Details of Drug Off-Target (DOT)

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

• DOT Name: Caspase recruitment domain-containing protein 19 (CARD19)
• Synonyms: Bcl10-interacting CARD protein; BinCARD
• Gene Name: CARD19
• UniProt ID: CAR19_HUMAN
• PDB ID: 4DWN; 4FH0
• Sequence:
  MTDQTYCDRLVQDTPFLTGHGRLSEQQVDRIILQLNRYYPQILTNKEAEKFRNPKASLRV
  RLCDLLSHLQRSGERDCQEFYRALYIHAQPLHSRLPSRHALRKFHITNHACLVLARGGHP
  SLPLMAWMSSMTTQVCCSPGLASPLASAPPQRPPSGPEGRVWQAQAVQMLVSVSHFLPLP
  PSLSHGSFHTAWGILYVHSCPSFSNLIPRGSLHVCVDSNLVPTAAWRS
• Function: Plays a role in inhibiting the effects of BCL10-induced activation of NF-kappa-B. May inhibit the phosphorylation of BCL10 in a CARD-dependent manner.
• Tissue Specificity: Expressed in ovary, testis, placenta, skeletal muscle, kidney, lung, heart and liver (at protein level). Expressed in thymus and brain.

Molecular Interaction Atlas (MIA) of This DOT

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 Caspase recruitment domain-containing protein 19 (CARD19).	[1]

10 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 Caspase recruitment domain-containing protein 19 (CARD19).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Caspase recruitment domain-containing protein 19 (CARD19).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Caspase recruitment domain-containing protein 19 (CARD19).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Caspase recruitment domain-containing protein 19 (CARD19).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Caspase recruitment domain-containing protein 19 (CARD19).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Caspase recruitment domain-containing protein 19 (CARD19).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Caspase recruitment domain-containing protein 19 (CARD19).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Caspase recruitment domain-containing protein 19 (CARD19).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Caspase recruitment domain-containing protein 19 (CARD19).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Caspase recruitment domain-containing protein 19 (CARD19).	[11]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] 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.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.