Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4GVSU3)

• DOT Name: Septin-1 (SEPTIN1)
• Synonyms: LARP; Peanut-like protein 3; Serologically defined breast cancer antigen NY-BR-24
• Gene Name: SEPTIN1
• Related Disease:
  Latent tuberculosis infection
  Tuberculosis
  Advanced cancer
  Alzheimer disease
  Duchenne muscular dystrophy
  Myocardial infarction
  Neoplasm
  Non-insulin dependent diabetes
  Oral cancer
  Osteosarcoma
  Trachoma
  Adenovirus infection
  Neuroblastoma
  Stroke
• UniProt ID: SEPT1_HUMAN
• PDB ID: 6WBE
• Pfam ID: PF00735
• Sequence:
  MAGGVMDKEYVGFAALPNQLHRKSVKKGFDFTLMVAGESGLGKSTLINSLFLTNLYEDRQ
  VPEASARLTQTLAIERRGVEIEEGGVKVKLTLVDTPGFGDSVDCSDCWLPVVKFIEEQFE
  QYLRDESGLNRKNIQDSRVHCCLYFISPFGRGLRPLDVAFLRAVHEKVNIIPVIGKADAL
  MPQETQALKQKIRDQLKEEEIHIYQFPECDSDEDEDFKRQDAEMKESIPFAVVGSCEVVR
  DGGNRPVRGRRYSWGTVEVENPHHCDFLNLRRMLVQTHLQDLKEVTHDLLYEGYRARCLQ
  SLARPGARDRASRSKLSRQSATEIPLPMLPLADTEKLIREKDEELRRMQEMLEKMQAQMQ
  QSQAQGEQSDAL
• Function: Filament-forming cytoskeletal GTPase. May play a role in cytokinesis (Potential).
• Tissue Specificity: Expressed at high levels in lymphoid and hematopoietic tissues.
• KEGG Pathway: Bacterial invasion of epithelial cells (hsa05100)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Latent tuberculosis infection	DIS6R1EH	Definitive	Biomarker	[1]
Tuberculosis	DIS2YIMD	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[4]
Myocardial infarction	DIS655KI	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[7]
Oral cancer	DISLD42D	Strong	Altered Expression	[2]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Trachoma	DIS2WZUR	Strong	Biomarker	[8]
Adenovirus infection	DISUYSBZ	moderate	Biomarker	[9]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[10]
Stroke	DISX6UHX	Limited	Biomarker	[5]

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 Septin-1 (SEPTIN1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Septin-1 (SEPTIN1).	[12]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Septin-1 (SEPTIN1).	[13]

References

• [1] Incidence of active tuberculosis in individuals with latent tuberculosis infection in rural China: follow-up results of a population-based, multicentre, prospective cohort study.Lancet Infect Dis. 2017 Oct;17(10):1053-1061. doi: 10.1016/S1473-3099(17)30402-4. Epub 2017 Jul 14.
• [2] Overexpression of Septin1: possible contribution to the development of oral cancer.Int J Oncol. 2007 Nov;31(5):1021-8.
• [3] Identification of septins in neurofibrillary tangles in Alzheimer's disease.Am J Pathol. 1998 Nov;153(5):1551-60. doi: 10.1016/S0002-9440(10)65743-4.
• [4] Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014 Oct;13(10):987-96.
• [5] National Performance on the Medicare SEP-1 Sepsis Quality Measure.Crit Care Med. 2019 Aug;47(8):1026-1032. doi: 10.1097/CCM.0000000000003613.
• [6] The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma.Gene. 2002 Oct 2;298(2):121-7. doi: 10.1016/s0378-1119(02)00929-0.
• [7] Gastric bypass versus sleeve gastrectomy in patients with type 2 diabetes (Oseberg): a single-centre, triple-blind, randomised controlled trial.Lancet Diabetes Endocrinol. 2019 Dec;7(12):912-924. doi: 10.1016/S2213-8587(19)30344-4. Epub 2019 Oct 31.
• [8] Feasibility and safety of mass drug coadministration with azithromycin and ivermectin for the control of neglected tropical diseases: a single-arm intervention trial.Lancet Glob Health. 2018 Oct;6(10):e1132-e1138. doi: 10.1016/S2214-109X(18)30397-8.
• [9] Molecular monitoring of adenovirus reactivation in faeces after haematopoietic stem-cell transplantation to predict systemic infection: a retrospective cohort study.Lancet Haematol. 2018 Sep;5(9):e422-e429. doi: 10.1016/S2352-3026(18)30130-3.
• [10] Identification of human SEP1 as a glial cell line-derived neurotrophic factor-inducible protein and its expression in the nervous system.Neuroscience. 2003;121(4):899-906. doi: 10.1016/s0306-4522(03)00487-1.
• [11] 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.
• [12] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.