Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNURO9F)

• DOT Name: DAZ-associated protein 2 (DAZAP2)
• Synonyms: Deleted in azoospermia-associated protein 2; Proline-rich transcript in brain protein
• Gene Name: DAZAP2
• Related Disease:
  Depression
  Immunodeficiency
  Plasma cell myeloma
  Advanced cancer
• UniProt ID: DAZP2_HUMAN
• Pfam ID: PF11029
• Sequence:
  MNSKGQYPTQPTYPVQPPGNPVYPQTLHLPQAPPYTDAPPAYSELYRPSFVHPGAATVPT
  MSAAFPGASLYLPMAQSVAVGPLGSTIPMAYYPVGPIYPPGSTVLVEGGYDAGARFGAGA
  TAGNIPPPPPGCPPNAAQLAVMQGANVLVTQRKGNFFMGGSDGGYTIW
• Function: In unstressed cells, promotes SIAH1-mediated polyubiquitination and degradation of the serine/threonine-protein kinase HIPK2, probably by acting as a loading factor that potentiates complex formation between HIPK2 and ubiquitin ligase SIAH1. In response to DNA damage, localizes to the nucleus following phosphorylation by HIPK2 and modulates the expression of a subset of TP53/p53 target genes by binding to TP53 at target gene promoters. This limits the expression of a number of cell death-mediating TP53 target genes, reducing DNA damage-induced cell death. Enhances the binding of transcription factor TCF7L2/TCF4, a Wnt signaling pathway effector, to the promoters of target genes. Plays a role in stress granule formation.
• Tissue Specificity: Widely expressed. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocytes. Down-regulated in multiple myeloma.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Depression	DIS3XJ69	Strong	Posttranslational Modification	[1]
Immunodeficiency	DIS093I0	Strong	Biomarker	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Posttranslational Modification	[3]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[3]

10 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 DAZ-associated protein 2 (DAZAP2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of DAZ-associated protein 2 (DAZAP2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DAZ-associated protein 2 (DAZAP2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of DAZ-associated protein 2 (DAZAP2).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of DAZ-associated protein 2 (DAZAP2).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of DAZ-associated protein 2 (DAZAP2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of DAZ-associated protein 2 (DAZAP2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DAZ-associated protein 2 (DAZAP2).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of DAZ-associated protein 2 (DAZAP2).	[12]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of DAZ-associated protein 2 (DAZAP2).	[13]

References

• [1] Epigenome-wide association study of depression symptomatology in elderly monozygotic twins.Transl Psychiatry. 2019 Sep 2;9(1):214. doi: 10.1038/s41398-019-0548-9.
• [2] Deleted in azoospermia-associated protein 2 regulates innate immunity by stimulating Hippo signaling in crab.J Biol Chem. 2019 Oct 4;294(40):14704-14716. doi: 10.1074/jbc.RA119.009559. Epub 2019 Aug 8.
• [3] Promoter methylation induced epigenetic silencing of DAZAP2, a downstream effector of p38/MAPK pathway, in multiple myeloma cells.Cell Signal. 2019 Aug;60:136-145. doi: 10.1016/j.cellsig.2019.04.012. Epub 2019 Apr 26.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [13] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.