Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU5TYJA)

• DOT Name: Spermatogenesis-associated protein 33 (SPATA33)
• Gene Name: SPATA33
• Related Disease:
  Melanoma
  Squamous cell carcinoma
• UniProt ID: SPT33_HUMAN
• Pfam ID: PF15382
• Sequence:
  MVTHAAGARTFCEEQKKGSTYSVPKSKEKLMEKHSQEARQADRESEKPVDSLHPGAGTAK
  HPPPAASLEEKPDVKQKSSRKKVVVPQIIITRASNETLVSCSSSGSDQQRTIREPEDWGP
  YRRHRNPSTADAYNSHLKE
• Function: Plays an important role in sperm motility and male fertility. Required for sperm midpiece flexibility and for the localization of sperm calcineurin to the mitochondria. Promotes mitophagy as well as acts as an autophagy mediator in male germline cells. Links damaged mitochondria to autophagosomes via its binding to the outer mitochondrial membrane protein VDAC2, as well as to key autophagy machinery component ATG16L1.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Genetic Variation	[1]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[2]

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 Spermatogenesis-associated protein 33 (SPATA33).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Spermatogenesis-associated protein 33 (SPATA33).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Spermatogenesis-associated protein 33 (SPATA33).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Spermatogenesis-associated protein 33 (SPATA33).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Spermatogenesis-associated protein 33 (SPATA33).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Spermatogenesis-associated protein 33 (SPATA33).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Spermatogenesis-associated protein 33 (SPATA33).	[9]

References

• [1] A unique genome-wide association analysis in extended Utah high-risk pedigrees identifies a novel melanoma risk variant on chromosome arm 10q.Hum Genet. 2012 Jan;131(1):77-85. doi: 10.1007/s00439-011-1048-z. Epub 2011 Jun 26.
• [2] Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma.J Invest Dermatol. 2016 May;136(5):930-937. doi: 10.1016/j.jid.2016.01.013. Epub 2016 Jan 29.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] 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.
• [9] 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.