Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC2DD7L)

• DOT Name: Pyrin domain-containing protein 1 (PYDC1)
• Synonyms: PAAD-only protein 1; Pyrin-only protein 1; cellular POP1; cPOP1
• Gene Name: PYDC1
• Related Disease:
  Advanced cancer
  Cataract
  Juvenile idiopathic arthritis
  Neoplasm
  Rheumatoid arthritis
  Vitiligo
• UniProt ID: PYDC1_HUMAN
• PDB ID: 2HM2; 4QOB
• Pfam ID: PF02758
• Sequence:
  MGTKREAILKVLENLTPEELKKFKMKLGTVPLREGFERIPRGALGQLDIVDLTDKLVASY
  YEDYAAELVVAVLRDMRMLEEAARLQRAA
• Function: Associates with PYCARD/ASC and modulates its ability to collaborate with MEFV/pyrin and NLRP3/cryopyrin in NF-kappa-B and pro-caspase-1 activation. Suppresses kinase activity of NF-kappa-B inhibitor kinase (IKK) complex, expression of NF-kappa-B inducible genes and inhibits NF-kappa-B activation by cytokines and LPS.
• Tissue Specificity: Predominantly expressed in monocytes, macrophages and granulocytes.
• KEGG Pathway: NOD-like receptor sig.ling pathway (hsa04621)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Cataract	DISUD7SL	Strong	Biomarker	[2]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[3]
Vitiligo	DISR05SL	Strong	Genetic Variation	[3]

2 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 Pyrin domain-containing protein 1 (PYDC1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Pyrin domain-containing protein 1 (PYDC1).	[7]

2 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 Pyrin domain-containing protein 1 (PYDC1).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Pyrin domain-containing protein 1 (PYDC1).	[8]

References

• [1] A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo.J Biol Chem. 1999 Nov 26;274(48):34283-93. doi: 10.1074/jbc.274.48.34283.
• [2] Multiple developmental defects derived from impaired recruitment of ASC-2 to nuclear receptors in mice: implication for posterior lenticonus with cataract.Mol Cell Biol. 2002 Dec;22(24):8409-14. doi: 10.1128/MCB.22.24.8409-8414.2002.
• [3] Inflammasomes and human autoimmunity: A comprehensive review.J Autoimmun. 2015 Jul;61:1-8. doi: 10.1016/j.jaut.2015.05.001. Epub 2015 May 23.
• [4] Somatic mutations of the mixed-lineage leukemia 3 (MLL3) gene in primary breast cancers.Pathol Oncol Res. 2011 Jun;17(2):429-33. doi: 10.1007/s12253-010-9316-0. Epub 2010 Nov 30.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.