SDHC

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006121 mitochondrial electron transport, succinate to ubiquinone	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for the biological process of electron transport from succinate to ubiquinone. This is the defining biological process for Complex II/SDH in the mitochondrial electron transport chain. SDHC, together with SDHD, forms the membrane arm where ubiquinone is ultimately reduced to ubiquinol. SDHC provides key residues (Ile56, Trp61, Met65, Ile69) that directly contact ubiquinone at the Q-site (PMID:37098072). The heme b coordinated by His127 of SDHC may serve as an electron sink during the two-electron reduction of ubiquinone (PMID:37098072). The IBA is phylogenetically supported with evidence from orthologous SDH cytochrome b560 subunits. Reason: This is a core biological process for SDHC. SDHC is essential for the terminal step of electron transfer from succinate to ubiquinone in Complex II, providing the Q-site and heme b environment. Well-supported by IBA phylogenetic inference and confirmed by the human Complex II cryo-EM structure (PMID:37098072). Supporting Evidence: PMID:37098072 UQ is also observed to bind at the entrance of the pocket formed by the transmembrane helix I of SDHC, transmembrane helix II of SDHD, and the C-terminal segment of SDHB. It interacts with Pro-SDHB197, Trp-SDHB201, Ile-SDHB246, Ile-SDHC56, Trp-SDHC61, Met-SDHC65, Ile-SDHC69, and Tyr-SDHD114 PMID:9533030 Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex in both the tricarboxylic acid cycle and the aerobic respiratory chains of mitochondria in eukaryotic cells and prokaryotic organisms
GO:0045273 respiratory chain complex II (succinate dehydrogenase)	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation that SDHC is part of respiratory chain complex II. SDHC is one of the four core subunits of SDH/Complex II, serving as a membrane anchor. The cryo-EM structure of human Complex II at 2.86 angstroms (PMID:37098072) directly resolved SDHC with three transmembrane helices in the membrane domain. All four subunits (SDHA, SDHB, SDHC, SDHD) were confirmed by SDS-PAGE and mass spectrometry (PMID:37098072). Reason: SDHC is unambiguously a subunit of Complex II. This is confirmed by the cryo-EM structure (PMID:37098072), the original cDNA cloning study (PMID:9533030), and is a core structural annotation. The IBA is phylogenetically sound. Supporting Evidence: PMID:37098072 All the four subunits (SDHA, SDHB, SDHC, and SDHD) were detected by SDS-PAGE (SI Appendix, Fig. S1D) and mass spectrometry (MS) (SI Appendix, Table S1). PMID:9533030 the amino acid sequences of the large (cybL) and small (cybS) subunits of cytochrome b in human liver complex II were deduced from cDNAs isolated by homology probing
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation based on UniProt subcellular location mapping. SDHC is an integral membrane protein with three transmembrane helices that spans the mitochondrial inner membrane. This is confirmed by the cryo-EM structure (PMID:37098072) and the UniProt annotation (ECO:0000269\|PubMed:37098072). SDHC topology shows matrix-facing N-terminus, three transmembrane helices, and short intermembrane space loops. Reason: Correct localization. SDHC is an integral multi-pass protein of the mitochondrial inner membrane, confirmed by cryo-EM at 2.86 angstroms. This is a core localization annotation. Supporting Evidence: PMID:37098072 The entire hydrophobic domain contains two membrane-anchored subunits: SDHC and SDHD
GO:0006099 tricarboxylic acid cycle	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for TCA cycle involvement from combined automated methods including ortholog transfer from mouse (UniProtKB:Q9CZB0) and InterPro/UniPathway mapping. Complex II is the only membrane-bound member of the TCA cycle, catalyzing the oxidation of succinate to fumarate. SDHC contributes to this reaction by anchoring the complex in the membrane and providing the Q-site for ubiquinone reduction, which is coupled to succinate oxidation. Reason: TCA cycle involvement is a core function of SDHC as part of Complex II. The original cDNA cloning study (PMID:9533030) describes Complex II as an enzyme in both the TCA cycle and the respiratory chain. Supporting Evidence: PMID:9533030 Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex in both the tricarboxylic acid cycle and the aerobic respiratory chains of mitochondria in eukaryotic cells and prokaryotic organisms
GO:0009055 electron transfer activity	IEA GO_REF:0000002	MODIFY	Summary: IEA annotation for electron transfer activity from InterPro (IPR014314, IPR018495). SDHC contributes to electron transfer within Complex II by harboring the heme b prosthetic group (axially coordinated by His127 of SDHC) and providing residues that form the ubiquinone binding pocket. The heme b serves as an electron sink that stabilizes the semiquinone radical during the two-electron reduction of ubiquinone (PMID:37098072). However, SDHC does not independently perform electron transfer; it contributes to the complex-level activity. The qualifier should ideally be 'contributes_to' rather than 'enables'. Reason: SDHC contributes to electron transfer as part of Complex II via heme b and the Q-site, but it does not independently enable electron transfer activity. The InterPro-based annotation is reasonable but the qualifier should be 'contributes_to'. Additionally, a more specific term would be preferred if available. Accept the annotation concept but flag that the qualifier in GOA is 'enables' whereas 'contributes_to' would be more appropriate for a membrane anchor subunit. Proposed replacements: electron transfer activity Supporting Evidence: PMID:37098072 the heme b is proposed to serve as an electron sink in the electron transfer pathway
GO:0016020 membrane	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation for general membrane localization from InterPro (IPR018495, IPR034804). SDHC is an integral membrane protein with three transmembrane helices. This is correct but very general; the more specific term GO:0005743 (mitochondrial inner membrane) is also annotated and provides a much more informative localization. Reason: Correct but general. SDHC is an integral membrane protein with three transmembrane helices. It is acceptable for IEA annotations to be broader than experimental annotations. The more specific GO:0005743 is also present.
GO:0046872 metal ion binding	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation from UniProt keyword (KW-0479 Metal-binding) mapping. SDHC coordinates heme b iron via the axial ligand His127 (shared with SDHD). The heme b iron is the relevant metal ion. This annotation is correct but very general; the more specific GO:0020037 (heme binding) is also annotated via ISS. Reason: Correct but general. SDHC binds the iron atom of heme b through axial coordination at His127. The more specific child term GO:0020037 (heme binding) is also annotated. It is acceptable for IEA keyword-based annotations to use broader terms. Supporting Evidence: PMID:37098072 The two membrane-anchored proteins (SDHC and SDHD) in human CII, each with three transmembrane helices, contain only one heme b group
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: IPI annotation from a large-scale neurodegenerative disease interactome mapping study (Haenig et al. 2020) using systematic yeast two-hybrid screening. The GOA contains five separate entries for this PMID with different interactors: PRKCA (P17252), YWHAG (P61981), SETDB1 (Q15047-2), LMO3 (Q8TAP4-4), and KAT5 (Q92993). These interactions were detected in a high-throughput screen focused on neurodegenerative disease-associated proteins. SDHC is a small transmembrane mitochondrial protein with limited cytoplasmic exposure; direct physical interactions with nuclear/cytoplasmic proteins like PRKCA, YWHAG, KAT5, SETDB1, and LMO3 are of uncertain biological significance and may reflect Y2H artifacts from overexpression of fragments outside their native membrane context. Reason: The 'protein binding' term is uninformative per GO curation guidelines. Furthermore, these interactions were detected in a high-throughput Y2H screen focused on neurodegenerative disease networks. The biological relevance of interactions between a small mitochondrial inner membrane protein (SDHC) and nuclear/cytoplasmic proteins (PRKCA, YWHAG, KAT5, SETDB1, LMO3) is highly questionable. Y2H is known to produce false positives, especially for membrane proteins tested outside their native lipid environment. The core protein-protein interactions of SDHC (with SDHD, SDHB, SDHA within Complex II) are already captured by the CC annotation GO:0045273. Supporting Evidence: PMID:32814053 we report on an interactome map that focuses on neurodegenerative disease (ND), connects
GO:0005739 mitochondrion	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation for mitochondrial localization via Ensembl Compara ortholog transfer from mouse (UniProtKB:Q9CZB0). SDHC has a mitochondrial transit peptide (residues 1-29, inferred by similarity) and is localized to the mitochondrial inner membrane as part of Complex II. Confirmed by the cryo-EM structure (PMID:37098072) and mass spectrometry identification in the mitochondrial proteome (PMID:34800366). Reason: Correct localization, well supported by structural evidence (PMID:37098072) and proteomics (PMID:34800366, PMID:21269460, PMID:25944712). SDHC is a well-established mitochondrial protein.
GO:0005759 mitochondrial matrix	IEA GO_REF:0000107	REMOVE	Summary: IEA annotation for mitochondrial matrix localization via Ensembl Compara ortholog transfer from mouse (UniProtKB:Q9CZB0). The GOA qualifier is 'is_active_in'. This is problematic for SDHC because SDHC is an integral transmembrane protein that spans the inner membrane, not a matrix protein. While the N-terminal domain of SDHC (residues 30-65) faces the matrix, the majority of the protein consists of three transmembrane helices spanning the membrane. Describing SDHC as 'is_active_in' the mitochondrial matrix is misleading; it is more accurately localized to the mitochondrial inner membrane (GO:0005743). Reason: SDHC is an integral multi-pass transmembrane protein of the inner mitochondrial membrane, not a matrix protein. The cryo-EM structure (PMID:37098072) clearly shows SDHC embedded in the membrane with three transmembrane helices. The N-terminal domain extends into the matrix but the protein's primary localization is the inner membrane itself, which is already annotated. Mitochondrial matrix (with qualifier 'is_active_in') is misleading for a transmembrane anchor subunit. Supporting Evidence: PMID:37098072 The entire hydrophobic domain contains two membrane-anchored subunits: SDHC and SDHD
GO:0008177 succinate dehydrogenase (quinone) activity	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation for SDH quinone reductase activity via Ensembl Compara ortholog transfer from mouse (UniProtKB:Q9CZB0). GO:0008177 is defined as the overall reaction of the SDH complex (succinate + quinone -> fumarate + quinol). The qualifier 'contributes_to' is appropriate for SDHC, which does not independently catalyze this reaction but provides essential structural components: the membrane anchor, the Q-binding site (residues Ile56, Trp61, Met65, Ile69 directly contact ubiquinone), and the heme b environment (His127 as axial ligand). Without SDHC, the complex cannot reduce ubiquinone. Reason: The 'contributes_to' qualifier is correctly used here. SDHC provides essential structural contributions to the SDH quinone activity by forming part of the Q-site and harboring the heme b, but does not independently catalyze the reaction. This is consistent with the pattern used for Complex II subunit annotations in the SDHA and SDHB reviews. Supporting Evidence: PMID:37098072 UQ is also observed to bind at the entrance of the pocket formed by the transmembrane helix I of SDHC, transmembrane helix II of SDHD, and the C-terminal segment of SDHB. It interacts with Pro-SDHB197, Trp-SDHB201, Ile-SDHB246, Ile-SDHC56, Trp-SDHC61, Met-SDHC65, Ile-SDHC69, and Tyr-SDHD114 file:human/SDHC/SDHC-deep-research-falcon.md Correct gene/protein: SDHC encodes the membrane-embedded cytochrome b560 subunit of mitochondrial succinate dehydrogenase (Complex II), forming the membrane arm with SDHD. It houses the heme b and contributes to the ubiquinone-binding pocket
GO:0045273 respiratory chain complex II (succinate dehydrogenase)	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation for Complex II membership via Ensembl Compara ortholog transfer from mouse (UniProtKB:Q9CZB0). Consistent with IBA, ISS, IDA, and TAS annotations for the same term. Reason: Correct and consistent with multiple lines of evidence from different sources. SDHC is unambiguously a subunit of Complex II.
GO:0005743 mitochondrial inner membrane	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	ACCEPT	Summary: NAS annotation from ComplexPortal based on review by Signes and Fernandez-Vizarra (2018) on assembly of OXPHOS complexes. SDHC is an integral multi-pass protein of the mitochondrial inner membrane, forming the membrane anchor of Complex II together with SDHD. Confirmed by cryo-EM (PMID:37098072). Reason: Correct localization. SDHC is an integral protein of the inner mitochondrial membrane with three transmembrane helices, confirmed by the cryo-EM structure (PMID:37098072). Supporting Evidence: PMID:37098072 The entire hydrophobic domain contains two membrane-anchored subunits: SDHC and SDHD
GO:0006099 tricarboxylic acid cycle	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	ACCEPT	Summary: NAS annotation from ComplexPortal for TCA cycle involvement based on the OXPHOS assembly review (PMID:30030361). SDHC is a structural subunit of Complex II which catalyzes the succinate to fumarate step of the TCA cycle. Reason: Correct and consistent with IEA and TAS annotations for the same term. TCA cycle involvement is a core function of SDHC as part of Complex II. Supporting Evidence: PMID:30030361 The assembly of the five oxidative phosphorylation system (OXPHOS) complexes in the inner mitochondrial membrane is an intricate process
GO:0006121 mitochondrial electron transport, succinate to ubiquinone	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	ACCEPT	Summary: NAS annotation from ComplexPortal for the specific electron transport process from succinate to ubiquinone. SDHC is essential for this process because it forms part of the ubiquinone binding site and provides the heme b environment needed for electron flow from the [3Fe-4S] cluster to ubiquinone. Consistent with the IBA annotation for the same term. Reason: Core biological process for SDHC. SDHC provides the terminal portion of the electron transfer pathway in Complex II by forming the Q-binding pocket with SDHD and SDHB. Supporting Evidence: PMID:37098072 The edge-to-edge distance between these redox-active prosthetic groups is less than 14 Å (Fig. 3), a distance range that can efficiently support the delivery of electrons between these redox centers (22)
GO:0042776 proton motive force-driven mitochondrial ATP synthesis	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	REMOVE	Summary: NAS annotation from ComplexPortal suggesting SDHC is involved in proton motive force-driven mitochondrial ATP synthesis. This annotation is problematic because Complex II does NOT pump protons across the inner mitochondrial membrane. Unlike Complexes I, III, and IV which translocate protons to generate the proton motive force, Complex II transfers electrons from succinate to ubiquinone without any proton pumping. Complex II contributes to ATP synthesis only indirectly by feeding reduced ubiquinol into the Q pool, which is then oxidized by Complex III (which does pump protons). The same annotation was marked REMOVE for SDHB in the parallel review. Reason: Complex II is the only OXPHOS complex that does NOT pump protons. The proton motive force is generated by Complexes I, III, and IV. Complex II feeds electrons into the ubiquinone pool but does not directly contribute to the proton gradient. This annotation is misleading and was also marked REMOVE for SDHB. The correct process annotation for SDHC is GO:0006121 (mitochondrial electron transport, succinate to ubiquinone). Supporting Evidence: PMID:37098072 The respiratory chain (also called electron transport chain) consists of complexes I-IV. It oxidizes the reducing equivalents in nicotinamide adenine dinucleotide (NADH) and succinate using molecular oxygen and couples the translocation of protons from the mitochondrial matrix into the intermembrane space
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: HTP annotation for mitochondrial localization from a quantitative high-confidence human mitochondrial proteome study (Morgenstern et al. 2021). SDHC was identified in the mitochondrial proteome by quantitative mass spectrometry. Reason: Correct. SDHC is a well-established mitochondrial protein confirmed by proteomics and structural studies. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context [SDHC identified by quantitative mass spectrometry]
GO:0045273 respiratory chain complex II (succinate dehydrogenase)	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for Complex II membership by manual transfer from ortholog (UniProtKB:D0VWV4, bovine). Consistent with all other annotations for this term. Reason: Correct. Transfer from the well-characterized bovine SDH complex. SDHC is unambiguously a subunit of Complex II.
GO:0045273 respiratory chain complex II (succinate dehydrogenase)	IDA PMID:37098072 Structure of the human respiratory complex II.	ACCEPT	Summary: IDA annotation for Complex II membership from the cryo-EM structure study (Du et al. 2023). This study resolved the human Complex II structure at 2.86 angstroms showing all four subunits including SDHC in the membrane domain. SDHC was directly identified in the complex by cryo-EM, SDS-PAGE, and mass spectrometry. Reason: Direct experimental evidence from the human Complex II cryo-EM structure. This is the strongest evidence for SDHC's membership in Complex II. Supporting Evidence: PMID:37098072 All the four subunits (SDHA, SDHB, SDHC, and SDHD) were detected by SDS-PAGE (SI Appendix, Fig. S1D) and mass spectrometry (MS) (SI Appendix, Table S1).
GO:0045273 respiratory chain complex II (succinate dehydrogenase)	TAS PMID:9533030 Cytochrome b in human complex II (succinate-ubiquinone oxido...	ACCEPT	Summary: TAS annotation for Complex II membership from the original cDNA cloning study of SDHC and SDHD (Hirawake et al. 1997). This study cloned the cDNA for the large (cybL/SDHC) and small (cybS/SDHD) subunits of cytochrome b in human liver Complex II and determined their role as membrane-anchors. Reason: The original characterization study of SDHC establishes it as a subunit of Complex II. Supporting Evidence: PMID:9533030 the amino acid sequences of the large (cybL) and small (cybS) subunits of cytochrome b in human liver complex II were deduced from cDNAs isolated by homology probing
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-70994	ACCEPT	Summary: TAS annotation for inner mitochondrial membrane localization from Reactome pathway R-HSA-70994 (SDH complex dehydrogenates succinate). Reactome models Complex II as located in the inner mitochondrial membrane where it catalyzes the oxidation of succinate coupled to ubiquinone reduction. Reason: Correct localization, consistent with all other inner membrane annotations.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9855252	ACCEPT	Summary: TAS annotation for inner mitochondrial membrane localization from Reactome pathway R-HSA-9855252 (SDHA:SDHB binds to SDHC:SDHD). This Reactome entry models the assembly of Complex II by association of the catalytic SDHA:SDHB subcomplex with the membrane-anchored SDHC:SDHD subcomplex at the inner mitochondrial membrane. Reason: Correct localization. The Reactome assembly model places SDHC:SDHD at the inner mitochondrial membrane, consistent with experimental evidence.
GO:0005743 mitochondrial inner membrane	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for inner mitochondrial membrane localization by manual transfer from ortholog (UniProtKB:D0VWV4, bovine). Consistent with all other inner membrane annotations. Reason: Correct. Transfer from the well-characterized bovine SDH complex. SDHC is located in the inner mitochondrial membrane.
GO:0020037 heme binding	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for heme binding by manual transfer from ortholog (UniProtKB:D0VWV4, bovine). SDHC provides the axial His127 ligand to the heme b (cytochrome b560) iron atom. The heme b is shared between SDHC and SDHD, with each subunit providing one histidine as an axial ligand. The cryo-EM structure (PMID:37098072, PDB:8GS8) directly confirmed the heme b binding site in the SDHC/SDHD interface. UniProt annotates the binding site at residue 127 with evidence ECO:0000269\|PubMed:37098072. The heme b is important for protein stability and may serve as an electron sink during ubiquinone reduction. Reason: Heme binding is a core molecular function of SDHC. The His127 axial ligand coordinates the heme b iron atom, confirmed by cryo-EM structure (PMID:37098072). This is one of the few subunit-specific molecular functions of SDHC. Supporting Evidence: PMID:37098072 The two membrane-anchored proteins (SDHC and SDHD) in human CII, each with three transmembrane helices, contain only one heme b group PMID:37098072 the heme cofactor is also crucial for the heme protein to achieve its proper fold and thus become a stable, functional structure PMID:9533030 Histidine residues, which are possible heme axial ligands in cytochrome b of complex II, were found in the second transmembrane segment of each subunit
GO:0005739 mitochondrion	TAS PMID:2302193 Human complex II (succinate-ubiquinone oxidoreductase): cDNA...	ACCEPT	Summary: TAS annotation for mitochondrial localization from Kita et al. (1990). This study cloned the cDNA for the iron-sulfur subunit of human liver Complex II and established that Complex II is located in mitochondria. Note that PMID:2302193 specifically describes the Ip (SDHB) subunit, not SDHC directly, but the TAS inference to SDHC as a subunit of the same complex is reasonable since Complex II is exclusively mitochondrial. Reason: Correct localization. While the publication specifically cloned the SDHB subunit, the inference that SDHC is mitochondrial as a subunit of Complex II is well-supported. Supporting Evidence: PMID:2302193 Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex of both the tricarboxylic acid cycle and of the aerobic respiratory chains of mitochondria in eukaryotic cell and prokaryotic organisms
GO:0006099 tricarboxylic acid cycle	TAS PMID:9533030 Cytochrome b in human complex II (succinate-ubiquinone oxido...	ACCEPT	Summary: TAS annotation for TCA cycle involvement from the original cDNA cloning study (Hirawake et al. 1997). This study explicitly describes Complex II as an enzyme involved in both the TCA cycle and aerobic respiration. Reason: Correct. TCA cycle involvement is a core biological process for SDHC as part of Complex II. Consistent with IEA and NAS annotations for the same term. Supporting Evidence: PMID:9533030 Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex in both the tricarboxylic acid cycle and the aerobic respiratory chains of mitochondria in eukaryotic cells and prokaryotic organisms
GO:0009060 aerobic respiration	TAS PMID:9533030 Cytochrome b in human complex II (succinate-ubiquinone oxido...	ACCEPT	Summary: TAS annotation for aerobic respiration from the original cDNA cloning study (Hirawake et al. 1997). Complex II is part of the aerobic respiratory chain, linking succinate oxidation in the TCA cycle to ubiquinone reduction in the electron transport chain. Reason: Correct. Aerobic respiration is a core biological process for SDHC as part of Complex II. Complex II participates in both the TCA cycle and the electron transport chain during aerobic respiration. Supporting Evidence: PMID:9533030 Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex in both the tricarboxylic acid cycle and the aerobic respiratory chains of mitochondria in eukaryotic cells and prokaryotic organisms
GO:0016020 membrane	TAS PMID:9533030 Cytochrome b in human complex II (succinate-ubiquinone oxido...	ACCEPT	Summary: TAS annotation for general membrane localization from the original cDNA cloning study (Hirawake et al. 1997). SDHC was predicted to have three transmembrane segments, indicating its role as a membrane-anchor. This is correct but very general; the more specific term GO:0005743 (mitochondrial inner membrane) is also annotated. Reason: Correct but general. The original study predicted three transmembrane segments for SDHC, establishing its role as a membrane protein. The more specific inner membrane term is also annotated from multiple evidence sources. Supporting Evidence: PMID:9533030 From hydrophobicity analysis, both cybL and cybS appear to have three transmembrane segments, indicating their role as membrane-anchors for the enzyme complex
GO:0048039 ubiquinone binding	IDA PMID:37098072 Structure of the human respiratory complex II.	NEW	Summary: The cryo-EM structure of human Complex II (PMID:37098072) directly demonstrates that ubiquinone binds at a pocket formed jointly by SDHC, SDHD, and SDHB. Specific SDHC residues Ile56, Trp61, Met65, and Ile69 directly contact ubiquinone. This is a subunit-specific molecular function of SDHC that is not currently annotated. Reason: Ubiquinone binding is a key subunit-specific molecular function of SDHC that is missing from the current annotation set. The cryo-EM structure (PMID:37098072) provides direct structural evidence for SDHC residues contacting ubiquinone. The qualifier should be 'contributes_to' since the Q-site is shared with SDHD and SDHB. Supporting Evidence: PMID:37098072 UQ is also observed to bind at the entrance of the pocket formed by the transmembrane helix I of SDHC, transmembrane helix II of SDHD, and the C-terminal segment of SDHB. It interacts with Pro-SDHB197, Trp-SDHB201, Ile-SDHB246, Ile-SDHC56, Trp-SDHC61, Met-SDHC65, Ile-SDHC69, and Tyr-SDHD114

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

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