Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWY1A9V)

• DOT Name: Deleted in azoospermia protein 4 (DAZ4)
• Gene Name: DAZ4
• Related Disease:
  Oligospermia
  Male infertility
• UniProt ID: DAZ4_HUMAN
• Pfam ID: PF18872 ; PF00076
• Sequence:
  MSAANPETPNSTISREASTQSSSAAASQGWVLPEGKIVPNTVFVGGIDARMDETEIGSCF
  GRYGSVKEVKIITNRTGVSKGYGFVSFVNDVDVQKIVGSQIHFHGKKLKLGPAIRKQKLC
  ARHVQPRPLVVNPPPPPQFQNVWRNPNTETYLQPQITPNPVTQHVQSAANPETPNSTISR
  EASTQSSSAAASQGWVLPEGKIVPNTVFVGGIDARMDETEIGSCFGRYGSVKEVKIITNR
  TGVSKGYGFVSFVNDVDVQKIVGSQIHFHGKKLKLGPAIRKQKLCARHVQPRPLVVNPPP
  PPQFQNVWRNPNTETYLQPQITPNPVTQHVQAYSAYPHSPGQVITGCQLLVYNYQEYPTY
  PDSAFQVTTGYQLPVYNYQPFPAYPRSPFQVTAGYQLPVYNYQAFPAYPNSPFQVATGYQ
  FPVYNYQPFPAYPSSPFQVTAGYQLPVYNYQAFPAYPNSPFQVATGYQFPVYNYQAFPAY
  PNSPVQVTTGYQLPVYNYQAFPAYPSSPFQVTTGYQLPVYNYQAFPAYPNSAVQVTTGYQ
  FHVYNYQMPPQCPVGEQRRNLWTEAYKWWYLVCLIQRRD
• Function: RNA-binding protein that plays an essential role in spermatogenesis. May act by binding to the 3'-UTR of mRNAs and regulating their translation.
• Tissue Specificity: Testis-specific. Expression restricted to premeiotic germ cells, particularly in spermatogonia (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oligospermia	DIS6YJF3	Strong	Biomarker	[1]
Male infertility	DISY3YZZ	Limited	Genetic Variation	[2]

1 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 Deleted in azoospermia protein 4 (DAZ4).	[3]

2 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 Deleted in azoospermia protein 4 (DAZ4).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Deleted in azoospermia protein 4 (DAZ4).	[5]

References

• [1] Combined deletion of DAZ2 and DAZ4 copies of Y chromosome DAZ gene is associated with male infertility in Tunisian men.Gene. 2014 Sep 1;547(2):191-4. doi: 10.1016/j.gene.2014.05.061. Epub 2014 May 28.
• [2] gr/gr-DAZ2-DAZ4-CDY1b deletion is a high-risk factor for male infertility in Tunisian population.Gene. 2016 Oct 30;592(1):29-35. doi: 10.1016/j.gene.2016.07.050. Epub 2016 Jul 22.
• [3] 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.
• [4] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [5] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.