id: O75251
gene_symbol: NDUFS7
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: NDUFS7 (PSST subunit; Complex I-20kD) is a nuclear-encoded core catalytic
  subunit of mitochondrial respiratory Complex I (NADH:ubiquinone oxidoreductase,
  EC 7.1.1.2). It is one of the fourteen conserved core subunits and belongs to the
  iron-sulfur (IP) fragment in the Q-module, adjacent to the ubiquinone-reduction
  site at the junction between the peripheral and membrane arms. NDUFS7 coordinates
  a [4Fe-4S] cluster corresponding to cluster N2, the terminal iron-sulfur cluster
  of the electron-transfer chain that donates electrons to ubiquinone, placing it
  directly in the redox-active electron-transfer pathway of the enzyme. Complex I
  oxidizes NADH, reduces ubiquinone, and couples this
  electron transfer to proton pumping across the inner membrane, generating the proton
  motive force used for ATP synthesis. NDUFS7 is a peripheral membrane protein of
  the mitochondrial inner membrane, exposed on the matrix side. It is hydroxylated
  at an arginine by NDUFAF5 early in Complex I assembly. Loss-of-function variants
  cause mitochondrial complex I deficiency (MC1DN3) and Leigh syndrome.
alternative_products:
- name: '1'
  id: O75251-1
- name: '2'
  id: O75251-2
  sequence_note: VSP_057067
existing_annotations:
- term:
    id: GO:0009060
    label: aerobic respiration
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Core subunit of the mitochondrial membrane respiratory chain
- term:
    id: GO:0045271
    label: respiratory chain complex I
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: NDUFS7 is a bona fide core subunit of mitochondrial respiratory chain
      Complex I, established biochemically, structurally, and by phylogenetic inference.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Core subunit of respiratory chain NADH dehydrogenase (Complex
    - reference_id: PMID:12611891
      supporting_text: we can resolve and identify the human homologues of 42 polypeptides
        detected so far in the more extensively studied beef heart complex I
- term:
    id: GO:0008137
    label: NADH dehydrogenase (ubiquinone) activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: using ubiquinone as an electron
    - reference_id: PMID:27226634
      supporting_text: transfer of two electrons, one at a time, from the terminal
        electron acceptor iron-sulfur cluster N2 to ubiquinone
- term:
    id: GO:0015990
    label: electron transport coupled proton transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Complex I couples electron transfer from NADH to ubiquinone with proton
      translocation across the inner membrane. NDUFS7 participates as a core subunit.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:27226634
      supporting_text: couples electron transfer through the complex to the generation
        of the proton-motive force across the inner membrane
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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).
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Mitochondrion inner membrane
- term:
    id: GO:0008137
    label: NADH dehydrogenase (ubiquinone) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation (InterPro/RHEA/EC mapping) of the Complex I catalytic
      activity, redundant with the IBA and IMP annotations to the same term.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: EC=7.1.1.2
- term:
    id: GO:0048038
    label: quinone binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:27226634
      supporting_text: transfer of two electrons, one at a time, from the terminal
        electron acceptor iron-sulfur cluster N2 to ubiquinone
- term:
    id: GO:0051536
    label: iron-sulfur cluster binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: NDUFS7 coordinates an iron-sulfur cluster (the [4Fe-4S] cluster N2, the
      terminal electron donor to ubiquinone).
    action: MODIFY
    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_replacement_terms:
    - id: GO:0051539
      label: 4 iron, 4 sulfur cluster binding
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Binds 1 [4Fe-4S] cluster
- term:
    id: GO:0051539
    label: 4 iron, 4 sulfur cluster binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Binds 1 [4Fe-4S] cluster
    - reference_id: PMID:27226634
      supporting_text: transfer of two electrons, one at a time, from the terminal
        electron acceptor iron-sulfur cluster N2 to ubiquinone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: High-throughput yeast two-hybrid interactome screen reporting an interaction
      between NDUFS7 and JPH3 (Q8WXH2). Bare protein binding is uninformative about
      molecular function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: 'O75251; Q8WXH2: JPH3'
- term:
    id: GO:0002020
    label: protease binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Electronic annotation transferred from a rat ortholog (Ensembl Compara).
      There is no direct human evidence that NDUFS7 functions as a protease binder.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Electronic annotation transferred from a rat ortholog reflecting high
      neuronal expression rather than a subcellular localization distinct from mitochondria.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0097060
    label: synaptic membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0045271
    label: respiratory chain complex I
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    reason: Complex I membership is correct and well-supported experimentally; this
      orthology-based IEA is consistent with the direct evidence.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Core subunit of respiratory chain NADH dehydrogenase (Complex
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IDA
  original_reference_id: PMID:28844695
  qualifier: located_in
  review:
    summary: Cryo-EM structure of the human respiratory megacomplex places NDUFS7
      within Complex I embedded in the inner membrane; direct assay (ComplexPortal
      IDA).
    action: ACCEPT
    reason: Direct experimental (structural) evidence for inner-membrane localization
      of the assembled Complex I containing NDUFS7. This is the core anatomical CC.
    supported_by:
    - reference_id: PMID:28844695
      supporting_text: The structure not only reveals the precise assignment of individual
        subunits of human CI and CIII
- term:
    id: GO:0009060
    label: aerobic respiration
  evidence_type: NAS
  original_reference_id: PMID:30030361
  qualifier: involved_in
  review:
    summary: Review of OXPHOS complex assembly noting Complex I core proteins perform
      the catalytic activities of aerobic respiration. Author statement (NAS).
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:30030361
      supporting_text: The human enzymes comprise core proteins, performing the catalytic
        activities
- term:
    id: GO:0042776
    label: proton motive force-driven mitochondrial ATP synthesis
  evidence_type: NAS
  original_reference_id: PMID:30030361
  qualifier: involved_in
  review:
    summary: Complex I contributes to the proton motive force that drives ATP synthase,
      but it is not itself part of the ATP-synthesis reaction.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:27226634
      supporting_text: contributing to the generation of the proton motive force
- term:
    id: GO:0045271
    label: respiratory chain complex I
  evidence_type: IPI
  original_reference_id: PMID:28844695
  qualifier: part_of
  review:
    summary: Structural (cryo-EM) identification of NDUFS7 as a component of human
      Complex I within the respiratory megacomplex (ComplexPortal IPI).
    action: ACCEPT
    reason: Direct structural evidence for Complex I membership; consistent with all
      other complex-membership annotations.
    supported_by:
    - reference_id: PMID:28844695
      supporting_text: reveals the precise assignment of individual subunits of human
        CI and CIII
- term:
    id: GO:0003954
    label: NADH dehydrogenase activity
  evidence_type: IMP
  original_reference_id: PMID:14749350
  qualifier: contributes_to
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:14749350
      supporting_text: an important decrease in the levels of intact complex I in patients
        harboring mutations in nuclear-encoded complex I subunits
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput mitochondrial proteomics (MitoCoP) identifies NDUFS7
      as a high-confidence mitochondrial protein.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: defined a mitochondrial high-confidence proteome of >1,100 proteins
        (MitoCoP)
- term:
    id: GO:0045271
    label: respiratory chain complex I
  evidence_type: IMP
  original_reference_id: PMID:11112787
  qualifier: part_of
  review:
    summary: Monoclonal antibody / assembly analysis of Complex I-deficient patients,
      including an NDUFS7 patient, confirming NDUFS7 as a Complex I subunit.
    action: ACCEPT
    reason: Experimental support for Complex I membership; the study directly examined
      an NDUFS7-defective patient.
    supported_by:
    - reference_id: PMID:11112787
      supporting_text: the other patients had defects in NDUFV1, NDUFS2 (two patients),
        NDUFS4 (two patients), NDUFS7, and NDUFS8
- term:
    id: GO:0045271
    label: respiratory chain complex I
  evidence_type: IDA
  original_reference_id: PMID:12611891
  qualifier: part_of
  review:
    summary: One-step immunopurification and mass spectrometry of human NADH dehydrogenase
      (Complex I) resolved its subunit composition, identifying NDUFS7 among the core
      subunits.
    action: ACCEPT
    reason: Direct experimental identification of NDUFS7 as a Complex I subunit by
      immunopurification/MS. Core cellular-component assignment.
    supported_by:
    - reference_id: PMID:12611891
      supporting_text: The subunit composition of the human NADH dehydrogenase obtained
        by rapid one-step immunopurification
- term:
    id: GO:0006120
    label: mitochondrial electron transport, NADH to ubiquinone
  evidence_type: IMP
  original_reference_id: PMID:17275378
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:17275378
      supporting_text: severe complex I defect and a novel mutation in the NDUFS7 gene
        subunit
- term:
    id: GO:0008137
    label: NADH dehydrogenase (ubiquinone) activity
  evidence_type: IMP
  original_reference_id: PMID:17275378
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Experimental support for the core catalytic molecular function; NDUFS7
      is essential for Complex I catalytic activity.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Essential for the catalytic activity of
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27226634
  qualifier: enables
  review:
    summary: Interaction reported in the context of NDUFAF5-mediated hydroxylation
      of NDUFS7 during Complex I assembly (partner Q5TEU4). Bare protein binding is
      uninformative.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:27226634
      supporting_text: NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly
        of Human Complex I
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-163217
  qualifier: located_in
  review:
    summary: The peripheral (IP) arm of Complex I, which contains NDUFS7, protrudes
      into the mitochondrial matrix; NDUFS7 is a matrix-side peripheral membrane protein.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788523
  qualifier: located_in
  review:
    summary: Reactome pathway (NUBPL transfers 4Fe-4S to Complex I subunits) locating
      Complex I assembly intermediates in the matrix.
    action: KEEP_AS_NON_CORE
    reason: Matrix-side localization consistent with the peripheral arm; non-core relative
      to the inner-membrane assignment.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799178
  qualifier: located_in
  review:
    summary: Reactome Complex I biogenesis reaction, locating assembly intermediates
      in the matrix.
    action: KEEP_AS_NON_CORE
    reason: Matrix-side localization consistent with the peripheral arm; non-core relative
      to the inner-membrane assignment.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799179
  qualifier: located_in
  review:
    summary: Reactome Complex I biogenesis reaction, locating assembly intermediates
      in the matrix.
    action: KEEP_AS_NON_CORE
    reason: Matrix-side localization consistent with the peripheral arm; non-core relative
      to the inner-membrane assignment.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799191
  qualifier: located_in
  review:
    summary: Reactome Complex I biogenesis reaction, locating assembly intermediates
      in the matrix.
    action: KEEP_AS_NON_CORE
    reason: Matrix-side localization consistent with the peripheral arm; non-core relative
      to the inner-membrane assignment.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799196
  qualifier: located_in
  review:
    summary: Reactome Complex I biogenesis reaction, locating assembly intermediates
      in the matrix.
    action: KEEP_AS_NON_CORE
    reason: Matrix-side localization consistent with the peripheral arm; non-core relative
      to the inner-membrane assignment.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799197
  qualifier: located_in
  review:
    summary: Reactome Complex I biogenesis reaction, locating assembly intermediates
      in the matrix.
    action: KEEP_AS_NON_CORE
    reason: Matrix-side localization consistent with the peripheral arm; non-core relative
      to the inner-membrane assignment.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799202
  qualifier: located_in
  review:
    summary: Reactome Complex I biogenesis reaction, locating assembly intermediates
      in the matrix.
    action: KEEP_AS_NON_CORE
    reason: Matrix-side localization consistent with the peripheral arm; non-core relative
      to the inner-membrane assignment.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799203
  qualifier: located_in
  review:
    summary: Reactome Complex I biogenesis reaction, locating assembly intermediates
      in the matrix.
    action: KEEP_AS_NON_CORE
    reason: Matrix-side localization consistent with the peripheral arm; non-core relative
      to the inner-membrane assignment.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800868
  qualifier: located_in
  review:
    summary: Reactome Complex I biogenesis reaction (NDUF subunits bind to form the
      IP subcomplex), locating assembly intermediates in the matrix.
    action: KEEP_AS_NON_CORE
    reason: Matrix-side localization consistent with the peripheral (IP) arm that contains
      NDUFS7; non-core relative to the inner-membrane assignment.
    supported_by:
    - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:0032981
    label: mitochondrial respiratory chain complex I assembly
  evidence_type: IMP
  original_reference_id: PMID:11112787
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:11112787
      supporting_text: helps distinguish catalytic versus assembly defects and further
        distinguishes between mutations in different subunits
    - reference_id: PMID:27226634
      supporting_text: This modification occurs early in the pathway of assembly of
        complex
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15186778
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:15186778
      supporting_text: the p75 subunit of complex I of the electron transport chain
- term:
    id: GO:0006120
    label: mitochondrial electron transport, NADH to ubiquinone
  evidence_type: NAS
  original_reference_id: PMID:9878551
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9878551
      supporting_text: Its main function is the transport of electrons from NADH to
        ubiquinone
- term:
    id: GO:0008137
    label: NADH dehydrogenase (ubiquinone) activity
  evidence_type: NAS
  original_reference_id: PMID:9878551
  qualifier: enables
  review:
    summary: Author statement describing Complex I (NADH:ubiquinone oxidoreductase)
      activity, of which NDUFS7 is a core catalytic subunit.
    action: ACCEPT
    reason: Correct core molecular function (duplicate of the IBA/IMP/IEA annotations
      to GO:0008137).
    supported_by:
    - reference_id: PMID:9878551
      supporting_text: Its main function is the transport of electrons from NADH to
        ubiquinone
- term:
    id: GO:0006120
    label: mitochondrial electron transport, NADH to ubiquinone
  evidence_type: NAS
  original_reference_id: PMID:8938450
  qualifier: involved_in
  review:
    summary: Characterization of the PSST (NDUFS7) subunit of human Complex I (NADH:ubiquinone
      oxidoreductase); author statement supporting the NADH-to-ubiquinone electron
      transport process.
    action: ACCEPT
    reason: Correct core biological process for the PSST/NDUFS7 subunit (duplicate
      of other GO:0006120 annotations).
    supported_by:
    - reference_id: PMID:8938450
      supporting_text: 'PSST subunit of human mitochondrial nicotinamide adenine dinucleotide
        (NADH): ubiquinone oxidoreductase'
- term:
    id: GO:0016655
    label: oxidoreductase activity, acting on NAD(P)H, quinone or similar compound
      as acceptor
  evidence_type: NAS
  original_reference_id: PMID:8938450
  qualifier: enables
  review:
    summary: General oxidoreductase class term (parent of NADH:ubiquinone oxidoreductase
      activity) for the PSST/NDUFS7 subunit of Complex I.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:8938450
      supporting_text: 'PSST subunit of human mitochondrial nicotinamide adenine dinucleotide
        (NADH): ubiquinone oxidoreductase'
core_functions:
- description: Core catalytic subunit of mitochondrial respiratory Complex I that binds
    the [4Fe-4S] cluster N2 and catalyzes electron transfer from NADH to ubiquinone.
  supported_by:
  - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
    supporting_text: Core subunit of the mitochondrial membrane respiratory chain
  - reference_id: PMID:27226634
    supporting_text: transfer of two electrons, one at a time, from the terminal electron
      acceptor iron-sulfur cluster N2 to ubiquinone
  molecular_function:
    id: GO:0008137
    label: NADH dehydrogenase (ubiquinone) activity
  directly_involved_in:
  - id: GO:0006120
    label: mitochondrial electron transport, NADH to ubiquinone
  in_complex:
    id: GO:0045271
    label: respiratory chain complex I
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
- description: Binds one [4Fe-4S] iron-sulfur cluster (cluster N2), the terminal electron
    donor to ubiquinone, contributing a genuine redox function to Complex I.
  supported_by:
  - reference_id: file:human/NDUFS7/NDUFS7-uniprot.txt
    supporting_text: Binds 1 [4Fe-4S] cluster
  molecular_function:
    id: GO:0051539
    label: 4 iron, 4 sulfur cluster binding
  directly_involved_in:
  - id: GO:0006120
    label: mitochondrial electron transport, NADH to ubiquinone
  in_complex:
    id: GO:0045271
    label: respiratory chain complex I
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
references:
- id: file:human/NDUFS7/NDUFS7-uniprot.txt
  title: UniProtKB entry O75251 (NDUS7_HUMAN)
  findings: []
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11112787
  title: Human complex I defects can be resolved by monoclonal antibody analysis into
    distinct subunit assembly patterns.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; examines an NDUFS7-defective patient and Complex
      I assembly patterns.
- id: PMID:12611891
  title: The subunit composition of the human NADH dehydrogenase obtained by rapid
    one-step immunopurification.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Immunopurification/MS of human Complex I resolving its subunit composition.
- id: PMID:14749350
  title: Differences in assembly or stability of complex I and other mitochondrial
    OXPHOS complexes in inherited complex I deficiency.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Blue-native analysis of complex I deficiency; supports assembly/activity
      role of nuclear core subunits.
- id: PMID:15186778
  title: Disruption of mitochondrial function during apoptosis is mediated by caspase
    cleavage of the p75 subunit of complex I of the electron transport chain.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Primarily about NDUFS1 (p75) caspase cleavage; cited as an interaction
      partner for the NDUFS7 protein-binding IPI.
- id: PMID:17275378
  title: A novel mutation in the human complex I NDUFS7 subunit associated with Leigh
    syndrome.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Pathogenic NDUFS7 R145H variant causing Complex I deficiency / Leigh
      syndrome; establishes catalytic activity and requirement in electron transport.
- id: PMID:27226634
  title: NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex
    I.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full-text available; documents NDUFS7 hydroxylation by NDUFAF5 in
      early Complex I assembly and describes the N2 cluster electron transfer to ubiquinone.
- id: PMID:28844695
  title: Architecture of Human Mitochondrial Respiratory Megacomplex I(2)III(2)IV(2).
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cryo-EM structure assigning individual human Complex I subunits;
      supports Complex I membership and inner-membrane localization.
- id: PMID:30030361
  title: Assembly of mammalian oxidative phosphorylation complexes I-V and supercomplexes.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Review of OXPHOS assembly; supports aerobic respiration but the ATP-synthesis
      annotation is an over-attribution to a Complex I subunit.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Large-scale Y2H interactome; source of the JPH3 protein-binding IPI,
      not a characterized functional interaction.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: MitoCoP high-confidence mitochondrial proteome; supports mitochondrial
      localization.
- id: PMID:8938450
  title: Assignment of the PSST subunit gene of human mitochondrial complex I to chromosome
    19p13.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Characterizes the PSST (NDUFS7) subunit cDNA and identity as a Complex
      I subunit.
- id: PMID:9878551
  title: 'cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase:
    human complex I cDNA characterization completed.'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Review/characterization of nuclear-encoded Complex I subunits; supports
      the NADH-to-ubiquinone electron transport process.
- id: Reactome:R-HSA-163217
  title: Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2
  findings: []
- id: Reactome:R-HSA-6788523
  title: NUBPL transfers 4Fe-4S to Complex I subunits
  findings: []
- id: Reactome:R-HSA-6799178
  title: Intermediate 1 binds HP subcomplex to form Intermediate 2
  findings: []
- id: Reactome:R-HSA-6799179
  title: Peripheral arm subunits bind the 815kDa complex to form a 980kDa complex
  findings: []
- id: Reactome:R-HSA-6799191
  title: Intermediate 2 binds MT-ND1:NDUFAF5:NDUFAF6 to form a 315kDa subcomplex
  findings: []
- id: Reactome:R-HSA-6799196
  title: The MCIA complex, NDUFAF2-7 all dissociate from the 980kDa complex, resulting
    in Complex I
  findings: []
- id: Reactome:R-HSA-6799197
  title: ND4, ND5 bind the 550kDa complex to form the 815kDa complex
  findings: []
- id: Reactome:R-HSA-6799202
  title: The 315kDa subcomplex binds the 370kDa subcomplex to form the 550kDa complex
  findings: []
- id: Reactome:R-HSA-6799203
  title: IP subcomplex binds NDUFAF3, NDUFAF4, TIMMDC1 to form Intermediate 1
  findings: []
- id: Reactome:R-HSA-6800868
  title: NDUF subunits bind to form the IP subcomplex
  findings: []