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Overview

Uniprot IDP13073
Protein NameCytochrome c oxidase subunit 4 isoform 1, mitochondrial
Gene NameCOX4I1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
149 TKRMLDMKVNPIQGL
29 RAHESVVKSEDFSLP
53 LPEVAHVKHLSASQK
60 KHLSASQKALKEKEK
67 KALKEKEKASWSSLS
87 ELYRIKFKESFAEMN

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

Protein Sequence

10 MLATRVFSLV 20 GKRAISTSVC 30 VRAHESVVKS 40 EDFSLPAYMD 50 RRDHPLPEVA 60 HVKHLSASQK 70 ALKEKEKASW 80 SSLSMDEKVE 90 LYRIKFKESF 100 AEMNRGSNEW 110 KTVVGGAMFF 120 IGFTALVIMW 130 QKHYVYGPLP 140 QSFDKEWVAK 150 QTKRMLDMKV 160 NPIQGLASKW DYEKNEWKK

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005829 cytosol
Cellular Component GO:0016020 membrane
Cellular Component GO:0005743 mitochondrial inner membrane
Cellular Component GO:0005758 mitochondrial intermembrane space
Cellular Component GO:0031966 mitochondrial membrane
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0045277 respiratory chain complex IV
Molecular Function GO:0004129 cytochrome-c oxidase activity
Biological Process GO:0045333 cellular respiration
Biological Process GO:0006091 generation of precursor metabolites and energy
Biological Process GO:0006123 mitochondrial electron transport, cytochrome c to oxygen
Biological Process GO:0007584 response to nutrient

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] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

[3] 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.

[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.