UQCRB (ubiquinol-cytochrome c reductase binding protein; also QP-C / cytochrome b-c1 complex subunit 7 / QCR7) is a small (~13.5 kDa, 111 aa) nuclear-encoded, non-catalytic structural subunit of mitochondrial respiratory Complex III (the cytochrome b-c1 complex / ubiquinol-cytochrome c oxidoreductase). It is one of the low-molecular-weight subunits of the 11-subunit complex; the redox catalysis of Complex III is carried out by the catalytic subunits cytochrome b, the Rieske iron-sulfur protein (UQCRFS1) and cytochrome c1, whereas UQCRB contributes to assembly and structural integrity of the complex rather than to catalysis. Complex III is an obligate dimer embedded as a peripheral protein on the matrix side of the mitochondrial inner membrane, and it associates with Complex I and Complex IV to form respiratory supercomplexes and megacomplexes. Within the electron transport chain, Complex III transfers electrons from ubiquinol to cytochrome c, coupling this redox reaction to proton translocation across the inner membrane (the Q cycle) and thereby contributing to oxidative phosphorylation and aerobic respiration. UQCRB was originally proposed to be the ubiquinone-binding protein, but this ubiquinone-binding role is no longer considered established. Loss-of-function variants in UQCRB cause mitochondrial complex III deficiency (nuclear type 3), a mitochondrial disorder that can present with hypoglycemia and lactic acidosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0045275 respiratory chain complex III | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation placing UQCRB as part of respiratory chain complex III. This is the defining, well-established localization/membership of this subunit and is supported by cryo-EM structures of human Complex III and by UniProt. Reason: UQCRB is a bona fide low-molecular-weight subunit of the cytochrome b-c1 complex (Complex III). This is confirmed structurally and by the family definition, and the complex membership is a core aspect of the gene's function. Supporting Evidence: file:human/UQCRB/UQCRB-uniprot.txt Component of the ubiquinol-cytochrome c oxidoreductase, a |
| GO:0006122 mitochondrial electron transport, ubiquinol to cytochrome c | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation to the specific Complex III process, transfer of electrons from ubiquinol to cytochrome c. As a structural subunit of Complex III, UQCRB participates in this process. Reason: This is the core biological process of Complex III and the most appropriate specific BP term for a CIII subunit. Well supported by the complex's catalytic role. Supporting Evidence: file:human/UQCRB/UQCRB-uniprot.txt transfer from ubiquinol to cytochrome c, linking this redox reaction to |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation from UniProt Subcellular Location mapping placing UQCRB in the mitochondrial inner membrane. Consistent with its role as a peripheral inner-membrane Complex III subunit. Reason: Complex III, and hence UQCRB, resides in the mitochondrial inner membrane. This is the correct, specific location and matches the UniProt subcellular location. Supporting Evidence: file:human/UQCRB/UQCRB-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0006122 mitochondrial electron transport, ubiquinol to cytochrome c | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic annotation to the Complex III electron transport process, based on the QCR7 family signatures (IPR003197, IPR036544). Duplicates the IBA/NAS annotations to the same specific BP. Reason: The InterPro-to-GO mapping is appropriate for this family and points to the correct, specific Complex III process. Consistent with the experimental and phylogenetic evidence. Supporting Evidence: file:human/UQCRB/UQCRB-uniprot.txt transfer from ubiquinol to cytochrome c, linking this redox reaction to |
| GO:0016020 membrane | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Generic ARBA machine-learning electronic annotation to "membrane". This is correct but far less informative than the specific mitochondrial inner membrane location that is also annotated. Reason: "membrane" is a high-level parent of the specific and better-supported term mitochondrial inner membrane (GO:0005743). It is not wrong, but it is uninformatively general given more precise annotations exist. Supporting Evidence: file:human/UQCRB/UQCRB-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0045275 respiratory chain complex III | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic annotation for complex III membership based on the QCR7 family superfamily signature (IPR036544). Duplicates the IBA and experimental (ComplexPortal IPI) annotations to the same term. Reason: Correct complex membership for a QCR7-family protein; consistent with structural and phylogenetic evidence. Supporting Evidence: file:human/UQCRB/UQCRB-uniprot.txt Component of the ubiquinol-cytochrome c oxidoreductase, a |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MARK AS OVER ANNOTATED | Summary: Large-scale protein-protein interaction (IntAct/IPI) annotation to the uninformative term "protein binding". From a high-throughput human interactome screen. Reason: "protein binding" (GO:0005515) is an uninformative molecular function term that does not capture the actual, specific function of UQCRB. This is an experimental IntAct record, so it is retained rather than removed, but flagged as over-annotated per curation policy that discourages bare "protein binding". |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Large-scale interactome (HuRI / IPI) annotation to the uninformative term "protein binding". Reason: Uninformative "protein binding" from a high-throughput interactome map. Retained as an experimental IntAct record but flagged as over-annotated; it does not describe UQCRB's specific structural function within Complex III. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Large-scale interactome (BioPlex / IPI) annotation to the uninformative term "protein binding". Reason: Uninformative "protein binding" from a high-throughput interactome study. Retained as an experimental IntAct record but flagged as over-annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Large-scale binary interactome (HuRI reference map / IPI) annotation to the uninformative term "protein binding". Reason: Uninformative "protein binding" from a high-throughput binary interactome map. Retained as an experimental IntAct record but flagged as over-annotated. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Large-scale interactome (neurodegenerative-disease interactome / IPI) annotation to the uninformative term "protein binding". Reason: Uninformative "protein binding" from a high-throughput interactome study. Retained as an experimental IntAct record but flagged as over-annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Large-scale interactome (BioPlex 3.0 dual-cell networks / IPI) annotation to the uninformative term "protein binding". Reason: Uninformative "protein binding" from a high-throughput interactome study. Retained as an experimental IntAct record but flagged as over-annotated. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Large-scale multimodal cell-map interactome (IPI) annotation to the uninformative term "protein binding". Reason: Uninformative "protein binding" from a high-throughput interactome/cell-map study. Retained as an experimental IntAct record but flagged as over-annotated. |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Curator-judged sequence-similarity (ISS) transfer of the mitochondrial inner membrane location from the bovine ortholog (UniProtKB:P00128). Consistent with all other location evidence. Reason: The inner-membrane localization is well established for Complex III subunits across species; the ISS transfer from the bovine QCR7 ortholog is appropriate and matches the specific, correct location. Supporting Evidence: file:human/UQCRB/UQCRB-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | IDA PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ... | ACCEPT | Summary: Direct experimental (IDA, ComplexPortal) assignment of UQCRB to the mitochondrial inner membrane, based on the cryo-EM structure of the human respiratory megacomplex in which Complex III is resolved in the inner membrane. Reason: Strong experimental support: the cryo-EM structure of the human MCI2III2IV2 megacomplex places the dimeric Complex III (and thus its UQCRB subunit) in the mitochondrial inner membrane. This is the core, specific location. Supporting Evidence: PMID:28844695 The MCI2III2IV2 forms a circular structure with the dimeric CIII located in the center, where it is surrounded by two copies each of CI and CIV. |
| GO:0006122 mitochondrial electron transport, ubiquinol to cytochrome c | NAS PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ... | ACCEPT | Summary: Non-traceable author statement (NAS, ComplexPortal) that UQCRB, as a Complex III subunit, is involved in mitochondrial electron transport from ubiquinol to cytochrome c. Reason: This is the core, specific process of Complex III and is consistent with the IBA/InterPro annotations to the same term and with the structural characterization of the electron transport chain in this study. Supporting Evidence: PMID:28844695 Two cytochrome c (Cyt.c) molecules are positioned to accept electrons on the surface of the c1 state CIII dimer. |
| GO:0045275 respiratory chain complex III | IPI PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ... | ACCEPT | Summary: Experimental (IPI, ComplexPortal) assignment of UQCRB as part of respiratory chain complex III, based on the cryo-EM structure that resolves the individual subunits of human Complex III. Reason: Direct structural evidence for UQCRB being a component of Complex III. Core complex membership annotation. Supporting Evidence: PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII |
| GO:0045333 cellular respiration | NAS PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ... | KEEP AS NON CORE | Summary: Non-traceable author statement (NAS, ComplexPortal) annotating UQCRB to the broad process "cellular respiration". Reason: Correct but general: cellular respiration is a broad parent process. The more specific and informative BP is mitochondrial electron transport, ubiquinol to cytochrome c (GO:0006122), which is separately annotated and represents the core function. Retained as valid but non-core. Supporting Evidence: file:human/UQCRB/UQCRB-uniprot.txt electron transport chain which drives oxidative phosphorylation |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput (HTP) proteomic identification of UQCRB in the mitochondrion, from a quantitative high-confidence human mitochondrial proteome (MitoCoP). Correct but less specific than the mitochondrial inner membrane location. Reason: Reliable high-throughput evidence for mitochondrial localization. It is a general parent of the more specific inner-membrane location, but it is correct and independently corroborates the organellar assignment. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP) |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-164651 | ACCEPT | Summary: Traceable author statement (Reactome) placing UQCRB in the mitochondrial inner membrane, associated with the reaction "Electron transfer from ubiquinol to cytochrome c of complex III". Reason: Correct, specific location consistent with all other evidence. Reactome pathway context matches the Complex III role. Supporting Evidence: Reactome:R-HSA-164651 The protonmotive Q cycle is the mechanism by which complex III transfers electrons from ubiquinol to cytochrome c, linking this process to translocation of protons across the membrane. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9906017 | ACCEPT | Summary: Traceable author statement (Reactome) placing UQCRB in the mitochondrial inner membrane, in the context of Complex III assembly (proteolytic processing of the UQCRFS1 subunit). Reason: Correct, specific location. The Reactome reaction concerns Complex III assembly in the inner membrane, consistent with UQCRB's structural/assembly role. Supporting Evidence: Reactome:R-HSA-9906017 Proteolytic processing is necessary for the correct insertion of UQCRFS1 in the complex III dimer. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9906042 | ACCEPT | Summary: Traceable author statement (Reactome) placing UQCRB in the mitochondrial inner membrane, in the context of Complex III maturation (TTC19 clearance of UQCRFS1 fragments). Reason: Correct, specific location consistent with the Complex III assembly/maturation pathway context. Supporting Evidence: Reactome:R-HSA-9906042 N-terminal cleavage fragments of UQCRFS1 are cleared by TTC19, stabilizing the final complex. |
| GO:0006119 oxidative phosphorylation | TAS PMID:3056408 Cloning and sequencing of a cDNA for human mitochondrial ubi... | ACCEPT | Summary: Traceable author statement (from the original human QP-C/UQCRB cDNA cloning paper) annotating involvement in oxidative phosphorylation, reflecting Complex III's role in driving OXPHOS via the electron transport chain. Reason: Complex III is a core component of the electron transport chain that drives oxidative phosphorylation, so this is a valid process annotation for UQCRB. It is broader than the specific electron-transport step (GO:0006122) but correctly captures the downstream energetic role. Supporting Evidence: file:human/UQCRB/UQCRB-uniprot.txt electron transport chain which drives oxidative phosphorylation |
| GO:0009060 aerobic respiration | TAS PMID:3056408 Cloning and sequencing of a cDNA for human mitochondrial ubi... | KEEP AS NON CORE | Summary: Traceable author statement (original QP-C cDNA cloning paper) annotating involvement in aerobic respiration. Reason: Correct but broad. Aerobic respiration is a high-level process; the core, specific function is captured by mitochondrial electron transport, ubiquinol to cytochrome c (GO:0006122). Retained as valid but non-core. Supporting Evidence: PMID:3056408 The ubiquinone-binding protein (QP-C) is a nuclear-encoded component of ubiquinol-cytochrome c oxidoreductase in the mitochondrial respiratory chain and plays an important role in electron transfer |
| GO:0098803 respiratory chain complex | TAS PMID:3056408 Cloning and sequencing of a cDNA for human mitochondrial ubi... | MARK AS OVER ANNOTATED | Summary: Traceable author statement placing UQCRB in a respiratory chain complex, based on the original cDNA cloning paper identifying QP-C as a component of ubiquinol-cytochrome c oxidoreductase. Reason: Correct but general: respiratory chain complex (GO:0098803) is a parent of the specific and better-supported term respiratory chain complex III (GO:0045275), which is annotated by IBA, InterPro and experimental (ComplexPortal IPI) evidence. Retained but flagged as over-general. Supporting Evidence: PMID:3056408 The ubiquinone-binding protein (QP-C) is a nuclear-encoded component of ubiquinol-cytochrome c oxidoreductase in the mitochondrial respiratory chain |
| GO:0005198 structural molecule activity | ISS file:human/UQCRB/UQCRB-uniprot.txt | NEW | Summary: Proposed molecular function annotation. UQCRB has no informative molecular function in GOA (only the uninformative "protein binding" IPIs). As a non-catalytic subunit of Complex III, its molecular function is best captured as structural molecule activity, contributing to the structural integrity of the cytochrome b-c1 complex. Reason: The catalytic activity of Complex III (electron transfer from ubiquinol to cytochrome c) is carried by cytochrome b, the Rieske iron-sulfur protein and cytochrome c1; UQCRB is a low-molecular-weight, non-catalytic structural subunit. Structural molecule activity (GO:0005198) is the appropriate subunit-specific molecular function, and it is not currently represented in GOA. No catalytic activity is asserted for UQCRB. Supporting Evidence: file:human/UQCRB/UQCRB-uniprot.txt Component of the ubiquinol-cytochrome c oxidoreductase, a |
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