Details of Drug Off-Target (DOT)

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

DOT Name DET1- and DDB1-associated protein 1 (DDA1)
Synonyms Placenta cross-immune reaction antigen 1; PCIA-1
Gene Name DDA1
Related Disease
Acute myelogenous leukaemia ( )
Breast cancer ( )
Colon cancer ( )
Colon carcinoma ( )
Epithelial ovarian cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Rheumatoid arthritis ( )
Lung cancer ( )
Lung carcinoma ( )
UniProt ID
DDA1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6DSZ; 6PAI; 6Q0R; 6Q0V; 6Q0W; 6SJ7; 6UD7; 6UE5; 8G46
Pfam ID
PF10172
Sequence
MADFLKGLPVYNKSNFSRFHADSVCKASNRRPSVYLPTREYPSEQIIVTEKTNILLRYLH
QQWDKKNAAKKRDQEQVELEGESSAPPRKVARTDSPDMHEDT
Function
Functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. In the DCX complexes, acts as a scaffolding subunit required to stabilize the complex.
Reactome Pathway
Neddylation (R-HSA-8951664 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [1]
Breast cancer DIS7DPX1 Strong Genetic Variation [2]
Colon cancer DISVC52G Strong Biomarker [3]
Colon carcinoma DISJYKUO Strong Biomarker [3]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [4]
Ovarian cancer DISZJHAP Strong Biomarker [4]
Ovarian neoplasm DISEAFTY Strong Biomarker [4]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [5]
Lung cancer DISCM4YA Limited Altered Expression [6]
Lung carcinoma DISTR26C Limited Altered Expression [6]
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⏷ Show the Full List of 10 Disease(s)
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 decreases the methylation of DET1- and DDB1-associated protein 1 (DDA1). [7]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of DET1- and DDB1-associated protein 1 (DDA1). [13]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of DET1- and DDB1-associated protein 1 (DDA1). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of DET1- and DDB1-associated protein 1 (DDA1). [9]
Temozolomide DMKECZD Approved Temozolomide increases the expression of DET1- and DDB1-associated protein 1 (DDA1). [10]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of DET1- and DDB1-associated protein 1 (DDA1). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of DET1- and DDB1-associated protein 1 (DDA1). [12]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of DET1- and DDB1-associated protein 1 (DDA1). [14]
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⏷ Show the Full List of 6 Drug(s)

References

1 LncRNA HOTTIP promotes proliferation and cell cycle progression of acute myeloid leukemia cells.Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):2908-2915. doi: 10.26355/eurrev_201904_17569.
2 A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population.Nat Genet. 2010 Oct;42(10):885-92. doi: 10.1038/ng.669. Epub 2010 Sep 19.
3 DDA1 promotes stage IIB-IIC colon cancer progression by activating NFB/CSN2/GSK-3 signaling.Oncotarget. 2016 Apr 12;7(15):19794-812. doi: 10.18632/oncotarget.7847.
4 DDA1 is induced by NR2F6 in ovarian cancer and predicts poor survival outcome.Eur Rev Med Pharmacol Sci. 2017 Mar;21(6):1206-1213.
5 Genetics of rheumatoid arthritis contributes to biology and drug discovery.Nature. 2014 Feb 20;506(7488):376-81. doi: 10.1038/nature12873. Epub 2013 Dec 25.
6 DDA1, a novel oncogene, promotes lung cancer progression through regulation of cell cycle.J Cell Mol Med. 2017 Aug;21(8):1532-1544. doi: 10.1111/jcmm.13084. Epub 2017 Feb 17.
7 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.
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 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 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
12 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.
13 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.
14 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.