Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJI08YX)

• DOT Name: Septin-7 (SEPTIN7)
• Synonyms: CDC10 protein homolog
• Gene Name: SEPTIN7
• Related Disease:
  Adult glioblastoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Diabetic kidney disease
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Invasive breast carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Oral candidiasis
  Polyposis
  Schizophrenia
  Acute myelogenous leukaemia
  Kennedy disease
• UniProt ID: SEPT7_HUMAN
• PDB ID: 2QAG; 3T5D; 3TW4; 6N0B; 6N12; 6UQQ; 7M6J
• Pfam ID: PF00735
• Sequence:
  MSVSARSAAAEERSVNSSTMVAQQKNLEGYVGFANLPNQVYRKSVKRGFEFTLMVVGESG
  LGKSTLINSLFLTDLYSPEYPGPSHRIKKTVQVEQSKVLIKEGGVQLLLTIVDTPGFGDA
  VDNSNCWQPVIDYIDSKFEDYLNAESRVNRRQMPDNRVQCCLYFIAPSGHGLKPLDIEFM
  KRLHEKVNIIPLIAKADTLTPEECQQFKKQIMKEIQEHKIKIYEFPETDDEEENKLVKKI
  KDRLPLAVVGSNTIIEVNGKRVRGRQYPWGVAEVENGEHCDFTILRNMLIRTHMQDLKDV
  TNNVHYENYRSRKLAAVTYNGVDNNKNKGQLTKSPLAQMEEERREHVAKMKKMEMEMEQV
  FEMKVKEKVQKLKDSEAELQRRHEQMKKNLEAQHKELEEKRRQFEDEKANWEAQQRILEQ
  QNSSRTLEKNKKKGKIF
• Function: Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Required for normal progress through mitosis. Involved in cytokinesis. Required for normal association of CENPE with the kinetochore. Plays a role in ciliogenesis and collective cell movements. 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: Shigellosis (hsa05131)
• Reactome Pathway: MAPK6/MAPK4 signaling (R-HSA-5687128)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[4]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Invasive breast carcinoma	DISANYTW	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[8]
Oral candidiasis	DISAVKAH	Strong	Biomarker	[9]
Polyposis	DISZSPOK	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[10]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[11]
Kennedy disease	DISXZVM1	Limited	Biomarker	[12]

2 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 Septin-7 (SEPTIN7).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Septin-7 (SEPTIN7).	[14]

7 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 Septin-7 (SEPTIN7).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Septin-7 (SEPTIN7).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Septin-7 (SEPTIN7).	[17]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Septin-7 (SEPTIN7).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Septin-7 (SEPTIN7).	[19]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Septin-7 (SEPTIN7).	[20]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Septin-7 (SEPTIN7).	[21]

References

• [1] MiR-30a-5p antisense oligonucleotide suppresses glioma cell growth by targeting SEPT7.PLoS One. 2013;8(1):e55008. doi: 10.1371/journal.pone.0055008. Epub 2013 Jan 28.
• [2] iTRAQ-based proteomic analysis of DMH-induced colorectal cancer in mice reveals the expressions of -catenin, decorin, septin-7, and S100A10 expression in 53 cases of human hereditary polyposis colorectal cancer.Clin Transl Oncol. 2019 Feb;21(2):220-231. doi: 10.1007/s12094-018-1912-6. Epub 2018 Jun 28.
• [3] The requirement of SEPT2 and SEPT7 for migration and invasion in human breast cancer via MEK/ERK activation.Oncotarget. 2016 Sep 20;7(38):61587-61600. doi: 10.18632/oncotarget.11402.
• [4] Septin 7 mediates high glucose-induced podocyte apoptosis.Biochem Biophys Res Commun. 2018 Nov 30;506(3):522-528. doi: 10.1016/j.bbrc.2018.10.081. Epub 2018 Oct 22.
• [5] MicroRNA-127-3p promotes glioblastoma cell migration and invasion by targeting the tumor-suppressor gene SEPT7.Oncol Rep. 2014 May;31(5):2261-9. doi: 10.3892/or.2014.3055. Epub 2014 Mar 5.
• [6] SEPT7 overexpression inhibits glioma cell migration by targeting the actin cytoskeleton pathway.Oncol Rep. 2016 Apr;35(4):2003-10. doi: 10.3892/or.2016.4609. Epub 2016 Feb 3.
• [7] MicroRNA-127 post-transcriptionally downregulates Sept7 and suppresses cell growth in hepatocellular carcinoma cells.Cell Physiol Biochem. 2014;33(5):1537-46. doi: 10.1159/000358717. Epub 2014 May 14.
• [8] Activity and safety of AZD3759 in EGFR-mutant non-small-cell lung cancer with CNS metastases (BLOOM): a phase 1, open-label, dose-escalation and dose-expansion study.Lancet Respir Med. 2017 Nov;5(11):891-902. doi: 10.1016/S2213-2600(17)30378-8. Epub 2017 Oct 19.
• [9] Genotypes of Candida albicans isolated from healthy individuals and their distribution in patients with oral candidiasis.J Infect Chemother. 2013 Dec;19(6):1072-9. doi: 10.1007/s10156-013-0626-5. Epub 2013 Jun 12.
• [10] Schizophrenia is associated with dysregulation of a Cdk5 activator that regulates synaptic protein expression and cognition.Brain. 2011 Aug;134(Pt 8):2408-21. doi: 10.1093/brain/awr155. Epub 2011 Jul 19.
• [11] AF17q25, a putative septin family gene, fuses the MLL gene in acute myeloid leukemia with t(11;17)(q23;q25).Cancer Res. 1999 Sep 1;59(17):4261-5.
• [12] Septin-dependent remodeling of cortical microtubule drives cell reshaping during epithelial wound healing.J Cell Sci. 2018 Jun 28;131(12):jcs212647. doi: 10.1242/jcs.212647.
• [13] 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.
• [14] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [15] 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.
• [16] 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.
• [17] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [18] Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines. Anticancer Res. 2005 Sep-Oct;25(5):3293-302.
• [19] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [20] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [21] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.