Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZI1KFR)

• DOT Name: Small integral membrane protein 20 (SMIM20)
• Synonyms: Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 7 kDa; MITRAC7
• Gene Name: SMIM20
• Related Disease:
  Alzheimer disease
  Anorexia nervosa cachexia
  Anxiety
  Anxiety disorder
  Eating disorder
  Pneumothorax
• UniProt ID: SIM20_HUMAN
• Pfam ID: PF15061
• Sequence:
  MSRNLRTALIFGGFISLIGAAFYPIYFRPLMRLEEYKKEQAINRAGIVQEDVQPPGLKVW
  SDPFGRK
• Function: [Small integral membrane protein 20]: Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. Promotes the progression of complex assembly after the association of MT-CO1/COX1 with COX4I1 and COX6C. Chaperone-like assembly factor required to stabilize newly synthesized MT-CO1/COX1 and to prevent its premature turnover ; [Phoenixin-14]: Peptide involved in a broad spectrum of regulatory functions. Is a ligand for GPR173. As part of the reproductive cycle, it regulates gonadotropin-releasing hormone (GnRH) signaling in the hypothalamus and pituitary gland which augments the release of luteinizing hormone. Plays a protective role in memory retention through activation of GNRHR. Regulates the secretion of AVP by hypothalamic neurons. Plays a role in the transduction of the itch sensation. Induces anxiolytic effects, reducing behavior associated with anxiety. Regulates food intake as well as satiation and satiety. In the ovary, it regulates follicular growth by stimulating granulosa cell proliferation by increasing the expression of GPR173, CREB1, CYP19A1, KITLG, FSHR, and LHCGR. It also increases the production of estradiol (E2). In the heart, it regulates contractility and relaxation. It also plays a cardioprotective role during ischemia, where it activates the SAFE and RISK pathways. Stimulates the proliferation and differentiation of preadipocytes. In pancreatic islet cells, it induces proliferation of islet cells as well as the production of INS; [Phoenixin-20]: Peptide involved in a broad spectrum of regulatory functions. Is a ligand for GPR173. As part of the reproductive cycle, it regulates gonadotropin-releasing hormone (GnRH) signaling in the hypothalamus and pituitary gland which augments the release of luteinizing hormone. Plays a protective role in memory retention through activation of GNRHR. Regulates the secretion of AVP by hypothalamic neurons. Plays a role in the transduction of the itch sensation. Induces anxiolytic effects, reducing behavior associated with anxiety. Regulates food intake as well as satiation and satiety. In the ovary, it regulates follicular growth by stimulating granulosa cell proliferation by increasing the expression of GPR173, CREB1, CYP19A1, KITLG, FSHR, and LHCGR. It also increases the production of estradiol (E2). In the heart, it regulates contractility and relaxation. It also plays a cardioprotective role during ischemia, where it activates the SAFE and RISK pathways. Stimulates the proliferation and differentiation of preadipocytes. In pancreatic islet cells, it induces proliferation of islet cells as well as the production of INS.
• Tissue Specificity: Expressed in the ovary, specifically in granulosa cells of follicles that have passed the primary stage and in oocytes (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Altered Expression	[2]
Anxiety	DISIJDBA	Strong	Biomarker	[3]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[3]
Eating disorder	DISVGXN0	Strong	Altered Expression	[2]
Pneumothorax	DISP86H1	Strong	Genetic Variation	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Small integral membrane protein 20 (SMIM20) affects the response to substance of Acetaminophen.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Small integral membrane protein 20 (SMIM20).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Small integral membrane protein 20 (SMIM20).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Small integral membrane protein 20 (SMIM20).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Small integral membrane protein 20 (SMIM20).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Small integral membrane protein 20 (SMIM20).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Small integral membrane protein 20 (SMIM20).	[10]

References

• [1] Does plasma phoenixin level associate with cognition? Comparison between subjective memory complaint, mild cognitive impairment, and mild Alzheimer's disease.Int Psychogeriatr. 2017 May 29:1-8. doi: 10.1017/S1041610217000825. Online ahead of print.
• [2] Longitudinal study on novel neuropeptides phoenixin, spexin and kisspeptin in adolescent inpatients with anorexia nervosa - association with psychiatric symptoms.Nutr Neurosci. 2021 Nov;24(11):896-906. doi: 10.1080/1028415X.2019.1692494. Epub 2019 Nov 18.
• [3] The role of phoenixin in behavior and food intake.Peptides. 2019 Apr;114:38-43. doi: 10.1016/j.peptides.2019.04.002. Epub 2019 Apr 3.
• [4] Extra-pleuric coaxial system for CT-guided percutaneous fine-needle aspiration biopsy (FNAB) of small (?0mm) lung nodules: a novel technique using multiplanar reconstruction (MPR) images.Med Oncol. 2017 Feb;34(2):17. doi: 10.1007/s12032-016-0871-4. Epub 2016 Dec 29.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [10] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [11] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.