Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCWSM5T)

• DOT Name: Proline-rich protein 3 (PRR3)
• Synonyms: MHC class I region proline-rich protein CAT56
• Gene Name: PRR3
• Related Disease: Graves disease
• UniProt ID: PRR3_HUMAN
• Pfam ID: PF00642
• Sequence:
  MPKRKKQNHHQPPTQQQPPLPEREETGDEEDGSPIGPPSLLGPPPMANGKPGDPKSALHR
  GPPGSRGPLIPPLLSLPPPPWGRGPIRRGLGPRSSPYGRGWWGVNAEPPFPGPGHGGPTR
  GSFHKEQRNPRRLKSWSLIKNTCPPKDDPQVMEDKSDRPVCRHFAKKGHCRYEDLCAFYH
  PGVNGPPL

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Graves disease	DISU4KOQ	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Proline-rich protein 3 (PRR3) increases the response to substance of Arsenic trioxide.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Proline-rich protein 3 (PRR3).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Proline-rich protein 3 (PRR3).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Proline-rich protein 3 (PRR3).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Proline-rich protein 3 (PRR3).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Proline-rich protein 3 (PRR3).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Proline-rich protein 3 (PRR3).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Proline-rich protein 3 (PRR3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Proline-rich protein 3 (PRR3).	[8]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Proline-rich protein 3 (PRR3).	[9]

References

• [1] Single nucleotide polymorphisms at the PRR3, ABCF1, and GNL1 genes in the HLA class I region are associated with Graves' ophthalmopathy in a gender-dependent manner.Ophthalmology. 2014 Oct;121(10):2033-9. doi: 10.1016/j.ophtha.2014.04.027. Epub 2014 Jun 5.
• [2] 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.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [10] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.