Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLM93UO)

• DOT Name: Ankyrin repeat, SAM and basic leucine zipper domain-containing protein 1 (ASZ1)
• Synonyms: Ankyrin-like protein 1; Germ cell-specific ankyrin, SAM and basic leucine zipper domain-containing protein
• Gene Name: ASZ1
• Related Disease:
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Bacillary dysentery
  Colitis
  Esophageal adenocarcinoma
  Gastroenteritis
  Influenza
  Prostate cancer
  Prostate neoplasm
  Coronary heart disease
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
  Middle East Respiratory Syndrome (MERS)
• UniProt ID: ASZ1_HUMAN
• Pfam ID: PF00023 ; PF12796 ; PF07647
• Sequence:
  MAASALRGLPVAGGGESSESEDDGWEIGYLDRTSQKLKRLLPIEEKKEKFKKAMTIGDVS
  LVQELLDSGISVDSNFQYGWTPLMYAASVANAELVRVLLDRGANASFEKDKQSILITACS
  AHGSEEQILKCVELLLSRNADPNVACRRLMTPIMYAARDGHTQVVALLVAHGAEVNTQDE
  NGYTALTWAARQGHKNIVLKLLELGANKMLQTKDGKMPSEIAKRNKHHEIFNLLSFTLNP
  LEGKLQQLTKEDTICKILTTDSDREKDHIFSSYTAFGDLEVFLHGLGLEHMTDLLKERDI
  TLRHLLTMREDEFTKNGITSKDQQKILAALKELQVEEIQFGELSEETKLEISGDEFLNFL
  LKLNKQCGHLITAVQNVITELPVNSQKITLEWASPQNFTSVCEELVNNVEDLSEKVCKLK
  DLIQKLQNERENDPTHIQLREEVSTWNSRILKRTAITICGFGFLLFICKLTFQRK
• Function: Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with pi-bodies suggests a participation in the primary piRNAs metabolic process. Required prior to the pachytene stage to facilitate the production of multiple types of piRNAs, including those associated with repeats involved in the regulation of retrotransposons. May act by mediating protein-protein interactions during germ cell maturation.
• Tissue Specificity: Expressed exclusively in the testis and ovary and at higher levels in the adult testis compared with the adult ovary.
• Reactome Pathway: PIWI-interacting RNA (piRNA) biogenesis (R-HSA-5601884)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Bacillary dysentery	DISFZHKN	Strong	Genetic Variation	[3]
Colitis	DISAF7DD	Strong	Biomarker	[4]
Esophageal adenocarcinoma	DISODWFP	Strong	Genetic Variation	[5]
Gastroenteritis	DISXQCG5	Strong	Altered Expression	[6]
Influenza	DIS3PNU3	Strong	Biomarker	[7]
Prostate cancer	DISF190Y	Strong	Biomarker	[8]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[8]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[9]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Moderate	Autosomal recessive	[10]
Middle East Respiratory Syndrome (MERS)	DIS5VPYU	Limited	Genetic Variation	[11]

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 Ankyrin repeat, SAM and basic leucine zipper domain-containing protein 1 (ASZ1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ankyrin repeat, SAM and basic leucine zipper domain-containing protein 1 (ASZ1).	[13]

References

• [1] Protein isoforms encoded by the pX region of human T-cell leukemia/lymphotropic virus type I.Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8813-7. doi: 10.1073/pnas.89.18.8813.
• [2] Porcine circovirus type 2 ORF3 protein induces apoptosis in melanoma cells.BMC Cancer. 2018 Dec 10;18(1):1237. doi: 10.1186/s12885-018-5090-2.
• [3] EspG, a novel type III system-secreted protein from enteropathogenic Escherichia coli with similarities to VirA of Shigella flexneri.Infect Immun. 2001 Jun;69(6):4027-33. doi: 10.1128/IAI.69.6.4027-4033.2001.
• [4] Structural characterization of water-soluble polysaccharide from Arctium lappa and its effects on colitis mice.Carbohydr Polym. 2019 Jun 1;213:89-99. doi: 10.1016/j.carbpol.2019.02.090. Epub 2019 Feb 27.
• [5] Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.Lancet Oncol. 2016 Oct;17(10):1363-1373. doi: 10.1016/S1470-2045(16)30240-6. Epub 2016 Aug 12.
• [6] Molecular epidemiology of outbreaks of gastroenteritis associated with small round structured viruses in Germany in 1997/98.Arch Virol. 2000;145(3):443-53. doi: 10.1007/s007050050038.
• [7] The role of ORF3 accessory protein in replication of cell-adapted porcine epidemic diarrhea virus (PEDV).Arch Virol. 2017 Sep;162(9):2553-2563. doi: 10.1007/s00705-017-3390-5. Epub 2017 May 4.
• [8] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [9] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [10] A genomics approach to male infertility. Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.
• [11] MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis.mBio. 2017 Aug 22;8(4):e00665-17. doi: 10.1128/mBio.00665-17.
• [12] 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.
• [13] 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.