Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6BQJ5E)

• DOT Name: Leucine-rich repeat-containing protein 59 (LRRC59)
• Synonyms: Ribosome-binding protein p34; p34
• Gene Name: LRRC59
• Related Disease:
  Ataxia-telangiectasia
  Breast cancer
  Breast carcinoma
  Familial adenomatous polyposis
  Prostate carcinoma
  Skin disease
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Xeroderma pigmentosum
• UniProt ID: LRC59_HUMAN
• Pfam ID: PF00560 ; PF13855
• Sequence:
  MTKAGSKGGNLRDKLDGNELDLSLSDLNEVPVKELAALPKATILDLSCNKLTTLPSDFCG
  LTHLVKLDLSKNKLQQLPADFGRLVNLQHLDLLNNKLVTLPVSFAQLKNLKWLDLKDNPL
  DPVLAKVAGDCLDEKQCKQCANKVLQHMKAVQADQERERQRRLEVEREAEKKREAKQRAK
  EAQERELRKREKAEEKERRRKEYDALKAAKREQEKKPKKEANQAPKSKSGSRPRKPPPRK
  HTRSWAVLKLLLLLLLFGVAGGLVACRVTELQQQPLCTSVNTIYDNAVQGLRRHEILQWV
  LQTDSQQ
• Function: Required for nuclear import of FGF1, but not that of FGF2. Might regulate nuclear import of exogenous FGF1 by facilitating interaction with the nuclear import machinery and by transporting cytosolic FGF1 to, and possibly through, the nuclear pores.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[4]
Skin disease	DISDW8R6	Strong	Genetic Variation	[5]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[6]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[6]
Xeroderma pigmentosum	DISQ9H19	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Leucine-rich repeat-containing protein 59 (LRRC59) affects the binding of 4-hydroxy-2-nonenal.	[18]

10 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 Leucine-rich repeat-containing protein 59 (LRRC59).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Leucine-rich repeat-containing protein 59 (LRRC59).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Leucine-rich repeat-containing protein 59 (LRRC59).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Leucine-rich repeat-containing protein 59 (LRRC59).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Leucine-rich repeat-containing protein 59 (LRRC59).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Leucine-rich repeat-containing protein 59 (LRRC59).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Leucine-rich repeat-containing protein 59 (LRRC59).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Leucine-rich repeat-containing protein 59 (LRRC59).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Leucine-rich repeat-containing protein 59 (LRRC59).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Leucine-rich repeat-containing protein 59 (LRRC59).	[17]

References

• [1] Ionizing radiation-induced phosphorylation of RPA p34 is deficient in ataxia telangiectasia and reduced in aged normal fibroblasts.Radiother Oncol. 1996 Apr;39(1):43-52. doi: 10.1016/0167-8140(96)01712-4.
• [2] Translating Proteomic Into Functional Data: An High Mobility Group A1 (HMGA1) Proteomic Signature Has Prognostic Value in Breast Cancer.Mol Cell Proteomics. 2016 Jan;15(1):109-23. doi: 10.1074/mcp.M115.050401. Epub 2015 Nov 2.
• [3] Phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) by the cyclin-dependent kinase p34.J Biol Chem. 1997 Aug 29;272(35):21681-4. doi: 10.1074/jbc.272.35.21681.
• [4] Leucine-rich repeat-containing protein 59 mediates nuclear import of cancerous inhibitor of PP2A in prostate cancer cells.Tumour Biol. 2015 Aug;36(8):6383-90. doi: 10.1007/s13277-015-3326-1. Epub 2015 Apr 2.
• [5] Clathrin Adaptor Complex-interacting Protein Irc6 Functions through the Conserved C-Terminal Domain.Sci Rep. 2019 Mar 14;9(1):4436. doi: 10.1038/s41598-019-40852-8.
• [6] Identification of recurrent fusion genes across multiple cancer types.Sci Rep. 2019 Jan 31;9(1):1074. doi: 10.1038/s41598-019-38550-6.
• [7] The intricate network between the p34 and p44 subunits is central to the activity of the transcription/DNA repair factor TFIIH.Nucleic Acids Res. 2017 Oct 13;45(18):10872-10883. doi: 10.1093/nar/gkx743.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] 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.
• [10] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [11] 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.
• [12] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [13] 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.
• [14] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [15] 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.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Site-specific protein adducts of 4-hydroxy-2(E)-nonenal in human THP-1 monocytic cells: protein carbonylation is diminished by ascorbic acid. Chem Res Toxicol. 2010 Jan;23(1):37-47. doi: 10.1021/tx9002462.