Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2HI0QE)

• DOT Name: La-related protein 4B (LARP4B)
• Synonyms: La ribonucleoprotein domain family member 4B; La ribonucleoprotein domain family member 5; La-related protein 5
• Gene Name: LARP4B
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Chronic renal failure
  Liver cancer
  Acute myelogenous leukaemia
  Adenocarcinoma
  Advanced cancer
  Familial prostate carcinoma
  Glioblastoma multiforme
  Glioma
  Neoplasm
  Prostate cancer
  Prostate cancer, hereditary, 1
  Prostate carcinoma
• UniProt ID: LAR4B_HUMAN
• PDB ID: 3PTH
• Pfam ID: PF05383
• Sequence:
  MTSDQDAKVVAEPQTQRVQEGKDSAHLMNGPISQTTSQTSSIPPLSQVPATKVSELNPNA
  EVWGAPVLHLEASSAADGVSAAWEEVAGHHADRGPQGSDANGDGDQGHENAALPDPQESD
  PADMNALALGPSEYDSLPENSETGGNESQPDSQEDPREVLKKTLEFCLSRENLASDMYLI
  SQMDSDQYVPITTVANLDHIKKLSTDVDLIVEVLRSLPLVQVDEKGEKVRPNQNRCIVIL
  REISESTPVEEVEALFKGDNLPKFINCEFAYNDNWFITFETEADAQQAYKYLREEVKTFQ
  GKPIKARIKAKAIAINTFLPKNGFRPLDVSLYAQQRYATSFYFPPMYSPQQQFPLYSLIT
  PQTWSATHSYLDPPLVTPFPNTGFINGFTSPAFKPAASPLTSLRQYPPRSRNPSKSHLRH
  AIPSAERGPGLLESPSIFNFTADRLINGVRSPQTRQAGQTRTRIQNPSAYAKREAGPGRV
  EPGSLESSPGLGRGRKNSFGYRKKREEKFTSSQTQSPTPPKPPSPSFELGLSSFPPLPGA
  AGNLKTEDLFENRLSSLIIGPSKERTLSADASVNTLPVVVSREPSVPASCAVSATYERSP
  SPAHLPDDPKVAEKQRETHSVDRLPSALTATACKSVQVNGAATELRKPSYAEICQRTSKE
  PPSSPLQPQKEQKPNTVGCGKEEKKLAEPAERYREPPALKSTPGAPRDQRRPAGGRPSPS
  AMGKRLSREQSTPPKSPQ
• Function: Stimulates mRNA translation.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Biomarker	[1]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[2]
Liver cancer	DISDE4BI	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[5]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[6]
Glioma	DIS5RPEH	Strong	Altered Expression	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Altered Expression	[7]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	La-related protein 4B (LARP4B) affects the response to substance of Fluorouracil.	[21]

11 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 La-related protein 4B (LARP4B).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of La-related protein 4B (LARP4B).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of La-related protein 4B (LARP4B).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of La-related protein 4B (LARP4B).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of La-related protein 4B (LARP4B).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of La-related protein 4B (LARP4B).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of La-related protein 4B (LARP4B).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of La-related protein 4B (LARP4B).	[15]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of La-related protein 4B (LARP4B).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of La-related protein 4B (LARP4B).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of La-related protein 4B (LARP4B).	[20]

4 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 affects the methylation of La-related protein 4B (LARP4B).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of La-related protein 4B (LARP4B).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of La-related protein 4B (LARP4B).	[19]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of La-related protein 4B (LARP4B).	[18]

References

• [1] Expression of La Ribonucleoprotein Domain Family Member 4B (LARP4B) in Liver Cancer and Their Clinical and Prognostic Significance.Dis Markers. 2019 Oct 22;2019:1569049. doi: 10.1155/2019/1569049. eCollection 2019.
• [2] A catalog of genetic loci associated with kidney function from analyses of a million individuals.Nat Genet. 2019 Jun;51(6):957-972. doi: 10.1038/s41588-019-0407-x. Epub 2019 May 31.
• [3] La-related protein 4B maintains murine MLL-AF9 leukemia stem cell self-renewal by regulating cell cycle progression.Exp Hematol. 2015 Apr;43(4):309-18.e2. doi: 10.1016/j.exphem.2014.12.003. Epub 2014 Dec 20.
• [4] A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay.Nat Commun. 2017 Jun 26;8:15943. doi: 10.1038/ncomms15943.
• [5] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [6] Identification of RNA-Binding Protein LARP4B as a Tumor Suppressor in Glioma.Cancer Res. 2016 Apr 15;76(8):2254-64. doi: 10.1158/0008-5472.CAN-15-2308. Epub 2016 Mar 1.
• [7] MicroRNA?06b functions as an oncogene and regulates tumor viability and metastasis by targeting LARP4B in prostate cancer.Mol Med Rep. 2019 Aug;20(2):951-958. doi: 10.3892/mmr.2019.10343. Epub 2019 Jun 5.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [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] Inhibition of fatty acid synthase expression by 1alpha,25-dihydroxyvitamin D3 in prostate cancer cells. J Steroid Biochem Mol Biol. 2003 May;85(1):1-8. doi: 10.1016/s0960-0760(03)00142-0.
• [15] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [16] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [17] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [18] 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.
• [19] 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.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.