Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7U0C5Y)

• DOT Name: Pentatricopeptide repeat-containing protein 1, mitochondrial (PTCD1)
• Gene Name: PTCD1
• Related Disease: Alzheimer disease
• UniProt ID: PTCD1_HUMAN
• Pfam ID: PF13812 ; PF17177
• Sequence:
  MDFVRLARLFARARPMGLFILQHLDPCRARWAGGREGLMRPMWAPFSSSSSQLPLGQERQ
  ENTGSLGSDPSHSNSTATQEEDEEEEESFGTLSDKYSSRRLFRKSAAQFHNLRFGERRDE
  QMEPEPKLWRGRRNTPYWYFLQCKHLIKEGKLVEALDLFERQMLKEERLQPMESNYTVLI
  GGCGRVGYLKKAFNLYNQMKKRDLEPSDATYTALFNVCAESPWKDSALQSALKLRQQLQA
  KNFELNLKTYHALLKMAAKCADLRMCLDVFKEIIHKGHVVTEETFSFLLMGCIQDKKTGF
  RYALQVWRLMLSLGLQPSRDSYNLLLVAARDCGLGDPQVASELLLKPREEATVLQPPVSR
  QRPRRTAQAKAGNLMSAMLHVEALERQLFLEPSQALGPPEPPEARVPGKAQPEVDTKAEP
  SHTAALTAVALKPPPVELEVNLLTPGAVPPTVVSFGTVTTPADRLALIGGLEGFLSKMAE
  HRQQPDIRTLTLLAEVVESGSPAESLLLALLDEHQVEADLTFFNTLVRKKSKLGDLEGAK
  ALLPVLAKRGLVPNLQTFCNLAIGCHRPKDGLQLLTDMKKSQVTPNTHIYSALINAAIRK
  LNYTYLISILKDMKQNRVPVNEVVIRQLEFAAQYPPTFDRYQGKNTYLEKIDGFRAYYKQ
  WLTVMPAEETPHPWQKFRTKPQGDQDTGKEADDGCALGGR
• Function: Mitochondrial protein implicated in negative regulation of leucine tRNA levels, as well as negative regulation of mitochondria-encoded proteins and COX activity. Affects also the 3'-processing of mitochondrial tRNAs.
• Tissue Specificity: Abundant in testes, skeletal muscle and heart.

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	Genetic Variation	[1]

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 Pentatricopeptide repeat-containing protein 1, mitochondrial (PTCD1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pentatricopeptide repeat-containing protein 1, mitochondrial (PTCD1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Pentatricopeptide repeat-containing protein 1, mitochondrial (PTCD1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Pentatricopeptide repeat-containing protein 1, mitochondrial (PTCD1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Pentatricopeptide repeat-containing protein 1, mitochondrial (PTCD1).	[6]

References

• [1] PTCD1 Is Required for Mitochondrial Oxidative-Phosphorylation: Possible Genetic Association with Alzheimer's Disease.J Neurosci. 2019 Jun 12;39(24):4636-4656. doi: 10.1523/JNEUROSCI.0116-19.2019. Epub 2019 Apr 4.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Gene expression profiling analysis of bisphenol A-induced perturbation in biological processes in ER-negative HEK293 cells. PLoS One. 2014 Jun 5;9(6):e98635.