Details of Drug Off-Target (DOT)

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

• DOT Name: Protein C-mannosyl-transferase DPY19L1 (DPY19L1)
• Synonyms: EC 2.4.1.-; Dpy-19-like protein 1; Protein dpy-19 homolog 1
• Gene Name: DPY19L1
• UniProt ID: D19L1_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF10034
• Sequence:
  MEGRPPPEGRPPPRPRTGRAPRGRRRAVFAAVLHWSHITHLFENDRHFSHLSTLEREMAF
  RTEMGLYYSYFKTIVEAPSFLNGVWMIMNDKLTEYPLVINTLKRFNLYPEVILASWYRIY
  TKIMDLIGIQTKICWTVTRGEGLSPIESCEGLGDPACFYVAVIFILNGLMMALFFIYGTY
  LSGSRLGGLVTVLCFFFNHGECTRVMWTPPLRESFSYPFLVLQMLLVTHILRATKLYRGS
  LIALCISNVFFMLPWQFAQFVLLTQIASLFAVYVVGYIDICKLRKIIYIHMISLALCFVL
  MFGNSMLLTSYYASSLVIIWGILAMKPHFLKINVSELSLWVIQGCFWLFGTVILKYLTSK
  IFGIADDAHIGNLLTSKFFSYKDFDTLLYTCAAEFDFMEKETPLRYTKTLLLPVVLVVFV
  AIVRKIISDMWGVLAKQQTHVRKHQFDHGELVYHALQLLAYTALGILIMRLKLFLTPHMC
  VMASLICSRQLFGWLFCKVHPGAIVFAILAAMSIQGSANLQTQWNIVGEFSNLPQEELIE
  WIKYSTKPDAVFAGAMPTMASVKLSALRPIVNHPHYEDAGLRARTKIVYSMYSRKAAEEV
  KRELIKLKVNYYILEESWCVRRSKPGCSMPEIWDVEDPANAGKTPLCNLLVKDSKPHFTT
  VFQNSVYKVLEVVKE
• Function: C-mannosyltransferase that mediates the C-mannosylation tryptophan residues on target proteins. The reaction occurs on the luminal side of the endoplasmic reticulum and involves the transfer of a mannose unit from a dolichylphosphate mannose (Dol-P-Man) donor to an acceptor protein containing a WxxW consensus sequence. C-mannosylates the first two tryptophans in the WxxWxxWxxC motif in thrombospondin (TSP) type-1 of UNC5A. Regulates neurite extension during development.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Protein C-mannosyl-transferase DPY19L1 (DPY19L1) affects the response to substance of Fluorouracil.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[1]

10 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 Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[7]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[8]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[9]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Protein C-mannosyl-transferase DPY19L1 (DPY19L1).	[10]

References

• [1] 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.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [4] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] 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.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [9] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [10] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.
• [11] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.