Details of Drug Off-Target (DOT)

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

DOT Name PDZ domain-containing protein 8 (PDZD8)
Synonyms Sarcoma antigen NY-SAR-84/NY-SAR-104
Gene Name PDZD8
Related Disease
Herpes simplex infection ( )
Intellectual developmental disorder with autism and dysmorphic facies ( )
Post-traumatic stress disorder ( )
UniProt ID
PDZD8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7F6J
Pfam ID
PF00130 ; PF17820
Sequence
MGLLLMILASAVLGSFLTLLAQFFLLYRRQPEPPADEAARAGEGFRYIKPVPGLLLREYL
YGGGRDEEPSGAAPEGGATPTAAPETPAPPTRETCYFLNATILFLFRELRDTALTRRWVT
KKIKVEFEELLQTKTAGRLLEGLSLRDVFLGETVPFIKTIRLVRPVVPSATGEPDGPEGE
ALPAACPEELAFEAEVEYNGGFHLAIDVDLVFGKSAYLFVKLSRVVGRLRLVFTRVPFTH
WFFSFVEDPLIDFEVRSQFEGRPMPQLTSIIVNQLKKIIKRKHTLPNYKIRFKPFFPYQT
LQGFEEDEEHIHIQQWALTEGRLKVTLLECSRLLIFGSYDREANVHCTLELSSSVWEEKQ
RSSIKTVELIKGNLQSVGLTLRLVQSTDGYAGHVIIETVAPNSPAAIADLQRGDRLIAIG
GVKITSTLQVLKLIKQAGDRVLVYYERPVGQSNQGAVLQDNFGQLEENFLSSSCQSGYEE
EAAGLTVDTESRELDSEFEDLASDVRAQNEFKDEAQSLSHSPKRVPTTLSIKPLGAISPV
LNRKLAVGSHPLPPKIQSKDGNKPPPLKTSEITDPAQVSKPTQGSAFKPPVPPRPQAKVP
LPSADAPNQAEPDVLVEKPEKVVPPPLVDKSAEKQAKNVDAIDDAAAPKQFLAKQEVAKD
VTSETSCPTKDSSDDRQTWESSEILYRNKLGKWTRTRASCLFDIEACHRYLNIALWCRDP
FKLGGLICLGHVSLKLEDVALGCLATSNTEYLSKLRLEAPSPKAIVTRTALRNLSMQKGF
NDKFCYGDITIHFKYLKEGESDHHVVTNVEKEKEPHLVEEVSVLPKEEQFVGQMGLTENK
HSFQDTQFQNPTWCDYCKKKVWTKAASQCMFCAYVCHKKCQEKCLAETSVCGATDRRIDR
TLKNLRLEGQETLLGLPPRVDAEASKSVNKTTGLTRHIINTSSRLLNLRQVSKTRLSEPG
TDLVEPSPKHTPNTSDNEGSDTEVCGPNSPSKRGNSTGIKLVRKEGGLDDSVFIAVKEIG
RDLYRGLPTEERIQKLEFMLDKLQNEIDQELEHNNSLVREEKETTDTRKKSLLSAALAKS
GERLQALTLLMIHYRAGIEDIETLESLSLDQHSKKISKYTDDTEEDLDNEISQLIDSQPF
SSISDDLFGPSESV
Function
Molecular tethering protein that connects endoplasmic reticulum and mitochondria membranes. PDZD8-dependent endoplasmic reticulum-mitochondria membrane tethering is essential for endoplasmic reticulum-mitochondria Ca(2+) transfer. In neurons, involved in the regulation of dendritic Ca(2+) dynamics by regulating mitochondrial Ca(2+) uptake in neurons. Plays an indirect role in the regulation of cell morphology and cytoskeletal organization. May inhibit herpes simplex virus 1 infection at an early stage.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Herpes simplex infection DISL1SAV Strong Biomarker [1]
Intellectual developmental disorder with autism and dysmorphic facies DISFU3UM Limited Autosomal recessive [2]
Post-traumatic stress disorder DISHL1EY Limited Genetic Variation [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 PDZ domain-containing protein 8 (PDZD8). [4]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of PDZ domain-containing protein 8 (PDZD8). [15]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of PDZ domain-containing protein 8 (PDZD8). [5]
Tretinoin DM49DUI Approved Tretinoin increases the expression of PDZ domain-containing protein 8 (PDZD8). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of PDZ domain-containing protein 8 (PDZD8). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of PDZ domain-containing protein 8 (PDZD8). [8]
Estradiol DMUNTE3 Approved Estradiol increases the expression of PDZ domain-containing protein 8 (PDZD8). [9]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of PDZ domain-containing protein 8 (PDZD8). [10]
Temozolomide DMKECZD Approved Temozolomide increases the expression of PDZ domain-containing protein 8 (PDZD8). [11]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of PDZ domain-containing protein 8 (PDZD8). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of PDZ domain-containing protein 8 (PDZD8). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of PDZ domain-containing protein 8 (PDZD8). [14]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of PDZ domain-containing protein 8 (PDZD8). [16]
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⏷ Show the Full List of 11 Drug(s)

References

1 PDZD8 is a novel moesin-interacting cytoskeletal regulatory protein that suppresses infection by herpes simplex virus type 1.Virology. 2011 Jul 5;415(2):114-21. doi: 10.1016/j.virol.2011.04.006. Epub 2011 May 6.
2 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3 Genetic risk mechanisms of posttraumatic stress disorder in the human brain.J Neurosci Res. 2018 Jan;96(1):21-30. doi: 10.1002/jnr.23957. Epub 2016 Oct 24.
4 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.
5 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
6 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
7 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.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
10 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.
11 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.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 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.
14 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.
15 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.
16 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.