Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWFM930)

• DOT Name: p53-induced death domain-containing protein 1 (PIDD1)
• Synonyms: EC 3.4.21.-; Leucine-rich repeat and death domain-containing protein
• Gene Name: PIDD1
• Related Disease:
  Advanced cancer
  Attention deficit hyperactivity disorder
  B-cell neoplasm
  Breast carcinoma
  Clear cell renal carcinoma
  Melanoma
  Neoplasm
  Non-small-cell lung cancer
  Papillary renal cell carcinoma
  Renal cell carcinoma
  Squamous cell carcinoma
• UniProt ID: PIDD1_HUMAN
• PDB ID: 2OF5
• EC Number: 3.4.21.-
• Pfam ID: PF00531 ; PF13855 ; PF10461 ; PF00791
• Sequence:
  MAATVEGPELEAAAAAGDASEDSDAGSRALPFLGGNRLSLDLYPGGCQQLLHLCVQQPLQ
  LLQVEFLRLSTHEDPQLLEATLAQLPQSLSCLRSLVLKGGQRRDTLGACLRGALTNLPAG
  LSGLAHLAHLDLSFNSLETLPACVLQMRGLGALLLSHNCLSELPEALGALPALTFLTVTH
  NRLQTLPPALGALSTLQRLDLSQNLLDTLPPEIGGLGSLLELNLASNRLQSLPASLAGLR
  SLRLLVLHSNLLASVPADLARLPLLTRLDLRDNQLRDLPPELLDAPFVRLQGNPLGEASP
  DAPSSPVAALIPEMPRLFLTSDLDSFPVTPQGCSVTLACGVRLQFPAGATATPITIRYRL
  LLPEPGLVPLGPHDALLSHVLELQPHGVAFQQDVGLWLLFTPPQARRCREVVVRTRNDNS
  WGDLETYLEEEAPQRLWAHCQVPHFSWFLVVSRPVSNACLVPPEGTLLCSSGHPGVKVIF
  PPGATEEPRRVSMQVVRMAGRELQALLGEPEAAVSPLLCLSQSGPPSFLQPVTVQLPLPS
  GITGLSLDRSRLHLLYWAPPAATWDDITAQVVLELTHLYARFQVTHFSWYWLWYTTKNCV
  GGLARKAWERLRLHRVNLIALQRRRDPEQVLLQCLPRNKVDATLRRLLERYRGPEPSDTV
  EMFEGEEFFAAFERGIDVDADRPDCVEGRICFVFYSHLKNVKEVYVTTTLDREAQAVRGQ
  VSFYRGAVPVRVPEEAEAARQRKGADALWMATLPIKLPRLRGSEGPRRGAGLSLAPLNLG
  DAETGFLTQSNLLSVAGRLGLDWPAVALHLGVSYREVQRIRHEFRDDLDEQIRHMLFSWA
  ERQAGQPGAVGLLVQALEQSDRQDVAEEVRAVLELGRRKYQDSIRRMGLAPKDPALPGSS
  APQPPEPAQA
• Function: Component of the DNA damage/stress response pathway that functions downstream of p53/TP53 and can either promote cell survival or apoptosis. Associated with CRADD and the CASP2 caspase, it forms the PIDDosome a complex that activates CASP2 and triggers apoptosis. Associated with IKBKG and RIPK1, it enhances sumoylation and ubiquitination of IKBKG which is important for activation of the transcription factor NF-kappa-B.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  NF-kappa B sig.ling pathway (hsa04064)
  p53 sig.ling pathway (hsa04115)
  Apoptosis (hsa04210)
• Reactome Pathway: TP53 Regulates Transcription of Caspase Activators and Caspases (R-HSA-6803207)
• BioCyc Pathway: MetaCyc:ENSG00000177595-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[2]
B-cell neoplasm	DISVY326	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[4]
Melanoma	DIS1RRCY	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[4]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[7]

5 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 p53-induced death domain-containing protein 1 (PIDD1).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of p53-induced death domain-containing protein 1 (PIDD1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of p53-induced death domain-containing protein 1 (PIDD1).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of p53-induced death domain-containing protein 1 (PIDD1).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of p53-induced death domain-containing protein 1 (PIDD1).	[27]

21 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 p53-induced death domain-containing protein 1 (PIDD1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[13]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[14]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[17]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[17]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[18]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of p53-induced death domain-containing protein 1 (PIDD1).	[19]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[19]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[20]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[19]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[20]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[21]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[24]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[28]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of p53-induced death domain-containing protein 1 (PIDD1).	[29]

References

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• [29] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.