Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIUX6XG)

• DOT Name: Ferritin, mitochondrial (FTMT)
• Synonyms: EC 1.16.3.1
• Gene Name: FTMT
• Related Disease:
  Age-related macular degeneration
  Alzheimer disease
  Anemia
  Friedreich ataxia 1
  Friedreich's ataxia
  Hyperinsulinemia
  Movement disorder
  Neoplasm
  Neuroferritinopathy
  Parkinson disease
  Polycystic ovarian syndrome
  Roberts-SC phocomelia syndrome
  Sideroblastic anemia
  X-linked sideroblastic anemia 1
  Alpha thalassemia
  Myelodysplastic syndrome
  Neuroblastoma
• UniProt ID: FTMT_HUMAN
• PDB ID: 1R03; 5Z8J; 5Z8S; 5Z8U; 5Z91; 7O63; 7O64; 7O65; 7O66; 7O67; 7O68; 7O69; 7O6A; 7O6C; 7O6D; 7OWY
• EC Number: 1.16.3.1
• Pfam ID: PF00210
• Sequence:
  MLSCFRLLSRHISPSLASLRPVRCCFALPLRWAPGRPLDPRQIAPRRPLAAAASSRDPTG
  PAAGPSRVRQNFHPDSEAAINRQINLELYASYVYLSMAYYFSRDDVALNNFSRYFLHQSR
  EETEHAEKLMRLQNQRGGRIRLQDIKKPEQDDWESGLHAMECALLLEKNVNQSLLELHAL
  ASDKGDPHLCDFLETYYLNEQVKSIKELGDHVHNLVKMGAPDAGLAEYLFDTHTLGNENK
  QN
• Function: Catalyzes the oxidation of ferrous iron(II) to ferric iron(III) and stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation.
• Tissue Specificity: Detected in testis and erythroleukemia. Expression is very low or not detectable in brain, colon, heart, kidney, liver, lung, muscle, placental, spleen and small intestine.
• KEGG Pathway:
  Porphyrin metabolism (hsa00860)
  Ferroptosis (hsa04216)
• Reactome Pathway: Iron uptake and transport (R-HSA-917937)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Anemia	DISTVL0C	Strong	Biomarker	[3]
Friedreich ataxia 1	DIS285GE	Strong	Altered Expression	[4]
Friedreich's ataxia	DIS5DV35	Strong	Altered Expression	[5]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[6]
Movement disorder	DISOJJ2D	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Neuroferritinopathy	DIS0E4F3	Strong	Biomarker	[7]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[9]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[6]
Roberts-SC phocomelia syndrome	DIS4JXZ4	Strong	Biomarker	[10]
Sideroblastic anemia	DIS4F3X1	Strong	Altered Expression	[11]
X-linked sideroblastic anemia 1	DISWBQC7	Strong	Biomarker	[11]
Alpha thalassemia	DIS5XGK0	moderate	Altered Expression	[12]
Myelodysplastic syndrome	DISYHNUI	Limited	Biomarker	[7]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[13]

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 Ferritin, mitochondrial (FTMT).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ferritin, mitochondrial (FTMT).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ferritin, mitochondrial (FTMT).	[15]
Marinol	DM70IK5	Approved	Marinol affects the expression of Ferritin, mitochondrial (FTMT).	[16]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Ferritin, mitochondrial (FTMT).	[17]

References

• [1] Mitochondrial ferritin affects mitochondria by stabilizing HIF-1 in retinal pigment epithelium: implications for the pathophysiology of age-related macular degeneration.Neurobiol Aging. 2016 Nov;47:168-179. doi: 10.1016/j.neurobiolaging.2016.07.025. Epub 2016 Aug 12.
• [2] Mitochondrial Ferritin Deletion Exacerbates -Amyloid-Induced Neurotoxicity in Mice.Oxid Med Cell Longev. 2017;2017:1020357. doi: 10.1155/2017/1020357. Epub 2017 Jan 16.
• [3] Aberrant splicing of genes involved in haemoglobin synthesis and impaired terminal erythroid maturation in SF3B1 mutated refractory anaemia with ring sideroblasts.Br J Haematol. 2015 Nov;171(4):478-90. doi: 10.1111/bjh.13610. Epub 2015 Aug 10.
• [4] Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia.Hum Mol Genet. 2009 Jan 1;18(1):1-11. doi: 10.1093/hmg/ddn308. Epub 2008 Sep 24.
• [5] Characterization of human mitochondrial ferritin promoter: identification of transcription factors and evidences of epigenetic control.Sci Rep. 2016 Sep 14;6:33432. doi: 10.1038/srep33432.
• [6] Metformin augments the levels of molecules that regulate the expression of the insulin-dependent glucose transporter GLUT4 in the endometria of hyperinsulinemic PCOS patients.Hum Reprod. 2013 Aug;28(8):2235-44. doi: 10.1093/humrep/det116. Epub 2013 Apr 17.
• [7] Sequence variations in mitochondrial ferritin: distribution in healthy controls and different types of patients.Genet Test Mol Biomarkers. 2010 Dec;14(6):793-6. doi: 10.1089/gtmb.2010.0076. Epub 2010 Oct 12.
• [8] A novel method for quantification of beam's-eye-view tumor tracking performance.Med Phys. 2017 Nov;44(11):5650-5659. doi: 10.1002/mp.12572. Epub 2017 Oct 13.
• [9] Mitochondrial ferritin protects SH-SY5Y cells against H(2)O(2)-induced oxidative stress and modulates -synuclein expression.Exp Neurol. 2017 May;291:51-61. doi: 10.1016/j.expneurol.2017.02.001. Epub 2017 Feb 3.
• [10] The Role of Endotoxin in Sterile Inflammation After Implanted Acellular Dermal Matrix: Red Breast Syndrome Explained?.Aesthet Surg J. 2020 Mar 23;40(4):392-399. doi: 10.1093/asj/sjz208.
• [11] Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia.Blood. 2003 Mar 1;101(5):1996-2000. doi: 10.1182/blood-2002-07-2006. Epub 2002 Oct 24.
• [12] Mitochondrial ferritin expression in erythroid cells from patients with alpha-thalassaemia.Hematology. 2018 Dec;23(10):844-848. doi: 10.1080/10245332.2018.1496812. Epub 2018 Jul 11.
• [13] Mitochondrial Ferritin Protects Hydrogen Peroxide-Induced Neuronal Cell Damage.Aging Dis. 2017 Jul 21;8(4):458-470. doi: 10.14336/AD.2016.1108. eCollection 2017 Jul.
• [14] 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.
• [15] 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.
• [16] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [17] Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
• [18] 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.