NDUFS7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0009060 aerobic respiration	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Complex I is the entry point of the mitochondrial electron transport chain and is essential for aerobic respiration; NDUFS7 is a core catalytic subunit. This is a correct but broad process term. Reason: Aerobic respiration is a valid high-level process for a Complex I core subunit, but the specific and informative core BP is GO:0006120 (mitochondrial electron transport, NADH to ubiquinone). Kept as non-core because it is a broad umbrella process rather than the gene's precise function. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain
GO:0045271 respiratory chain complex I	IBA GO_REF:0000033	ACCEPT	Summary: NDUFS7 is a bona fide core subunit of mitochondrial respiratory chain Complex I, established biochemically, structurally, and by phylogenetic inference. Reason: Complex I membership is the central, well-supported cellular-component assignment for this subunit and is the current (non-obsolete) term carried by GOA. The IBA is consistent with multiple experimental annotations to the same term. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Core subunit of respiratory chain NADH dehydrogenase (Complex PMID:12611891 we can resolve and identify the human homologues of 42 polypeptides detected so far in the more extensively studied beef heart complex I
GO:0008137 NADH dehydrogenase (ubiquinone) activity	IBA GO_REF:0000033	ACCEPT	Summary: NADH:ubiquinone oxidoreductase activity is the catalytic reaction of Complex I. NDUFS7 is a core catalytic subunit that coordinates the terminal Fe-S cluster N2 donating electrons to ubiquinone, so it directly contributes to this activity. Reason: This is the precise, physiologically relevant molecular function of the Complex I core, and is supported experimentally (IMP PMID:17275378) and by phylogeny. Retained as a core molecular function. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt using ubiquinone as an electron PMID:27226634 transfer of two electrons, one at a time, from the terminal electron acceptor iron-sulfur cluster N2 to ubiquinone
GO:0015990 electron transport coupled proton transport	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Complex I couples electron transfer from NADH to ubiquinone with proton translocation across the inner membrane. NDUFS7 participates as a core subunit. Reason: Accurate process for Complex I, but the more specific and informative BP for this subunit is GO:0006120 (electron transport, NADH to ubiquinone). Proton pumping occurs in the membrane arm; NDUFS7 sits at the Fe-S/quinone site, so it enables the redox step that is energetically coupled to proton transport. Supporting Evidence: PMID:27226634 couples electron transfer through the complex to the generation of the proton-motive force across the inner membrane
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000120	ACCEPT	Summary: NDUFS7 is a peripheral membrane protein of the mitochondrial inner membrane (matrix side), consistent with Complex I being embedded in and protruding from the inner membrane. Reason: The inner membrane is the correct anatomical localization for this Complex I subunit; supported by UniProt subcellular location and by IDA (ComplexPortal, PMID:28844695). Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Mitochondrion inner membrane
GO:0008137 NADH dehydrogenase (ubiquinone) activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (InterPro/RHEA/EC mapping) of the Complex I catalytic activity, redundant with the IBA and IMP annotations to the same term. Reason: The InterPro/EC 7.1.1.2/RHEA:29091 mapping to GO:0008137 is correct for this core catalytic subunit and matches the UniProt-annotated catalytic activity. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt EC=7.1.1.2
GO:0048038 quinone binding	IEA GO_REF:0000002	ACCEPT	Summary: The ubiquinone-reduction site of Complex I lies at the junction between the peripheral and membrane arms, at the interface involving NDUFS7 (Q-module) and ND1. Quinone binding is consistent with the Fe-S cluster N2 to ubiquinone electron transfer. Reason: InterPro (IPR006138) mapping to quinone binding is biologically appropriate given NDUFS7's position adjacent to the ubiquinone-reduction site and its Fe-S cluster N2 that donates electrons to ubiquinone. Supporting Evidence: PMID:27226634 transfer of two electrons, one at a time, from the terminal electron acceptor iron-sulfur cluster N2 to ubiquinone
GO:0051536 iron-sulfur cluster binding	IEA GO_REF:0000002	MODIFY	Summary: NDUFS7 coordinates an iron-sulfur cluster (the [4Fe-4S] cluster N2, the terminal electron donor to ubiquinone). Reason: Iron-sulfur cluster binding is correct but general. UniProt and InterPro (IPR006138) specify a [4Fe-4S] cluster, so the more precise child term GO:0051539 (4 iron, 4 sulfur cluster binding) should be used. Proposed replacements: 4 iron, 4 sulfur cluster binding Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Binds 1 [4Fe-4S] cluster
GO:0051539 4 iron, 4 sulfur cluster binding	IEA GO_REF:0000002	ACCEPT	Summary: NDUFS7 binds one [4Fe-4S] cluster (cluster N2), coordinated by four cysteine residues (positions 88, 89, 153, 183). This cluster is the terminal electron donor to ubiquinone, giving NDUFS7 a genuine redox molecular function. Reason: Directly supported by UniProt cofactor and binding-site annotation and by InterPro (IPR006138). This is a core molecular function distinguishing NDUFS7 from purely accessory subunits. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Binds 1 [4Fe-4S] cluster PMID:27226634 transfer of two electrons, one at a time, from the terminal electron acceptor iron-sulfur cluster N2 to ubiquinone
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: High-throughput yeast two-hybrid interactome screen reporting an interaction between NDUFS7 and JPH3 (Q8WXH2). Bare protein binding is uninformative about molecular function. Reason: Per curation policy, bare protein binding (GO:0005515) IPIs are retained but marked over-annotated because they do not convey a specific molecular function. This interaction is from a large-scale neurodegeneration Y2H network and is not part of NDUFS7's characterized function within Complex I. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt O75251; Q8WXH2: JPH3
GO:0002020 protease binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic annotation transferred from a rat ortholog (Ensembl Compara). There is no direct human evidence that NDUFS7 functions as a protease binder. Reason: This is a weak orthology-based electronic transfer (from rat) that is not supported by the human functional literature and is not part of NDUFS7's role as a Complex I core subunit. Retained but flagged as over-annotation rather than removed, since it is an IEA and not clearly contradicted.
GO:0043025 neuronal cell body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic annotation transferred from a rat ortholog reflecting high neuronal expression rather than a subcellular localization distinct from mitochondria. Reason: NDUFS7 is a mitochondrial inner-membrane protein; neuronal cell body reflects the cell type in which the rat ortholog was detected, not an organelle localization. Kept as non-core; the informative CC is the mitochondrial inner membrane.
GO:0097060 synaptic membrane	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic annotation transferred from a rat ortholog. NDUFS7 is a mitochondrial Complex I subunit; any synaptic association reflects the abundance of mitochondria at synapses rather than a plasma/synaptic-membrane function. Reason: The protein resides in the mitochondrial inner membrane; synaptic membrane is an orthology-based over-interpretation of neuronal mitochondrial localization and does not reflect a genuine synaptic-membrane localization of NDUFS7.
GO:0045271 respiratory chain complex I	IEA GO_REF:0000107	ACCEPT	Summary: Electronic annotation (Ensembl Compara, transferred from the mouse ortholog) of Complex I membership, redundant with the experimental and IBA annotations to the same term. Reason: Complex I membership is correct and well-supported experimentally; this orthology-based IEA is consistent with the direct evidence. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Core subunit of respiratory chain NADH dehydrogenase (Complex
GO:0005743 mitochondrial inner membrane	IDA PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: Cryo-EM structure of the human respiratory megacomplex places NDUFS7 within Complex I embedded in the inner membrane; direct assay (ComplexPortal IDA). Reason: Direct experimental (structural) evidence for inner-membrane localization of the assembled Complex I containing NDUFS7. This is the core anatomical CC. Supporting Evidence: PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII
GO:0009060 aerobic respiration	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	KEEP AS NON CORE	Summary: Review of OXPHOS complex assembly noting Complex I core proteins perform the catalytic activities of aerobic respiration. Author statement (NAS). Reason: Correct but broad umbrella process (duplicate of the IBA aerobic respiration annotation). The specific core BP for NDUFS7 is GO:0006120. Kept as non-core. Supporting Evidence: PMID:30030361 The human enzymes comprise core proteins, performing the catalytic activities
GO:0042776 proton motive force-driven mitochondrial ATP synthesis	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	MARK AS OVER ANNOTATED	Summary: Complex I contributes to the proton motive force that drives ATP synthase, but it is not itself part of the ATP-synthesis reaction. Reason: This annotation conflates Complex I's contribution to the proton motive force with ATP synthesis, which is carried out by Complex V (ATP synthase). NDUFS7's role is upstream (electron transport and proton pumping); the specific ATP-synthesis process belongs to ATP synthase subunits, so this is an over-annotation for a Complex I subunit. Supporting Evidence: PMID:27226634 contributing to the generation of the proton motive force
GO:0045271 respiratory chain complex I	IPI PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: Structural (cryo-EM) identification of NDUFS7 as a component of human Complex I within the respiratory megacomplex (ComplexPortal IPI). Reason: Direct structural evidence for Complex I membership; consistent with all other complex-membership annotations. Supporting Evidence: PMID:28844695 reveals the precise assignment of individual subunits of human CI and CIII
GO:0003954 NADH dehydrogenase activity	IMP PMID:14749350 Differences in assembly or stability of complex I and other ...	ACCEPT	Summary: Complex I-deficient patient studies (blue native electrophoresis) show that mutations in nuclear-encoded core subunits, including NDUFS7, compromise Complex I assembly and NADH dehydrogenase activity. The contributes_to qualifier correctly reflects that the activity is a property of the whole complex. Reason: Appropriate contributes_to annotation for a core catalytic subunit whose loss reduces the diaphorase (NADH dehydrogenase) activity of Complex I. The physiologically precise term is GO:0008137 (NADH:ubiquinone activity), also annotated, so this more general NADH dehydrogenase term is retained but is the less specific of the two. Supporting Evidence: PMID:14749350 an important decrease in the levels of intact complex I in patients harboring mutations in nuclear-encoded complex I subunits
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput mitochondrial proteomics (MitoCoP) identifies NDUFS7 as a high-confidence mitochondrial protein. Reason: Correct but non-specific; the informative CC terms are mitochondrial inner membrane (GO:0005743) and respiratory chain complex I (GO:0045271). Kept as non-core. Supporting Evidence: PMID:34800366 defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
GO:0045271 respiratory chain complex I	IMP PMID:11112787 Human complex I defects can be resolved by monoclonal antibo...	ACCEPT	Summary: Monoclonal antibody / assembly analysis of Complex I-deficient patients, including an NDUFS7 patient, confirming NDUFS7 as a Complex I subunit. Reason: Experimental support for Complex I membership; the study directly examined an NDUFS7-defective patient. Supporting Evidence: PMID:11112787 the other patients had defects in NDUFV1, NDUFS2 (two patients), NDUFS4 (two patients), NDUFS7, and NDUFS8
GO:0045271 respiratory chain complex I	IDA PMID:12611891 The subunit composition of the human NADH dehydrogenase obta...	ACCEPT	Summary: One-step immunopurification and mass spectrometry of human NADH dehydrogenase (Complex I) resolved its subunit composition, identifying NDUFS7 among the core subunits. Reason: Direct experimental identification of NDUFS7 as a Complex I subunit by immunopurification/MS. Core cellular-component assignment. Supporting Evidence: PMID:12611891 The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	IMP PMID:17275378 A novel mutation in the human complex I NDUFS7 subunit assoc...	ACCEPT	Summary: A pathogenic NDUFS7 mutation (R145H) causes severe Complex I deficiency and decreased enzyme activity in a Leigh syndrome patient, demonstrating NDUFS7's requirement for NADH-to-ubiquinone electron transport. This is the core biological process. Reason: Experimental (IMP) support that NDUFS7 is required for mitochondrial electron transport from NADH to ubiquinone. This is the precise core BP for the gene. Supporting Evidence: PMID:17275378 severe complex I defect and a novel mutation in the NDUFS7 gene subunit
GO:0008137 NADH dehydrogenase (ubiquinone) activity	IMP PMID:17275378 A novel mutation in the human complex I NDUFS7 subunit assoc...	ACCEPT	Summary: The R145H NDUFS7 variant decreases Complex I enzyme activity, supporting that NDUFS7 is essential for NADH:ubiquinone oxidoreductase activity. UniProt annotates the catalytic activity (EC 7.1.1.2) with this reference. Reason: Experimental support for the core catalytic molecular function; NDUFS7 is essential for Complex I catalytic activity. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Essential for the catalytic activity of
GO:0005515 protein binding	IPI PMID:27226634 NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembl...	MARK AS OVER ANNOTATED	Summary: Interaction reported in the context of NDUFAF5-mediated hydroxylation of NDUFS7 during Complex I assembly (partner Q5TEU4). Bare protein binding is uninformative. Reason: Per curation policy, bare protein binding IPIs are retained but flagged as over-annotation. The biologically informative aspect (hydroxylation by the assembly factor NDUFAF5 during Complex I biogenesis) is captured by the assembly annotation and PTM, not by generic protein binding. Supporting Evidence: PMID:27226634 NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-163217	KEEP AS NON CORE	Summary: The peripheral (IP) arm of Complex I, which contains NDUFS7, protrudes into the mitochondrial matrix; NDUFS7 is a matrix-side peripheral membrane protein. Reason: The matrix-facing location is consistent with NDUFS7 being on the matrix side of the inner membrane, but the precise anatomical CC is the inner membrane (peripheral membrane protein, matrix side). Kept as non-core. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Matrix side
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6788523	KEEP AS NON CORE	Summary: Reactome pathway (NUBPL transfers 4Fe-4S to Complex I subunits) locating Complex I assembly intermediates in the matrix. Reason: Matrix-side localization consistent with the peripheral arm; non-core relative to the inner-membrane assignment. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Matrix side
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799178	KEEP AS NON CORE	Summary: Reactome Complex I biogenesis reaction, locating assembly intermediates in the matrix. Reason: Matrix-side localization consistent with the peripheral arm; non-core relative to the inner-membrane assignment. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Matrix side
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799179	KEEP AS NON CORE	Summary: Reactome Complex I biogenesis reaction, locating assembly intermediates in the matrix. Reason: Matrix-side localization consistent with the peripheral arm; non-core relative to the inner-membrane assignment. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Matrix side
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799191	KEEP AS NON CORE	Summary: Reactome Complex I biogenesis reaction, locating assembly intermediates in the matrix. Reason: Matrix-side localization consistent with the peripheral arm; non-core relative to the inner-membrane assignment. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Matrix side
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799196	KEEP AS NON CORE	Summary: Reactome Complex I biogenesis reaction, locating assembly intermediates in the matrix. Reason: Matrix-side localization consistent with the peripheral arm; non-core relative to the inner-membrane assignment. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Matrix side
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799197	KEEP AS NON CORE	Summary: Reactome Complex I biogenesis reaction, locating assembly intermediates in the matrix. Reason: Matrix-side localization consistent with the peripheral arm; non-core relative to the inner-membrane assignment. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Matrix side
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799202	KEEP AS NON CORE	Summary: Reactome Complex I biogenesis reaction, locating assembly intermediates in the matrix. Reason: Matrix-side localization consistent with the peripheral arm; non-core relative to the inner-membrane assignment. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Matrix side
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6799203	KEEP AS NON CORE	Summary: Reactome Complex I biogenesis reaction, locating assembly intermediates in the matrix. Reason: Matrix-side localization consistent with the peripheral arm; non-core relative to the inner-membrane assignment. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Matrix side
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6800868	KEEP AS NON CORE	Summary: Reactome Complex I biogenesis reaction (NDUF subunits bind to form the IP subcomplex), locating assembly intermediates in the matrix. Reason: Matrix-side localization consistent with the peripheral (IP) arm that contains NDUFS7; non-core relative to the inner-membrane assignment. Supporting Evidence: file:human/NDUFS7/NDUFS7-uniprot.txt Matrix side
GO:0032981 mitochondrial respiratory chain complex I assembly	IMP PMID:11112787 Human complex I defects can be resolved by monoclonal antibo...	ACCEPT	Summary: Patient mutations in NDUFS7 lead to distinct Complex I subunit assembly patterns, showing NDUFS7 is required for proper Complex I assembly. NDUFS7 is part of the early-forming IP subcomplex. Reason: Experimental support that NDUFS7 loss affects Complex I assembly; NDUFS7 is hydroxylated by NDUFAF5 early in assembly and is part of the IP subcomplex. A valid, biologically informative process. Supporting Evidence: PMID:11112787 helps distinguish catalytic versus assembly defects and further distinguishes between mutations in different subunits PMID:27226634 This modification occurs early in the pathway of assembly of complex
GO:0005515 protein binding	IPI PMID:15186778 Disruption of mitochondrial function during apoptosis is med...	MARK AS OVER ANNOTATED	Summary: Interaction annotation associated with a study of caspase cleavage of the p75 (NDUFS1) subunit of Complex I during apoptosis (partner P28331 = NDUFS1). Bare protein binding is uninformative. Reason: Per curation policy, bare protein binding IPIs are retained but flagged as over-annotation. The interacting partner is another Complex I subunit (NDUFS1), so this reflects intra-complex association rather than a distinct molecular function. Supporting Evidence: PMID:15186778 the p75 subunit of complex I of the electron transport chain
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox...	ACCEPT	Summary: Review of the nuclear-encoded Complex I subunits describing the enzyme's transport of electrons from NADH to ubiquinone. Author statement supporting the core BP. Reason: Correct core biological process (duplicate of the IMP annotation to the same term); NDUFS7 is a core catalytic subunit of the enzyme catalyzing this electron transport. 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...	ACCEPT	Summary: Author statement describing Complex I (NADH:ubiquinone oxidoreductase) activity, of which NDUFS7 is a core catalytic subunit. Reason: Correct core molecular function (duplicate of the IBA/IMP/IEA annotations to GO:0008137). Supporting Evidence: PMID:9878551 Its main function is the transport of electrons from NADH to ubiquinone
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	NAS PMID:8938450 Assignment of the PSST subunit gene of human mitochondrial c...	ACCEPT	Summary: Characterization of the PSST (NDUFS7) subunit of human Complex I (NADH:ubiquinone oxidoreductase); author statement supporting the NADH-to-ubiquinone electron transport process. Reason: Correct core biological process for the PSST/NDUFS7 subunit (duplicate of other GO:0006120 annotations). Supporting Evidence: PMID:8938450 PSST subunit of human mitochondrial nicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase
GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	NAS PMID:8938450 Assignment of the PSST subunit gene of human mitochondrial c...	MARK AS OVER ANNOTATED	Summary: General oxidoreductase class term (parent of NADH:ubiquinone oxidoreductase activity) for the PSST/NDUFS7 subunit of Complex I. Reason: This is a broad parent of the specific and better-supported GO:0008137 (NADH dehydrogenase (ubiquinone) activity), which is already annotated. The general term adds no specificity for a core catalytic subunit whose precise activity is known. Supporting Evidence: PMID:8938450 PSST subunit of human mitochondrial nicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase

Gene Description

Existing Annotations Review

Core Functions

Core catalytic subunit of mitochondrial respiratory Complex I that binds the [4Fe-4S] cluster N2 and catalyzes electron transfer from NADH to ubiquinone.

Binds one [4Fe-4S] iron-sulfur cluster (cluster N2), the terminal electron donor to ubiquinone, contributing a genuine redox function to Complex I.

References

📚 Additional Documentation

Notes

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