Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT56XAQK)

• DOT Name: Proline-rich protein 7 (PRR7)
• Synonyms: Synaptic proline-rich membrane protein
• Gene Name: PRR7
• UniProt ID: PRR7_HUMAN
• Sequence:
  MVMSQGTYTFLTCFAGFWLIWGLIVLLCCFCSFLRRRLKRRQEERLREQNLRALELEPLE
  LEGSLAGSPPGLAPPQPPPHRSRLEAPAHAHSHPHVHVHPLLHHGPAQPHAHAHPHPHHH
  ALPHPPPTHLSVPPRPWSYPRQAESDMSKPPCYEEAVLMAEPPPPYSEVLTDTRGLYRKI
  VTPFLSRRDSAEKQEQPPPSYKPLFLDRGYTSALHLPSAPRPAPPCPALCLQADRGRRVF
  PSWTDSELSSREPLEHGAWRLPVSIPLFGRTTAV
• Function: Acts as a synapse-to-nucleus messenger to promote NMDA receptor-mediated excitotoxicity in neurons in a JUN-dependent manner. Inhibits ubiquitination-mediated degradation and promotes phosphorylation and transcriptional activity of transcription factor JUN. Might play a redundant role in the regulation of T cell receptor signaling. Might promote apoptosis in T cells.
• Tissue Specificity: Strongly expressed in brain tissue including the hippocampus, and moderately expressed in esophagus, trachea, lung, ovary, cervix, prostate, testes, thyroid, thymus, lymph nodes and peripheral blood lymphocytes.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Proline-rich protein 7 (PRR7).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Proline-rich protein 7 (PRR7).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Proline-rich protein 7 (PRR7).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Proline-rich protein 7 (PRR7).	[4]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Proline-rich protein 7 (PRR7).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Proline-rich protein 7 (PRR7).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Proline-rich protein 7 (PRR7).	[7]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Proline-rich protein 7 (PRR7).	[8]

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] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [3] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [4] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [8] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.