Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBXN4YZ)

• DOT Name: Chromatin accessibility complex protein 1 (CHRAC1)
• Synonyms: CHRAC-1; Chromatin accessibility complex 15 kDa protein; CHRAC-15; HuCHRAC15; DNA polymerase epsilon subunit p15
• Gene Name: CHRAC1
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: CHRC1_HUMAN
• Pfam ID: PF00808
• Sequence:
  MADVVVGKDKGGEQRLISLPLSRIRVIMKSSPEVSSINQEALVLTAKATELFVQCLATYS
  YRHGSGKEKKVLTYSDLANTAQQSETFQFLADILPKKILASKYLKMLKEEKREEDEENDN
  DNESDHDEADS
• Function: Forms a complex with DNA polymerase epsilon subunit POLE3 and binds naked DNA, which is then incorporated into chromatin, aided by the nucleosome remodeling activity of ISWI/SNF2H and ACF1. Does not enhance nucleosome sliding activity of the ACF-5 ISWI chromatin remodeling complex.
• Tissue Specificity: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]

8 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 Chromatin accessibility complex protein 1 (CHRAC1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Chromatin accessibility complex protein 1 (CHRAC1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chromatin accessibility complex protein 1 (CHRAC1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Chromatin accessibility complex protein 1 (CHRAC1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Chromatin accessibility complex protein 1 (CHRAC1).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Chromatin accessibility complex protein 1 (CHRAC1).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Chromatin accessibility complex protein 1 (CHRAC1).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Chromatin accessibility complex protein 1 (CHRAC1).	[8]

References

• [1] Allelic expression imbalance polymorphisms in susceptibility chromosome regions and the risk and survival of breast cancer.Mol Carcinog. 2017 Jan;56(1):300-311. doi: 10.1002/mc.22493. Epub 2016 Apr 29.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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.