UQCC3 (ubiquinol-cytochrome-c reductase complex assembly factor 3; formerly C11orf83) is a small (93-residue) single-pass mitochondrial inner-membrane protein and the functional human equivalent of yeast Cbp4p. It is a non-catalytic assembly factor for respiratory chain Complex III (cytochrome bc1 / ubiquinol-cytochrome c reductase): acting downstream of UQCC1/UQCC2, it mediates recruitment and stabilization of the cytochrome b (MT-CYB) subunit within the early bc1 core assembly intermediate, and is therefore required for Complex III assembly, holocomplex accumulation, and mitochondrial electron transport from ubiquinol to cytochrome c. UQCC3 also binds cardiolipin (via its intermembrane-space-facing Ξ±-helices), influences mitochondrial cardiolipin composition and cristae morphology, and helps stabilize bc1-containing respiratory supercomplexes (notably the III2/IV supercomplex). Its N-terminus sits in the matrix, followed by a transmembrane helix and an intermembrane-space-facing C-terminal lipid-binding region; the protein is cleaved by the OMA1 metalloprotease upon mitochondrial depolarization. Loss of function causes mitochondrial complex III deficiency, nuclear type 9 (MC3DN9), presenting with severe lactic acidosis, hypoglycemia, hypotonia, and delayed psychomotor development.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005743 mitochondrial inner membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) inference that UQCC3 is active in the mitochondrial inner membrane. This is the correct compartment for this Complex III assembly factor and is strongly corroborated by direct experimental localization. Reason: Well supported by direct (IDA) localization in two primary studies and by the UniProt subcellular location; UQCC3 is a single-pass inner-membrane protein where Complex III assembly occurs. This is a core cellular component annotation. Supporting Evidence: PMID:25605331 is a mitochondrial inner membrane protein facing the intermembrane space file:human/UQCC3/UQCC3-uniprot.txt Mitochondrion inner membrane |
| GO:0006122 mitochondrial electron transport, ubiquinol to cytochrome c | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference that UQCC3 is involved in Complex III-mediated electron transport from ubiquinol to cytochrome c. UQCC3 is a non-catalytic assembly factor, so it participates in this process only indirectly, by building and stabilizing Complex III; loss of UQCC3 abolishes Complex III activity. Reason: Defensible (UQCC3 loss impairs electron transport because Complex III is not assembled), but UQCC3 is not part of the electron-transfer machinery itself; the core function is Complex III assembly. Keep as a non-core process annotation reflecting the downstream physiological consequence. Supporting Evidence: file:human/UQCC3/UQCC3-uniprot.txt Required for the assembly of the ubiquinol-cytochrome c reductase complex |
| GO:0034551 mitochondrial respiratory chain complex III assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that UQCC3 is involved in mitochondrial respiratory chain Complex III assembly. This is the central, well-established function of UQCC3 and matches its yeast ortholog Cbp4p. Reason: This is the core biological process for UQCC3, independently supported by IMP evidence (patient-cell and knockdown studies) and by InterPro-based IEA. UQCC3 acts downstream of UQCC1/UQCC2 to stabilize the cytochrome-b-containing bc1 core assembly intermediate. Supporting Evidence: PMID:25008109 UQCC3 functions in the complex III assembly pathway downstream of UQCC1 and UQCC2 PMID:25605331 involved in the early stages of its assembly by stabilizing the bc1 core complex |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation mapped from the UniProt Swiss-Prot subcellular location "Mitochondrion inner membrane". Correct and consistent with the experimental localization. Reason: The UniProt subcellular location it is derived from is itself experimentally supported (IDA in two studies). This is the correct compartment. Supporting Evidence: file:human/UQCC3/UQCC3-uniprot.txt Mitochondrion inner membrane |
| GO:0034551 mitochondrial respiratory chain complex III assembly | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic annotation (InterPro:IPR027896, the UQCC3 family) to Complex III assembly. The UQCC3 family signature is diagnostic of exactly this function, so the mapping is appropriate. Reason: The InterPro entry IPR027896 is specific to the UQCC3 family whose defining function is Complex III assembly; the IEA is consistent with experimental and phylogenetic evidence. Core biological process. Supporting Evidence: PMID:25605331 involved in the early stages of its assembly by stabilizing the bc1 core complex |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Direct immunofluorescence localization (Human Protein Atlas) to the mitochondrion. Correct but less specific than the mitochondrial inner membrane localization. Reason: Accurate direct localization; the parent compartment (mitochondrion) is subsumed by the more specific inner-membrane annotation but is not wrong. Retained as a valid, if broader, CC annotation. Supporting Evidence: PMID:25605331 is a mitochondrial inner membrane protein facing the intermembrane space |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput mitochondrial proteomics assigns UQCC3 to the mitochondrion. Consistent with the curated inner-membrane localization. Reason: High-throughput proteomic detection agrees with the direct localization data; correct though broader than the mitochondrial inner membrane term. Supporting Evidence: file:human/UQCC3/UQCC3-uniprot.txt Mitochondrion inner membrane |
| GO:0006122 mitochondrial electron transport, ubiquinol to cytochrome c | IMP PMID:25008109 A mutation in the human CBP4 ortholog UQCC3 impairs complex ... | KEEP AS NON CORE | Summary: Mutant-phenotype evidence: patient fibroblasts carrying a UQCC3 loss-of-function variant have reduced Complex III activity and holocomplex levels, and cytochrome b is absent from the high-molecular-weight complex, impairing ubiquinol-to-cytochrome c electron transport. UQCC3 mediates this process indirectly, as a non-catalytic assembly factor. Reason: The IMP is valid β UQCC3 loss impairs Complex III-mediated electron transport β but UQCC3 does not itself carry electrons; the phenotype is a downstream consequence of failed Complex III assembly. Kept as non-core, with assembly (GO:0034551) as the core process. Supporting Evidence: PMID:25008109 reduced complex III activity and lower levels PMID:25008109 cytochrome b is absent from a high-molecular-weight complex III |
| GO:0034551 mitochondrial respiratory chain complex III assembly | IMP PMID:25605331 C11orf83, a mitochondrial cardiolipin-binding protein involv... | ACCEPT | Summary: Mutant/knockdown-phenotype evidence that UQCC3 is required for Complex III assembly: it is specifically associated with the bc1 complex and stabilizes the bc1 core complex during the early stages of assembly. Reason: Direct experimental (IMP) support for the core function. Depletion of UQCC3 impairs bc1 assembly, and UQCC3 stabilizes the early bc1 core intermediate. This is the primary, core biological process of the gene. Supporting Evidence: PMID:25605331 specifically associated with the bc1 complex of the electron PMID:25605331 involved in the early stages of its assembly by stabilizing the bc1 core complex |
| GO:0042407 cristae formation | IMP PMID:25605331 C11orf83, a mitochondrial cardiolipin-binding protein involv... | KEEP AS NON CORE | Summary: Depletion of UQCC3 (C11orf83) in HeLa cells causes abnormal crista morphology, linking UQCC3 to cristae organization. This is a downstream phenotypic consequence of its roles in Complex III/supercomplex assembly and cardiolipin homeostasis rather than a direct structural role in cristae biogenesis. Reason: The mutant phenotype is real (abnormal crista morphology on depletion), but it is a secondary consequence of impaired supercomplex organization and altered cardiolipin composition, not a distinct core molecular activity of UQCC3. Retained as a non-core process annotation. Supporting Evidence: PMID:25605331 C11orf83 depletion in HeLa cells caused abnormal crista morphology |
| GO:0070300 phosphatidic acid binding | IDA PMID:25605331 C11orf83, a mitochondrial cardiolipin-binding protein involv... | KEEP AS NON CORE | Summary: Direct-assay lipid-binding annotation. UQCC3 has an intermembrane-space-facing lipid-binding region and binds anionic phospholipids; the physiologically salient ligand demonstrated in this study is cardiolipin, with phosphatidic acid binding reported in the full-text lipid-binding assays. Reason: Experimental IDA from the same study; per curation policy an experimental lipid-binding annotation should not be removed. The cached abstract documents cardiolipin binding explicitly (see GO:1901612), and UniProt records a dedicated lipid-binding region; phosphatidic acid binding is a genuine but secondary lipid-binding activity, so kept as non-core while cardiolipin binding is treated as the core molecular function. Supporting Evidence: file:human/UQCC3/UQCC3-uniprot.txt Mediates lipid-binding |
| GO:1901612 cardiolipin binding | IDA PMID:25605331 C11orf83, a mitochondrial cardiolipin-binding protein involv... | ACCEPT | Summary: Direct-assay evidence that UQCC3 (C11orf83) binds cardiolipin through its Ξ±-helices 2 and 3, correlating with effects on mitochondrial cardiolipin composition and supercomplex stability. This is the one informative molecular function of this otherwise non-catalytic assembly factor. Reason: Well-supported experimental (IDA) molecular function; cardiolipin is the physiologically relevant lipid ligand and this binding underpins UQCC3's role in supercomplex/cristae stabilization. Core molecular function. Supporting Evidence: PMID:25605331 We showed that C11orf83 binds to cardiolipin by its Ξ±-helices 2 and 3 |
| GO:0005743 mitochondrial inner membrane | IDA PMID:25008109 A mutation in the human CBP4 ortholog UQCC3 impairs complex ... | ACCEPT | Summary: Direct localization of UQCC3 to the mitochondrial inner membrane, the compartment where Complex III assembly occurs. UQCC3 is a single-pass inner-membrane protein. Reason: Direct experimental support for the core cellular component. Consistent with the second primary study and UniProt. Supporting Evidence: file:human/UQCC3/UQCC3-uniprot.txt Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | IDA PMID:25605331 C11orf83, a mitochondrial cardiolipin-binding protein involv... | ACCEPT | Summary: Direct localization showing UQCC3 (C11orf83) is a mitochondrial inner membrane protein facing the intermembrane space. Core cellular component. Reason: Direct experimental support; the topology (matrix N-terminus, single TM helix, IMS-facing C-terminus) places UQCC3 firmly in the inner membrane. Core CC. Supporting Evidence: PMID:25605331 is a mitochondrial inner membrane protein facing the intermembrane space |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)