Details of Drug Off-Target (DOT)

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

• DOT Name: Dynamin-3 (DNM3)
• Synonyms: EC 3.6.5.5; Dynamin, testicular; T-dynamin
• Gene Name: DNM3
• Related Disease:
  Thyroid gland papillary carcinoma
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Glioma
  Hepatocellular carcinoma
  Kidney cancer
  Kidney neoplasm
  Liposarcoma
  Mycosis fungoides
  Neoplasm
  Obesity
  Obsessive compulsive disorder
  Osteoporosis
  Ovarian neoplasm
  Sezary syndrome
  Uterine fibroids
  Glioblastoma multiforme
  High blood pressure
  Metastatic malignant neoplasm
  Parkinsonian disorder
• UniProt ID: DYN3_HUMAN
• PDB ID: 3L43; 5A3F
• EC Number: 3.6.5.5
• Pfam ID: PF01031 ; PF00350 ; PF02212 ; PF00169
• Sequence:
  MGNREMEELIPLVNRLQDAFSALGQSCLLELPQIAVVGGQSAGKSSVLENFVGRDFLPRG
  SGIVTRRPLVLQLVTSKAEYAEFLHCKGKKFTDFDEVRLEIEAETDRVTGMNKGISSIPI
  NLRVYSPHVLNLTLIDLPGITKVPVGDQPPDIEYQIREMIMQFITRENCLILAVTPANTD
  LANSDALKLAKEVDPQGLRTIGVITKLDLMDEGTDARDVLENKLLPLRRGYVGVVNRSQK
  DIDGKKDIKAAMLAERKFFLSHPAYRHIADRMGTPHLQKVLNQQLTNHIRDTLPNFRNKL
  QGQLLSIEHEVEAYKNFKPEDPTRKTKALLQMVQQFAVDFEKRIEGSGDQVDTLELSGGA
  KINRIFHERFPFEIVKMEFNEKELRREISYAIKNIHGIRTGLFTPDMAFEAIVKKQIVKL
  KGPSLKSVDLVIQELINTVKKCTKKLANFPRLCEETERIVANHIREREGKTKDQVLLLID
  IQVSYINTNHEDFIGFANAQQRSSQVHKKTTVGNQGTNLPPSRQIVIRKGWLTISNIGIM
  KGGSKGYWFVLTAESLSWYKDDEEKEKKYMLPLDNLKVRDVEKSFMSSKHIFALFNTEQR
  NVYKDYRFLELACDSQEDVDSWKASLLRAGVYPDKSVAENDENGQAENFSMDPQLERQVE
  TIRNLVDSYMSIINKCIRDLIPKTIMHLMINNVKDFINSELLAQLYSSEDQNTLMEESAE
  QAQRRDEMLRMYQALKEALGIIGDISTATVSTPAPPPVDDSWIQHSRRSPPPSPTTQRRP
  TLSAPLARPTSGRGPAPAIPSPGPHSGAPPVPFRPGPLPPFPSSSDSFGAPPQVPSRPTR
  APPSVPSRRPPPSPTRPTIIRPLESSLLD
• Function: Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Most probably involved in vesicular trafficking processes, in particular endocytosis.
• KEGG Pathway:
  Phospholipase D sig.ling pathway (hsa04072)
  Endocytosis (hsa04144)
  Sy.ptic vesicle cycle (hsa04721)
  Endocrine and other factor-regulated calcium reabsorption (hsa04961)
  Bacterial invasion of epithelial cells (hsa05100)
• Reactome Pathway:
  Retrograde neurotrophin signalling (R-HSA-177504)
  MHC class II antigen presentation (R-HSA-2132295)
  Recycling pathway of L1 (R-HSA-437239)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Altered Expression	[3]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[5]
Kidney cancer	DISBIPKM	Strong	Biomarker	[6]
Kidney neoplasm	DISBNZTN	Strong	Biomarker	[6]
Liposarcoma	DIS8IZVM	Strong	Biomarker	[7]
Mycosis fungoides	DIS62RB8	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Obesity	DIS47Y1K	Strong	Genetic Variation	[9]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Biomarker	[10]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[9]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[11]
Sezary syndrome	DISFMTC7	Strong	Altered Expression	[8]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[12]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[13]
High blood pressure	DISY2OHH	moderate	Biomarker	[14]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[15]
Parkinsonian disorder	DISHGY45	Limited	Genetic Variation	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Dynamin-3 (DNM3).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Dynamin-3 (DNM3).	[18]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Dynamin-3 (DNM3).	[20]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Dynamin-3 (DNM3).	[21]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Dynamin-3 (DNM3).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Dynamin-3 (DNM3).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Dynamin-3 (DNM3).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Dynamin-3 (DNM3).	[27]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Dynamin-3 (DNM3).	[28]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Dynamin-3 (DNM3).	[29]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Dynamin-3 (DNM3).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Dynamin-3 (DNM3).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Dynamin-3 (DNM3).	[26]

References

• [1] Linc01278 inhibits the development of papillary thyroid carcinoma by regulating miR-376c-3p/DNM3 axis.Cancer Manag Res. 2019 Sep 19;11:8557-8569. doi: 10.2147/CMAR.S217886. eCollection 2019.
• [2] Construction of a recombinant eukaryotic expression vector containing DNM3 gene and its expression in colon cancer cells.Onco Targets Ther. 2018 Oct 9;11:6665-6671. doi: 10.2147/OTT.S176388. eCollection 2018.
• [3] siPRDX2-elevated DNM3 inhibits the proliferation and metastasis of colon cancer cells via AKT signaling pathway.Cancer Manag Res. 2019 Jun 28;11:5799-5811. doi: 10.2147/CMAR.S193805. eCollection 2019.
• [4] Exosomal miR-221 targets DNM3 to induce tumor progression and temozolomide resistance in glioma.J Neurooncol. 2017 Jan;131(2):255-265. doi: 10.1007/s11060-016-2308-5. Epub 2016 Nov 11.
• [5] Dynamin 3 suppresses growth and induces apoptosis of hepatocellular carcinoma cells by activating inducible nitric oxide synthase production.Oncol Lett. 2017 Jun;13(6):4776-4784. doi: 10.3892/ol.2017.6057. Epub 2017 Apr 20.
• [6] Investigation of the early-response genes in chemical-induced renal carcinogenicity for the prediction of chemical carcinogenicity in rats.J Toxicol Sci. 2017;42(2):175-181. doi: 10.2131/jts.42.175.
• [7] Evaluation of well-differentiated/de-differentiated liposarcomas by high-resolution oligonucleotide array-based comparative genomic hybridization.Genes Chromosomes Cancer. 2011 Feb;50(2):95-112. doi: 10.1002/gcc.20835.
• [8] Szary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3.Leukemia. 2008 Feb;22(2):393-9. doi: 10.1038/sj.leu.2405044. Epub 2007 Nov 22.
• [9] Identification of Novel Potentially Pleiotropic Variants Associated With Osteoporosis and Obesity Using the cFDR Method.J Clin Endocrinol Metab. 2018 Jan 1;103(1):125-138. doi: 10.1210/jc.2017-01531.
• [10] Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia.Transl Psychiatry. 2016 Mar 29;6(3):e768. doi: 10.1038/tp.2016.34.
• [11] Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1.PLoS One. 2018 Dec 17;13(12):e0209096. doi: 10.1371/journal.pone.0209096. eCollection 2018.
• [12] A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids.Front Genet. 2019 Jun 12;10:511. doi: 10.3389/fgene.2019.00511. eCollection 2019.
• [13] DNM3, p65 and p53 from exosomes represent potential clinical diagnosis markers for glioblastoma multiforme.Ther Adv Med Oncol. 2017 Dec;9(12):741-754. doi: 10.1177/1758834017737471. Epub 2017 Nov 6.
• [14] Genetic mapping of habitual substance use, obesity-related traits, responses to mental and physical stress, and heart rate and blood pressure measurements reveals shared genes that are overrepresented in the neural synapse.Hypertens Res. 2012 Jun;35(6):585-91. doi: 10.1038/hr.2011.233. Epub 2012 Feb 2.
• [15] DNM3 Attenuates Hepatocellular Carcinoma Growth by Activating P53.Med Sci Monit. 2016 Jan 19;22:197-205. doi: 10.12659/msm.896545.
• [16] DNM3 and genetic modifiers of age of onset in LRRK2 Gly2019Ser parkinsonism: a genome-wide linkage and association study.Lancet Neurol. 2016 Nov;15(12):1248-1256. doi: 10.1016/S1474-4422(16)30203-4. Epub 2016 Sep 28.
• [17] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [18] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [19] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [20] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [21] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [22] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [23] 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.
• [24] 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.
• [25] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [26] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [27] 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.
• [28] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [29] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.