Details of Drug Off-Target (DOT)

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

• DOT Name: PDZ domain-containing protein 4 (PDZD4)
• Synonyms: PDZ domain-containing RING finger protein 4-like protein
• Gene Name: PDZD4
• Related Disease:
  Nephrogenic diabetes insipidus
  Synovial sarcoma
• UniProt ID: PDZD4_HUMAN
• Pfam ID: PF00595
• Sequence:
  MGCNMCVVQKPEEQYKVMLQVNGKELSKLSQEQTLQALRSSKEPLVIQVLRRSPRLRGDS
  SCHDLQLVDSGTQTDITFEHIMALGKLRPPTPPMVILEPPPISHEYYDPAEFMEGGPQEA
  DRLDELEYEEVELYKSSHRDKLGLMVCYRTDDEEDLGIYVGEVNPNSIAAKDGRIREGDR
  IIQINGVDVQNREEAVAILSQEENTNISLLVARPESQLAKRWKDSDRDDFLDDFGSENEG
  ELRARKLKSPPAQQPGNEEEKGAPDAGPGLSNSQELDSGVGRTDESTRNEESSEHDLLGD
  EPPSSTNTPGSLRKFGLQGDALQSRDFHFSMDSLLAEGAGLGGGDVPGLTDEEYERYREL
  LEIKCHLENGNQLGLLFPRASGGNSALDVNRNESLGHEMAMLEEELRHLEFKCRNILRAQ
  KMQQLRERCMKAWLLEEESLYDLAASEPKKHELSDISELPEKSDKDSTSAYNTGESCRST
  PLLVEPLPESPLRRAMAGNSNLNRTPPGPAVATPAKAAPPPGSPAKFRSLSRDPEAGRRQ
  HAEERGRRNPKTGLTLERVGPESSPYLSRRHRGQGQEGEHYHSCVQLAPTRGLEELGHGP
  LSLAGGPRVGGVAAAATEAPRMEWKVKVRSDGTRYVAKRPVRDRLLKARALKIREERSGM
  TTDDDAVSEMKMGRYWSKEERKQHLIRAREQRKRREFMMQSRLECLREQQNGDSKPELNI
  IALSHRKTMKKRNKKILDNWITIQEMLAHGARSADGKRVYNPLLSVTTV
• Tissue Specificity: Brain-specific. Expressed in fetal and adult brain. Up-regulated in synovial carcinomas.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephrogenic diabetes insipidus	DISKNSJK	Strong	Genetic Variation	[1]
Synovial sarcoma	DISEZJS7	Strong	Altered Expression	[2]

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 PDZ domain-containing protein 4 (PDZD4).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of PDZ domain-containing protein 4 (PDZD4).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of PDZ domain-containing protein 4 (PDZD4).	[5]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of PDZ domain-containing protein 4 (PDZD4).	[6]

References

• [1] L1CAM whole gene deletion in a child with L1 syndrome.Am J Med Genet A. 2014 Jun;164A(6):1555-8. doi: 10.1002/ajmg.a.36474. Epub 2014 Mar 25.
• [2] Identification of PDZK4, a novel human gene with PDZ domains, that is upregulated in synovial sarcomas.Oncogene. 2004 Jul 15;23(32):5551-7. doi: 10.1038/sj.onc.1207710.
• [3] 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.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [6] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.