  QVRKAGKP
• Function: May activate or repress transcription via interactions with sequence specific DNA-binding proteins. Repression may be mediated at least in part by histone deacetylase activity (HDAC activity). Acts as a corepressor and in concert with CRY1, represses the transcription of the core circadian clock component PER2. Preferentially binds to dimethylated histone H3 'Lys-9' (H3K9me2) on the PER2 promoter. Has a role in rRNA biogenesis together with PWP1.
• Reactome Pathway: B-WICH complex positively regulates rRNA expression (R-HSA-5250924)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[1]
Androgen insensitivity syndrome	DISUZBBO	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Glucocorticoid resistance	DIS3HNXT	Strong	Genetic Variation	[5]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[6]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[6]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[7]
Kidney cancer	DISBIPKM	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[9]
Oropharyngeal squamous cell carcinoma	DIS7D7QV	Strong	Biomarker	[6]
Pancreatitis	DIS0IJEF	Strong	Genetic Variation	[10]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[11]
Pulmonary tuberculosis	DIS6FLUM	Strong	Biomarker	[12]
Renal carcinoma	DISER9XT	Strong	Biomarker	[8]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[13]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[14]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[15]
Prostate carcinoma	DISMJPLE	Disputed	Genetic Variation	[16]
Tuberculosis	DIS2YIMD	Disputed	Biomarker	[17]
Prostate cancer	DISF190Y	Limited	Biomarker	[11]

3 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 Myb-binding protein 1A (MYBBP1A).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Myb-binding protein 1A (MYBBP1A).	[31]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Myb-binding protein 1A (MYBBP1A).	[31]

15 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Myb-binding protein 1A (MYBBP1A).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myb-binding protein 1A (MYBBP1A).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Myb-binding protein 1A (MYBBP1A).	[21]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Myb-binding protein 1A (MYBBP1A).	[22]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Myb-binding protein 1A (MYBBP1A).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Myb-binding protein 1A (MYBBP1A).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Myb-binding protein 1A (MYBBP1A).	[25]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Myb-binding protein 1A (MYBBP1A).	[26]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Myb-binding protein 1A (MYBBP1A).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Myb-binding protein 1A (MYBBP1A).	[28]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Myb-binding protein 1A (MYBBP1A).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Myb-binding protein 1A (MYBBP1A).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Myb-binding protein 1A (MYBBP1A).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Myb-binding protein 1A (MYBBP1A).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Myb-binding protein 1A (MYBBP1A).	[33]

References

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• [9] Cytotoxic Effects of 24-Methylenecyloartanyl Ferulate on A549 Nonsmall Cell Lung Cancer Cells through MYBBP1A Up-Regulation and AKT and Aurora B Kinase Inhibition.J Agric Food Chem. 2018 Apr 11;66(14):3726-3733. doi: 10.1021/acs.jafc.8b00491. Epub 2018 Mar 29.
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• [14] New approach to human high-risk papillomavirus (HR-HPV) genotyping.Neoplasma. 2002;49(4):217-24.
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• [16] Prostate cancer-associated mutations in speckle-type POZ protein (SPOP) regulate steroid receptor coactivator 3 protein turnover.Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):6997-7002. doi: 10.1073/pnas.1304502110. Epub 2013 Apr 4.
• [17] Identification of genetic associations of SP110/MYBBP1A/RELA with pulmonary tuberculosis in the Chinese Han population.Hum Genet. 2013 Mar;132(3):265-73. doi: 10.1007/s00439-012-1244-5. Epub 2012 Nov 6.
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• [19] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
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• [22] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [23] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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