Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6TKZTU)

DOT Name Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3)
Synonyms LIG-3
Gene Name LRIG3
Related Disease
Ependymoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Charcot marie tooth disease ( )
Glioblastoma multiforme ( )
Glioma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Neoplasm ( )
Pituitary tumor ( )
UniProt ID
LRIG3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF07679 ; PF13927 ; PF00560 ; PF13855
Sequence
MSAPSLRARAAGLGLLLCAVLGRAGRSDSGGRGELGQPSGVAAERPCPTTCRCLGDLLDC
SRKRLARLPEPLPSWVARLDLSHNRLSFIKASSMSHLQSLREVKLNNNELETIPNLGPVS
ANITLLSLAGNRIVEILPEHLKEFQSLETLDLSSNNISELQTAFPALQLKYLYLNSNRVT
SMEPGYFDNLANTLLVLKLNRNRISAIPPKMFKLPQLQHLELNRNKIKNVDGLTFQGLGA
LKSLKMQRNGVTKLMDGAFWGLSNMEILQLDHNNLTEITKGWLYGLLMLQELHLSQNAIN
RISPDAWEFCQKLSELDLTFNHLSRLDDSSFLGLSLLNTLHIGNNRVSYIADCAFRGLSS
LKTLDLKNNEISWTIEDMNGAFSGLDKLRRLILQGNRIRSITKKAFTGLDALEHLDLSDN
AIMSLQGNAFSQMKKLQQLHLNTSSLLCDCQLKWLPQWVAENNFQSFVNASCAHPQLLKG
RSIFAVSPDGFVCDDFPKPQITVQPETQSAIKGSNLSFICSAASSSDSPMTFAWKKDNEL
LHDAEMENYAHLRAQGGEVMEYTTILRLREVEFASEGKYQCVISNHFGSSYSVKAKLTVN
MLPSFTKTPMDLTIRAGAMARLECAAVGHPAPQIAWQKDGGTDFPAARERRMHVMPEDDV
FFIVDVKIEDIGVYSCTAQNSAGSISANATLTVLETPSFLRPLLDRTVTKGETAVLQCIA
GGSPPPKLNWTKDDSPLVVTERHFFAAGNQLLIIVDSDVSDAGKYTCEMSNTLGTERGNV
RLSVIPTPTCDSPQMTAPSLDDDGWATVGVVIIAVVCCVVGTSLVWVVIIYHTRRRNEDC
SITNTDETNLPADIPSYLSSQGTLADRQDGYVSSESGSHHQFVTSSGAGFFLPQHDSSGT
CHIDNSSEADVEAATDLFLCPFLGSTGPMYLKGNVYGSDPFETYHTGCSPDPRTVLMDHY
EPSYIKKKECYPCSHPSEESCERSFSNISWPSHVRKLLNTSYSHNEGPGMKNLCLNKSSL
DFSANPEPASVASSNSFMGTFGKALRRPHLDAYSSFGQPSDCQPRAFYLKAHSSPDLDSG
SEEDGKERTDFQEENHICTFKQTLENYRTPNFQSYDLDT
Function
May play a role in craniofacial and inner ear morphogenesis during embryonic development. May act within the otic vesicle epithelium to control formation of the lateral semicircular canal in the inner ear, possibly by restricting the expression of NTN1.
Tissue Specificity Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Ependymoma DISUMRNZ Definitive Altered Expression [1]
Adult glioblastoma DISVP4LU Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Altered Expression [3]
Alzheimer disease DISF8S70 Strong Biomarker [4]
Charcot marie tooth disease DIS3BT2L Strong Biomarker [5]
Glioblastoma multiforme DISK8246 Strong Biomarker [2]
Glioma DIS5RPEH Strong Biomarker [6]
Prostate cancer DISF190Y Strong Biomarker [7]
Prostate carcinoma DISMJPLE Strong Biomarker [7]
Neoplasm DISZKGEW Limited Biomarker [2]
Pituitary tumor DISN67JD Limited Altered Expression [8]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [9]
------------------------------------------------------------------------------------
13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [10]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [11]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [12]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [13]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [14]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [15]
Melphalan DMOLNHF Approved Melphalan decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [14]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [19]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [20]
Resorcinol DMM37C0 Investigative Resorcinol decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3). [21]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 Drug(s)

References

1 Expression of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins in human ependymoma relates to tumor location, WHO grade, and patient age.Clin Neuropathol. 2009 Jan-Feb;28(1):21-7. doi: 10.5414/npp28021.
2 The Prognostic and Therapeutic Potential of LRIG3 and Soluble LRIG3 in Glioblastoma.Front Oncol. 2019 Jun 6;9:447. doi: 10.3389/fonc.2019.00447. eCollection 2019.
3 LRIG1 is a triple threat: ERBB negative regulator, intestinal stem cell marker and tumour suppressor.Br J Cancer. 2013 May 14;108(9):1765-70. doi: 10.1038/bjc.2013.138. Epub 2013 Apr 4.
4 Upregulation of microRNA-196a improves cognitive impairment and alleviates neuronal damage in hippocampus tissues of Alzheimer's disease through downregulating LRIG3 expression.J Cell Biochem. 2019 Oct;120(10):17811-17821. doi: 10.1002/jcb.29047. Epub 2019 May 22.
5 Variants in the genes DCTN2, DNAH10, LRIG3, and MYO1A are associated with intermediate Charcot-Marie-Tooth disease in a Norwegian family.Acta Neurol Scand. 2016 Jul;134(1):67-75. doi: 10.1111/ane.12515. Epub 2015 Oct 12.
6 A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk.Acta Oncol. 2010 Aug;49(6):767-75. doi: 10.3109/0284186X.2010.480980.
7 Overexpressed LRIG3 gene ameliorates prostate cancer through suppression of cell invasion and migration.Int J Biol Macromol. 2019 Mar 1;124:1-9. doi: 10.1016/j.ijbiomac.2018.11.028. Epub 2018 Nov 7.
8 Down-regulation of leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) in HP75 pituitary adenoma cell line.J Huazhong Univ Sci Technolog Med Sci. 2007 Feb;27(1):91-4. doi: 10.1007/s11596-007-0126-x.
9 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
10 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
11 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
12 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.
13 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
14 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
15 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
16 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
17 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
18 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
19 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
20 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
21 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.