COX7B (cytochrome c oxidase subunit 7B, mitochondrial; polypeptide VIIb) is a small, nuclear-encoded structural subunit of mitochondrial respiratory Complex IV (cytochrome c oxidase, COX/CIV), the terminal enzyme of the electron transport chain. Complex IV comprises a mitochondrially encoded catalytic core (MT-CO1, MT-CO2, MT-CO3) that carries out the reduction of oxygen to water, together with nuclear-encoded supernumerary subunits, of which COX7B is one. COX7B is a non-catalytic subunit that surrounds and supports the catalytic core and contributes to assembly and stability of the holoenzyme; it is a single-pass protein of the mitochondrial inner membrane (matrix-facing N-terminus, transmembrane helix, intermembrane-space C-terminus) synthesized as an 80-residue precursor with a cleaved mitochondrial transit peptide. Through its role in Complex IV it participates in mitochondrial electron transport from cytochrome c to oxygen and in oxidative phosphorylation. In humans COX7B is X-linked, and deleterious mutations cause an X-linked disorder, linear skin defects with multiple congenital anomalies (LSDMCA2), within the microphthalmia-with-linear-skin-defects (MLS/MIDAS) spectrum, an unconventional mitochondrial disease with a prominent neurodevelopmental phenotype.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: COX7B is a subunit of mitochondrial Complex IV and localizes to the mitochondrion. This phylogenetic (IBA) mitochondrial annotation is correct but general; the precise location is the mitochondrial inner membrane (GO:0005743). Reason: Correct localization to the mitochondrion, consistent with COX7B being a cytochrome c oxidase subunit of the inner membrane. Retained as a correct but non-core (broad) cellular component; the specific inner-membrane term captures the core localization. Supporting Evidence: PMID:8382530 Isolation of a cDNA specifying subunit VIIb of human cytochrome c oxidase. |
| GO:0045277 respiratory chain complex IV | IBA GO_REF:0000033 | ACCEPT | Summary: COX7B is a constitutive structural subunit of respiratory chain complex IV (cytochrome c oxidase). This phylogenetic annotation captures the core cellular component/complex membership of the gene. Reason: Complex IV membership is the defining property of COX7B, supported by structural and biochemical evidence that it is one of the 11 nuclear-encoded supernumerary subunits of the 14-subunit human cytochrome c oxidase. GO:0045277 is the current, non-obsolete term for this complex. Supporting Evidence: PMID:30030519 the intact monomeric complex-IV contains 14 subunits file:human/COX7B/COX7B-uniprot.txt COX7A2 (or COX7A1), COX7B, COX7C, COX8A and COXFA4, which are encoded |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: COX7B is a single-pass protein of the mitochondrial inner membrane, where Complex IV resides. This UniProt subcellular-location mapping is accurate and represents the core cellular component. Reason: The inner mitochondrial membrane is the precise, experimentally supported localization of COX7B and of the whole cytochrome c oxidase complex. Supporting Evidence: file:human/COX7B/COX7B-uniprot.txt Single-pass membrane protein PMID:30030519 CIV is the terminal oxidase of the electron transport chain in mitochondria |
| GO:0006123 mitochondrial electron transport, cytochrome c to oxygen | IEA GO_REF:0000002 | ACCEPT | Summary: As a subunit of Complex IV, COX7B participates in mitochondrial electron transport from cytochrome c to oxygen. This InterPro2GO mapping (from the COX7B/VIIb family signature) assigns the correct core biological process. Reason: GO:0006123 is the process carried out by the complex to which COX7B belongs and is the appropriate core BP for this structural subunit. Supporting Evidence: PMID:30030519 It accepts electrons from cytochrome c to reduce the oxygen to water |
| GO:0016020 membrane | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: This ARBA machine-learning annotation places COX7B in the generic 'membrane' component. It is not wrong (COX7B is an integral membrane protein) but is far more general than the well-supported mitochondrial inner membrane term. Reason: The generic 'membrane' term is uninformative given the precise, experimentally supported mitochondrial inner membrane localization (GO:0005743). Retained but flagged as over-general. Supporting Evidence: file:human/COX7B/COX7B-uniprot.txt Single-pass membrane protein |
| GO:1902600 proton transmembrane transport | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: This annotation is inferred by an inter-ontology logical link from the cytochrome-c oxidase activity of Complex IV (the complex pumps protons across the inner membrane). Proton pumping is a property of the mtDNA-encoded catalytic core; COX7B is a non-catalytic structural subunit that does not itself translocate protons. Reason: Complex IV does contribute to proton transmembrane transport, so the annotation is not incorrect at the complex level, but for the individual non-catalytic COX7B subunit this is a peripheral, complex-level property rather than a core function. Supporting Evidence: PMID:30030519 pumps two protons from the matrix side to the intermembrane space |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: A single high-throughput binary (yeast two-hybrid) interaction with GNMT (Q14749) reported in the HuRI human interactome map. Bare 'protein binding' provides no informative molecular function, and this cytosolic-methyltransferase partner has no clear relationship to an inner-membrane Complex IV subunit. Reason: Uninformative 'protein binding' from a single large-scale Y2H screen; it does not capture COX7B's actual molecular function (structural subunit of Complex IV). Retained (not removed) per policy on high-throughput IPI protein-binding annotations, but flagged as over-annotation. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI' |
| GO:0006119 oxidative phosphorylation | IEA GO_REF:0000041 | ACCEPT | Summary: Complex IV, and hence COX7B, participates in oxidative phosphorylation by contributing to the electron transport chain that builds the proton-motive force driving ATP synthase. This UniPathway-based mapping is correct but broader than the specific electron-transport process. Reason: Correct higher-level biological process for a Complex IV subunit; kept as a correct, non-core (broader) BP relative to GO:0006123. Supporting Evidence: file:human/COX7B/COX7B-uniprot.txt Energy metabolism; oxidative phosphorylation file:human/COX7B/COX7B-uniprot.txt electrochemical gradient over the inner membrane |
| GO:0006123 mitochondrial electron transport, cytochrome c to oxygen | NAS PMID:30030519 Structure of the intact 14-subunit human cytochrome c oxidas... | ACCEPT | Summary: ComplexPortal (CPX-6123) NAS annotation of the core electron-transport process for a Complex IV subunit, based on the intact 14-subunit human cytochrome c oxidase structure. Duplicates the InterPro IEA assignment of the same core BP. Reason: Correct core biological process for COX7B as a Complex IV subunit; consistent with the structural characterization of the complex. Supporting Evidence: PMID:30030519 It accepts electrons from cytochrome c to reduce the oxygen to water |
| GO:0031966 mitochondrial membrane | IDA PMID:30030519 Structure of the intact 14-subunit human cytochrome c oxidas... | ACCEPT | Summary: ComplexPortal IDA localization to the mitochondrial membrane, from the cryo-EM structure of human Complex IV. Correct, though broader than the mitochondrial inner membrane term that specifies COX7B's exact location. Reason: Accurate mitochondrial-membrane localization supported by structural data; retained as a correct but non-core (broader) cellular component relative to GO:0005743. Supporting Evidence: PMID:30030519 CIV is the terminal oxidase of the electron transport chain in mitochondria |
| GO:0045277 respiratory chain complex IV | IPI PMID:30030519 Structure of the intact 14-subunit human cytochrome c oxidas... | ACCEPT | Summary: ComplexPortal IPI membership of respiratory chain complex IV, established by the intact 14-subunit human cytochrome c oxidase structure in which COX7B is resolved as a subunit. This is the core complex membership for COX7B. Reason: Directly supported structural evidence that COX7B is part of complex IV; GO:0045277 is the current term for the complex. Supporting Evidence: PMID:30030519 the intact monomeric complex-IV contains 14 subunits |
| GO:0045333 cellular respiration | NAS PMID:30030519 Structure of the intact 14-subunit human cytochrome c oxidas... | ACCEPT | Summary: ComplexPortal NAS annotation to cellular respiration, the broad process encompassing the electron transport chain and oxidative phosphorylation to which Complex IV contributes. Reason: Correct high-level biological process for a Complex IV subunit; retained as a correct, non-core (broad) BP relative to the specific cytochrome-c-to-oxygen electron transport term. Supporting Evidence: PMID:30030519 CIV is the terminal oxidase of the electron transport chain in mitochondria |
| GO:0005743 mitochondrial inner membrane | EXP PMID:30030519 Structure of the intact 14-subunit human cytochrome c oxidas... | ACCEPT | Summary: Experimental (structural) localization of COX7B to the mitochondrial inner membrane, consistent with UniProt topology (matrix-facing N-terminus, single transmembrane helix, intermembrane-space C-terminus). This is the core cellular component. Reason: The mitochondrial inner membrane is the precise, experimentally supported localization of COX7B within Complex IV. Supporting Evidence: file:human/COX7B/COX7B-uniprot.txt Single-pass membrane protein |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput detection of COX7B in the high-confidence human mitochondrial proteome. Correct mitochondrial localization, though general relative to the inner-membrane term. Reason: Supports mitochondrial localization of COX7B; retained as a correct but non-core (broad) cellular component. Supporting Evidence: PMID:34800366 human mitochondrial proteome |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-163214 | ACCEPT | Summary: Reactome traceable-author-statement localization of COX7B to the mitochondrial inner membrane in the context of electron transfer from reduced cytochrome c to molecular oxygen. Consistent with the core localization. Reason: Correct inner-membrane localization from a curated pathway resource; consistent with experimental and structural evidence. Supporting Evidence: file:human/COX7B/COX7B-uniprot.txt Single-pass membrane protein |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9709406 | ACCEPT | Summary: Reactome TAS localization of COX7B to the mitochondrial inner membrane (in the CO-binding-to-cytochrome-c-oxidase reaction context). Consistent with the core localization. Reason: Correct inner-membrane localization from a curated pathway resource. Supporting Evidence: file:human/COX7B/COX7B-uniprot.txt Single-pass membrane protein |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9865579 | ACCEPT | Summary: Reactome TAS localization of COX7B to the mitochondrial inner membrane (Complex IV assembly context, MT-CO1/MT-CO2 heme installation). Consistent with the core localization. Reason: Correct inner-membrane localization from a curated pathway resource. Supporting Evidence: file:human/COX7B/COX7B-uniprot.txt Single-pass membrane protein |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9865663 | ACCEPT | Summary: Reactome TAS localization of COX7B to the mitochondrial inner membrane (Complex IV assembly context in which COX7B binds the holo-MT-CO1,2 complex). Consistent with the core localization. Reason: Correct inner-membrane localization from a curated pathway resource; the assembly context is consistent with COX7B being a supernumerary subunit added during Complex IV biogenesis. Supporting Evidence: file:human/COX7B/COX7B-uniprot.txt Single-pass membrane protein |
| GO:0007417 central nervous system development | IMP PMID:23122588 Mutations in COX7B cause microphthalmia with linear skin les... | KEEP AS NON CORE | Summary: COX7B knockdown in medaka recapitulates the microphthalmia-with-linear-skin-lesions (MLS) phenotype with microcephaly and microphthalmia, demonstrating that Complex IV activity is required for vertebrate CNS development. This is a downstream developmental consequence of loss of cytochrome c oxidase activity rather than a distinct molecular role of COX7B. Reason: The developmental/neurodevelopmental phenotype is a genuine, experimentally supported organismal consequence of COX7B loss-of-function (its disease mechanism), but it reflects the general requirement for Complex IV activity in energy metabolism, not a core molecular function of this structural subunit. Retained as an important non-core annotation. Supporting Evidence: PMID:23122588 essential function of complex IV activity in vertebrate CNS development PMID:23122588 COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase |
| GO:0004129 cytochrome-c oxidase activity | TAS PMID:8382530 Isolation of a cDNA specifying subunit VIIb of human cytochr... | MODIFY | Summary: This legacy TAS annotation assigns the whole-complex catalytic cytochrome-c oxidase activity to COX7B. COX7B is a non-catalytic supernumerary subunit; the oxygen-reduction chemistry is performed by the mtDNA-encoded catalytic core (MT-CO1, MT-CO2). The cited paper reports the cDNA of the nuclear-encoded structural subunit VIIb, not that COX7B itself catalyzes the reaction. Reason: COX7B does not itself enable cytochrome-c oxidase catalysis; its molecular function is structural, contributing to the integrity and assembly of the complex that performs catalysis. Replace the catalytic MF with structural molecule activity (GO:0005198). The catalytic activity is retained at the complex level via contributes_to in core_functions. Proposed replacements: structural molecule activity Supporting Evidence: PMID:8382530 the last remaining uncharacterized nuclear-encoded PMID:23122588 COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase |
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