Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXQ59IZ)

• DOT Name: Pentatricopeptide repeat-containing protein 2, mitochondrial (PTCD2)
• Gene Name: PTCD2
• Related Disease: Alzheimer disease
• UniProt ID: PTCD2_HUMAN
• Pfam ID: PF10037
• Sequence:
  MVRDSMAAAFRPSNRVLLQALQILVYPGVGGSGSVSCRCPLGAKRYLLTDNVVKLKEFQQ
  KKVAVACNLSGTKETYFRNLKKKLTQNKLILKGELITLLHLCESRDHVELAKNVIYRYHA
  ENKNFTLGEYKFGPLFVRLCYELDLEESAVELMKDQHLRGFFSDSTSFNILMDMLFIKGK
  YKSALQVLIEMKNQDVKFTKDTYVLAFAICYKLNSPESFKICTTLREEALLKGEILSRRA
  SCFAVALALNQNEMAKAVSIFSQIMNPESIACINLNIIIHIQSNMLENLIKTLKNAAEGN
  LSKFVKRHVFSEEVLAKVREKVKDVPALVAKFDEIYGTLHITGQVTTDSLDAVLCHTPRD
  RKSHTLLLNKRMVSRRTFQPLSQSLLAE
• Function: Involved in mitochondrial RNA maturation and mitochondrial respiratory chain function.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]

9 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 Pentatricopeptide repeat-containing protein 2, mitochondrial (PTCD2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pentatricopeptide repeat-containing protein 2, mitochondrial (PTCD2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pentatricopeptide repeat-containing protein 2, mitochondrial (PTCD2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pentatricopeptide repeat-containing protein 2, mitochondrial (PTCD2).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Pentatricopeptide repeat-containing protein 2, mitochondrial (PTCD2).	[6]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Pentatricopeptide repeat-containing protein 2, mitochondrial (PTCD2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pentatricopeptide repeat-containing protein 2, mitochondrial (PTCD2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Pentatricopeptide repeat-containing protein 2, mitochondrial (PTCD2).	[9]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Pentatricopeptide repeat-containing protein 2, mitochondrial (PTCD2).	[10]

References

• [1] Neuronal PAD4 expression and protein citrullination: possible role in production of autoantibodies associated with neurodegenerative disease.J Autoimmun. 2012 Jun;38(4):369-80. doi: 10.1016/j.jaut.2012.03.004. Epub 2012 May 2.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [10] 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.