Details of Drug Off-Target (DOT)

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

DOT Name Nuclear receptor coactivator 5 (NCOA5)
Synonyms NCoA-5; Coactivator independent of AF-2; CIA
Gene Name NCOA5
Related Disease
B-cell lymphoma ( )
Classic Hodgkin lymphoma ( )
Marginal zone lymphoma ( )
Melanoma ( )
Multiple sclerosis ( )
Advanced cancer ( )
Anemia ( )
Arthritis ( )
Autoimmune disease ( )
Behcet disease ( )
Bone disease ( )
Breast cancer ( )
Breast carcinoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Colorectal carcinoma ( )
Hepatocellular carcinoma ( )
Leukopenia ( )
Major depressive disorder ( )
Male infertility ( )
Mood disorder ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Psoriasis ( )
Rheumatoid arthritis ( )
Agranulocytosis ( )
Bone osteosarcoma ( )
Osteosarcoma ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid gland papillary carcinoma ( )
Thyroid tumor ( )
UniProt ID
NCOA5_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1V95; 2J7X; 2J7Y; 4ZI1
Sequence
MNTAPSRPSPTRRDPYGFGDSRDSRRDRSPIRGSPRREPRDGRNGRDARDSRDIRDPRDL
RDHRHSRDLRDHRDSRSVRDVRDVRDLRDFRDLRDSRDFRDQRDPMYDRYRDMRDSRDPM
YRREGSYDRYLRMDDYCRRKDDSYFDRYRDSFDGRGPPGPESQSRAKERLKREERRREEL
YRQYFEEIQRRFDAERPVDCSVIVVNKQTKDYAESVGRKVRDLGMVVDLIFLNTEVSLSQ
ALEDVSRGGSPFAIVITQQHQIHRSCTVNIMFGTPQEHRNMPQADAMVLVARNYERYKNE
CREKEREEIARQAAKMADEAILQERERGGPEEGVRGGHPPAIQSLINLLADNRYLTAEET
DKIINYLRERKERLMRSSTDSLPGPISRQPLGATSGASLKTQPSSQPLQSGQVLPSATPT
PSAPPTSQQELQAKILSLFNSGTVTANSSSASPSVAAGNTPNQNFSTAANSQPQQRSQAS
GNQPPSILGQGGSAQNMGPRPGAPSQGLFGQPSSRLAPASNMTSQRPVSSTGINFDNPSV
QKALDTLIQSGPALSHLVSQTTAQMGQPQAPMGSYQRHY
Function
Nuclear receptor coregulator that can have both coactivator and corepressor functions. Interacts with nuclear receptors for steroids (ESR1 and ESR2) independently of the steroid binding domain (AF-2) of the ESR receptors, and with the orphan nuclear receptor NR1D2. Involved in the coactivation of nuclear steroid receptors (ER) as well as the corepression of MYC in response to 17-beta-estradiol (E2).
Tissue Specificity Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
B-cell lymphoma DISIH1YQ Definitive Genetic Variation [1]
Classic Hodgkin lymphoma DISV1LU6 Definitive Genetic Variation [2]
Marginal zone lymphoma DISLZ4AO Definitive Genetic Variation [1]
Melanoma DIS1RRCY Definitive Genetic Variation [3]
Multiple sclerosis DISB2WZI Definitive Genetic Variation [1]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Anemia DISTVL0C Strong Biomarker [5]
Arthritis DIST1YEL Strong Biomarker [6]
Autoimmune disease DISORMTM Strong Genetic Variation [7]
Behcet disease DISSYMBS Strong Genetic Variation [8]
Bone disease DISE1F82 Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Breast carcinoma DIS2UE88 Strong Biomarker [10]
Cervical cancer DISFSHPF Strong Altered Expression [11]
Cervical carcinoma DIST4S00 Strong Altered Expression [11]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [12]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [4]
Leukopenia DISJMBMM Strong Biomarker [13]
Major depressive disorder DIS4CL3X Strong Genetic Variation [14]
Male infertility DISY3YZZ Strong Biomarker [15]
Mood disorder DISLVMWO Strong Genetic Variation [14]
Neoplasm DISZKGEW Strong Posttranslational Modification [11]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [16]
Psoriasis DIS59VMN Strong Genetic Variation [7]
Rheumatoid arthritis DISTSB4J Strong Biomarker [17]
Agranulocytosis DISJS4LS Disputed Genetic Variation [18]
Bone osteosarcoma DIST1004 Disputed Altered Expression [19]
Osteosarcoma DISLQ7E2 Disputed Altered Expression [19]
Thyroid cancer DIS3VLDH Limited Biomarker [20]
Thyroid gland carcinoma DISMNGZ0 Limited Biomarker [20]
Thyroid gland papillary carcinoma DIS48YMM Limited Altered Expression [20]
Thyroid tumor DISLVKMD Limited Biomarker [20]
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⏷ Show the Full List of 32 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Nuclear receptor coactivator 5 (NCOA5). [21]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Nuclear receptor coactivator 5 (NCOA5). [27]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Nuclear receptor coactivator 5 (NCOA5). [27]
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5 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 Nuclear receptor coactivator 5 (NCOA5). [22]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Nuclear receptor coactivator 5 (NCOA5). [23]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Nuclear receptor coactivator 5 (NCOA5). [24]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Nuclear receptor coactivator 5 (NCOA5). [25]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Nuclear receptor coactivator 5 (NCOA5). [26]
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References

1 Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.Genet Epidemiol. 2019 Oct;43(7):844-863. doi: 10.1002/gepi.22242. Epub 2019 Aug 13.
2 Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.Blood. 2018 Nov 8;132(19):2040-2052. doi: 10.1182/blood-2018-06-855296. Epub 2018 Sep 7.
3 Scleral Thinning Documented by Ultrasound Biomicroscopy after Plaque Therapy for Anterior Ciliary Melanoma.Semin Ophthalmol. 2018;33(4):571-575. doi: 10.1080/08820538.2017.1346131. Epub 2017 Jul 13.
4 Knockout of NCOA5 impairs proliferation and migration of hepatocellular carcinoma cells by suppressing epithelial-to-mesenchymal transition.Biochem Biophys Res Commun. 2018 Jun 2;500(2):177-183. doi: 10.1016/j.bbrc.2018.04.017. Epub 2018 Apr 14.
5 Synergetic pathogenicity of Newcastle disease vaccines LaSota strain and contaminated chicken infectious anemia virus.Poult Sci. 2019 May 1;98(5):1985-1992. doi: 10.3382/ps/pey555.
6 Combination of gp130-targeting and TNF-targeting small molecules in alleviating arthritis through the down-regulation of Th17 differentiation and osteoclastogenesis.Biochem Biophys Res Commun. 2020 Feb 19;522(4):1030-1036. doi: 10.1016/j.bbrc.2019.11.183. Epub 2019 Dec 6.
7 A CD40 and an NCOA5 gene polymorphism confer susceptibility to psoriasis in a Southern European population: a case-control study.Hum Immunol. 2011 Sep;72(9):761-5. doi: 10.1016/j.humimm.2011.05.014. Epub 2011 May 24.
8 Clinical significance of NCOA5 gene rs2903908 polymorphism in Behet's disease.EXCLI J. 2017 May 4;16:609-617. doi: 10.17179/excli2017-189. eCollection 2017.
9 Therapeutic role of a vaccine targeting RANKL and TNF- on collagen-induced arthritis.Biomaterials. 2012 Nov;33(32):8177-85. doi: 10.1016/j.biomaterials.2012.07.047. Epub 2012 Aug 9.
10 NCOA5 is correlated with progression and prognosis in luminal breast cancer.Biochem Biophys Res Commun. 2017 Jan 8;482(2):253-256. doi: 10.1016/j.bbrc.2016.11.051. Epub 2016 Nov 12.
11 Low expression of NCOA5 predicts poor prognosis in human cervical cancer and promotes proliferation, migration, and invasion of cervical cancer cell lines by regulating notch3 signaling pathway.J Cell Biochem. 2019 Apr;120(4):6237-6249. doi: 10.1002/jcb.27911. Epub 2018 Oct 18.
12 NCOA5 promotes proliferation, migration and invasion of colorectal cancer cells via activation of PI3K/AKT pathway.Oncotarget. 2017 Nov 14;8(64):107932-107946. doi: 10.18632/oncotarget.22429. eCollection 2017 Dec 8.
13 Efficacy and Safety of Supportive Care Biosimilars Among Cancer Patients: A Systematic Review and Meta-Analysis.BioDrugs. 2019 Aug;33(4):373-389. doi: 10.1007/s40259-019-00356-3.
14 Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
15 NCOA5 Haplo-insufficiency Results in Male Mouse Infertility through Increased IL-6 Expression in the Epididymis.Sci Rep. 2019 Oct 29;9(1):15525. doi: 10.1038/s41598-019-52105-9.
16 A single non-synonymous NCOA5 variation in type 2 diabetic patients with hepatocellular carcinoma impairs the function of NCOA5 in cell cycle regulation.Cancer Lett. 2017 Apr 10;391:152-161. doi: 10.1016/j.canlet.2017.01.028. Epub 2017 Jan 27.
17 PBT-6, a Novel PI3KC2 Inhibitor in Rheumatoid Arthritis.Biomol Ther (Seoul). 2020 Mar 1;28(2):172-183. doi: 10.4062/biomolther.2019.153.
18 Exploring off-targets and off-systems for adverse drug reactions via chemical-protein interactome--clozapine-induced agranulocytosis as a case study.PLoS Comput Biol. 2011 Mar;7(3):e1002016. doi: 10.1371/journal.pcbi.1002016. Epub 2011 Mar 31.
19 Association between expression of nuclear receptor co-activator 5 protein and prognosis in postoperative patients with osteosarcoma.Oncol Lett. 2018 Feb;15(2):1888-1892. doi: 10.3892/ol.2017.7513. Epub 2017 Dec 5.
20 A novel tumor suppressor gene NCOA5 is correlated with progression in papillary thyroid carcinoma.Onco Targets Ther. 2018 Jan 11;11:307-311. doi: 10.2147/OTT.S154158. eCollection 2018.
21 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.
22 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
23 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.
24 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.
25 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
26 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
27 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.