Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIV9RTK)

• DOT Name: Septin-6 (SEPTIN6)
• Gene Name: SEPTIN6
• UniProt ID: SEPT6_HUMAN
• PDB ID: 2QAG; 6UPA; 6WBP; 7M6J
• Pfam ID: PF00735
• Sequence:
  MAATDIARQVGEGCRTVPLAGHVGFDSLPDQLVNKSVSQGFCFNILCVGETGLGKSTLMD
  TLFNTKFEGEPATHTQPGVQLQSNTYDLQESNVRLKLTIVSTVGFGDQINKEDSYKPIVE
  FIDAQFEAYLQEELKIRRVLHTYHDSRIHVCLYFIAPTGHSLKSLDLVTMKKLDSKVNII
  PIIAKADAISKSELTKFKIKITSELVSNGVQIYQFPTDDESVAEINGTMNAHLPFAVIGS
  TEELKIGNKMMRARQYPWGTVQVENEAHCDFVKLREMLIRVNMEDLREQTHTRHYELYRR
  CKLEEMGFKDTDPDSKPFSLQETYEAKRNEFLGELQKKEEEMRQMFVQRVKEKEAELKEA
  EKELHEKFDRLKKLHQDEKKKLEDKKKSLDDEVNAFKQRKTAAELLQSQGSQAGGSQTLK
  RDKEKKNNPWLCTE
• Function: Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Involved in cytokinesis. May play a role in HCV RNA replication. Forms a filamentous structure with SEPTIN12, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Bacterial invasion of epithelial cells (hsa05100)
  Shigellosis (hsa05131)

Molecular Interaction Atlas (MIA) of This DOT

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 Septin-6 (SEPTIN6).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Septin-6 (SEPTIN6).	[13]

16 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 Septin-6 (SEPTIN6).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Septin-6 (SEPTIN6).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Septin-6 (SEPTIN6).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Septin-6 (SEPTIN6).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Septin-6 (SEPTIN6).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Septin-6 (SEPTIN6).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Septin-6 (SEPTIN6).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Septin-6 (SEPTIN6).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Septin-6 (SEPTIN6).	[10]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Septin-6 (SEPTIN6).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Septin-6 (SEPTIN6).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Septin-6 (SEPTIN6).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Septin-6 (SEPTIN6).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Septin-6 (SEPTIN6).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Septin-6 (SEPTIN6).	[15]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Septin-6 (SEPTIN6).	[16]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] 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.
• [7] An approach to elucidate potential mechanism of renal toxicity of arsenic trioxide. Exp Hematol. 2007 Feb;35(2):252-62.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [10] 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.
• [11] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] 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.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.