Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJF6EZR)

• DOT Name: Fidgetin (FIGN)
• Gene Name: FIGN
• Related Disease: Congenital heart disease
• UniProt ID: FIGN_HUMAN
• Pfam ID: PF00004 ; PF09336
• Sequence:
  MISSTSVYGLKMQWTPEHAQWPEQHFDITSTTRSPAHKVEAYRGHLQRTYQYAWANDDIS
  ALTASNLLKKYAEKYSGILEGPVDRPVLSNYSDTPSGLVNGRKNESEPWQPSLNSEAVYP
  MNCVPDVITASKAGVSSALPPADVSASIGSSPGVASNLTEPSYSSSTCGSHTVPSLHAGL
  PSQEYAPGYNGSYLHSTYSSQPAPALPSPHPSPLHSSGLLQPPPPPPPPPALVPGYNGTS
  NLSSYSYPSASYPPQTAVGSGYSPGGAPPPPSAYLPSGIPAPTPLPPTTVPGYTYQGHGL
  TPIAPSALTNSSASSLKRKAFYMAGQGDMDSSYGNYSYGQQRSTQSPMYRMPDNSISNTN
  RGNGFDRSAETSSLAFKPTKQLMSSEQQRKFSSQSSRALTPPSYSTAKNSLGSRSSESFG
  KYTSPVMSEHGDEHRQLLSHPMQGPGLRAATSSNHSVDEQLKNTDTHLIDLVTNEIITQG
  PPVDWNDIAGLDLVKAVIKEEVLWPVLRSDAFSGLTALPRSILLFGPRGTGKTLLGRCIA
  SQLGATFFKIAGSGLVAKWLGEAEKIIHASFLVARCRQPSVIFVSDIDMLLSSQVNEEHS
  PVSRMRTEFLMQLDTVLTSAEDQIVVICATSKPEEIDESLRRYFMKRLLIPLPDSTARHQ
  IIVQLLSQHNYCLNDKEFALLVQRTEGFSGLDVAHLCQEAVVGPLHAMPATDLSAIMPSQ
  LRPVTYQDFENAFCKIQPSISQKELDMYVEWNKMFGCSQ
• Function: ATP-dependent microtubule severing protein. Severs microtubules along their length and depolymerizes their ends, primarily the minus-end, that may lead to the suppression of microtubule growth from and attachment to centrosomes. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital heart disease	DISQBA23	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Fidgetin (FIGN).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fidgetin (FIGN).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fidgetin (FIGN).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fidgetin (FIGN).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Fidgetin (FIGN).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fidgetin (FIGN).	[7]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Fidgetin (FIGN).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fidgetin (FIGN).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Fidgetin (FIGN).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Fidgetin (FIGN).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Fidgetin (FIGN).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat affects the expression of Fidgetin (FIGN).	[14]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Fidgetin (FIGN).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fidgetin (FIGN).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the expression of Fidgetin (FIGN).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Fidgetin (FIGN).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Fidgetin (FIGN).	[19]
ORG2058	DMH1M6N	Investigative	ORG2058 decreases the expression of Fidgetin (FIGN).	[20]

2 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 Fidgetin (FIGN).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fidgetin (FIGN).	[17]

References

• [1] Lower Circulating Folate Induced by a Fidgetin Intronic Variant Is Associated With Reduced Congenital Heart Disease Susceptibility.Circulation. 2017 May 2;135(18):1733-1748. doi: 10.1161/CIRCULATIONAHA.116.025164. Epub 2017 Mar 16.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] 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.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [9] 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.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] 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.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [14] The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects. Clin Cancer Res. 2016 May 15;22(10):2534-44. doi: 10.1158/1078-0432.CCR-15-1666. Epub 2016 Jan 5.
• [15] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] 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.
• [19] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [20] The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5. Mol Endocrinol. 2010 Jul;24(7):1380-92. doi: 10.1210/me.2009-0516. Epub 2010 Jun 2.