Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA1KTRN)

• DOT Name: Ubiquinol-cytochrome c reductase complex assembly factor 2
• Synonyms: Breast cancer-associated protein SGA-81M; Mitochondrial nucleoid factor 1; Mitochondrial protein M19
• Gene Name: UQCC2
• Related Disease:
  Mitochondrial complex III deficiency
  Mitochondrial complex III deficiency nuclear type 7
• UniProt ID: UQCC2_HUMAN
• Pfam ID: PF20180
• Sequence:
  MAASRYRRFLKLCEEWPVDETKRGRDLGAYLRQRVAQAFREGENTQVAEPEACDQMYESL
  ARLHSNYYKHKYPRPRDTSFSGLSLEEYKLILSTDTLEELKEIDKGMWKKLQEKFAPKGP
  EEDHKA
• Function: Required for the assembly of the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex). Plays a role in the modulation of respiratory chain activities such as oxygen consumption and ATP production and via its modulation of the respiratory chain activity can regulate skeletal muscle differentiation and insulin secretion by pancreatic beta-cells. Involved in cytochrome b translation and/or stability.
• Tissue Specificity: Pancreas, skeletal muscle, kidney, liver and heart.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial complex III deficiency	DISSUPJ6	Supportive	Autosomal recessive	[1]
Mitochondrial complex III deficiency nuclear type 7	DIS90707	Limited	Unknown	[1]

13 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 Ubiquinol-cytochrome c reductase complex assembly factor 2.	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[12]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[13]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ubiquinol-cytochrome c reductase complex assembly factor 2.	[10]

References

• [1] Mutations in the UQCC1-interacting protein, UQCC2, cause human complex III deficiency associated with perturbed cytochrome b protein expression. PLoS Genet. 2013;9(12):e1004034. doi: 10.1371/journal.pgen.1004034. Epub 2013 Dec 26.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] 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.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [13] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.
• [14] The marine toxin okadaic acid induces alterations in the expression level of cancer-related genes in human neuronal cells. Ecotoxicol Environ Saf. 2013 Jun;92:303-11. doi: 10.1016/j.ecoenv.2013.03.009. Epub 2013 Apr 3.