UQCRC1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0017087 mitochondrial processing peptidase complex	IBA GO_REF:0000033	REMOVE	Summary: IBA annotation placing UQCRC1 as part_of the mitochondrial processing peptidase (MPP) complex. This is phylogenetically inferred based on homology to beta-MPP across the M16 peptidase family (PANTHER PTN000220169). In yeast, the Complex III core proteins Cor1 (UQCRC1 homolog) and Cor2 (UQCRC2 homolog) have been shown to retain MPP-like processing activity within the assembled complex. However, in mammals, UQCRC1 and UQCRC2 have diverged from their MPP ancestors and there is no direct experimental evidence that mammalian UQCRC1 is part of an MPP complex or retains peptidase activity (PMID:8407948). UniProt describes this function as "Probable" based on similarity to yeast. Reactome R-HSA-9906017 notes that the peptidase responsible for cleaving UQCRFS1 in humans is "unknown" with UQCRC1/UQCRC2 listed only as "possible candidates." The IBA inference from yeast is phylogenetically reasonable but likely does not accurately reflect mammalian biology. Reason: In mammals, UQCRC1 is best supported as a non-catalytic structural core subunit of Complex III rather than a component of a dedicated mitochondrial processing peptidase complex. The peptidase that cleaves human UQCRFS1 remains unresolved in Reactome, with UQCRC1 listed only as a possible candidate. Given the lack of direct mammalian evidence for UQCRC1 membership in an MPP complex, this annotation is removed from the core review set. Supporting Evidence: PMID:8407948 The predicted human protein shows significant homology with core I protein from Saccharomyces cerevisiae, rather high homology (64% similarity, 46% identity) with the processing enhancing protein, which functions as core I protein in Neurospora crassa, and, surprisingly, highest homology with the small subunit of the mitochondrial processing peptidase of rat (74% similarity, 55% identity). Reactome:R-HSA-9906017 An unknown peptidase cleaves the N-terminal 78 amino acids of UQCRFS1 ...Possible candidates for the peptidase are the UQCRC1 and UQCRC2 subunits (as hinted at in the cattle model) or the SPY complex
GO:1902600 proton transmembrane transport	IEA GO_REF:0000108	ACCEPT	Summary: IEA annotation inferred from the quinol-cytochrome-c reductase activity (GO:0008121) annotation via logical inter-ontology links. Complex III couples electron transfer to proton translocation across the inner mitochondrial membrane during the Q-cycle. As a structural core subunit of Complex III, UQCRC1 contributes to maintaining the integrity of the complex that performs proton transmembrane transport (PMID:28844695). While UQCRC1 does not itself directly translocate protons, it is a necessary structural component of the complex that does. Reason: This is a valid biological process annotation for UQCRC1 as a subunit of Complex III, which couples electron transfer to proton translocation. The IEA inference from GO:0008121 is logically sound. The term is at an appropriate level of specificity for a structural subunit.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for mitochondrial inner membrane localization, transferred from mouse ortholog (UniProtKB:Q9CZ13). UQCRC1 is a peripheral membrane protein on the matrix side of the inner mitochondrial membrane, confirmed by cryo-EM structures (PMID:28844695, PDB:5XTE) and UniProt subcellular localization annotation. Reason: Correct localization. UQCRC1 is part of Complex III which is embedded in the inner mitochondrial membrane. Cryo-EM structural data directly confirms this (PMID:28844695). This IEA is consistent with multiple higher-confidence annotations for the same term.
GO:0016020 membrane	IEA GO_REF:0000117	ACCEPT	Summary: IEA annotation for generic membrane localization via ARBA machine learning. UQCRC1 is indeed associated with the inner mitochondrial membrane as part of Complex III. However, this term is very general and is fully subsumed by the more specific GO:0005743 (mitochondrial inner membrane) annotations already present from multiple evidence sources. Reason: While very broad, this annotation is not incorrect. UQCRC1 is a peripheral membrane protein associated with the inner mitochondrial membrane. More specific annotations (GO:0005743) are also present. Acceptable as a broader IEA that is consistent with the more specific annotations.
GO:0022904 respiratory electron transport chain	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation from UniProtKB keyword mapping (KW:Electron transport). UQCRC1 is a structural subunit of Complex III which is part of the respiratory electron transport chain. While UQCRC1 does not itself perform electron transfer chemistry, it is an integral structural component of the complex that does. This is a broader parent of the more specific GO:0006122 (mitochondrial electron transport, ubiquinol to cytochrome c) which is also annotated. Reason: Valid biological process annotation. As a structural core subunit of Complex III, UQCRC1 is involved in the respiratory electron transport chain, even though it does not directly participate in redox chemistry. The broader term is acceptable alongside the more specific GO:0006122.
GO:0046872 metal ion binding	IEA GO_REF:0000002	REMOVE	Summary: IEA annotation from InterPro domain mapping (IPR011249, Metalloenz_LuxS/M16). The M16 peptidase family to which UQCRC1 belongs is characterized by a zinc-binding metallopeptidase active site. However, in mammalian UQCRC1, the catalytic zinc-binding residues are not conserved and there is no evidence that human UQCRC1 actually binds metal ions. The InterPro domain annotation reflects the evolutionary origin of the fold rather than the current function of the human protein. UniProt does not annotate any metal binding sites for UQCRC1, and the cryo-EM structures (PDB:5XTE) do not show bound metal ions at the ancestral active site. Reason: This annotation is based on the M16 peptidase domain architecture, but mammalian UQCRC1 has lost the catalytic metal-binding residues that define active M16 family peptidases. There is no experimental evidence for metal ion binding by human UQCRC1, and UniProt does not annotate any metal binding sites. This represents a case where domain-based inference incorrectly transfers an ancestral function that has been lost in the mammalian lineage. Supporting Evidence: file:human/UQCRC1/UQCRC1-deep-research-falcon.md UQCRC1 has no demonstrated enzymatic activity within Complex III. It is a structural core protein; catalytic chemistry (Q cycle) is executed by cytochrome b, Rieske (UQCRFS1), and cytochrome c1 (CYC1).
GO:0098803 respiratory chain complex	IEA GO_REF:0000117	ACCEPT	Summary: IEA annotation for respiratory chain complex localization via ARBA machine learning. UQCRC1 is indeed a component of respiratory chain complex III. This is a parent of the more specific GO:0045275 (respiratory chain complex III) also annotated via IEA. Acceptable but less informative than the more specific term. Reason: Correct but broad. UQCRC1 is unambiguously a component of respiratory chain complex III. The more specific GO:0045275 is also present. This broader IEA annotation is consistent.
GO:0005515 protein binding	IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by...	MARK AS OVER ANNOTATED	Summary: IPI annotation for protein binding based on large-scale mass spectrometry interactome mapping (Ewing et al. 2007). The WITH/FROM column indicates UQCRC2 (P22695) as the interacting partner. UQCRC1 and UQCRC2 are the two core subunits of Complex III and directly interact within the complex (PMID:28844695). However, "protein binding" is an uninformative term that does not convey the nature of the interaction. Reason: The interaction between UQCRC1 and UQCRC2 within Complex III is well established, but "protein binding" is uninformative. This interaction is better captured by the CC annotation GO:0045275 (respiratory chain complex III), which implies subunit-subunit interactions. Per curation guidelines, generic "protein binding" annotations should be avoided. Supporting Evidence: PMID:17353931 Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions.
GO:0005515 protein binding	IPI PMID:19688755 LC-MS/MS as an alternative for SDS-PAGE in blue native analy...	MARK AS OVER ANNOTATED	Summary: IPI annotation for protein binding based on BN-PAGE/LC-MS/MS analysis of OXPHOS complexes (Wessels et al. 2009). WITH/FROM indicates UQCRC2 (P22695). This study used blue native gel analysis combined with LC-MS/MS to characterize protein complexes in the mitochondrial fraction. The UQCRC1-UQCRC2 interaction within Complex III is well-established. Reason: Same as above: the UQCRC1-UQCRC2 interaction is real but better captured by complex membership annotations (GO:0045275). "Protein binding" is uninformative per curation guidelines. Supporting Evidence: PMID:19688755 We demonstrate the feasibility of this approach by considering the oxidative phosphorylation complexes I-V in the native human embryonic kidney 293 mitochondrial fraction
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: IPI annotation for protein binding based on interactome mapping of neurodegenerative disease proteins (Haenig et al. 2020). This study identified numerous interaction partners for UQCRC1 in a large-scale Y2H screen. The WITH/FROM column lists many interactors (NPHP1, PRMT5, SULT1B1, BECN1, ARHGDIB, etc.), most of which are not known Complex III subunits and likely represent non-specific or indirect interactions from a high-throughput screen. These interactions have not been validated by targeted studies. Reason: High-throughput interactome screen results. Most of the listed interactors are not known mitochondrial proteins or Complex III components. "Protein binding" is uninformative and these are likely non-specific high-throughput hits. Per curation guidelines, generic "protein binding" should be avoided. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: IPI annotation for protein binding from the BioPlex 3.0 proteome-scale interactome (Huttlin et al. 2021). WITH/FROM indicates UQCRC2 (P22695). The UQCRC1-UQCRC2 interaction within Complex III is well-established from structural data (PMID:28844695, PDB:5XTE). Reason: The UQCRC1-UQCRC2 interaction is real but "protein binding" is uninformative. This interaction is already captured by complex membership annotations. Per curation guidelines, generic "protein binding" should be avoided. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks.
GO:0005739 mitochondrion	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for mitochondrial localization, combined automated annotation from multiple sources including mouse ortholog (UniProtKB:Q9CZ13) and ARBA. UQCRC1 is a well-established mitochondrial protein. This is consistent with multiple higher-confidence annotations. Reason: Correct localization. UQCRC1 is unambiguously a mitochondrial protein. Confirmed by IDA, HDA, and HTP annotations from independent sources.
GO:0014823 response to activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: IEA annotation transferred from rat ortholog (UniProtKB:Q68FY0) via Ensembl Compara. This likely reflects expression changes in UQCRC1 observed in response to physical exercise or similar activity stimuli in rat studies. While mitochondrial OXPHOS proteins can be upregulated in response to exercise, this annotation represents a secondary downstream response rather than a core function of UQCRC1. Reason: This annotation likely reflects expression-level changes of UQCRC1 in response to activity/exercise. While plausible for a mitochondrial OXPHOS protein, this is not a core function and represents a pleiotropic response. Keeping as non-core.
GO:0043279 response to alkaloid	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: IEA annotation transferred from rat ortholog (UniProtKB:Q68FY0) via Ensembl Compara. This likely reflects expression changes in response to alkaloid treatment in rat studies. Not a core function of UQCRC1. Many mitochondrial proteins show expression changes in response to various chemical stimuli without those being core functions. Reason: Pleiotropic response annotation. While UQCRC1 expression may change in response to alkaloids (many of which affect mitochondrial function), this is not a core evolved function. Keeping as non-core.
GO:0044877 protein-containing complex binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: IEA annotation transferred from rat ortholog (UniProtKB:Q68FY0) via Ensembl Compara. UQCRC1 does participate in protein complexes (Complex III, supercomplexes), but "protein-containing complex binding" is vague. The actual function is being a structural subunit of Complex III, which is captured by CC annotations. This MF term does not add informative annotation beyond what is already captured by the complex membership terms. Reason: While UQCRC1 is a subunit of Complex III and participates in supercomplexes, "protein-containing complex binding" is an uninformative MF term. The structural role within Complex III is better described by the CC term GO:0045275 (respiratory chain complex III). This term does not convey the specific nature of UQCRC1's participation in protein complexes.
GO:0045275 respiratory chain complex III	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for respiratory chain complex III membership, transferred from ortholog data. UQCRC1 is one of the two core structural subunits of Complex III (along with UQCRC2). This is confirmed by cryo-EM structures of the human respiratory megacomplex (PMID:28844695, PDB:5XTE) and extensive biochemical evidence. Complex III is an obligatory dimer (CIII2) and UQCRC1 is present in both copies. Reason: Core annotation. UQCRC1 is unambiguously a component of respiratory chain complex III. This is confirmed by structural data (PMID:28844695), UniProt annotation, and ComplexPortal (CPX-560). This is one of the most important annotations for this protein. 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:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: IDA annotation for mitochondrial localization from HPA immunofluorescence data (GO_REF:0000052). UQCRC1 is a well-established mitochondrial protein, and immunofluorescence confirmation is consistent with all other evidence. Reason: Direct experimental evidence confirming mitochondrial localization of UQCRC1 via immunofluorescence. Consistent with all other localization annotations and the known biology of this Complex III subunit.
GO:0005743 mitochondrial inner membrane	IDA PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: IDA annotation for mitochondrial inner membrane localization from ComplexPortal, citing the cryo-EM structure of the human respiratory megacomplex (Guo et al. 2017). The structure (PDB:5XTE) directly shows UQCRC1 as a peripheral protein on the matrix side of the inner mitochondrial membrane within Complex III. Reason: Direct structural evidence from cryo-EM at 3.4 Angstrom resolution places UQCRC1 on the matrix side of the mitochondrial inner membrane as part of Complex III. This is high-quality direct evidence. Supporting Evidence: PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII, but also enables future in-depth analysis of the electron transport chain as a whole.
GO:0006122 mitochondrial electron transport, ubiquinol to cytochrome c	NAS PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: NAS annotation from ComplexPortal for the core biological process of Complex III, citing Guo et al. 2017. Complex III catalyzes electron transfer from ubiquinol to cytochrome c via the Q-cycle mechanism. UQCRC1 is a structural core subunit that does not directly participate in redox chemistry but is required for complex integrity and therefore contributes to this process. The ComplexPortal annotation is at the complex level (CPX-560). Reason: Valid biological process annotation. While UQCRC1 is not catalytically active in the Q-cycle, it is an essential structural subunit of the complex that performs this electron transport. The NAS evidence code is appropriate as the publication describes the overall complex structure and function rather than specific biochemical activity of UQCRC1. Supporting Evidence: PMID:28844695 The respiratory megacomplex represents the highest-order assembly of respiratory chain complexes, and it allows mitochondria to respond to energy-requiring conditions.
GO:0045333 cellular respiration	NAS PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: NAS annotation from ComplexPortal for cellular respiration. Complex III is a key component of the mitochondrial respiratory chain, and UQCRC1 as a structural subunit contributes to this broader biological process. This is a parent process of the more specific GO:0006122 and GO:0009060 annotations also present. Reason: Valid broader biological process annotation. UQCRC1 is a structural subunit of Complex III which is part of the respiratory chain driving cellular respiration. Consistent with the more specific electron transport annotations. 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:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: HTP annotation for mitochondrial localization from the high-confidence human mitochondrial proteome study (Morgenstern et al. 2021). This quantitative proteomics study established a comprehensive inventory of the human mitochondrial proteome. UQCRC1 was identified as a high-confidence mitochondrial protein, consistent with its role as a Complex III core subunit. Reason: High-throughput proteomics confirmation of mitochondrial localization. Consistent with all other localization evidence. The Morgenstern et al. study is a high-quality, quantitative mitochondrial proteome resource. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
GO:0005515 protein binding	IPI PMID:35101990 The cardiac-enriched microprotein mitolamban regulates mitoc...	MARK AS OVER ANNOTATED	Summary: IPI annotation for protein binding from the mitolamban (Mtlbn) study (Makarewich et al. 2022). WITH/FROM indicates P0DP99 (STMP1/mitolamban). Mtlbn is a small inner mitochondrial membrane microprotein that interacts with Complex III subunits and regulates complex assembly. The interaction with UQCRC1 was detected by co-immunoprecipitation and mass spectrometry. This is a meaningful interaction relevant to Complex III assembly and regulation. Reason: While the UQCRC1-mitolamban interaction appears genuine and functionally relevant (mitolamban regulates Complex III assembly), "protein binding" is an uninformative term. A more appropriate annotation would capture the complex assembly context. Per curation guidelines, generic "protein binding" should be avoided. Supporting Evidence: PMID:35101990 Mtlbn localizes specifically to the inner mitochondrial membrane where it interacts with subunits of complex III of the electron transport chain and with mitochondrial respiratory supercomplexes.
GO:0005515 protein binding	IPI PMID:32161263 Mitochondrial peptide BRAWNIN is essential for vertebrate re...	MARK AS OVER ANNOTATED	Summary: IPI annotation for protein binding from the BRAWNIN/UQCC6 study (Zhang et al. 2020). WITH/FROM indicates Q69YU5 (UQCC6/BRAWNIN). UQCC6 is a mitochondrial peptide essential for Complex III assembly in vertebrates. The interaction with UQCRC1 is functionally relevant as UQCC6 is required for proper CIII2 assembly. UniProt also notes this interaction. Reason: The UQCRC1-UQCC6 interaction is biologically meaningful for Complex III assembly, but "protein binding" is uninformative. The interaction is better described through complex assembly annotations. Per curation guidelines, generic "protein binding" should be avoided. Supporting Evidence: PMID:32161263 Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in...	KEEP AS NON CORE	Summary: IPI annotation for ubiquitin protein ligase binding from a Parkin interactome study (Davison et al. 2009). WITH/FROM indicates O60260 (Parkin/PRKN). The study used tandem affinity purification/MS in HEK293 cells with inducible Parkin expression and identified UQCRC1 as one of 14 potential Parkin interactants. Nine of these interactants were directly involved in mitochondrial energy metabolism. Parkin is an E3 ubiquitin ligase involved in mitophagy, and its interaction with mitochondrial OXPHOS subunits including UQCRC1 is consistent with Parkin's role in mitochondrial quality control. This is relevant to the UQCRC1-associated parkinsonism phenotype (PMID:33141179). Reason: The UQCRC1-Parkin interaction is plausible given Parkin's established role in mitophagy and mitochondrial quality control. UQCRC1 was identified as one of multiple mitochondrial proteins interacting with Parkin. While not a core molecular function of UQCRC1, this interaction is biologically relevant, especially given the association of UQCRC1 mutations with parkinsonism (PMID:33141179). The term "ubiquitin protein ligase binding" is more informative than generic "protein binding." Supporting Evidence: PMID:19725078 Tandem affinity purification/MS revealed 14 potential interactants of Parkin; CKB, DBT, HSPD1, HSPA9, LRPPRC, NDUFS2, PRDX6, SLC25A5, TPI1, UCHL1, UQCRC1, VCL, YWHAZ, YWHAE. Nine of these are directly involved in mitochondrial energy metabolism
GO:0005739 mitochondrion	HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated...	ACCEPT	Summary: HDA annotation for mitochondrial localization from a phosphoproteomics study of functional mitochondria isolated from human skeletal muscle (Zhao et al. 2011). UQCRC1 was identified by mass spectrometry in purified mitochondrial fractions. This study also identified phosphorylation sites on mitochondrial proteins including OXPHOS complex subunits. Reason: High-throughput direct assay confirming mitochondrial localization of UQCRC1 via proteomics of isolated human muscle mitochondria. Consistent with all other localization evidence. Supporting Evidence: PMID:20833797 We performed a phosphoproteomics study of functional mitochondria isolated from human muscle biopsies with the aim to obtain a comprehensive overview of mitochondrial phosphoproteins.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-164651	ACCEPT	Summary: TAS annotation for mitochondrial inner membrane from Reactome pathway "Electron transfer from ubiquinol to cytochrome c of complex III" (R-HSA-164651). UQCRC1 is a subunit of Complex III which resides in the mitochondrial inner membrane, performing the Q-cycle. Reason: Correct localization from a curated Reactome pathway. Consistent with structural and experimental evidence.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9906017	ACCEPT	Summary: TAS annotation for mitochondrial inner membrane from Reactome pathway "Unknown peptidase cleaves UQCRFS1 subunit" (R-HSA-9906017). This Reactome entry describes the processing of the UQCRFS1 Rieske protein within Complex III. UQCRC1 is mentioned as a possible candidate for the unknown peptidase. The localization itself (inner membrane) is correct regardless of whether UQCRC1 has peptidase activity. Reason: Correct localization. UQCRC1 is located in the mitochondrial inner membrane as part of Complex III, regardless of the specific Reactome reaction context.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9906042	ACCEPT	Summary: TAS annotation for mitochondrial inner membrane from Reactome pathway "TTC19 clears UQCRFS1 fragments from Complex III" (R-HSA-9906042). The localization of UQCRC1 to the inner membrane is correct. Reason: Correct localization from curated Reactome pathway. UQCRC1 is part of Complex III in the inner mitochondrial membrane.
GO:0006119 oxidative phosphorylation	TAS PMID:8407948 Complete coding sequence, intron/exon organization, and chro...	ACCEPT	Summary: TAS annotation for oxidative phosphorylation from the original gene cloning paper (Hoffman et al. 1993). The paper describes UQCRC1 as a nuclear-encoded component of the ubiquinol-cytochrome c reductase complex of the mitochondrial respiratory chain. Complex III is a key component of the electron transport chain that drives oxidative phosphorylation. Reason: Valid biological process annotation. UQCRC1 is a structural subunit of Complex III, which is part of the OXPHOS pathway. The original cloning paper correctly places this protein in the respiratory chain context. Supporting Evidence: PMID:8407948 Core I protein is a nuclear-encoded component of the ubiquinol-cytochrome c reductase complex of the mitochondrial respiratory chain.
GO:0008121 quinol-cytochrome-c reductase activity	TAS PMID:8407948 Complete coding sequence, intron/exon organization, and chro...	MODIFY	Summary: TAS annotation for quinol-cytochrome-c reductase activity from the original gene cloning paper (Hoffman et al. 1993). This is the molecular function of Complex III as a whole. UQCRC1 is a structural core subunit that does not itself catalyze the Q-cycle reaction but is required for complex integrity. For OXPHOS complex subunits, the GO convention is to use "contributes_to" qualifier for the complex-level molecular function. The GOA TSV shows this with an "enables" qualifier, which may be too strong for a non-catalytic subunit. Reason: The quinol-cytochrome-c reductase activity (GO:0008121) is the molecular function of the entire Complex III. UQCRC1 is a non-catalytic structural core subunit that does not directly participate in the Q-cycle redox chemistry; the catalytic subunits are cytochrome b, UQCRFS1 (Rieske), and CYC1. For non-catalytic subunits of enzyme complexes, the appropriate qualifier should be "contributes_to" rather than "enables." The annotation itself is appropriate at the complex level but the qualifier should be changed to contributes_to if not already. Additionally, this annotation could be retained with that qualifier adjustment, recognizing that UQCRC1 contributes structurally to the activity without directly performing catalysis. Proposed replacements: quinol-cytochrome-c reductase activity Supporting Evidence: PMID:8407948 Core I protein is a nuclear-encoded component of the ubiquinol-cytochrome c reductase complex of the mitochondrial respiratory chain. file:human/UQCRC1/UQCRC1-deep-research-falcon.md UQCRC1 has no demonstrated enzymatic activity within Complex III. It is a structural core protein; catalytic chemistry (Q cycle) is executed by cytochrome b, Rieske (UQCRFS1), and cytochrome c1 (CYC1). Thus, there is no substrate specificity attributable to UQCRC1; its contribution is architectural and organizational.
GO:0009060 aerobic respiration	TAS PMID:8407948 Complete coding sequence, intron/exon organization, and chro...	ACCEPT	Summary: TAS annotation for aerobic respiration from the original gene cloning paper (Hoffman et al. 1993). Complex III is a key component of the aerobic respiratory chain. UQCRC1, as a structural subunit, contributes to this process. Reason: Valid biological process annotation. UQCRC1 is a structural subunit of Complex III, which functions in aerobic respiration. This is a parent term of GO:0006122 and consistent with the overall functional context. Supporting Evidence: PMID:8407948 Core I protein is a nuclear-encoded component of the ubiquinol-cytochrome c reductase complex of the mitochondrial respiratory chain.
GO:0098803 respiratory chain complex	TAS PMID:8407948 Complete coding sequence, intron/exon organization, and chro...	ACCEPT	Summary: TAS annotation for respiratory chain complex from the original gene cloning paper (Hoffman et al. 1993). UQCRC1 is a component of Complex III, which is a respiratory chain complex. This is consistent with the more specific GO:0045275 (respiratory chain complex III) annotation. Reason: Correct but broad CC annotation. UQCRC1 is unambiguously part of a respiratory chain complex (Complex III). The more specific GO:0045275 is also present. This TAS annotation from the original cloning paper is valid. Supporting Evidence: PMID:8407948 Core I protein is a nuclear-encoded component of the ubiquinol-cytochrome c reductase complex of the mitochondrial respiratory chain.

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