Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN20MEF)

• DOT Name: Non-histone chromosomal protein HMG-17 (HMGN2)
• Synonyms: High mobility group nucleosome-binding domain-containing protein 2
• Gene Name: HMGN2
• Related Disease:
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Lupus
  Promyelocytic leukaemia
  Psoriatic arthritis
  Systemic lupus erythematosus
  Bone osteosarcoma
  Isolated congenital microcephaly
  Neoplasm
  Osteosarcoma
  Al-Raqad syndrome
  Dental enamel hypoplasia
  Glucagonoma
  Insulinoma
  Squamous cell carcinoma
• UniProt ID: HMGN2_HUMAN
• Pfam ID: PF01101
• Sequence:
  MPKRKAEGDAKGDKAKVKDEPQRRSARLSAKPAPPKPEPKPKKAPAKKGEKVPKGKKGKA
  DAGKEGNNPAENGDAKTDQAQKAEGAGDAK
• Function: Binds to the inner side of the nucleosomal DNA thus altering the interaction between the DNA and the histone octamer. May be involved in the process which maintains transcribable genes in a unique chromatin conformation.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Lupus	DISOKJWA	Strong	Biomarker	[1]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[3]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[4]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[1]
Bone osteosarcoma	DIST1004	moderate	Altered Expression	[5]
Isolated congenital microcephaly	DISUXHZ6	moderate	Altered Expression	[6]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]
Osteosarcoma	DISLQ7E2	moderate	Altered Expression	[5]
Al-Raqad syndrome	DISR2J8Q	Limited	Altered Expression	[7]
Dental enamel hypoplasia	DISN6ZMR	Limited	Altered Expression	[7]
Glucagonoma	DISDU90K	Limited	Altered Expression	[8]
Insulinoma	DISIU1JS	Limited	Biomarker	[8]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[9]

1 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 Non-histone chromosomal protein HMG-17 (HMGN2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[14]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[18]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[21]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Non-histone chromosomal protein HMG-17 (HMGN2).	[24]

References

• [1] Rabbit anti-HMG-17 antibodies recognize similar epitopes on the HMG-17 molecule as lupus autoantibodies. Relation with histone H1 defined epitopes.J Pept Sci. 2002 Dec;8(12):683-94. doi: 10.1002/psc.429.
• [2] Effect of HMGN2 on proliferation and apoptosis of MCF-7 breast cancer cells.Oncol Lett. 2019 Jan;17(1):1160-1166. doi: 10.3892/ol.2018.9668. Epub 2018 Nov 5.
• [3] Expression of chromosomal proteins HMG-14 and HMG-17 in transformed human cells.Cancer Res. 1990 Apr 1;50(7):2022-6.
• [4] Nuclear protein HMGN2 attenuates pyocyanin-induced oxidative stress via Nrf2 signaling and inhibits Pseudomonas aeruginosa internalization in A549 cells.Free Radic Biol Med. 2017 Jul;108:404-417. doi: 10.1016/j.freeradbiomed.2017.04.007. Epub 2017 Apr 10.
• [5] Nucleosome-binding protein HMGN2 exhibits antitumor activity in human SaO2 and U2-OS osteosarcoma cell lines.Oncol Rep. 2015 Mar;33(3):1300-6. doi: 10.3892/or.2014.3689. Epub 2014 Dec 22.
• [6] High-mobility group nucleosomal binding domain 2 protects against microcephaly by maintaining global chromatin accessibility during corticogenesis.J Biol Chem. 2020 Jan 10;295(2):468-480. doi: 10.1074/jbc.RA119.010616. Epub 2019 Nov 7.
• [7] A model for the molecular underpinnings of tooth defects in Axenfeld-Rieger syndrome.Hum Mol Genet. 2014 Jan 1;23(1):194-208. doi: 10.1093/hmg/ddt411. Epub 2013 Aug 23.
• [8] Protein HMG-17 is hyper-expressed in rat glucagonoma. Single-step isolation and sequencing.Eur J Biochem. 1990 Aug 28;192(1):81-6. doi: 10.1111/j.1432-1033.1990.tb19198.x.
• [9] Increased expression of high-mobility group nucleosomal-binding domain 2 protein in various tumor cell lines.Oncol Lett. 2018 Apr;15(4):4517-4522. doi: 10.3892/ol.2018.7898. Epub 2018 Jan 29.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [15] 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.
• [16] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [17] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [18] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [19] Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR. Int J Cancer. 2006 Oct 1;119(7):1599-606.
• [20] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [21] Comparison of quantitation methods in proteomics to define relevant toxicological information on AhR activation of HepG2 cells by BaP. Toxicology. 2021 Jan 30;448:152652. doi: 10.1016/j.tox.2020.152652. Epub 2020 Dec 2.
• [22] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [23] 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.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.