Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOMK4KH)

• DOT Name: Chromatin assembly factor 1 subunit B (CHAF1B)
• Synonyms: CAF-1 subunit B; Chromatin assembly factor I p60 subunit; CAF-I 60 kDa subunit; CAF-I p60; M-phase phosphoprotein 7
• Gene Name: CHAF1B
• Related Disease:
  Adolescent meningitis
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Carcinoma
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Non-small-cell lung cancer
  Renal cell carcinoma
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Advanced cancer
  Laryngeal carcinoma
  Laryngeal disorder
  Laryngeal squamous cell carcinoma
  Neoplasm
  Cutaneous melanoma
  facioscapulohumeral muscular dystrophy
  Intellectual disability
  Mouth disorder
• UniProt ID: CAF1B_HUMAN
• PDB ID: 7Y5K; 7Y5L; 7Y5O; 7Y5U; 7Y5V; 7Y60; 7Y61; 8IQF; 8IQG; 8J6S; 8J6T
• Pfam ID: PF15512 ; PF00400
• Sequence:
  MKVITCEIAWHNKEPVYSLDFQHGTAGRIHRLASAGVDTNVRIWKVEKGPDGKAIVEFLS
  NLARHTKAVNVVRFSPTGEILASGGDDAVILLWKVNDNKEPEQIAFQDEDEAQLNKENWT
  VVKTLRGHLEDVYDICWATDGNLMASASVDNTAIIWDVSKGQKISIFNEHKSYVQGVTWD
  PLGQYVATLSCDRVLRVYSIQKKRVAFNVSKMLSGIGAEGEARSYRMFHDDSMKSFFRRL
  SFTPDGSLLLTPAGCVESGENVMNTTYVFSRKNLKRPIAHLPCPGKATLAVRCCPVYFEL
  RPVVETGVELMSLPYRLVFAVASEDSVLLYDTQQSFPFGYVSNIHYHTLSDISWSSDGAF
  LAISSTDGYCSFVTFEKDELGIPLKEKPVLNMRTPDTAKKTKSQTHRGSSPGPRPVEGTP
  ASRTQDPSSPGTTPPQARQAPAPTVIRDPPSITPAVKSPLPGPSEEKTLQPSSQNTKAHP
  SRRVTLNTLQAWSKTTPRRINLTPLKTDTPPSSVPTSVISTPSTEEIQSETPGDAQGSPP
  ELKRPRLDENKGGTESLDP
• Function: Complex that is thought to mediate chromatin assembly in DNA replication and DNA repair. Assembles histone octamers onto replicating DNA in vitro. CAF-1 performs the first step of the nucleosome assembly process, bringing newly synthesized histones H3 and H4 to replicating DNA; histones H2A/H2B can bind to this chromatin precursor subsequent to DNA replication to complete the histone octamer.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adolescent meningitis	DISYHNYB	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Carcinoma	DISH9F1N	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
leukaemia	DISS7D1V	Strong	Altered Expression	[5]
Leukemia	DISNAKFL	Strong	Altered Expression	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[3]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[7]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[8]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[9]
Laryngeal carcinoma	DISNHCIV	moderate	Genetic Variation	[10]
Laryngeal disorder	DISDKUQO	moderate	Biomarker	[10]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Altered Expression	[10]
Neoplasm	DISZKGEW	moderate	Biomarker	[6]
Cutaneous melanoma	DIS3MMH9	Limited	Biomarker	[11]
facioscapulohumeral muscular dystrophy	DISSE0H0	Limited	Altered Expression	[12]
Intellectual disability	DISMBNXP	Limited	Autosomal recessive	[13]
Mouth disorder	DISX82BI	Limited	Biomarker	[14]

21 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 Chromatin assembly factor 1 subunit B (CHAF1B).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[19]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[21]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[21]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[22]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[23]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[19]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[19]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[19]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[24]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[26]
Arecoline	DMFJZK3	Phase 1	Arecoline decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[28]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[31]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Chromatin assembly factor 1 subunit B (CHAF1B).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Chromatin assembly factor 1 subunit B (CHAF1B).	[29]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Chromatin assembly factor 1 subunit B (CHAF1B).	[29]

References

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• [2] Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down syndrome brain.J Neural Transm Suppl. 2003;(67):117-28. doi: 10.1007/978-3-7091-6721-2_10.
• [3] Clinical significance and prognostic value of chromatin assembly factor-1 overexpression in human solid tumours.Histopathology. 2010 Nov;57(5):716-24. doi: 10.1111/j.1365-2559.2010.03681.x.
• [4] CHAF1B knockdown blocks migration in a hepatocellular carcinoma model.Oncol Rep. 2018 Jul;40(1):405-413. doi: 10.3892/or.2018.6437. Epub 2018 May 16.
• [5] A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis.Cancer Cell. 2018 Nov 12;34(5):707-723.e7. doi: 10.1016/j.ccell.2018.10.004.
• [6] CHAF1B promotes proliferation and reduces apoptosis in 95D lung cancer cells and predicts a poor prognosis in nonsmall cell lung cancer.Oncol Rep. 2019 Apr;41(4):2518-2528. doi: 10.3892/or.2019.6994. Epub 2019 Feb 1.
• [7] CAF-1 Subunits Levels Suggest Combined Treatments with PARP-Inhibitors and Ionizing Radiation in Advanced HNSCC.Cancers (Basel). 2019 Oct 17;11(10):1582. doi: 10.3390/cancers11101582.
• [8] Antiribonuclease H2 antibodies are an immune biomarker for systemic lupus erythematosus.Autoimmunity. 2017 Jun;50(4):241-246. doi: 10.1080/08916934.2017.1329422. Epub 2017 May 27.
• [9] AURKA Phe31Ile polymorphism interacted with use of alcohol, betel quid, and cigarettes at multiplicative risk of oral cancer occurrence.Clin Oral Investig. 2015 Nov;19(8):1825-32. doi: 10.1007/s00784-015-1432-5. Epub 2015 Feb 21.
• [10] Overexpression of chromatin assembly factor-1/p60 predicts biological behaviour of laryngeal carcinomas.Acta Otorhinolaryngol Ital. 2017 Feb;37(1):17-24. doi: 10.14639/0392-100X-867.
• [11] Tissue microarray-based evaluation of Chromatin Assembly Factor-1 (CAF-1)/p60 as tumour prognostic marker.Int J Mol Sci. 2012;13(9):11044-11062. doi: 10.3390/ijms130911044. Epub 2012 Sep 5.
• [12] NuRD and CAF-1-mediated silencing of the D4Z4 array is modulated by DUX4-induced MBD3L proteins.Elife. 2018 Mar 13;7:e31023. doi: 10.7554/eLife.31023.
• [13] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [14] Characterization of arecoline-induced effects on cytotoxicity in normal human gingival fibroblasts by global gene expression profiling. Toxicol Sci. 2007 Nov;100(1):66-74.
• [15] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [16] 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.
• [17] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [20] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [21] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [22] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [23] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [24] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [25] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [26] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [27] Characterization of arecoline-induced effects on cytotoxicity in normal human gingival fibroblasts by global gene expression profiling. Toxicol Sci. 2007 Nov;100(1):66-74.
• [28] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [29] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [30] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [31] 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.
• [32] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.