Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8VGE2O)

DOT Name Condensin complex subunit 1 (NCAPD2)
Synonyms Chromosome condensation-related SMC-associated protein 1; Chromosome-associated protein D2; hCAP-D2; Non-SMC condensin I complex subunit D2; XCAP-D2 homolog
Gene Name NCAPD2
Related Disease
Advanced cancer ( )
Alzheimer disease ( )
Parkinson disease ( )
Triple negative breast cancer ( )
Microcephaly 21, primary, autosomal recessive ( )
UniProt ID
CND1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12717 ; PF12922
Sequence
MAPQMYEFHLPLSPEELLKSGGVNQYVVQEVLSIKHLPPQLRAFQAAFRAQGPLAMLQHF
DTIYSILHHFRSIDPGLKEDTLQFLIKVVSRHSQELPAILDDTTLSGSDRNAHLNALKMN
CYALIRLLESFETMASQTNLVDLDLGGKGKKARTKAAHGFDWEEERQPILQLLTQLLQLD
IRHLWNHSIIEEEFVSLVTGCCYRLLENPTINHQKNRPTREAITHLLGVALTRYNHMLSA
TVKIIQMLQHFEHLAPVLVAAVSLWATDYGMKSIVGEIVREIGQKCPQELSRDPSGTKGF
AAFLTELAERVPAILMSSMCILLDHLDGENYMMRNAVLAAMAEMVLQVLSGDQLEAAARD
TRDQFLDTLQAHGHDVNSFVRSRVLQLFTRIVQQKALPLTRFQAVVALAVGRLADKSVLV
CKNAIQLLASFLANNPFSCKLSDADLAGPLQKETQKLQEMRAQRRTAAASAVLDPEEEWE
AMLPELKSTLQQLLQLPQGEEEIPEQIANTETTEDVKGRIYQLLAKASYKKAIILTREAT
GHFQESEPFSHIDPEESEETRLLNILGLIFKGPAASTQEKNPRESTGNMVTGQTVCKNKP
NMSDPEESRGNDELVKQEMLVQYLQDAYSFSRKITEAIGIISKMMYENTTTVVQEVIEFF
VMVFQFGVPQALFGVRRMLPLIWSKEPGVREAVLNAYRQLYLNPKGDSARAKAQALIQNL
SLLLVDASVGTIQCLEEILCEFVQKDELKPAVTQLLWERATEKVACCPLERCSSVMLLGM
MARGKPEIVGSNLDTLVSIGLDEKFPQDYRLAQQVCHAIANISDRRKPSLGKRHPPFRLP
QEHRLFERLRETVTKGFVHPDPLWIPFKEVAVTLIYQLAEGPEVICAQILQGCAKQALEK
LEEKRTSQEDPKESPAMLPTFLLMNLLSLAGDVALQQLVHLEQAVSGELCRRRVLREEQE
HKTKDPKEKNTSSETTMEEELGLVGATADDTEAELIRGICEMELLDGKQTLAAFVPLLLK
VCNNPGLYSNPDLSAAASLALGKFCMISATFCDSQLRLLFTMLEKSPLPIVRSNLMVATG
DLAIRFPNLVDPWTPHLYARLRDPAQQVRKTAGLVMTHLILKDMVKVKGQVSEMAVLLID
PEPQIAALAKNFFNELSHKGNAIYNLLPDIISRLSDPELGVEEEPFHTIMKQLLSYITKD
KQTESLVEKLCQRFRTSRTERQQRDLAYCVSQLPLTERGLRKMLDNFDCFGDKLSDESIF
SAFLSVVGKLRRGAKPEGKAIIDEFEQKLRACHTRGLDGIKELEIGQAGSQRAPSAKKPS
TGSRYQPLASTASDNDFVTPEPRRTTRRHPNTQQRASKKKPKVVFSSDESSEEDLSAEMT
EDETPKKTTPILRASARRHRS
Function
Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. May target the condensin complex to DNA via its C-terminal domain. 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. Required for decatenation of non-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 Prometaphase Chromosomes (R-HSA-2514853 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Alzheimer disease DISF8S70 Strong Biomarker [2]
Parkinson disease DISQVHKL Strong Genetic Variation [2]
Triple negative breast cancer DISAMG6N Strong Biomarker [1]
Microcephaly 21, primary, autosomal recessive DISR20LN Moderate Autosomal recessive [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 complex subunit 1 (NCAPD2). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Condensin complex subunit 1 (NCAPD2). [17]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Condensin complex subunit 1 (NCAPD2). [20]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Condensin complex subunit 1 (NCAPD2). [20]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid decreases the phosphorylation of Condensin complex subunit 1 (NCAPD2). [26]
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23 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 complex subunit 1 (NCAPD2). [5]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Condensin complex subunit 1 (NCAPD2). [6]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Condensin complex subunit 1 (NCAPD2). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Condensin complex subunit 1 (NCAPD2). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Condensin complex subunit 1 (NCAPD2). [9]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Condensin complex subunit 1 (NCAPD2). [10]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Condensin complex subunit 1 (NCAPD2). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Condensin complex subunit 1 (NCAPD2). [12]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Condensin complex subunit 1 (NCAPD2). [13]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Condensin complex subunit 1 (NCAPD2). [13]
Dasatinib DMJV2EK Approved Dasatinib decreases the expression of Condensin complex subunit 1 (NCAPD2). [14]
Cidofovir DMA13GD Approved Cidofovir affects the expression of Condensin complex subunit 1 (NCAPD2). [15]
Ifosfamide DMCT3I8 Approved Ifosfamide increases the expression of Condensin complex subunit 1 (NCAPD2). [15]
Palbociclib DMD7L94 Approved Palbociclib decreases the expression of Condensin complex subunit 1 (NCAPD2). [16]
Adefovir dipivoxil DMMAWY1 Approved Adefovir dipivoxil increases the expression of Condensin complex subunit 1 (NCAPD2). [15]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Condensin complex subunit 1 (NCAPD2). [11]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Condensin complex subunit 1 (NCAPD2). [18]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Condensin complex subunit 1 (NCAPD2). [19]
Scriptaid DM9JZ21 Preclinical Scriptaid affects the expression of Condensin complex subunit 1 (NCAPD2). [21]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Condensin complex subunit 1 (NCAPD2). [22]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Condensin complex subunit 1 (NCAPD2). [23]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Condensin complex subunit 1 (NCAPD2). [24]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Condensin complex subunit 1 (NCAPD2). [25]
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⏷ Show the Full List of 23 Drug(s)

References

1 Non-SMC Condensin I Complex Subunit D2 Is a Prognostic Factor in Triple-Negative Breast Cancer for the Ability to Promote Cell Cycle and Enhance Invasion.Am J Pathol. 2020 Jan;190(1):37-47. doi: 10.1016/j.ajpath.2019.09.014. Epub 2019 Oct 12.
2 Non-SMC condensin I complex, subunit D2 gene polymorphisms are associated with Parkinson's disease: a Han Chinese study.Genome. 2014 May;57(5):253-7. doi: 10.1139/gen-2014-0032. Epub 2014 Aug 11.
3 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.
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 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.
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 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
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 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
11 Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
12 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.
13 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
14 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.
15 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
16 Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
17 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
18 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
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 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.
21 Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. Int J Oncol. 2008 Oct;33(4):767-76.
22 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.
23 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
24 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
25 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
26 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.