Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSASNX6)

• DOT Name: Condensin-2 complex subunit H2 (NCAPH2)
• Synonyms: Chromosome-associated protein H2; hCAP-H2; Kleisin-beta; Non-SMC condensin II complex subunit H2
• Gene Name: NCAPH2
• Related Disease:
  Alzheimer disease
  Classic Hodgkin lymphoma
  Plasma cell myeloma
  Small lymphocytic lymphoma
  Dilated cardiomyopathy
• UniProt ID: CNDH2_HUMAN
• Pfam ID: PF16858 ; PF16869 ; PF06278
• Sequence:
  MEDVEARFAHLLQPIRDLTKNWEVDVAAQLGEYLEELDQICISFDEGKTTMNFIEAALLI
  QGSACVYSKKVEYLYSLVYQALDFISGKRRAKQLSSVQEDRANGVASSGVPQEAENEFLS
  LDDFPDSRTNVDLKNDQTPSEVLIIPLLPMALVAPDEMEKNNNPLYSRQGEVLASRKDFR
  MNTCVPHPRGAFMLEPEGMSPMEPAGVSPMPGTQKDTGRTEEQPMEVSVCRSPVPALGFS
  QEPGPSPEGPMPLGGGEDEDAEEAVELPEASAPKAALEPKESRSPQQSAALPRRYMLRER
  EGAPEPASCVKETPDPWQSLDPFDSLESKPFKKGRPYSVPPCVEEALGQKRKRKGAAKLQ
  DFHQWYLAAYADHADSRRLRRKGPSFADMEVLYWTHVKEQLETLRKLQRREVAEQWLRPA
  EEDHLEDSLEDLGAADDFLEPEEYMEPEGADPREAADLDAVPMSLSYEELVRRNVELFIA
  TSQKFVQETELSQRIRDWEDTVQPLLQEQEQHVPFDIHTYGDQLVSRFPQLNEWCPFAEL
  VAGQPAFEVCRSMLASLQLANDYTVEITQQPGLEMAVDTMSLRLLTHQRAHKRFQTYAAP
  SMAQP
• Function: Regulatory subunit of the condensin-2 complex, a complex that seems to provide chromosomes with an additional level of organization and rigidity and in establishing mitotic chromosome architecture. 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 chromatin bridges at 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. Seems to have lineage-specific role in T-cell development.
• Reactome Pathway: Condensation of Prophase Chromosomes (R-HSA-2299718)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[2]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[2]
Dilated cardiomyopathy	DISX608J	moderate	Genetic Variation	[3]

5 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Condensin-2 complex subunit H2 (NCAPH2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Condensin-2 complex subunit H2 (NCAPH2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Condensin-2 complex subunit H2 (NCAPH2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Condensin-2 complex subunit H2 (NCAPH2).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Condensin-2 complex subunit H2 (NCAPH2).	[9]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Condensin-2 complex subunit H2 (NCAPH2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Condensin-2 complex subunit H2 (NCAPH2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Condensin-2 complex subunit H2 (NCAPH2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Condensin-2 complex subunit H2 (NCAPH2).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Condensin-2 complex subunit H2 (NCAPH2).	[12]

References

• [1] Development of Biomarkers Based on DNA Methylation in the NCAPH2/LMF2 Promoter Region for Diagnosis of Alzheimer's Disease and Amnesic Mild Cognitive Impairment.PLoS One. 2016 Jan 7;11(1):e0146449. doi: 10.1371/journal.pone.0146449. eCollection 2016.
• [2] Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci.Sci Rep. 2017 Jan 23;7:41071. doi: 10.1038/srep41071.
• [3] A novel mutation in the SCO2 gene in a neonate with early-onset cardioencephalomyopathy.Pediatr Neurol. 2010 Mar;42(3):227-30. doi: 10.1016/j.pediatrneurol.2009.10.004.
• [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] 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.
• [6] 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.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.