NDUFS3

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0045271 respiratory chain complex I	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation of NDUFS3 as part of respiratory chain complex I. This is the correct, well-supported complex-membership assignment and reflects the deeply conserved role of the 30 kDa/S3 core subunit across eukaryotes and its bacterial NuoC ortholog. Reason: NDUFS3 is a conserved core subunit of Complex I; complex membership is directly demonstrated by immunopurification and structural studies (PMID:12611891, PMID:28844695). GO:0045271 is the current, non-obsolete term for Complex I membership. Supporting Evidence: file:human/NDUFS3/NDUFS3-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (IEA) annotation to the mitochondrial inner membrane, consistent with the curated subcellular location and independently supported by experimental IDA annotations (PMID:18826940). Reason: Correct anatomical location. NDUFS3 is a peripheral membrane component of Complex I on the matrix side of the inner membrane. Supporting Evidence: file:human/NDUFS3/NDUFS3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	IEA GO_REF:0000117	ACCEPT	Summary: Electronic (IEA, ARBA) annotation to the core Complex I biological process, electron transport from NADH to ubiquinone. This is the central physiological role of the complex NDUFS3 is part of and is redundantly supported by experimental IMP annotations. Reason: Core BP of Complex I; well supported by disease-variant functional studies showing NDUFS3 mutations abolish NADH:ubiquinone electron transfer (PMID:14729820, PMID:30140060). Supporting Evidence: file:human/NDUFS3/NDUFS3-uniprot.txt NADH through the respiratory chain, using ubiquinone as an electron
GO:0008137 NADH dehydrogenase (ubiquinone) activity	IEA GO_REF:0000120	MODIFY	Summary: Electronic (IEA) annotation of the complex-level catalytic activity NADH dehydrogenase (ubiquinone) activity (EC 7.1.1.2, RHEA:29091) with the enables qualifier. This is the holoenzyme activity of Complex I; NDUFS3 is a core structural subunit that contributes to but does not independently possess this activity. Reason: The catalytic activity is a property of the assembled complex, not of NDUFS3 in isolation (NDUFS3 carries no redox cofactor). The complex-level MF is best expressed with the contributes_to qualifier (as in the curated IMP annotation from PMID:30140060), rather than enables. Retain the term but with contributes_to. Proposed replacements: NADH dehydrogenase (ubiquinone) activity Supporting Evidence: file:human/NDUFS3/NDUFS3-uniprot.txt catalytic activity and assembly of complex I
GO:0016651 oxidoreductase activity, acting on NAD(P)H	IEA GO_REF:0000002	ACCEPT	Summary: Electronic (InterPro2GO) annotation to the broad parent MF oxidoreductase activity, acting on NAD(P)H. This is a correct but general ancestor of the specific NADH dehydrogenase (ubiquinone) activity. Reason: A correct, if general, MF ancestor consistent with the complex-level activity. IEA terms may legitimately be broader than the experimentally supported specific term.
GO:0045271 respiratory chain complex I	IEA GO_REF:0000117	ACCEPT	Summary: Electronic (IEA, ARBA) complex-membership annotation, redundant with the IBA and IDA annotations to the same term. Reason: Correct Complex I membership; duplicates are acceptable and reinforce the assignment. Supporting Evidence: file:human/NDUFS3/NDUFS3-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain
GO:1902600 proton transmembrane transport	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Electronic annotation (inferred from GO:0008137 via inter-ontology links) to proton transmembrane transport. Complex I couples NADH:ubiquinone electron transfer to translocation of protons across the inner membrane, so this is valid at the complex level, but for NDUFS3 (a peripheral-arm subunit not part of the membrane proton pump) it is a downstream/complex-level consequence rather than a core function. Reason: Proton pumping is performed by the membrane arm; NDUFS3 sits in the peripheral arm. The term is not wrong at the complex level but is peripheral to NDUFS3's own role. Supporting Evidence: PMID:9878551 which is accompanied by translocation of protons from the mitochondrial matrix to the intermembrane space
GO:0005515 protein binding	IPI PMID:15250827 Structural organization of mitochondrial human complex I: ro...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from a study of Complex I structural organization. Provides no specific molecular-function information. Reason: Per curation guidelines the uninformative protein binding term is not retained as a function. Biologically meaningful interactions of NDUFS3 (with other Complex I subunits and assembly factors) are captured by the complex-membership and assembly annotations.
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: Bare protein binding IPI derived from a blue-native/LC-MS-MS methods study. No specific molecular function is conveyed. Reason: Uninformative protein binding; meaningful interactions are covered elsewhere.
GO:0005515 protein binding	IPI PMID:21310150 NDUFB7 and NDUFA8 are located at the intermembrane surface o...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from a study localizing NDUFB7/NDUFA8 in Complex I. No specific molecular function is conveyed for NDUFS3. Reason: Uninformative protein binding; complex membership is already captured by GO:0045271.
GO:0005515 protein binding	IPI PMID:24344204 TIMMDC1/C3orf1 functions as a membrane-embedded mitochondria...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from a study of the assembly factor TIMMDC1/MCIA complex. No specific molecular function is conveyed. Reason: Uninformative protein binding; the biologically relevant assembly context is captured by GO:0032981 (Complex I assembly).
GO:0005515 protein binding	IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from a mitochondrial protein-interaction mapping study. No specific molecular function is conveyed. Reason: Uninformative protein binding; meaningful partners are captured by complex and assembly annotations.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from a large-scale human interactome study. No specific molecular function is conveyed. Reason: Uninformative protein binding; high-throughput interactome data do not add a specific function beyond known Complex I membership.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from the HuRI binary interactome reference map. No specific molecular function is conveyed. Reason: Uninformative protein binding from a genome-scale two-hybrid screen.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from a neurodegenerative-disease interactome study. No specific molecular function is conveyed. Reason: Uninformative protein binding.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from the BioPlex proteome-scale interactome. No specific molecular function is conveyed. Reason: Uninformative protein binding.
GO:0005743 mitochondrial inner membrane	IDA PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: Experimental (IDA, ComplexPortal) localization of NDUFS3 to the mitochondrial inner membrane, from cryo-EM of the human respiratory megacomplex I2III2IV2, in which Complex I (including NDUFS3) is resolved in the inner membrane. Reason: Correct, structurally supported anatomical location for the Complex I holoenzyme containing NDUFS3. Supporting Evidence: PMID:28844695 the human respiratory chain megacomplex-I2III2IV2 (MCI2III2IV2) with 140 subunits
GO:0009060 aerobic respiration	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	KEEP AS NON CORE	Summary: Author-statement (NAS, ComplexPortal) annotation of the Complex I holoenzyme to aerobic respiration. This is a valid complex-level physiological role but a broad, high-level process rather than NDUFS3's specific molecular contribution. Reason: Complex I is essential for aerobic respiration/OXPHOS, but this general process term is peripheral to NDUFS3's core electron-transport/assembly role and is better captured by GO:0006120. Supporting Evidence: PMID:30030361 The assembly of the five oxidative phosphorylation system (OXPHOS) complexes
GO:0042776 proton motive force-driven mitochondrial ATP synthesis	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	KEEP AS NON CORE	Summary: Author-statement (NAS, ComplexPortal) annotation to proton motive force-driven mitochondrial ATP synthesis, reflecting Complex I's contribution to the proton-motive force. ATP synthesis itself is carried out by Complex V; Complex I contributes upstream via proton pumping. Reason: A downstream, complex-level physiological consequence. Not a core molecular function of NDUFS3, which is a peripheral-arm structural/catalytic subunit. Supporting Evidence: PMID:30030361 oxidative phosphorylation system (OXPHOS)
GO:0045271 respiratory chain complex I	IPI PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: Experimental (IPI, ComplexPortal) annotation of NDUFS3 as part of respiratory chain complex I, from the cryo-EM megacomplex structure resolving Complex I subunits. Reason: Directly supported Complex I membership from a structural study. Supporting Evidence: PMID:28844695 the precise assignment of individual subunits of human CI and CIII
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Experimental (IDA, HPA immunofluorescence) localization to the mitochondrion. Correct but less specific than the inner-membrane annotation. Reason: Correct general localization; consistent with the more specific GO:0005743 annotation.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput (HTP) mitochondrial-proteome localization to the mitochondrion. Consistent with all other localization evidence. Reason: Correct general localization; NDUFS3 is a bona fide component of the human mitochondrial proteome.
GO:0045271 respiratory chain complex I	IDA PMID:12611891 The subunit composition of the human NADH dehydrogenase obta...	ACCEPT	Summary: Experimental (IDA) Complex I membership from one-step immunopurification and mass-spectrometric identification of the human NADH dehydrogenase subunit composition, in which NDUFS3 was identified as a bona fide subunit. Reason: Direct biochemical evidence for Complex I membership. Supporting Evidence: PMID:12611891 an immunocapture procedure for isolating this multisubunit membrane-bound complex from human tissue
GO:0045271 respiratory chain complex I	IDA PMID:17209039 Identification of mitochondrial complex I assembly intermedi...	ACCEPT	Summary: Experimental (IDA) Complex I membership; NDUFS3 was tagged and traced through Complex I assembly intermediates, confirming it is an integral subunit of the assembled complex. Reason: Direct evidence; NDUFS3-GFP incorporates into the fully assembled Complex I. Supporting Evidence: PMID:17209039 six distinct NDUFS3-GFP-containing subcomplexes gradually appeared
GO:0045271 respiratory chain complex I	IDA PMID:18826940 Subunits of mitochondrial complex I exist as part of matrix-...	ACCEPT	Summary: Experimental (IDA) Complex I membership; NDUFS3 was among the GFP-tagged subunits shown to be present in the immobile holoenzyme fraction as well as a matrix-soluble subassembly. Reason: Direct evidence for Complex I membership from live-cell subassembly analysis. Supporting Evidence: PMID:18826940 each subunit was partially present in a virtually immobile fraction, possibly representing the holo-enzyme
GO:0045271 respiratory chain complex I	IDA PMID:31536960 Rewiring of the Human Mitochondrial Interactome during Neuro...	ACCEPT	Summary: Experimental (IDA) Complex I membership from a mitochondrial interactome study that also identified the NDUFS3-RAB5IF interaction. Reason: Consistent with all other Complex I membership evidence. Supporting Evidence: PMID:31536960 Regulators of the Respirasome
GO:0045271 respiratory chain complex I	NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox...	ACCEPT	Summary: Author-statement (NAS) Complex I membership from the cDNA characterization of the nuclear-encoded Complex I subunits, describing NADH:ubiquinone oxidoreductase as a multiprotein complex of the inner mitochondrial membrane. Reason: Correct membership; redundant with stronger experimental evidence. Supporting Evidence: PMID:9878551 NADH:ubiquinone oxidoreductase (complex I) is an extremely complicated multiprotein complex located in the inner mitochondrial membrane
GO:0008137 NADH dehydrogenase (ubiquinone) activity	IMP PMID:30140060 A Novel NDUFS3 mutation in a Chinese patient with severe Lei...	ACCEPT	Summary: Experimental (IMP) annotation with the contributes_to qualifier: a novel NDUFS3 variant (R140W) in a Chinese Leigh syndrome patient decreased NDUFS3 amount and Complex I assembly, demonstrating that NDUFS3 contributes to the complex-level NADH:ubiquinone catalytic activity. This is the correctly-framed core molecular function for a structural core subunit. Reason: contributes_to GO:0008137 is the appropriate MF for a core subunit that is required for, but does not independently possess, the complex-level catalytic activity. Loss of function reduces Complex I activity/assembly. Supporting Evidence: PMID:30140060 decreased amount of NDUFS3 and complex I assembly when compared with two control cells
GO:0005743 mitochondrial inner membrane	IDA PMID:18826940 Subunits of mitochondrial complex I exist as part of matrix-...	ACCEPT	Summary: Experimental (IDA) inner-membrane localization with topology (matrix side) determined by submitochondrial FRAP of GFP-tagged NDUFS3. Reason: Direct, well-controlled evidence for the curated subcellular location. Supporting Evidence: PMID:18826940 matrix- and membrane-associated subcomplexes in living cells
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	IMP PMID:14729820 Mutant NDUFS3 subunit of mitochondrial complex I causes Leig...	ACCEPT	Summary: Experimental (IMP) annotation to the core Complex I biological process. NDUFS3 mutations identified in Leigh syndrome patients cause Complex I deficiency, directly implicating NDUFS3 in NADH-to-ubiquinone electron transport. Reason: This is a core biological process of NDUFS3. Mutations abolish/reduce NADH:ubiquinone electron transfer, causing complex I deficiency. Supporting Evidence: PMID:14729820 coding for the seventh and last subunit of complex I core, were shown to cause late onset Leigh syndrome, optic atrophy, and complex I deficiency
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	IMP PMID:30140060 A Novel NDUFS3 mutation in a Chinese patient with severe Lei...	ACCEPT	Summary: Experimental (IMP) annotation to the core Complex I biological process from a second Leigh syndrome patient with NDUFS3 variants and demonstrated Complex I deficiency. Reason: Core BP; independently supports GO:0006120 for NDUFS3. Supporting Evidence: PMID:30140060 two missense mutations of NDUFS3
GO:0008137 NADH dehydrogenase (ubiquinone) activity	IMP PMID:14729820 Mutant NDUFS3 subunit of mitochondrial complex I causes Leig...	MODIFY	Summary: Experimental (IMP) annotation of the complex-level NADH dehydrogenase (ubiquinone) activity with the enables qualifier, from NDUFS3 disease-variant characterization. NDUFS3 is required for this activity but, as a cofactor-less structural subunit, does not carry it out independently. Reason: The activity is a property of the assembled complex. contributes_to is the more accurate qualifier (as used in the PMID:30140060 IMP annotation). Retain the term with contributes_to rather than enables. Proposed replacements: NADH dehydrogenase (ubiquinone) activity Supporting Evidence: PMID:14729820 coding for the seventh and last subunit of complex I core
GO:0032981 mitochondrial respiratory chain complex I assembly	IMP PMID:30140060 A Novel NDUFS3 mutation in a Chinese patient with severe Lei...	ACCEPT	Summary: Experimental (IMP) annotation to Complex I assembly. NDUFS3 patient variants reduced NDUFS3 protein levels and impaired Complex I assembly in patient-derived cells, consistent with NDUFS3 acting as an early nucleation point of the peripheral arm (PMID:17209039). Reason: Core biological process. NDUFS3 is required for correct stepwise assembly of Complex I; its loss impairs assembly. Supporting Evidence: PMID:30140060 decreased amount of NDUFS3 and complex I assembly when compared with two control cells
GO:0005515 protein binding	IPI PMID:31536960 Rewiring of the Human Mitochondrial Interactome during Neuro...	MARK AS OVER ANNOTATED	Summary: Curated protein binding IPI capturing the NDUFS3-RAB5IF interaction. While this is a genuine curated interaction, the bare protein binding term itself is uninformative as a molecular function. Reason: Per curation guidelines protein binding is not retained as an informative function. The interaction is noted, but conveys no specific molecular activity. Supporting Evidence: PMID:31536960 Regulators of the Respirasome and Neurogenesis
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-163217	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix, from the reaction in which Complex I oxidizes NADH and reduces CoQ. NDUFS3 is a matrix-side peripheral-arm subunit, so the matrix location is compatible, though the primary curated anatomical location is the inner membrane (GO:0005743). Reason: Compatible with NDUFS3's matrix-facing topology but less precise than the inner-membrane annotation; retained as non-core localization context.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799178	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix from a Complex I biogenesis reaction (Intermediate 1 binds HP subcomplex to form Intermediate 2). Reason: Assembly-intermediate localization context; compatible with matrix-side topology but less precise than GO:0005743.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799179	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix from a Complex I biogenesis reaction (peripheral arm subunits bind the 815 kDa complex). Reason: Assembly-intermediate localization context; less precise than GO:0005743.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799191	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix from a Complex I biogenesis reaction (Intermediate 2 binds MT-ND1:NDUFAF5:NDUFAF6). Reason: Assembly-intermediate localization context; less precise than GO:0005743.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799196	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix from a Complex I biogenesis reaction (dissociation of assembly factors to form Complex I). Reason: Assembly-intermediate localization context; less precise than GO:0005743.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799197	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix from a Complex I biogenesis reaction (ND4, ND5 bind the 550 kDa complex). Reason: Assembly-intermediate localization context; less precise than GO:0005743.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799202	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix from a Complex I biogenesis reaction (315 kDa binds 370 kDa to form 550 kDa complex). Reason: Assembly-intermediate localization context; less precise than GO:0005743.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799203	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix from a Complex I biogenesis reaction (IP subcomplex binds NDUFAF3, NDUFAF4, TIMMDC1). NDUFS3 is part of the IP subcomplex referenced here. Reason: Assembly-intermediate localization context; less precise than GO:0005743.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6800868	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix from the reaction forming the IP subcomplex, of which NDUFS3 is a component. Reason: Assembly-intermediate localization context; less precise than GO:0005743.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838035	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix from a mitochondrial protein quality-control reaction (CLPXP binds matrix proteins). This reflects NDUFS3 as a potential CLPXP substrate rather than a Complex I function. Reason: Localization is compatible but the reaction is a generic matrix quality-control context, not a core NDUFS3 function.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838289	KEEP AS NON CORE	Summary: Reactome TAS annotation to the mitochondrial matrix from a mitochondrial protein quality-control reaction (CLPXP degrades matrix proteins). Reason: Generic matrix quality-control context, not a core NDUFS3 function; localization is compatible.
GO:0005515 protein binding	IPI PMID:19822128 DJ-1 binds to mitochondrial complex I and maintains its acti...	MARK AS OVER ANNOTATED	Summary: protein binding IPI from the study showing DJ-1 (PARK7) binds Complex I and maintains its activity. The bare protein binding term is uninformative as a molecular function. Reason: Per curation guidelines protein binding is not retained. Note the study primarily demonstrated DJ-1 binding to NDUFA4 and ND1, not directly to NDUFS3. Supporting Evidence: PMID:19822128 DJ-1 directly bound to NDUFA4 and ND1
GO:0021762 substantia nigra development	HEP PMID:22926577 Quantitative proteomic analysis of human substantia nigra in...	MARK AS OVER ANNOTATED	Summary: HEP (inferred from high-throughput expression) annotation to substantia nigra development, from a differential proteomics survey of human substantia nigra in neurodegenerative disease. This reflects differential NDUFS3 expression/abundance, not a role in the development of the substantia nigra. Reason: The evidence is a differential-abundance proteomics comparison in disease tissue; it does not establish a developmental function for NDUFS3. This is an over-annotation driven by expression detection in substantia nigra. Supporting Evidence: PMID:22926577 Using a quantitative proteomic approach, we investigated protein expressions in the substantia nigra
GO:0072593 reactive oxygen species metabolic process	IMP PMID:16826196 Coupling mitochondrial respiratory chain to cell death: an e...	KEEP AS NON CORE	Summary: Experimental (IMP) annotation to reactive oxygen species metabolic process. siRNA knockdown of NDUFS3 in cancer cell lines reduced ROS production and conferred resistance to IFN-beta/RA-induced apoptosis. This is a downstream physiological consequence of reduced Complex I function rather than a core molecular role of NDUFS3. Reason: Reduced ROS on NDUFS3 knockdown reflects loss of Complex I activity (a known ROS source), a secondary/downstream effect. Retained as a non-core process. Supporting Evidence: PMID:16826196 two subunits of MRC complex I, by siRNA in two cancer cell lines conferred resistance to IFN-beta/RA-induced apoptosis and reduced ROS production
GO:0005515 protein binding	IPI PMID:19463981 Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66...	MARK AS OVER ANNOTATED	Summary: Curated protein binding IPI capturing the interaction between NDUFS3 and the Complex I assembly factor NDUFAF3. Although a genuine, biologically meaningful interaction, the bare protein binding term itself conveys no specific molecular function. Reason: Per curation guidelines protein binding is not retained as a function. The assembly-factor interaction is relevant context for GO:0032981 (Complex I assembly). Supporting Evidence: PMID:19463981 NDUFAF3 is a genuine mitochondrial complex I assembly protein that interacts with complex I subunits
GO:0003954 NADH dehydrogenase activity	IMP PMID:16826196 Coupling mitochondrial respiratory chain to cell death: an e...	MARK AS OVER ANNOTATED	Summary: Experimental (IMP) annotation to the broader NADH dehydrogenase activity, from the NDUFS3 siRNA-knockdown study affecting Complex I function. This is a looser parent of the specific NADH dehydrogenase (ubiquinone) activity and, like the specific term, is a complex-level activity NDUFS3 contributes to rather than independently enables. Reason: Broader/looser than the specific GO:0008137 already captured with contributes_to, and framed as enables for a cofactor-less structural subunit. The specific complex-level term is preferred. Supporting Evidence: PMID:16826196 NDUFS3 (NADH dehydrogenase (ubiquinone) Fe-S protein 3), two subunits of MRC complex I
GO:0003954 NADH dehydrogenase activity	IMP PMID:11112787 Human complex I defects can be resolved by monoclonal antibo...	MARK AS OVER ANNOTATED	Summary: Experimental (IMP) annotation to NADH dehydrogenase activity from a monoclonal antibody study of Complex I subunit assembly patterns (the 30 kDa subunit is NDUFS3). A broad complex-level activity term framed with enables. Reason: Broader than the specific GO:0008137 captured as contributes_to; the activity is a complex-level property, not independently enabled by NDUFS3. Supporting Evidence: PMID:11112787 a new set of monoclonal antibodies that react with 39-, 30-, 20-, 18-, 15-, and 8-kDa subunits of Complex I
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox...	ACCEPT	Summary: Author-statement (NAS) annotation to the core Complex I biological process, from the cDNA characterization paper describing Complex I's main function as transport of electrons from NADH to ubiquinone. Reason: Correct core BP; redundant with the experimental IMP annotations. Supporting Evidence: PMID:9878551 Its main function is the transport of electrons from NADH to ubiquinone
GO:0008137 NADH dehydrogenase (ubiquinone) activity	NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox...	MODIFY	Summary: Author-statement (NAS) annotation of the complex-level NADH dehydrogenase (ubiquinone) activity with enables, from the cDNA characterization paper. Reason: The activity is a property of the assembled complex; contributes_to is more accurate for this cofactor-less core subunit than enables. Retain term with contributes_to. Proposed replacements: NADH dehydrogenase (ubiquinone) activity Supporting Evidence: PMID:9878551 NADH:ubiquinone oxidoreductase (complex I)
GO:0005739 mitochondrion	NAS PMID:9647766 cDNA sequence and chromosomal localization of the remaining ...	ACCEPT	Summary: Author-statement (NAS) mitochondrial localization from the cDNA cloning of the human IP-fraction Complex I subunits including NDUFS3 (30 kDa). Reason: Correct general localization, consistent with all other evidence. Supporting Evidence: PMID:9647766 NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	NAS PMID:9647766 cDNA sequence and chromosomal localization of the remaining ...	ACCEPT	Summary: Author-statement (NAS) annotation to the core Complex I biological process, from the cDNA cloning paper of the IP-fraction subunits. Reason: Correct core BP; redundant with experimental IMP annotations. Supporting Evidence: PMID:9647766 NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain
GO:0008137 NADH dehydrogenase (ubiquinone) activity	NAS PMID:9647766 cDNA sequence and chromosomal localization of the remaining ...	MODIFY	Summary: Author-statement (NAS) annotation of the complex-level NADH dehydrogenase (ubiquinone) activity with enables, from the IP-fraction cDNA cloning paper. Reason: Complex-level activity; contributes_to is more accurate than enables for this cofactor-less structural subunit. Retain term with contributes_to. Proposed replacements: NADH dehydrogenase (ubiquinone) activity Supporting Evidence: PMID:9647766 important prosthetic groups highly conserved among species
GO:0009055 electron transfer activity	NAS PMID:9647766 cDNA sequence and chromosomal localization of the remaining ...	MARK AS OVER ANNOTATED	Summary: Author-statement (NAS) annotation to electron transfer activity. In Complex I, the electron-transfer chemistry is carried out by the flavin (in NDUFV1) and the chain of iron-sulfur clusters (in NDUFV1/NDUFV2/NDUFS1/NDUFS7/NDUFS8 etc.). NDUFS3, despite its historical "iron-sulfur protein 3" name, carries no redox cofactor and does not itself transfer electrons. Reason: NDUFS3 is a cofactor-less structural core subunit; it does not carry a redox center and does not itself have electron transfer activity. Assigning this MF to NDUFS3 is an over-annotation stemming from the misleading "IP/iron-sulfur protein" naming. Supporting Evidence: PMID:9647766 it contains important prosthetic groups highly conserved among species
GO:0031966 mitochondrial membrane	IDA PMID:17209039 Identification of mitochondrial complex I assembly intermedi...	ACCEPT	Summary: Experimental (IDA) annotation to the mitochondrial membrane, from the tagged-NDUFS3 assembly-tracing study. Consistent with, but less specific than, the inner-membrane annotation. Reason: Correct, if general, membrane localization; subsumed by the more specific GO:0005743. Supporting Evidence: PMID:17209039 the entry point of mitochondrial subunits
GO:0005198 structural molecule activity	IMP PMID:30140060 A Novel NDUFS3 mutation in a Chinese patient with severe Lei...	NEW	Summary: Proposed subunit-specific molecular function. NDUFS3 is a cofactor-less core structural subunit of the Complex I peripheral (Q-module) arm; its own molecular role is to provide a structural scaffold required for holoenzyme assembly and catalysis, rather than to independently carry out the complex-level NADH:ubiquinone oxidoreductase reaction. This captures the structural-constituent role that underlies the contributes_to GO:0008137 annotation. Reason: NDUFS3 loss-of-function reduces both Complex I assembly and activity, consistent with a structural constituent role. Added to reflect the subunit-specific MF paired with the complex-level contributes_to GO:0008137 activity in core_functions. Supporting Evidence: PMID:30140060 decreased amount of NDUFS3 and complex I assembly when compared with two control cells file:human/NDUFS3/NDUFS3-uniprot.txt catalytic activity and assembly of complex I

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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