Cytochrome c oxidase subunit FA4
Also known as: COXFA4, NDUFA4
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 unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. COXFA4 is required for complex IV maintenance.
Classification
- Family (Pfam)
- PF06522 B12D
- InterPro
- B12D
- Functional cluster
- Photosystem II Reaction-Center & Antimicrobial Peptides
Experimental structures · PDB · 2
A predicted model is available from AlphaFold.
Gene Ontology · 10
- GO:0005743 mitochondrial inner membrane
- GO:0031966 mitochondrial membrane
- GO:0005739 mitochondrion
- GO:0045271 respiratory chain complex I
- GO:0045277 respiratory chain complex IV
- GO:0008137 NADH dehydrogenase (ubiquinone) activity
- GO:0044877 protein-containing complex binding
- GO:0045333 cellular respiration
- GO:0006123 mitochondrial electron transport, cytochrome c to oxygen
- GO:0006120 mitochondrial electron transport, NADH to ubiquinone
Disease associations
- mitochondrial complex IV deficiency, nuclear type 21 MONDO:0033656
Drugs targeting this protein · 2
- METFORMIN HYDROCHLORIDE inhibitor
- ME-344 inhibitor
Related proteins · sequence + function similarity
- Cytochrome c oxidase subunit FA4 1.00
- Cytochrome c oxidase subunit FA4 0.99
- Cytochrome c oxidase subunit FA4 0.99
- Cytochrome c oxidase subunit FA4 0.97
- Cytochrome c oxidase subunit FA4 0.97
- Cytochrome c oxidase subunit FA4 0.97
- Cytochrome c oxidase subunit FA4 0.97
- Cytochrome c oxidase subunit FA4 0.95
- Cytochrome c oxidase hypoxia associated subunit FA4L2 0.90
- Cytochrome c oxidase hypoxia associated subunit FA4L2 0.89
- Cytochrome c oxidase hypoxia associated subunit FA4L2 0.85
- Cytochrome c oxidase associated subunit FA4L3 0.82
Co-cited proteins · studied together in the literature
- Cytochrome c oxidase subunit FA4 1 shared papers
- Cytochrome c oxidase subunit 6B1 1 shared papers
- Cytochrome c oxidase subunit 7C, mitochondrial 2 shared papers
- Cytochrome c oxidase subunit 8A, mitochondrial 1 shared papers
- Cytochrome c oxidase subunit 7B, mitochondrial 1 shared papers
- Cytochrome c oxidase subunit 5A, mitochondrial 2 shared papers
- NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial 1 shared papers
- NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial 1 shared papers
- Neudesin 1 shared papers
- GEL complex subunit OPTI 1 shared papers
- NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial 1 shared papers
- Cytochrome c oxidase subunit 4 isoform 1, mitochondrial 1 shared papers
Literature · 12 cited papers
- Rewiring of the Human Mitochondrial Interactome during Neuronal Reprogramming Reveals Regulators of the Respirasome and Neurogenesis. IScience · 2019
- Structure of the intact 14-subunit human cytochrome c oxidase. Cell Res. · 2018
- N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological disease. Cell Rep. · 2013
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. Cell Metab. · 2012
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Human chromosome 7: DNA sequence and biology. Science · 2003
- The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification. J. Biol. Chem. · 2003
- Cloning of the human cDNA sequence encoding the NADH:ubiquinone oxidoreductase MLRQ subunit. Biochem. Mol. Biol. Int. · 1997