Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3JDA0R)

• DOT Name: DnaJ homolog subfamily C member 2 (DNAJC2)
• Synonyms: M-phase phosphoprotein 11; Zuotin-related factor 1
• Gene Name: DNAJC2
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Gastric cancer
  Head-neck squamous cell carcinoma
  Invasive ductal breast carcinoma
  leukaemia
  Leukemia
  Melanoma
  Neoplasm
  Squamous cell carcinoma
  Stomach cancer
• UniProt ID: DNJC2_HUMAN
• PDB ID: 2M2E; 6CGH
• Pfam ID: PF00226 ; PF00249 ; PF16717
• Sequence:
  MLLLPSAADGRGTAITHALTSASTLCQVEPVGRWFEAFVKRRNRNASASFQELEDKKELS
  EESEDEELQLEEFPMLKTLDPKDWKNQDHYAVLGLGHVRYKATQRQIKAAHKAMVLKHHP
  DKRKAAGEPIKEGDNDYFTCITKAYEMLSDPVKRRAFNSVDPTFDNSVPSKSEAKDNFFE
  VFTPVFERNSRWSNKKNVPKLGDMNSSFEDVDIFYSFWYNFDSWREFSYLDEEEKEKAEC
  RDERRWIEKQNRATRAQRKKEEMNRIRTLVDNAYSCDPRIKKFKEEEKAKKEAEKKAKAE
  AKRKEQEAKEKQRQAELEAARLAKEKEEEEVRQQALLAKKEKDIQKKAIKKERQKLRNSC
  KTWNHFSDNEAERVKMMEEVEKLCDRLELASLQCLNETLTSCTKEVGKAALEKQIEEINE
  QIRKEKEEAEARMRQASKNTEKSTGGGGNGSKNWSEDDLQLLIKAVNLFPAGTNSRWEVI
  ANYMNIHSSSGVKRTAKDVIGKAKSLQKLDPHQKDDINKKAFDKFKKEHGVVPQADNATP
  SERFEGPYTDFTPWTTEEQKLLEQALKTYPVNTPERWEKIAEAVPGRTKKDCMKRYKELV
  EMVKAKKAAQEQVLNASRAKK
• Function: Acts both as a chaperone in the cytosol and as a chromatin regulator in the nucleus. When cytosolic, acts as a molecular chaperone: component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, stimulates the ATPase activity of the ribosome-associated pool of Hsp70-type chaperones HSPA14 that bind to the nascent polypeptide chain. When nuclear, mediates the switching from polycomb-repressed genes to an active state: specifically recruited at histone H2A ubiquitinated at 'Lys-119' (H2AK119ub), and promotes the displacement of the polycomb PRC1 complex from chromatin, thereby facilitating transcription activation.
• Tissue Specificity: Widely expressed.
• Reactome Pathway: Regulation of HSF1-mediated heat shock response (R-HSA-3371453)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[1]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[4]
Invasive ductal breast carcinoma	DIS43J58	Strong	Biomarker	[2]
leukaemia	DISS7D1V	Strong	Biomarker	[5]
Leukemia	DISNAKFL	Strong	Biomarker	[5]
Melanoma	DIS1RRCY	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[4]
Stomach cancer	DISKIJSX	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of DnaJ homolog subfamily C member 2 (DNAJC2).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DnaJ homolog subfamily C member 2 (DNAJC2).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DnaJ homolog subfamily C member 2 (DNAJC2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DnaJ homolog subfamily C member 2 (DNAJC2).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DnaJ homolog subfamily C member 2 (DNAJC2).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DnaJ homolog subfamily C member 2 (DNAJC2).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DnaJ homolog subfamily C member 2 (DNAJC2).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of DnaJ homolog subfamily C member 2 (DNAJC2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DnaJ homolog subfamily C member 2 (DNAJC2).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DnaJ homolog subfamily C member 2 (DNAJC2).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of DnaJ homolog subfamily C member 2 (DNAJC2).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of DnaJ homolog subfamily C member 2 (DNAJC2).	[15]

References

• [1] Overexpression of ZRF1 is related to tumor malignant potential and a poor outcome of gastric carcinoma.Carcinogenesis. 2018 Feb 9;39(2):263-271. doi: 10.1093/carcin/bgx139.
• [2] Role for the transcriptional activator ZRF1 in early metastatic events in breast cancer progression and endocrine resistance.Oncotarget. 2018 Jun 19;9(47):28666-28690. doi: 10.18632/oncotarget.25596. eCollection 2018 Jun 19.
• [3] Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades.Dis Markers. 2016;2016:5128720. doi: 10.1155/2016/5128720. Epub 2016 Oct 25.
• [4] A putative oncogenic role for MPP11 in head and neck squamous cell cancer.Cancer Res. 2000 Oct 1;60(19):5529-35.
• [5] ZRF1 controls the retinoic acid pathway and regulates leukemogenic potential in acute myeloid leukemia.Oncogene. 2014 Nov 27;33(48):5501-10. doi: 10.1038/onc.2013.501. Epub 2013 Dec 2.
• [6] Characterization of several leukemia-associated antigens inducing humoral immune responses in acute and chronic myeloid leukemia.Int J Cancer. 2003 Aug 20;106(2):224-31. doi: 10.1002/ijc.11200.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [15] 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.
• [16] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [17] 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.