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Overview

Uniprot IDO00483
Protein NameCytochrome c oxidase subunit FA4
Gene NameCOXFA4
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
10 RQIIGQAKKHPSLIP
73 SVNVDYSKLKKERPD

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 (PubMed:22902835). COXFA4 is required for complex IV maintenance (PubMed:22902835)

Protein Sequence

10 MLRQIIGQAK 20 KHPSLIPLFV 30 FIGTGATGAT 40 LYLLRLALFN 50 PDVCWDRNNP 60 EPWNKLGPND 70 QYKFYSVNVD 80 YSKLKKERPD F

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005743 mitochondrial inner membrane
Cellular Component GO:0031966 mitochondrial membrane
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0045271 respiratory chain complex I
Cellular Component GO:0045277 respiratory chain complex IV
Molecular Function GO:0008137 NADH dehydrogenase (ubiquinone) activity
Molecular Function GO:0044877 protein-containing complex binding
Biological Process GO:0045333 cellular respiration
Biological Process GO:0006123 mitochondrial electron transport, cytochrome c to oxygen
Biological Process GO:0006120 mitochondrial electron transport, NADH to ubiquinone

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.