Gene Ontology annotation through association of InterPro records with GO terms.
-
InterPro2GO mapping infers GO terms (e.g. mitochondrial envelope, cytochrome c to O2 electron transport, respiratory chain complex IV) for COX5B from its conserved cytochrome c oxidase subunit Vb domain signature.
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping.
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
-
UniProtKB keyword-to-GO mappings (e.g. Electron transport, Mitochondrion, Respiratory chain) produce broad IEA annotations linking COX5B to mitochondrial electron transport and oxidative phosphorylation.
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.
Gene Ontology annotation based on curation of immunofluorescence data
Automatic assignment of GO terms using logical inference, based on on inter-ontology links.
Structure of the human cytochrome c oxidase subunit Vb gene and chromosomal mapping of the coding gene and of seven pseudogenes.
-
Cloned the human COX5B gene, defined its 5-exon / 4-intron structure, and mapped the single expressed locus to chromosome 2 (cen-q13) alongside seven pseudogenes; establishes COX5B as the nuclear gene encoding cytochrome c oxidase subunit Vb.
"We have cloned the gene for human COX subunit Vb (COX5B) and determined the exon-intron structure by both hybridization analysis and DNA sequencing."
-
Confirms that COX subunit Vb is encoded by a single nuclear gene that is assembled with the other 12 (now known to be 13) COX subunits encoded in mitochondrial and nuclear DNA.
"Subunit Vb of mammalian cytochrome c oxidase (COX; EC 1.9.3.1) is encoded by a nuclear gene and assembled with the other 12 COX subunits encoded in both mitochondrial and nuclear DNA."
Huntingtin interacting proteins are genetic modifiers of neurodegeneration.
-
Reports a yeast-two-hybrid / mass-spectrometry interactome of huntingtin that includes COX5B as an Htt-associated protein; supports a non-functional protein-binding IPI rather than a specific COX5B molecular function.
"This effort led to the identification of 234 high-confidence Htt-associated proteins"
Next-generation sequencing to generate interactome datasets.
-
Describes the Stitch-seq massively parallel interactome mapping method used to generate human binary interactome datasets in which COX5B appears as an interactor; provides only generic "protein binding" support for COX5B.
"We describe a massively parallel interactome-mapping pipeline, Stitch-seq, that combines PCR stitching with next-generation sequencing and used it to generate a new human interactome dataset."
A proteome-scale map of the human interactome network.
Structure of the intact 14-subunit human cytochrome c oxidase.
-
Determines the 3.3 Å cryo-EM structure of intact human Complex IV from the I1III2IV1 supercomplex and assigns NDUFA4 to Complex IV, supporting the view that the intact monomeric CIV holoenzyme contains 14 subunits including COX5B.
"we propose that the intact complex-IV is a monomer containing 14 subunits."
-
Defines the catalytic action of Complex IV (electron acceptance from cytochrome c, reduction of O2 to water, proton pumping) that COX5B's structural role enables.
"It accepts electrons from cytochrome c to reduce the oxygen to water and meanwhile pumps two protons from the matrix side to the intermembrane space (IMS)"
Pyridine nucleotide-disulphide oxidoreductase domain 2 (PYROXD2): Role in mitochondrial function.
-
PYROXD2 is targeted to the mitochondrial inner membrane/matrix via Tom40/Tim23 and physically interacts with Complex IV subunit COX5B; PYROXD2 knockout decreases CIV activity, supporting a regulatory partnership but not a specific COX5B molecular function beyond generic protein binding.
"PYROXD2 interacted with complex IV subunit COX5B. Knockout of PYROXD2 decreased MMP, intracellular ROS, complex IV activity, cell proliferation, ATP content and mtDNA copy number"
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
First identification of ITM2B interactome in the human retina.
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
-
Quantitative mass-spectrometry-based mitochondrial proteomics confirms COX5B as a high-confidence mitochondrial protein and provides HTP evidence for its mitochondrion / inner membrane localization.
"Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context"
Electron transfer from reduced cytochrome c to molecular oxygen
CO binds to Cytochrome c oxidase
LONP1 binds mitochondrial inner membrane proteins
LONP1 degrades mitochondrial inner membrane proteins
MT-CO3, COX6A,B,7A and NDUFA4 bind to holo-MT-CO1,2 complex
-
Reactome reaction describing the late stage of human Complex IV assembly where nuclear-encoded subunits (MT-CO3, COX6A/B, COX7A, NDUFA4) bind the holo-MT-CO1/2 intermediate; places COX5B within the assembled CIV at the mitochondrial inner membrane.
Deep research on COX5B function
-
Perplexity deep-research synthesis describing COX5B as a nuclear-encoded peripheral (matrix-facing) accessory subunit of Complex IV that is required for assembly, stability, and optimal cytochrome c oxidase activity; consistent with structural and knockdown evidence.
Falcon deep research: COX5B functional annotation synthesis (Edison Scientific Literature)
-
COX5B is a matrix-facing, nuclear-encoded accessory subunit of mitochondrial Complex IV, lacking a transmembrane domain.
"COX5B is described as **matrix-facing** and **lacking a transmembrane domain**, consistent with a peripheral location on the matrix side of CIV rather than forming the membrane-embedded catalytic core."
-
COX5B knockdown causes decreased COX activity, decreased ΔΨm, increased ROS, and accumulation of COX assembly intermediates.
"A COX5B knockdown phenotype summarized in an authoritative review reports that reducing COX5B in a macrophage cell line led to decreased **cytochrome c oxidase activity**, decreased **mitochondrial membrane potential (Δψm)**, increased **reactive oxygen species (ROS)**, and accumulation of **COX assembly intermediates**, supporting a role for COX5B in COX assembly and respiratory-chain homeostasis."
-
COX5B participates in respiratory supercomplexes; in COX2-deficient cybrids it associates with COX1/COX4/COX7A2 in an atypical SC I+III2+ species, and pulls down complex I and III subunits.
"In COX2-deficient cybrids, COX5B was found co-migrating with COX1/COX4/COX7A2 in a species termed **SC I+III2plus**, and anti-COX5B immunoprecipitation pulled down subunits of complex I and complex III, consistent with COX5B-containing CIV modules associating with CI/CIII within supercomplex contexts."
-
COX5B is incorporated into the S3 intermediate during stepwise modular CIV assembly.
"COX5B is present in defined CIV assembly intermediates. In particular, it is included in the **S3 assembly intermediate** of CIV, indicating incorporation during stepwise assembly rather than being a late peripheral add-on."
Role of cytochrome c oxidase nuclear-encoded subunits in health and disease.
-
Review covering the roles of nuclear-encoded cytochrome c oxidase subunits (including COX5B) in CIV assembly, regulation, and human disease; used as a curation-context reference rather than a primary functional source for COX5B.
Multiple pathways coordinate assembly of human mitochondrial complex IV and stabilization of respiratory supercomplexes.