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Details on Person UniProt:O00483 COXFA4

Class:IdReferenceGeneProduct:60618
_chainChangeLogchain:1-81 added on Fri February 6 2015
_displayNameUniProt:O00483 COXFA4
_timestamp2026-02-20 23:17:06
chainchain:1-81
checksum2FA1D1115EDE24C7
commentFUNCTION 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 (PubMed:22902835). COXFA4 is required for complex IV maintenance (PubMed:22902835).SUBUNIT Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I1 (or COX4I2), COX5A, COX5B, COX6A1 (or COX6A2), COX6B1 (or COX6B2), COX6C, COX7A2 (or COX7A1), COX7B, COX7C, COX8A and COXFA4, which are encoded in the nuclear genome (PubMed:22902835, PubMed:23746447, PubMed:30030519). The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (Probable). Interacts with RAB5IF (PubMed:31536960). Interacts with FLVCR2; this interaction occurs in the absence of heme and is disrupted upon heme binding.INTERACTION The disease may be caused by variants affecting the gene represented in this entry.MISCELLANEOUS During complex IV purifications dissociates from complex IV upon treatment with standard detergent DDM (decyl beta-D-maltoside) in high concentrations (PubMed:22902835, PubMed:23746447).SIMILARITY Belongs to the complex IV COXFA4 subunit family.CAUTION Was initially believed to be a subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I).
descriptionrecommendedName: fullName evidence="6"Cytochrome c oxidase subunit FA4 alternativeName: Complex I-MLRQ shortName: CI-MLRQ alternativeName: Cytochrome c oxidase subunit NDUFA4 alternativeName: NADH-ubiquinone oxidoreductase MLRQ subunit
geneNameCOXFA4
NDUFA4
identifierO00483
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Electron transport
Leigh syndrome
Membrane
Mitochondrion
Mitochondrion inner membrane
Phosphoprotein
Primary mitochondrial disease
Proteomics identification
Reference proteome
Respiratory chain
Transmembrane
Transmembrane helix
Transport
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9841277] Weiser, Joel
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameCOXFA4
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8989084] ENSEMBL:ENSG00000189043 COXFA4 [Homo sapiens]
secondaryIdentifierCXFA4_HUMAN
A4D109
Q6FHN5
sequenceLength81
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:60617] NDUFA4 [mitochondrial inner membrane] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:O00483 COXFA4 (60618)