Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC3BCO6)

• DOT Name: PDZ domain-containing protein 11 (PDZD11)
• Synonyms: ATPase-interacting PDZ protein; Plasma membrane calcium ATPase-interacting single-PDZ protein; PMCA-interacting single-PDZ protein
• Gene Name: PDZD11
• UniProt ID: PDZ11_HUMAN
• Pfam ID: PF00595
• Sequence:
  MDSRIPYDDYPVVFLPAYENPPAWIPPHERVHHPDYNNELTQFLPRTITLKKPPGAQLGF
  NIRGGKASQLGIFISKVIPDSDAHRAGLQEGDQVLAVNDVDFQDIEHSKAVEILKTAREI
  SMRVRFFPYNYHRQKERTVH
• Function: Mediates docking of ADAM10 to zonula adherens by interacting with PLEKHA7 which is required for PLEKHA7 to interact with the ADAM10-binding protein TSPAN33.
• Tissue Specificity: Widely expressed (at protein level).
• Reactome Pathway:
  Vitamin B5 (pantothenate) metabolism (R-HSA-199220)
  Transport of vitamins, nucleosides, and related molecules (R-HSA-425397)
  Ion influx/efflux at host-pathogen interface (R-HSA-6803544)
  Ion transport by P-type ATPases (R-HSA-936837)
  Biotin transport and metabolism (R-HSA-196780)

Molecular Interaction Atlas (MIA) of This DOT

5 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 PDZ domain-containing protein 11 (PDZD11).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PDZ domain-containing protein 11 (PDZD11).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PDZ domain-containing protein 11 (PDZD11).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of PDZ domain-containing protein 11 (PDZD11).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of PDZ domain-containing protein 11 (PDZD11).	[6]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of PDZ domain-containing protein 11 (PDZD11).	[4]

References

• [1] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.