Details of Drug Off-Target (DOT)

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

DOT Name CCR4-NOT transcription complex subunit 7 (CNOT7)
Synonyms EC 3.1.13.4; BTG1-binding factor 1; CCR4-associated factor 1; CAF-1; Caf1a
Gene Name CNOT7
Related Disease
Adolescent meningitis ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Neoplasm ( )
Renal cell carcinoma ( )
Squamous cell carcinoma ( )
Systemic lupus erythematosus ( )
Acute myelogenous leukaemia ( )
Adenovirus infection ( )
Advanced cancer ( )
Laryngeal carcinoma ( )
Laryngeal disorder ( )
Laryngeal squamous cell carcinoma ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Cutaneous melanoma ( )
facioscapulohumeral muscular dystrophy ( )
Male infertility ( )
Marinesco-Sjogren syndrome ( )
UniProt ID
CNOT7_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2D5R; 4GMJ; 7AX1; 7VOI
EC Number
3.1.13.4
Pfam ID
PF04857
Sequence
MPAATVDHSQRICEVWACNLDEEMKKIRQVIRKYNYVAMDTEFPGVVARPIGEFRSNADY
QYQLLRCNVDLLKIIQLGLTFMNEQGEYPPGTSTWQFNFKFNLTEDMYAQDSIELLTTSG
IQFKKHEEEGIETQYFAELLMTSGVVLCEGVKWLSFHSGYDFGYLIKILTNSNLPEEELD
FFEILRLFFPVIYDVKYLMKSCKNLKGGLQEVAEQLELERIGPQHQAGSDSLLTGMAFFK
MREMFFEDHIDDAKYCGHLYGLGSGSSYVQNGTGNAYEEEANKQS
Function
Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Its function seems to be partially redundant with that of CNOT8. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. During miRNA-mediated repression the complex seems also to act as translational repressor during translational initiation. Additional complex functions may be a consequence of its influence on mRNA expression. Associates with members of the BTG family such as TOB1 and BTG2 and is required for their anti-proliferative activity.
KEGG Pathway
R. degradation (hsa03018 )
Reactome Pathway
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain (R-HSA-6804115 )
M-decay (R-HSA-9820841 )
Deadenylation of mRNA (R-HSA-429947 )

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adolescent meningitis DISYHNYB Definitive Biomarker [1]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [2]
Carcinoma DISH9F1N Strong Biomarker [2]
Neoplasm DISZKGEW Strong Altered Expression [3]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [2]
Squamous cell carcinoma DISQVIFL Strong Biomarker [4]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [5]
Acute myelogenous leukaemia DISCSPTN moderate Genetic Variation [6]
Adenovirus infection DISUYSBZ moderate Altered Expression [7]
Advanced cancer DISAT1Z9 moderate Biomarker [8]
Laryngeal carcinoma DISNHCIV moderate Genetic Variation [9]
Laryngeal disorder DISDKUQO moderate Biomarker [9]
Laryngeal squamous cell carcinoma DIS9UUVF moderate Altered Expression [9]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [10]
Colorectal neoplasm DISR1UCN Limited Altered Expression [10]
Cutaneous melanoma DIS3MMH9 Limited Biomarker [8]
facioscapulohumeral muscular dystrophy DISSE0H0 Limited Altered Expression [11]
Male infertility DISY3YZZ Limited Biomarker [12]
Marinesco-Sjogren syndrome DISKEU0B Limited Genetic Variation [10]
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⏷ Show the Full List of 20 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of CCR4-NOT transcription complex subunit 7 (CNOT7). [13]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of CCR4-NOT transcription complex subunit 7 (CNOT7). [14]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of CCR4-NOT transcription complex subunit 7 (CNOT7). [15]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of CCR4-NOT transcription complex subunit 7 (CNOT7). [16]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of CCR4-NOT transcription complex subunit 7 (CNOT7). [17]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of CCR4-NOT transcription complex subunit 7 (CNOT7). [18]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of CCR4-NOT transcription complex subunit 7 (CNOT7). [19]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of CCR4-NOT transcription complex subunit 7 (CNOT7). [20]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of CCR4-NOT transcription complex subunit 7 (CNOT7). [21]
GALLICACID DM6Y3A0 Investigative GALLICACID increases the expression of CCR4-NOT transcription complex subunit 7 (CNOT7). [22]
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⏷ Show the Full List of 10 Drug(s)

References

1 Antibody against chromatin assembly factor-1 is a novel autoantibody specifically recognized in systemic lupus erythematosus.Lupus. 2014 Sep;23(10):1031-41. doi: 10.1177/0961203314536245. Epub 2014 May 16.
2 Clinical significance and prognostic value of chromatin assembly factor-1 overexpression in human solid tumours.Histopathology. 2010 Nov;57(5):716-24. doi: 10.1111/j.1365-2559.2010.03681.x.
3 Post-transcriptional Control of Tumor Cell Autonomous Metastatic Potential by CCR4-NOT Deadenylase CNOT7.PLoS Genet. 2016 Jan 25;12(1):e1005820. doi: 10.1371/journal.pgen.1005820. eCollection 2016 Jan.
4 CAF-1 Subunits Levels Suggest Combined Treatments with PARP-Inhibitors and Ionizing Radiation in Advanced HNSCC.Cancers (Basel). 2019 Oct 17;11(10):1582. doi: 10.3390/cancers11101582.
5 Antiribonuclease H2 antibodies are an immune biomarker for systemic lupus erythematosus.Autoimmunity. 2017 Jun;50(4):241-246. doi: 10.1080/08916934.2017.1329422. Epub 2017 May 27.
6 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
7 Degradation of a Novel DNA Damage Response Protein, Tankyrase 1 Binding Protein 1, following Adenovirus Infection.J Virol. 2018 May 29;92(12):e02034-17. doi: 10.1128/JVI.02034-17. Print 2018 Jun 15.
8 Tissue microarray-based evaluation of Chromatin Assembly Factor-1 (CAF-1)/p60 as tumour prognostic marker.Int J Mol Sci. 2012;13(9):11044-11062. doi: 10.3390/ijms130911044. Epub 2012 Sep 5.
9 Overexpression of chromatin assembly factor-1/p60 predicts biological behaviour of laryngeal carcinomas.Acta Otorhinolaryngol Ital. 2017 Feb;37(1):17-24. doi: 10.14639/0392-100X-867.
10 Analysis of the transcription regulator, CNOT7, as a candidate chromosome 8 tumor suppressor gene in colorectal cancer.Int J Cancer. 2003 Sep 10;106(4):505-509. doi: 10.1002/ijc.11264.
11 NuRD and CAF-1-mediated silencing of the D4Z4 array is modulated by DUX4-induced MBD3L proteins.Elife. 2018 Mar 13;7:e31023. doi: 10.7554/eLife.31023.
12 Accumulated HSV1-TK proteins interfere with spermatogenesis through a disruption of the integrity of Sertoli-germ cell junctions.J Reprod Dev. 2012;58(5):544-51. doi: 10.1262/jrd.2011-010. Epub 2012 Jun 14.
13 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
14 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.
15 Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study. BMC Med Genomics. 2011 Mar 31;4:29. doi: 10.1186/1755-8794-4-29.
16 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.
17 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
18 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
19 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.
20 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.
21 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
22 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.