Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2O6F4D)

DOT Name E3 ubiquitin-protein ligase RNF170 (RNF170)
Synonyms EC 2.3.2.27; Putative LAG1-interacting protein; RING finger protein 170; RING-type E3 ubiquitin transferase RNF170
Gene Name RNF170
Related Disease
Autosomal dominant sensory ataxia 1 ( )
Hereditary spastic paraplegia ( )
Sensory ataxia ( )
Spastic paraplegia 85, autosomal recessive ( )
Vascular purpura ( )
UniProt ID
RN170_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.3.2.27
Pfam ID
PF06803 ; PF13445
Sequence
MAKYQGEVQSLKLDDDSVIEGVSDQVLVAVVVSFALIATLVYALFRNVHQNIHPENQELV
RVLREQLQTEQDAPAATRQQFYTDMYCPICLHQASFPVETNCGHLFCGACIIAYWRYGSW
LGAISCPICRQTVTLLLTVFGEDDQSQDVLRLHQDINDYNRRFSGQPRSIMERIMDLPTL
LRHAFREMFSVGGLFWMFRIRIILCLMGAFFYLISPLDFVPEALFGILGFLDDFFVIFLL
LIYISIMYREVITQRLTR
Function
E3 ubiquitin-protein ligase that plays an essential role in stimulus-induced inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) ubiquitination and degradation via the endoplasmic reticulum-associated degradation (ERAD) pathway. Also involved in ITPR1 turnover in resting cells. Selectively inhibits the TLR3-triggered innate immune response by promoting the 'Lys-48'-linked polyubiquitination and degradation of TLR3.
Tissue Specificity Expressed in the spinal chord.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal dominant sensory ataxia 1 DISYVXRX Strong Autosomal dominant [1]
Hereditary spastic paraplegia DISGZQV1 Strong Genetic Variation [2]
Sensory ataxia DISSMCYQ Strong Genetic Variation [3]
Spastic paraplegia 85, autosomal recessive DISSU1KS Strong Autosomal recessive [3]
Vascular purpura DIS6ZZMF Strong Genetic Variation [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 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 E3 ubiquitin-protein ligase RNF170 (RNF170). [4]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [5]
Tretinoin DM49DUI Approved Tretinoin increases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [6]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [8]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [10]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [11]
Malathion DMXZ84M Approved Malathion increases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [12]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [16]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [4]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of E3 ubiquitin-protein ligase RNF170 (RNF170). [17]
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⏷ Show the Full List of 13 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of E3 ubiquitin-protein ligase RNF170 (RNF170). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of E3 ubiquitin-protein ligase RNF170 (RNF170). [14]
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References

1 A mutation in the RNF170 gene causes autosomal dominant sensory ataxia. Brain. 2011 Feb;134(Pt 2):602-7. doi: 10.1093/brain/awq329. Epub 2010 Nov 28.
2 Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia.Nat Commun. 2019 Oct 21;10(1):4790. doi: 10.1038/s41467-019-12620-9.
3 Age-dependent gait abnormalities in mice lacking the Rnf170 gene linked to human autosomal-dominant sensory ataxia. Hum Mol Genet. 2015 Dec 20;24(25):7196-206. doi: 10.1093/hmg/ddv417. Epub 2015 Oct 3.
4 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.
5 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
6 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
7 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
10 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.
11 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
12 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
13 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
14 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.
15 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.
16 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
17 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.