Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY94WRA)

• DOT Name: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B)
• Synonyms: SMARCE1-related protein; BRCA2-associated factor 35; HMG box-containing protein 20B; HMG domain-containing protein 2; HMG domain-containing protein HMGX2; Sox-like transcriptional factor; Structural DNA-binding protein BRAF35
• Gene Name: HMG20B
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Glioma
• UniProt ID: HM20B_HUMAN
• Pfam ID: PF00505
• Sequence:
  MSHGPKQPGAAAAPAGGKAPGQHGGFVVTVKQERGEGPRAGEKGSHEEEPVKKRGWPKGK
  KRKKILPNGPKAPVTGYVRFLNERREQIRTRHPDLPFPEITKMLGAEWSKLQPTEKQRYL
  DEAEREKQQYMKELRAYQQSEAYKMCTEKIQEKKIKKEDSSSGLMNTLLNGHKGGDCDGF
  STFDVPIFTEEFLDQNKAREAELRRLRKMNVAFEEQNAVLQRHTQSMSSARERLEQELAL
  EERRTLALQQQLQAVRQALTASFASLPVPGTGETPTLGTLDFYMARLHGAIERDPAQHEK
  LIVRIKEILAQVASEHL
• Function: Required for correct progression through G2 phase of the cell cycle and entry into mitosis. Required for RCOR1/CoREST mediated repression of neuronal specific gene promoters.
• Tissue Specificity: Ubiquitously expressed in adult tissues.
• Reactome Pathway:
  Potential therapeutics for SARS (R-HSA-9679191)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  HDACs deacetylate histones (R-HSA-3214815)

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	moderate	Biomarker	[1]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[1]
Lung carcinoma	DISTR26C	moderate	Genetic Variation	[1]
Neoplasm	DISZKGEW	moderate	Biomarker	[1]
Glioma	DIS5RPEH	Disputed	Altered Expression	[2]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B) affects the response to substance of Etoposide.	[10]
Mitomycin	DMH0ZJE	Approved	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B) affects the response to substance of Mitomycin.	[10]
Mitoxantrone	DMM39BF	Approved	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B) affects the response to substance of Mitoxantrone.	[10]

2 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 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B).	[3]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B).	[4]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B).	[8]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related (HMG20B).	[9]

References

• [1] A cancer-associated mutation inactivates a region of the high-mobility group protein HMG20b essential for cytokinesis.Cell Cycle. 2014;13(16):2554-63. doi: 10.4161/15384101.2014.942204.
• [2] Expression of SoxE and SoxD genes in human gliomas.Neuropathol Appl Neurobiol. 2007 Dec;33(6):621-30. doi: 10.1111/j.1365-2990.2007.00881.x. Epub 2007 Oct 24.
• [3] 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.
• [4] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [5] Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer. 2006 May 18;5:20. doi: 10.1186/1476-4598-5-20.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [8] 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.
• [9] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [10] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.