Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ0KRYX)

• DOT Name: Proline-rich protein PRCC (PRCC)
• Synonyms: Papillary renal cell carcinoma translocation-associated gene protein
• Gene Name: PRCC
• Related Disease:
  Renal cell carcinoma
  Advanced cancer
  Clear cell renal carcinoma
  Lung cancer
  Lung carcinoma
  Multiple sclerosis
  Non-small-cell lung cancer
  Relapsing-remitting multiple sclerosis
  Renal carcinoma
  Papillary renal cell carcinoma
• UniProt ID: PRCC_HUMAN
• Pfam ID: PF10253
• Sequence:
  MSLVAYASSDESEPDEAEPEPEEEEAVAPTSGPALGGLFASLPAPKGPALLPPPPQMLAP
  AFPPPLLLPPPTGDPRLQPPPPLPFGLGGFPPPPGVSPAEAAGVGEGLGLGLPSPRGPGL
  NLPPPIGGAGPPLGLPKPKKRKEPVKIAAPELHKGDSDSEEDEPTKKKTILQGSSEGTGL
  SALLPQPKNLTVKETNRLLLPHAFSRKPSDGSPDTKPSRLASKTKTSSLAPVVGTTTTTP
  SPSAIKAAAKSAALQVTKQITQEEDDSDEEVAPENFFSLPEKAEPPGVEPYPYPIPTVPE
  ELPPGTEPEPAFQDDAANAPLEFKMAAGSSGAPWMPKPGDDYSYNQFSTYGDANAAGAYY
  QDYYSGGYYPAQDPALVPPQEIAPDASFIDDEAFKRLQGKRNRGREEINFVEIKGDDQLS
  GAQQWMTKSLTEEKTMKSFSKKKGEQPTGQQRRKHQITYLIHQAKERELELKNTWSENKL
  SRRQTQAKYGF
• Function: May regulate cell cycle progression through interaction with MAD2L2.
• Tissue Specificity: Ubiquitous in fetal and adult tissues.
• KEGG Pathway:
  Transcriptio.l misregulation in cancer (hsa05202)
  Re.l cell carcinoma (hsa05211)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Renal cell carcinoma	DISQZ2X8	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[3]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[3]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]
Relapsing-remitting multiple sclerosis	DISSXFCF	Strong	Biomarker	[4]
Renal carcinoma	DISER9XT	Strong	Altered Expression	[5]
Papillary renal cell carcinoma	DIS25HBV	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Proline-rich protein PRCC (PRCC).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Proline-rich protein PRCC (PRCC).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Proline-rich protein PRCC (PRCC).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Proline-rich protein PRCC (PRCC).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Proline-rich protein PRCC (PRCC).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Proline-rich protein PRCC (PRCC).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Proline-rich protein PRCC (PRCC).	[9]

References

• [1] TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease.Mol Cancer Res. 2019 Aug;17(8):1613-1626. doi: 10.1158/1541-7786.MCR-18-1235. Epub 2019 May 1.
• [2] Impairment of MAD2B-PRCC interaction in mitotic checkpoint defective t(X;1)-positive renal cell carcinomas.Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13808-13. doi: 10.1073/pnas.241304198.
• [3] Potential Oncogenic Role of the Papillary Renal Cell Carcinoma Gene in Non-Small Cell Lung Cancers.Yonsei Med J. 2019 Apr;60(4):326-335. doi: 10.3349/ymj.2019.60.4.326.
• [4] A computational approach based on the colored Petri net formalism for studying multiple sclerosis.BMC Bioinformatics. 2019 Dec 10;20(Suppl 6):623. doi: 10.1186/s12859-019-3196-4.
• [5] PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors.Oncogene. 2001 Jan 11;20(2):178-87. doi: 10.1038/sj.onc.1204056.
• [6] A Novel Genetic Screen Identifies Modifiers of Age-Dependent Amyloid Toxicity in the Drosophila Brain.Front Aging Neurosci. 2017 Mar 14;9:61. doi: 10.3389/fnagi.2017.00061. eCollection 2017.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] 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.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.