General Information of Drug Off-Target (DOT) (ID: OT6G8E4Q)

DOT Name Cytochrome c oxidase subunit 8C, mitochondrial (COX8C)
Synonyms Cytochrome c oxidase polypeptide 8 isoform 3; Cytochrome c oxidase polypeptide VIII isoform 3; COX VIII-3; Cytochrome c oxidase subunit 8-3; COX8-3; Cytochrome c oxidase subunit VIIIC
Gene Name COX8C
UniProt ID
COX8C_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF02285
Sequence
MPLLRGRCPARRHYRRLALLGLQPAPRFAHSGPPRQRPLSAAEMAVGLVVFFTTFLTPAA
YVLGNLKQFRRN
Function
Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
Tissue Specificity It is not yet known where COX8C is expressed.
KEGG Pathway
Oxidative phosphorylation (hsa00190 )
Metabolic pathways (hsa01100 )
Cardiac muscle contraction (hsa04260 )
Thermogenesis (hsa04714 )
Non-alcoholic fatty liver disease (hsa04932 )
Alzheimer disease (hsa05010 )
Parkinson disease (hsa05012 )
Amyotrophic lateral sclerosis (hsa05014 )
Huntington disease (hsa05016 )
Prion disease (hsa05020 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Diabetic cardiomyopathy (hsa05415 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Cytochrome c oxidase subunit 8C, mitochondrial (COX8C). [1]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Cytochrome c oxidase subunit 8C, mitochondrial (COX8C). [4]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Cytochrome c oxidase subunit 8C, mitochondrial (COX8C). [2]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Cytochrome c oxidase subunit 8C, mitochondrial (COX8C). [3]
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References

1 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.
2 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
3 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
4 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.