Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXG3OGK)

• DOT Name: Probable C-mannosyltransferase DPY19L2 (DPY19L2)
• Synonyms: EC 2.4.1.-; Dpy-19-like protein 2; Protein dpy-19 homolog 2
• Gene Name: DPY19L2
• Related Disease:
  Spermatogenic failure 9
  Male infertility due to globozoospermia
• UniProt ID: D19L2_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF10034
• Sequence:
  MRKQGVSSKRLQSSGRSQSKGRRGASLAREPEVEEEMEKSALGGGKLPRGSWRSSPGRIQ
  SLKERKGLELEVVAKTFLLGPFQFVRNSLAQLREKVQELQARRFSSRTTLGIAVFVAILH
  WLHLVTLFENDRHFSHLSSLEREMTFRTEMGLYYSYFKTIIEAPSFLEGLWMIMNDRLTE
  YPLIINAIKRFHLYPEVIIASWYCTFMGIMNLFGLETKTCWNVTRIEPLNEVQSCEGLGD
  PACFYVGVIFILNGLMMGLFFMYGAYLSGTQLGGLITVLCFFFNHGEATRVMWTPPLRES
  FSYPFLVLQMCILTLILRTSSNDRRPFIALCLSNVAFMLPWQFAQFILFTQIASLFPMYV
  VGYIEPSKFQKIIYMNMISVTLSFILMFGNSMYLSSYYSSSLLMTWAIILKRNEIQKLGV
  SKLNFWLIQGSAWWCGTIILKFLTSKILGVSDHIRLSDLIAARILRYTDFDTLIYTCAPE
  FDFMEKATPLRYTKTLLLPVVMVITCFIFKKTVRDISYVLATNIYLRKQLLEHSELAFHT
  LQLLVFTALAILIMRLKMFLTPHMCVMASLICSRQLFGWLFRRVRFEKVIFGILTVMSIQ
  GYANLRNQWSIIGEFNNLPQEELLQWIKYSTTSDAVFAGAMPTMASIKLSTLHPIVNHPH
  YEDADLRARTKIVYSTYSRKSAKEVRDKLLELHVNYYVLEEAWCVVRTKPGCSMLEIWDV
  EDPSNAANPPLCSVLLEDARPYFTTVFQNSVYRVLKVN
• Function: Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins; Required during spermatogenesis for sperm head elongation and acrosome formation. Also plays a role in acrosome attachment to the nuclear envelope.
• Tissue Specificity: Widely expressed with high expression in testis. Not detectable in ejaculated sperm (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
Spermatogenic failure 9	DISJEBH2	Strong	Autosomal recessive	[1]
Male infertility due to globozoospermia	DIS7EMCO	Supportive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Probable C-mannosyltransferase DPY19L2 (DPY19L2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable C-mannosyltransferase DPY19L2 (DPY19L2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Probable C-mannosyltransferase DPY19L2 (DPY19L2).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Probable C-mannosyltransferase DPY19L2 (DPY19L2).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Probable C-mannosyltransferase DPY19L2 (DPY19L2).	[8]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Probable C-mannosyltransferase DPY19L2 (DPY19L2).	[7]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] DPY19L2 deletion as a major cause of globozoospermia. Am J Hum Genet. 2011 Mar 11;88(3):344-50. doi: 10.1016/j.ajhg.2011.01.018.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] 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.