Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU2L002)

DOT Name SID1 transmembrane family member 2 (SIDT2)
Gene Name SIDT2
Related Disease
Alzheimer disease ( )
Herpes simplex infection ( )
Lung cancer ( )
Lung neoplasm ( )
Muscular dystrophy ( )
UniProt ID
SIDT2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7Y63; 7Y68; 7Y69
Pfam ID
PF13965
Sequence
MFALGLPFLVLLVASVESHLGVLGPKNVSQKDAEFERTYVDEVNSELVNIYTFNHTVTRN
RTEGVRVSVNVLNKQKGAPLLFVVRQKEAVVSFQVPLILRGMFQRKYLYQKVERTLCQPP
TKNESEIQFFYVDVSTLSPVNTTYQLRVSRMDDFVLRTGEQFSFNTTAAQPQYFKYEFPE
GVDSVIVKVTSNKAFPCSVISIQDVLCPVYDLDNNVAFIGMYQTMTKKAAITVQRKDFPS
NSFYVVVVVKTEDQACGGSLPFYPFAEDEPVDQGHRQKTLSVLVSQAVTSEAYVSGMLFC
LGIFLSFYLLTVLLACWENWRQKKKTLLVAIDRACPESGHPRVLADSFPGSSPYEGYNYG
SFENVSGSTDGLVDSAGTGDLSYGYQGRSFEPVGTRPRVDSMSSVEEDDYDTLTDIDSDK
NVIRTKQYLYVADLARKDKRVLRKKYQIYFWNIATIAVFYALPVVQLVITYQTVVNVTGN
QDICYYNFLCAHPLGNLSAFNNILSNLGYILLGLLFLLIILQREINHNRALLRNDLCALE
CGIPKHFGLFYAMGTALMMEGLLSACYHVCPNYTNFQFDTSFMYMIAGLCMLKLYQKRHP
DINASAYSAYACLAIVIFFSVLGVVFGKGNTAFWIVFSIIHIIATLLLSTQLYYMGRWKL
DSGIFRRILHVLYTDCIRQCSGPLYVDRMVLLVMGNVINWSLAAYGLIMRPNDFASYLLA
IGICNLLLYFAFYIIMKLRSGERIKLIPLLCIVCTSVVWGFALFFFFQGLSTWQKTPAES
REHNRDCILLDFFDDHDIWHFLSSIAMFGSFLVLLTLDDDLDTVQRDKIYVF
Function
Mediates the translocation of RNA and DNA across the lysosomal membrane during RNA and DNA autophagy (RDA), a process in which RNA or DNA is directly imported into lysosomes in an ATP-dependent manner, and degraded. Involved in the uptake of single-stranded oligonucleotides by living cells, a process called gymnosis. In vitro, mediates the uptake of linear DNA more efficiently than that of circular DNA, but exhibits similar uptake efficacy toward RNA and DNA. Binds long double-stranded RNA (dsRNA) (500 - 700 base pairs), but not dsRNA shorter than 100 bp.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Altered Expression [1]
Herpes simplex infection DISL1SAV Strong Biomarker [2]
Lung cancer DISCM4YA Strong Biomarker [3]
Lung neoplasm DISVARNB Strong Biomarker [3]
Muscular dystrophy DISJD6P7 Strong Biomarker [4]
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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 increases the methylation of SID1 transmembrane family member 2 (SIDT2). [5]
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19 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 SID1 transmembrane family member 2 (SIDT2). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of SID1 transmembrane family member 2 (SIDT2). [7]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of SID1 transmembrane family member 2 (SIDT2). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of SID1 transmembrane family member 2 (SIDT2). [9]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of SID1 transmembrane family member 2 (SIDT2). [10]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of SID1 transmembrane family member 2 (SIDT2). [11]
Decitabine DMQL8XJ Approved Decitabine affects the expression of SID1 transmembrane family member 2 (SIDT2). [12]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of SID1 transmembrane family member 2 (SIDT2). [13]
Menadione DMSJDTY Approved Menadione affects the expression of SID1 transmembrane family member 2 (SIDT2). [14]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of SID1 transmembrane family member 2 (SIDT2). [15]
Hydroquinone DM6AVR4 Approved Hydroquinone increases the expression of SID1 transmembrane family member 2 (SIDT2). [16]
Amsacrine DMZKYIV Approved Amsacrine increases the expression of SID1 transmembrane family member 2 (SIDT2). [17]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of SID1 transmembrane family member 2 (SIDT2). [18]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the expression of SID1 transmembrane family member 2 (SIDT2). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of SID1 transmembrane family member 2 (SIDT2). [20]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of SID1 transmembrane family member 2 (SIDT2). [21]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of SID1 transmembrane family member 2 (SIDT2). [22]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of SID1 transmembrane family member 2 (SIDT2). [15]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of SID1 transmembrane family member 2 (SIDT2). [23]
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⏷ Show the Full List of 19 Drug(s)

References

1 Identification of Sidt2 as a lysosomal cation-conducting protein.FEBS Lett. 2017 Jan;591(1):76-87. doi: 10.1002/1873-3468.12528. Epub 2017 Jan 2.
2 SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition.Immunity. 2017 Sep 19;47(3):498-509.e6. doi: 10.1016/j.immuni.2017.08.007. Epub 2017 Sep 12.
3 Bronchial airway gene expression signatures in mouse lung squamous cell carcinoma and their modulation by cancer chemopreventive agents.Oncotarget. 2017 Mar 21;8(12):18885-18900. doi: 10.18632/oncotarget.13806.
4 Skeletal muscle-specific Sidt2 knockout in mice induced muscular dystrophy-like phenotype.Metabolism. 2018 Aug;85:259-270. doi: 10.1016/j.metabol.2018.05.004. Epub 2018 May 9.
5 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.
6 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.
7 Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
8 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.
9 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
11 Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
12 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
13 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
14 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
15 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
16 Effects of SIDT2 on the miR-25/NOX4/HuR axis and SIRT3 mRNA stability lead to ROS-mediated TNF- expression in hydroquinone-treated leukemia cells. Cell Biol Toxicol. 2023 Oct;39(5):2207-2225. doi: 10.1007/s10565-022-09705-5. Epub 2022 Mar 18.
17 Amsacrine downregulates BCL2L1 expression and triggers apoptosis in human chronic myeloid leukemia cells through the SIDT2/NOX4/ERK/HuR pathway. Toxicol Appl Pharmacol. 2023 Sep 1;474:116625. doi: 10.1016/j.taap.2023.116625. Epub 2023 Jul 13.
18 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
19 Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
20 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
21 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.
22 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.
23 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.