Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD2JO6B)

• DOT Name: Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3)
• Synonyms: SDH assembly factor 3; SDHAF3
• Gene Name: SDHAF3
• Related Disease:
  Alcohol dependence
  Paraganglioma
  Pheochromocytoma
  Chronic obstructive pulmonary disease
• UniProt ID: SDHF3_HUMAN
• Pfam ID: PF13233
• Sequence:
  MPGRHVSRVRALYKRVLQLHRVLPPDLKSLGDQYVKDEFRRHKTVGSDEAQRFLQEWEVY
  ATALLQQANENRQNSTGKACFGTFLPEEKLNDFRDEQIGQLQELMQEATKPNRQFSISES
  MKPKF
• Function: Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Promotes maturation of the iron-sulfur protein subunit SDHB of the SDH catalytic dimer, protecting it from the deleterious effects of oxidants. May act together with SDHAF1.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[1]
Paraganglioma	DIS2XXH5	Strong	Genetic Variation	[2]
Pheochromocytoma	DIS56IFV	Strong	Genetic Variation	[2]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[3]

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 Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Succinate dehydrogenase assembly factor 3, mitochondrial (SDHAF3).	[14]

References

• [1] ACN9 and alcohol dependence: family-based association analysis in multiplex alcohol dependence families.Am J Med Genet B Neuropsychiatr Genet. 2015 Apr;168B(3):179-87. doi: 10.1002/ajmg.b.32295.
• [2] Analysis of SDHAF3 in familial and sporadic pheochromocytoma and paraganglioma.BMC Cancer. 2017 Jul 24;17(1):497. doi: 10.1186/s12885-017-3486-z.
• [3] Association of lung function genes with chronic obstructive pulmonary disease.Lung. 2014 Aug;192(4):473-80. doi: 10.1007/s00408-014-9579-4. Epub 2014 Apr 16.
• [4] 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.
• [5] 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.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] 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.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.