Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT48CG1W)

• DOT Name: DNL-type zinc finger protein (DNLZ)
• Synonyms: Hsp70-escort protein 1; HEP1; mtHsp70-escort protein
• Gene Name: DNLZ
• Related Disease:
  Advanced cancer
  Anemia
  Autosomal dominant familial periodic fever
  Breast adenocarcinoma
  Colon cancer
  Colon carcinoma
  Familial Alzheimer disease
  Fatty liver disease
  Hepatitis B virus infection
  Laryngeal squamous cell carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Non-alcoholic fatty liver disease
  Rabies
  Melanoma
  Glaucoma/ocular hypertension
  Neuroblastoma
• UniProt ID: DNLZ_HUMAN
• Pfam ID: PF05180
• Sequence:
  MLRTALRGAPRLLSRVQPRAPCLRRLWGRGARPEVAGRRRAWAWGWRRSSSEQGPGPAAA
  LGRVEAAHYQLVYTCKVCGTRSSKRISKLAYHQGVVIVTCPGCQNHHIIADNLGWFSDLN
  GKRNIEEILTARGEQVHRVAGEGALELVLEAAGAPTSTAAPEAGEDEGPPSPGKTEPS
• Function: May function as a co-chaperone towards HSPA9/mortalin which, by itself, is prone to self-aggregation.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Anemia	DISTVL0C	Strong	Biomarker	[2]
Autosomal dominant familial periodic fever	DISCRNV1	Strong	Genetic Variation	[3]
Breast adenocarcinoma	DISMPHJ0	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[5]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[6]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[7]
Laryngeal squamous cell carcinoma	DIS9UUVF	Strong	Biomarker	[8]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[6]
Rabies	DISSC4V5	Strong	Biomarker	[11]
Melanoma	DIS1RRCY	Disputed	Biomarker	[12]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[13]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[12]

2 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 DNL-type zinc finger protein (DNLZ).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of DNL-type zinc finger protein (DNLZ).	[17]

6 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 DNL-type zinc finger protein (DNLZ).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DNL-type zinc finger protein (DNLZ).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of DNL-type zinc finger protein (DNLZ).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNL-type zinc finger protein (DNLZ).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of DNL-type zinc finger protein (DNLZ).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DNL-type zinc finger protein (DNLZ).	[21]

References

• [1] Discovery, synthesis and molecular substantiation of N-(benzo[d]thiazol-2-yl)-2-hydroxyquinoline-4-carboxamides as anticancer agents.Bioorg Chem. 2019 Oct;91:103171. doi: 10.1016/j.bioorg.2019.103171. Epub 2019 Jul 30.
• [2] Hepcidin-25/erythroferrone ratio predicts improvement of anaemia in haemodialysis patients treated with ferric citrate hydrate.Nephrology (Carlton). 2019 Aug;24(8):819-826. doi: 10.1111/nep.13495. Epub 2019 Apr 29.
• [3] Novel markers of inflammation identified in tumor necrosis factor receptor-associated periodic syndrome (TRAPS) by transcriptomic analysis of effects of TRAPS-associated tumor necrosis factor receptor type I mutations in an endothelial cell line.Arthritis Rheum. 2009 Jan;60(1):269-80. doi: 10.1002/art.24147.
• [4] In vitro antiestrogenic effects of aryl methyl sulfone metabolites of polychlorinated biphenyls and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene on 17beta-estradiol-induced gene expression in several bioassay systems.Toxicol Sci. 2002 Oct;69(2):362-72. doi: 10.1093/toxsci/69.2.362.
• [5] Expression of mutant amyloid precursor proteins decreases adhesion and delays differentiation of Hep-1 cells.Brain Res. 2001 Mar 30;896(1-2):146-52. doi: 10.1016/s0006-8993(01)02153-9.
• [6] Roles of Autophagy and Protein Kinase C-epsilon in Lipid Metabolism of Nonalcoholic Fatty Liver Cell Models.Arch Med Res. 2018 Aug;49(6):381-390. doi: 10.1016/j.arcmed.2018.11.006. Epub 2018 Dec 17.
• [7] Effects of ethanol on hepatitis B virus Pre-S/S gene expression in the human hepatocellular carcinoma derived HEP G2 hepatitis B DNA positive cell line.J Hepatol. 1995 Aug;23(2):153-9. doi: 10.1016/0168-8278(95)80329-7.
• [8] Sulindac induces apoptosis and inhibits tumor growth in vivo in head and neck squamous cell carcinoma. Neoplasia. 2007 Mar;9(3):192-9. doi: 10.1593/neo.06781.
• [9] Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway.Oncol Rep. 2013 Aug;30(2):933-8. doi: 10.3892/or.2013.2487. Epub 2013 May 23.
• [10] Validation of R-2-[(18)F]Fluoropropionic Acid as a Potential Tracer for PET Imaging of Liver Cancer.Mol Imaging Biol. 2019 Dec;21(6):1127-1137. doi: 10.1007/s11307-019-01346-1.
• [11] Functional analysis of Rousettus aegyptiacus "signal transducer and activator of transcription 1" (STAT1).Dev Comp Immunol. 2010 May;34(5):598-602. doi: 10.1016/j.dci.2010.01.004. Epub 2010 Jan 15.
• [12] The Structure in Solution of Fibronectin Type III Domain 14 Reveals Its Synergistic Heparin Binding Site.Biochemistry. 2018 Oct 23;57(42):6045-6049. doi: 10.1021/acs.biochem.8b00771. Epub 2018 Oct 11.
• [13] Validation of the structure-function correlation report from the heidelberg edge perimeter and spectral-domain optical coherence tomography.Int Ophthalmol. 2019 Mar;39(3):533-540. doi: 10.1007/s10792-018-0836-z. Epub 2018 Feb 2.
• [14] 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.
• [15] 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.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] 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.
• [18] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [19] 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.
• [20] 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.
• [21] 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.