Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6JTJBO)

• DOT Name: Septin-5 (SEPTIN5)
• Synonyms: Cell division control-related protein 1; CDCrel-1; Peanut-like protein 1
• Gene Name: SEPTIN5
• Related Disease:
  Bernard-Soulier syndrome
  Acute lymphocytic leukaemia
  Autism spectrum disorder
  Autosomal recessive juvenile Parkinson disease 2
  Childhood acute lymphoblastic leukemia
  DiGeorge syndrome
  Parkinson disease
  Pervasive developmental disorder
  Schizophrenia
  Shprintzen-Goldberg syndrome
  Thrombocytopenia
  Velocardiofacial syndrome
  Acute myelogenous leukaemia
  Non-insulin dependent diabetes
• UniProt ID: SEPT5_HUMAN
• PDB ID: 6WCU
• Pfam ID: PF00735
• Sequence:
  MSTGLRYKSKLATPEDKQDIDKQYVGFATLPNQVHRKSVKKGFDFTLMVAGESGLGKSTL
  VHSLFLTDLYKDRKLLSAEERISQTVEILKHTVDIEEKGVKLKLTIVDTPGFGDAVNNTE
  CWKPITDYVDQQFEQYFRDESGLNRKNIQDNRVHCCLYFISPFGHGLRPVDVGFMKALHE
  KVNIVPLIAKADCLVPSEIRKLKERIREEIDKFGIHVYQFPECDSDEDEDFKQQDRELKE
  SAPFAVIGSNTVVEAKGQRVRGRLYPWGIVEVENQAHCDFVKLRNMLIRTHMHDLKDVTC
  DVHYENYRAHCIQQMTSKLTQDSRMESPIPILPLPTPDAETEKLIRMKDEELRRMQEMLQ
  RMKQQMQDQ
• Function: Filament-forming cytoskeletal GTPase. May play a role in cytokinesis (Potential). May play a role in platelet secretion.
• Tissue Specificity: Expressed at high levels in the CNS, as well as in heart and platelets (at protein level).
• KEGG Pathway:
  Parkinson disease (hsa05012)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bernard-Soulier syndrome	DISLD1FU	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
Autosomal recessive juvenile Parkinson disease 2	DISNSTD1	Strong	Biomarker	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[2]
DiGeorge syndrome	DIST1RKO	Strong	Biomarker	[5]
Parkinson disease	DISQVHKL	Strong	Biomarker	[6]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]
Shprintzen-Goldberg syndrome	DISQH6P3	Strong	Biomarker	[7]
Thrombocytopenia	DISU61YW	Strong	Genetic Variation	[8]
Velocardiofacial syndrome	DISOSBTY	Strong	Biomarker	[5]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[9]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[10]

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-5 (SEPTIN5).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Septin-5 (SEPTIN5).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Septin-5 (SEPTIN5).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Septin-5 (SEPTIN5).	[14]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Septin-5 (SEPTIN5).	[15]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Septin-5 (SEPTIN5).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Septin-5 (SEPTIN5).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Septin-5 (SEPTIN5).	[18]

References

• [1] Deletion of human GP1BB and SEPT5 is associated with Bernard-Soulier syndrome, platelet secretion defect, polymicrogyria, and developmental delay.Thromb Haemost. 2011 Sep;106(3):475-83. doi: 10.1160/TH11-05-0305. Epub 2011 Jul 28.
• [2] The CDCREL1 gene fused to MLL in de novo acute myeloid leukemia with t(11;22)(q23;q11.2) and its frequent expression in myeloid leukemia cell lines.Genes Chromosomes Cancer. 2001 Mar;30(3):230-5. doi: 10.1002/1098-2264(2000)9999:9999<::aid-gcc1084>3.0.co;2-j.
• [3] Modeling and Predicting Developmental Trajectories of Neuropsychiatric Dimensions Associated With Copy Number Variations.Int J Neuropsychopharmacol. 2019 Aug 1;22(8):488-500. doi: 10.1093/ijnp/pyz026.
• [4] Dopamine-dependent neurodegeneration in rats induced by viral vector-mediated overexpression of the parkin target protein, CDCrel-1.Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12438-43. doi: 10.1073/pnas.2132992100. Epub 2003 Oct 6.
• [5] Expression of Cdcrel-1 (Pnutl1), a gene frequently deleted in velo-cardio-facial syndrome/DiGeorge syndrome.Mech Dev. 2000 Aug;96(1):121-4. doi: 10.1016/s0925-4773(00)00370-1.
• [6] miR-185 and SEPT5 Genes May Contribute to Parkinson's Disease Pathophysiology.Oxid Med Cell Longev. 2019 Nov 14;2019:5019815. doi: 10.1155/2019/5019815. eCollection 2019.
• [7] A human gene similar to Drosophila melanogaster peanut maps to the DiGeorge syndrome region of 22q11.Hum Genet. 1997 Nov;101(1):6-12. doi: 10.1007/s004390050576.
• [8] Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.Blood. 2019 Dec 5;134(23):2082-2091. doi: 10.1182/blood.2018891192.
• [9] MLL-SEPT5 fusion transcript in infant acute myeloid leukemia with t(11;22)(q23;q11).Leuk Lymphoma. 2014 Mar;55(3):662-7. doi: 10.3109/10428194.2013.809528. Epub 2013 Aug 20.
• [10] Calpain inhibition stabilizes the platelet proteome and reactivity in diabetes.Blood. 2012 Jul 12;120(2):415-23. doi: 10.1182/blood-2011-12-399980. Epub 2012 Jun 4.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] 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.
• [14] 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.
• [15] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [16] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [17] Benzo(a)pyrene exposure in utero exacerbates Parkinson's Disease (PD)-like -synucleinopathy in A53T human alpha-synuclein transgenic mice. Toxicol Appl Pharmacol. 2021 Sep 15;427:115658. doi: 10.1016/j.taap.2021.115658. Epub 2021 Jul 29.
• [18] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.