Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3YMI6Z)

• DOT Name: Protein PRRC1 (PRRC1)
• Synonyms: Proline-rich and coiled-coil-containing protein 1
• Gene Name: PRRC1
• Related Disease: Acute lymphocytic leukaemia
• UniProt ID: PRRC1_HUMAN
• Pfam ID: PF01931
• Sequence:
  MMEESGIETTPPGTPPPNPAGLAATAMSSTPVPLAATSSFSSPNVSSMESFPPLAYSTPQ
  PPLPPVRPSAPLPFVPPPAVPSVPPLVTSMPPPVSPSTAAAFGNPPVSHFPPSTSAPNTL
  LPAPPSGPPISGFSVGSTYDITRGHAGRAPQTPLMPSFSAPSGTGLLPTPITQQASLTSL
  AQGTGTTSAITFPEEQEDPRITRGQDEASAGGIWGFIKGVAGNPMVKSVLDKTKHSVESM
  ITTLDPGMAPYIKSGGELDIVVTSNKEVKVAAVRDAFQEVFGLAVVVGEAGQSNIAPQPV
  GYAAGLKGAQERIDSLRRTGVIHEKQTAVSVENFIAELLPDKWFDIGCLVVEDPVHGIHL
  ETFTQATPVPLEFVQQAQSLTPQDYNLRWSGLLVTVGEVLEKSLLNVSRTDWHMAFTGMS
  RRQMIYSAARAIAGMYKQRLPPRTV
• Function: May act as a regulator of the protein kinase A (PKA) activity during embryonic development.
• Tissue Specificity: Ubiquitously expressed with higher expression in kidney, liver and placenta . Detected in embryonic kidney cells (HEK293 cells) (at protein level) .; [Isoform 4]: Specifically expressed in liver.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein PRRC1 (PRRC1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein PRRC1 (PRRC1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein PRRC1 (PRRC1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein PRRC1 (PRRC1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein PRRC1 (PRRC1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein PRRC1 (PRRC1).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein PRRC1 (PRRC1).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein PRRC1 (PRRC1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein PRRC1 (PRRC1).	[12]

2 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 increases the methylation of Protein PRRC1 (PRRC1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protein PRRC1 (PRRC1).	[11]

References

• [1] MLL partner genes in secondary acute lymphoblastic leukemia: report of a new partner PRRC1 and review of the literature.Leuk Res. 2014 Nov;38(11):1316-9. doi: 10.1016/j.leukres.2014.08.011. Epub 2014 Aug 29.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] 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.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [8] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [10] 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.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.