Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOZY2UL)

DOT Name Condensin-2 complex subunit D3 (NCAPD3)
Synonyms Non-SMC condensin II complex subunit D3; hCAP-D3
Gene Name NCAPD3
Related Disease
Neoplasm ( )
Oligospermia ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Bacterial infection ( )
Ulcerative colitis ( )
Autosomal recessive primary microcephaly ( )
Microcephaly 22, primary, autosomal recessive ( )
UniProt ID
CNDD3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12717
Sequence
MVALRGLGSGLQPWCPLDLRLEWVDTVWELDFTETEPLDPSIEAEIIETGLAAFTKLYES
LLPFATGEHGSMESIWTFFIENNVSHSTLVALFYHFVQIVHKKNVSVQYREYGLHAAGLY
FLLLEVPGSVANQVFHPVMFDKCIQTLKKSWPQESNLNRKRKKEQPKSSQANPGRHRKRG
KPPRREDIEMDEIIEEQEDENICFSARDLSQIRNAIFHLLKNFLRLLPKFSLKEKPQCVQ
NCIEVFVSLTNFEPVLHECHVTQARALNQAKYIPELAYYGLYLLCSPIHGEGDKVISCVF
HQMLSVILMLEVGEGSHRAPLAVTSQVINCRNQAVQFISALVDELKESIFPVVRILLQHI
CAKVVDKSEYRTFAAQSLVQLLSKLPCGEYAMFIAWLYKYSRSSKIPHRVFTLDVVLALL
ELPEREVDNTLSLEHQKFLKHKFLVQEIMFDRCLDKAPTVRSKALSSFAHCLELTVTSAS
ESILELLINSPTFSVIESHPGTLLRNSSAFSYQRQTSNRSEPSGEINIDSSGETVGSGER
CVMAMLRRRIRDEKTNVRKSALQVLVSILKHCDVSGMKEDLWILQDQCRDPAVSVRKQAL
QSLTELLMAQPRCVQIQKAWLRGVVPVVMDCESTVQEKALEFLDQLLLQNIRHHSHFHSG
DDSQVLAWALLTLLTTESQELSRYLNKAFHIWSKKEKFSPTFINNVISHTGTEHSAPAWM
LLSKIAGSSPRLDYSRIIQSWEKISSQQNPNSNTLGHILCVIGHIAKHLPKSTRDKVTDA
VKCKLNGFQWSLEVISSAVDALQRLCRASAETPAEEQELLTQVCGDVLSTCEHRLSNIVL
KENGTGNMDEDLLVKYIFTLGDIAQLCPARVEKRIFLLIQSVLASSADADHSPSSQGSSE
APASQPPPQVRGSVMPSVIRAHAIITLGKLCLQHEDLAKKSIPALVRELEVCEDVAVRNN
VIIVMCDLCIRYTIMVDKYIPNISMCLKDSDPFIRKQTLILLTNLLQEEFVKWKGSLFFR
FVSTLIDSHPDIASFGEFCLAHLLLKRNPVMFFQHFIECIFHFNNYEKHEKYNKFPQSER
EKRLFSLKGKSNKERRMKIYKFLLEHFTDEQRFNITSKICLSILACFADGILPLDLDASE
LLSDTFEVLSSKEIKLLAMRSKPDKDLLMEEDDMALANVVMQEAQKKLISQVQKRNFIEN
IIPIIISLKTVLEKNKIPALRELMHYLREVMQDYRDELKDFFAVDKQLASELEYDMKKYQ
EQLVQEQELAKHADVAGTAGGAEVAPVAQVALCLETVPVPAGQENPAMSPAVSQPCTPRA
SAGHVAVSSPTPETGPLQRLLPKARPMSLSTIAILNSVKKAVESKSRHRSRSLGVLPFTL
NSGSPEKTCSQVSSYSLEQESNGEIEHVTKRAISTPEKSISDVTFGAGVSYIGTPRTPSS
AKEKIEGRSQGNDILCLSLPDKPPPQPQQWNVRSPARNKDTPACSRRSLRKTPLKTAN
Function
Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis. May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Specifically required for decatenation of centromeric ultrafine DNA bridges during anaphase. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size.
Reactome Pathway
Condensation of Prophase Chromosomes (R-HSA-2299718 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Strong Biomarker [1]
Oligospermia DIS6YJF3 Strong Biomarker [2]
Prostate cancer DISF190Y Strong Altered Expression [1]
Prostate carcinoma DISMJPLE Strong Altered Expression [1]
Prostate neoplasm DISHDKGQ Strong Biomarker [1]
Bacterial infection DIS5QJ9S moderate Altered Expression [3]
Ulcerative colitis DIS8K27O moderate Altered Expression [3]
Autosomal recessive primary microcephaly DIS29IE3 Supportive Autosomal recessive [4]
Microcephaly 22, primary, autosomal recessive DISGL2KE Limited Unknown [4]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Condensin-2 complex subunit D3 (NCAPD3). [5]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Condensin-2 complex subunit D3 (NCAPD3). [13]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Condensin-2 complex subunit D3 (NCAPD3). [18]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Condensin-2 complex subunit D3 (NCAPD3). [18]
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14 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 Condensin-2 complex subunit D3 (NCAPD3). [6]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Condensin-2 complex subunit D3 (NCAPD3). [7]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Condensin-2 complex subunit D3 (NCAPD3). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Condensin-2 complex subunit D3 (NCAPD3). [9]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Condensin-2 complex subunit D3 (NCAPD3). [10]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Condensin-2 complex subunit D3 (NCAPD3). [11]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Condensin-2 complex subunit D3 (NCAPD3). [12]
Piroxicam DMTK234 Approved Piroxicam decreases the expression of Condensin-2 complex subunit D3 (NCAPD3). [14]
Dasatinib DMJV2EK Approved Dasatinib decreases the expression of Condensin-2 complex subunit D3 (NCAPD3). [15]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Condensin-2 complex subunit D3 (NCAPD3). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Condensin-2 complex subunit D3 (NCAPD3). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Condensin-2 complex subunit D3 (NCAPD3). [19]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Condensin-2 complex subunit D3 (NCAPD3). [20]
AM251 DMTAWHL Investigative AM251 decreases the expression of Condensin-2 complex subunit D3 (NCAPD3). [21]
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⏷ Show the Full List of 14 Drug(s)

References

1 hCAP-D3 expression marks a prostate cancer subtype with favorable clinical behavior and androgen signaling signature.Am J Surg Pathol. 2008 Feb;32(2):205-9. doi: 10.1097/PAS.0b013e318124a865.
2 Spermatozoa from infertile patients exhibit differences of DNA methylation associated with spermatogenesis-related processes: an array-based analysis.Reprod Biomed Online. 2016 Dec;33(6):709-719. doi: 10.1016/j.rbmo.2016.09.001. Epub 2016 Sep 15.
3 Chromosome-associated protein D3 promotes bacterial clearance in human intestinal epithelial cells by repressing expression of amino acid transporters.Gastroenterology. 2015 Jun;148(7):1405-1416.e3. doi: 10.1053/j.gastro.2015.02.013. Epub 2015 Feb 18.
4 Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis. Genes Dev. 2016 Oct 1;30(19):2158-2172. doi: 10.1101/gad.286351.116. Epub 2016 Oct 13.
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 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 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.
8 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
9 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.
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 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
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 Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
15 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
16 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
17 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.
18 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.
19 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
20 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
21 Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.