id: P48047
gene_symbol: ATP5PO
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ATP5PO encodes the oligomycin sensitivity conferral protein (OSCP), also called
  ATP synthase subunit O, the subunit at the top of the peripheral (stator) stalk of
  the mitochondrial F1Fo ATP synthase (Complex V). Synthesized with an N-terminal
  mitochondrial targeting sequence and imported to the mitochondrial inner membrane,
  OSCP caps the soluble F1 catalytic head and, together with the b, d and F6 subunits,
  forms the stationary peripheral stalk that holds the F1 alpha3beta3 catalytic hexamer
  static against the rotating central stalk. This stator function is essential for
  coupling proton flow through the membrane Fo domain to ATP synthesis in F1 and confers
  the complex's sensitivity to the inhibitor oligomycin. OSCP is a structural,
  non-catalytic subunit; its ATP hydrolase activity is only observed as an artificial
  in vitro reverse reaction of the whole complex. Loss-of-function variants cause
  mitochondrial complex V deficiency, and OSCP is implicated in permeability transition
  pore regulation through its interaction with cyclophilin D.
existing_annotations:
- term:
    id: GO:0005198
    label: structural molecule activity
  evidence_type: IDA
  original_reference_id: PMID:7490082
  qualifier: enables
  review:
    summary: >-
      OSCP is a non-catalytic structural subunit of the ATP synthase peripheral (stator)
      stalk; its molecular function is structural molecule activity, contributing to the
      structural integrity of Complex V. This term is not currently in GOA and is proposed
      here as the correct subunit-level molecular function for OSCP.
    action: NEW
    reason: >-
      The existing GOA molecular-function annotations for OSCP are either the catalytic
      rotational ATP synthase activity (which OSCP contributes_to but does not enable) or
      uninformative protein binding. OSCP's own molecular function is structural: it holds
      the F1 catalytic head static against the rotor. Structural molecule activity
      (GO:0005198) captures this correctly and is used as the core molecular function.
    supported_by:
    - reference_id: PMID:7490082
      supporting_text: >-
        This ATP5O subunit is a key structural component of the stalk of the mitochondrial
        respiratory chain
    - reference_id: file:human/ATP5PO/ATP5PO-uniprot.txt
      supporting_text: >-
        a stationary peripheral stalk (subunits F6, b, d, and
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetically inferred mitochondrial localization. OSCP is a subunit of the
      inner-membrane ATP synthase, so mitochondrial localization is correct, though the
      more specific mitochondrial inner membrane term is preferable.
    action: ACCEPT
    reason: >-
      OSCP is an established subunit of the mitochondrial F1Fo ATP synthase, confirmed by
      immunocapture and cryo-EM structure of the complex. Mitochondrion is correct but
      general; the inner-membrane annotations capture the precise location.
    supported_by:
    - reference_id: PMID:12110673
      supporting_text: >-
        The immunoprecipitated F(1)F(0) contained a full complement of
    - reference_id: PMID:37244256
      supporting_text: >-
        Biological energy currency ATP is produced by F1Fo-ATP synthase
- term:
    id: GO:0046933
    label: proton-transporting ATP synthase activity, rotational mechanism
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: contributes_to
  review:
    summary: >-
      OSCP contributes to the rotational ATP synthase molecular function as a structural
      (stator) subunit of the catalytic complex, without itself being catalytic. The
      contributes_to qualifier is the correct usage for a non-catalytic subunit of a
      complex that carries the activity.
    action: ACCEPT
    reason: >-
      OSCP is part of the peripheral stalk that holds the catalytic F1 head static against
      the rotor, so it contributes to (does not enable) the rotary ATP synthase activity.
      The contributes_to qualifier appropriately reflects that OSCP is a required
      structural component of the complex bearing this activity rather than the catalytic
      subunit itself.
    supported_by:
    - reference_id: file:human/ATP5PO/ATP5PO-uniprot.txt
      supporting_text: >-
        a stationary peripheral stalk (subunits F6, b, d, and
    - reference_id: PMID:12110673
      supporting_text: >-
        The captured complex V displayed ATP hydrolysis activity that was
- term:
    id: GO:0042776
    label: proton motive force-driven mitochondrial ATP synthesis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      OSCP is involved in proton motive force-driven mitochondrial ATP synthesis as an
      essential structural subunit of Complex V. This is the core biological process for
      the gene.
    action: ACCEPT
    reason: >-
      As the stator-stalk subunit coupling proton flow to F1 catalysis, OSCP is required
      for mitochondrial ATP synthesis. Knockdown/loss functionally impairs the complex,
      and OSCP is the target through which the F1Fo-ATPase inhibitor Bz-423 acts.
    supported_by:
    - reference_id: PMID:15850986
      supporting_text: >-
        reconstitution experiments demonstrated that inhibition was mediated by the
    - reference_id: file:human/ATP5PO/ATP5PO-uniprot.txt
      supporting_text: >-
        complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      UniProt SubCell mapping of mitochondrial localization. Correct but general.
    action: ACCEPT
    reason: >-
      Consistent with all experimental localization evidence placing OSCP in the
      mitochondrion (inner membrane); the general mitochondrion term is acceptable.
    supported_by:
    - reference_id: file:human/ATP5PO/ATP5PO-uniprot.txt
      supporting_text: >-
        Subunit OSCP, of the mitochondrial membrane ATP synthase
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      UniProt SubCell mapping to the mitochondrial inner membrane, the anatomical location
      of the ATP synthase complex. This is the precise, correct location for OSCP.
    action: ACCEPT
    reason: >-
      The F1Fo ATP synthase is embedded in the mitochondrial inner membrane, with OSCP
      capping the F1 head on the matrix side of the peripheral stalk. Corroborated by
      Reactome TAS and ComplexPortal annotations.
    supported_by:
    - reference_id: PMID:26297831
      supporting_text: >-
        the stator casings fixed with the peripheral stator stalk
- term:
    id: GO:0015986
    label: proton motive force-driven ATP synthesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      InterPro2GO mapping to proton motive force-driven ATP synthesis, the parent of the
      mitochondrion-specific term. Correct for OSCP as an ATP synthase subunit.
    action: ACCEPT
    reason: >-
      Broadly correct; the more specific GO:0042776 (mitochondrial) is also annotated and
      is the preferred core term, but this general parent is not wrong.
    supported_by:
    - reference_id: file:human/ATP5PO/ATP5PO-uniprot.txt
      supporting_text: >-
        complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: >-
      InterPro2GO generic membrane localization. Not wrong but uninformative given the
      specific mitochondrial inner membrane annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The generic 'membrane' term adds no information beyond the specific mitochondrial
      inner membrane annotations already present and should be treated as an
      over-annotation.
    supported_by:
    - reference_id: file:human/ATP5PO/ATP5PO-uniprot.txt
      supporting_text: >-
        a stationary peripheral stalk (subunits F6, b, d, and
- term:
    id: GO:0046933
    label: proton-transporting ATP synthase activity, rotational mechanism
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO annotation asserting OSCP enables the rotational ATP synthase activity.
      OSCP is a non-catalytic structural subunit and does not itself enable this catalytic
      molecular function; the contributes_to formulation (also annotated) is the correct
      one, so the 'enables' assertion over-annotates the subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      OSCP does not catalyze ATP synthesis; it is a stator-stalk structural subunit. The
      'enables' qualifier for the rotary catalytic MF over-assigns catalytic activity to a
      structural subunit. The activity is better represented by the contributes_to
      annotations to the same term, and OSCP's own molecular function is structural
      molecule activity (captured in core_functions).
    supported_by:
    - reference_id: PMID:7490082
      supporting_text: >-
        This ATP5O subunit is a key structural component of the stalk of the mitochondrial
        respiratory chain
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21516116
  qualifier: enables
  review:
    summary: >-
      Bare 'protein binding' from a high-throughput interactome dataset (interactor PNMA1).
      Uninformative molecular function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Per curation guidelines, bare protein binding tells us nothing about OSCP's actual
      function. The interaction is from a large-scale screen with no specific functional
      interpretation; not removed per policy, but flagged as uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: >-
      Bare 'protein binding' from a proteome-scale binary interactome map (multiple
      interactors). Uninformative molecular function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Large-scale interactome mapping yields a generic protein-binding annotation without
      functional specificity; retained per policy but flagged as uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27499296
  qualifier: enables
  review:
    summary: >-
      Bare 'protein binding' from a mitochondrial protein interaction map (interactor
      ATP5F1A/subunit alpha). The alpha-subunit interaction is biologically meaningful
      (OSCP caps the F1 alpha3beta3 head), but the annotation term itself is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction with the F1 alpha subunit is consistent with OSCP's structural role,
      but 'protein binding' conveys no functional information. Retained per policy, flagged
      as uninformative; the structural role is captured by the core annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30021884
  qualifier: enables
  review:
    summary: >-
      Bare 'protein binding' from crosslinking mass spectrometry (interactor ATP5F1A).
      Uninformative molecular function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding annotation without functional specificity; retained per
      policy but flagged as uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30266287
  qualifier: enables
  review:
    summary: >-
      'Protein binding' capturing the OSCP interaction with cyclophilin D (PPID) and with
      amyloid-beta (APP). This interaction is functionally meaningful, linking OSCP to
      permeability transition pore regulation and to F1Fo ATP synthase dysfunction in
      Alzheimer's disease, but the bare GO term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The cyclophilin D / amyloid-beta interactions are biologically important but the
      annotation term 'protein binding' does not convey this. Retained per policy and
      flagged; the functional significance is documented rather than represented by a core
      molecular function.
    supported_by:
    - reference_id: PMID:30266287
      supporting_text: >-
        increased physical interaction of OSCP with Cyclophilin D (CypD) in AD cases
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Bare 'protein binding' from a reference binary interactome map. Uninformative
      molecular function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding annotation without functional specificity; retained per
      policy but flagged as uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: >-
      'Protein binding' capturing the OSCP-huntingtin (HTT) interaction from a
      neurodegenerative-disease interactome. Uninformative molecular function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein-binding annotation; the disease-interactome context does not confer
      a specific molecular function for OSCP. Retained per policy but flagged as
      uninformative.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: >-
      Orthology-transferred (rat) cell-surface localization, consistent with reports of an
      ecto-ATP synthase surface pool. This is a minor, non-canonical localization for a
      protein whose core function is at the mitochondrial inner membrane.
    action: KEEP_AS_NON_CORE
    reason: >-
      A surface (ecto-ATP synthase) pool of OSCP has been reported, but this is a minor,
      non-core localization relative to the bulk mitochondrial-inner-membrane population.
    supported_by:
    - reference_id: PMID:17851741
      supporting_text: >-
        associated to the plasma membrane
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: contributes_to
  review:
    summary: >-
      Orthology-transferred (rat) ATP hydrolysis activity. The intact F1Fo complex can
      hydrolyze ATP as an artificial in vitro reverse reaction, but in vivo OSCP/Complex V
      only synthesizes ATP; this is not a physiological function of OSCP.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      UniProt states the complex in vivo can only synthesize ATP although its ATP hydrolase
      activity can be activated artificially in vitro. Assigning ATP hydrolysis activity to
      OSCP over-represents a non-physiological reverse reaction of the whole complex; OSCP
      itself is non-catalytic.
    supported_by:
    - reference_id: PMID:12110673
      supporting_text: >-
        The captured complex V displayed ATP hydrolysis activity that was
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: >-
      Orthology-transferred protein-containing complex binding. OSCP is an integral subunit
      of the ATP synthase complex rather than a factor that binds a complex from outside;
      the part_of complex annotation captures this more accurately.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      OSCP is a constitutive structural subunit of Complex V, so 'complex binding' is a
      weak, generic descriptor that is better represented by its part_of proton-transporting
      ATP synthase complex membership.
- term:
    id: GO:0045259
    label: proton-transporting ATP synthase complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: >-
      OSCP is a bona fide structural subunit of the proton-transporting ATP synthase
      complex. This is a core cellular-component annotation.
    action: ACCEPT
    reason: >-
      Membership confirmed by immunocapture of the complete complex and by the cryo-EM
      structure, in which OSCP (chain O) is resolved within the peripheral stalk.
    supported_by:
    - reference_id: file:human/ATP5PO/ATP5PO-uniprot.txt
      supporting_text: >-
        a stationary peripheral stalk (subunits F6, b, d, and
- term:
    id: GO:0071320
    label: cellular response to cAMP
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred (rat) response-to-cAMP process. Not a core, gene-specific
      function of a structural ATP synthase subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This process annotation was transferred from a rat ortholog and does not reflect a
      characterized OSCP-specific role; it over-annotates the gene's function.
- term:
    id: GO:0071345
    label: cellular response to cytokine stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-transferred (rat) response-to-cytokine process. Not a core, gene-specific
      function of a structural ATP synthase subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Transferred from a rat ortholog with no OSCP-specific mechanistic basis; over-annotates
      the gene relative to its established structural role in Complex V.
- term:
    id: GO:1903924
    label: estradiol binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: >-
      Orthology-transferred (rat) estradiol-binding molecular function. There is no
      established estradiol-binding role for human OSCP as a structural stator subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This molecular function was transferred by Ensembl Compara from a rat ortholog and is
      not supported by any characterization of human OSCP function; it over-annotates the
      gene.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: NAS
  original_reference_id: PMID:26297831
  qualifier: located_in
  review:
    summary: >-
      ComplexPortal-curated mitochondrial inner membrane localization for the ATP synthase
      complex. Correct core location for OSCP.
    action: ACCEPT
    reason: >-
      The ATP synthase holocomplex assembles in the mitochondrial inner membrane; OSCP is
      part of the peripheral (stator) stalk of that complex.
    supported_by:
    - reference_id: PMID:26297831
      supporting_text: >-
        the stator casings fixed with the peripheral stator stalk
- term:
    id: GO:0015986
    label: proton motive force-driven ATP synthesis
  evidence_type: NAS
  original_reference_id: PMID:26297831
  qualifier: involved_in
  review:
    summary: >-
      ComplexPortal-curated involvement of the ATP synthase complex in proton motive
      force-driven ATP synthesis. Correct for OSCP as a subunit.
    action: ACCEPT
    reason: >-
      OSCP is a required structural subunit of the complex that carries out proton motive
      force-driven ATP synthesis.
    supported_by:
    - reference_id: PMID:26297831
      supporting_text: >-
        Mitochondrial ATP synthase is a motor enzyme in which a central shaft rotates in
- term:
    id: GO:0045259
    label: proton-transporting ATP synthase complex
  evidence_type: NAS
  original_reference_id: PMID:26297831
  qualifier: part_of
  review:
    summary: >-
      ComplexPortal-curated membership of OSCP in the proton-transporting ATP synthase
      complex. Core cellular-component annotation.
    action: ACCEPT
    reason: >-
      OSCP is a stator-stalk subunit of the assembled ATP synthase complex; complex
      assembly studies place it in the stator (b-e-g / peripheral stalk) machinery.
    supported_by:
    - reference_id: PMID:26297831
      supporting_text: >-
        the stator casings fixed with the peripheral stator stalk
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: >-
      High-throughput mitochondrial-proteome localization. Consistent with OSCP being a
      mitochondrial protein; general term.
    action: ACCEPT
    reason: >-
      OSCP is robustly detected in the high-confidence human mitochondrial proteome,
      consistent with all other localization evidence.
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: >-
        Quantitative high-confidence human mitochondrial proteome and its dynamics
- term:
    id: GO:0045259
    label: proton-transporting ATP synthase complex
  evidence_type: IDA
  original_reference_id: PMID:12110673
  qualifier: part_of
  review:
    summary: >-
      Direct experimental demonstration that OSCP is a subunit of immunocaptured human
      F1Fo ATP synthase. Core cellular-component annotation.
    action: ACCEPT
    reason: >-
      Immunocapture of the intact complex identified OSCP among the subunits by specific
      antibodies and mass spectrometry, directly establishing complex membership.
    supported_by:
    - reference_id: PMID:12110673
      supporting_text: >-
        subunits that were identified with specific antibodies against five of the
- term:
    id: GO:0046933
    label: proton-transporting ATP synthase activity, rotational mechanism
  evidence_type: IDA
  original_reference_id: PMID:12110673
  qualifier: contributes_to
  review:
    summary: >-
      OSCP contributes to the rotational ATP synthase activity of the immunocaptured
      complex, which displayed oligomycin-sensitive activity. Correct contributes_to usage
      for a structural subunit.
    action: ACCEPT
    reason: >-
      The captured complex containing OSCP showed oligomycin-sensitive ATP synthase/hydrolase
      activity, and OSCP confers this oligomycin sensitivity; contributes_to appropriately
      reflects the non-catalytic structural contribution.
    supported_by:
    - reference_id: PMID:12110673
      supporting_text: >-
        fully oligomycin and inhibitor protein IF(1)-sensitive
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-164832
  qualifier: located_in
  review:
    summary: >-
      Reactome-asserted inner-membrane localization (ATPase synthesizes ATP reaction).
      Correct core location.
    action: ACCEPT
    reason: >-
      Reactome places OSCP with the ATP synthase in the mitochondrial inner membrane,
      consistent with structural and curated evidence.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-164834
  qualifier: located_in
  review:
    summary: >-
      Reactome-asserted inner-membrane localization (enzyme-bound ATP release reaction).
      Correct core location.
    action: ACCEPT
    reason: >-
      Consistent with OSCP's location in the inner-membrane ATP synthase complex.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-164840
  qualifier: located_in
  review:
    summary: >-
      Reactome-asserted inner-membrane localization (ADP and Pi binding reaction). Correct
      core location.
    action: ACCEPT
    reason: >-
      Consistent with OSCP's location in the inner-membrane ATP synthase complex.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8949580
  qualifier: located_in
  review:
    summary: >-
      Reactome-asserted inner-membrane localization (F1Fo ATP synthase dimerization).
      Correct core location.
    action: ACCEPT
    reason: >-
      Consistent with OSCP's location in the inner-membrane ATP synthase complex.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9837978
  qualifier: located_in
  review:
    summary: >-
      Reactome-asserted inner-membrane localization (LONP1 binds inner-membrane proteins).
      Correct core location.
    action: ACCEPT
    reason: >-
      Consistent with OSCP's location in the mitochondrial inner membrane.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9838004
  qualifier: located_in
  review:
    summary: >-
      Reactome-asserted inner-membrane localization (LONP1 degrades inner-membrane
      proteins). Correct core location.
    action: ACCEPT
    reason: >-
      Consistent with OSCP's location in the mitochondrial inner membrane.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:15850986
  qualifier: located_in
  review:
    summary: >-
      Direct experimental mitochondrial localization from the study identifying OSCP as the
      target of the F1Fo-ATPase inhibitor Bz-423. General but correct.
    action: ACCEPT
    reason: >-
      OSCP was studied as a mitochondrial F1Fo-ATPase component; mitochondrial localization
      is well supported.
    supported_by:
    - reference_id: PMID:15850986
      supporting_text: >-
        sensitivity conferring protein (OSCP) component of the mitochondrial
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  qualifier: located_in
  review:
    summary: >-
      Nuclear localization from a sperm-nucleus proteomics dataset. Almost certainly a
      mitochondrial-contaminant detection rather than a genuine nuclear function of a
      structural ATP synthase subunit.
    action: KEEP_AS_NON_CORE
    reason: >-
      High-throughput sperm-nucleus proteomics can detect abundant mitochondrial proteins
      as contaminants; there is no functional evidence for a nuclear role of OSCP. Kept as
      non-core rather than removed, but not part of the core function.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HDA
  original_reference_id: PMID:20833797
  qualifier: located_in
  review:
    summary: >-
      Mitochondrial localization from a phosphoproteome analysis of isolated human muscle
      mitochondria. Correct general localization.
    action: ACCEPT
    reason: >-
      OSCP was identified in purified functional mitochondria, consistent with its role as
      an inner-membrane ATP synthase subunit.
- term:
    id: GO:0006754
    label: ATP biosynthetic process
  evidence_type: NAS
  original_reference_id: PMID:17851741
  qualifier: involved_in
  review:
    summary: >-
      Author statement that OSCP is part of the ATP-synthesizing F0F1-ATP synthase. Correct
      but represented more specifically by proton motive force-driven mitochondrial ATP
      synthesis.
    action: ACCEPT
    reason: >-
      ATP biosynthetic process is a correct parent process; the more specific GO:0042776 is
      the preferred core term, but this broader annotation is not wrong.
    supported_by:
    - reference_id: PMID:17851741
      supporting_text: >-
        OSCP and beta subunits of F(0)F(1)ATPsynthase in HepG2 cells
- term:
    id: GO:0042776
    label: proton motive force-driven mitochondrial ATP synthesis
  evidence_type: IMP
  original_reference_id: PMID:15850986
  qualifier: involved_in
  review:
    summary: >-
      Mutational/functional evidence (RNAi knockdown of OSCP altering cellular sensitivity
      to the OSCP-targeted F1Fo-ATPase inhibitor Bz-423) supporting OSCP involvement in
      mitochondrial ATP synthesis. This is a core biological process annotation.
    action: ACCEPT
    reason: >-
      OSCP is directly implicated in F1Fo-ATPase function by the identification of OSCP as
      the Bz-423 target and by RNAi knockdown experiments, supporting its involvement in
      proton motive force-driven mitochondrial ATP synthesis.
    supported_by:
    - reference_id: PMID:15850986
      supporting_text: >-
        expression using RNA interference and studying the sensitivity of these cells to
- term:
    id: GO:0045259
    label: proton-transporting ATP synthase complex
  evidence_type: NAS
  original_reference_id: PMID:7490082
  qualifier: part_of
  review:
    summary: >-
      Author statement (cDNA cloning paper) that ATP5O/OSCP is a key structural component
      of the ATP synthase stalk. Core cellular-component annotation.
    action: ACCEPT
    reason: >-
      The cloning paper explicitly describes ATP5O as a key structural component of the
      stalk of the mitochondrial F1F0-ATP synthase, directly supporting complex membership.
    supported_by:
    - reference_id: PMID:7490082
      supporting_text: >-
        This ATP5O subunit is a key structural component of the stalk of the mitochondrial
        respiratory chain
- term:
    id: GO:1902600
    label: proton transmembrane transport
  evidence_type: NAS
  original_reference_id: PMID:17851741
  qualifier: involved_in
  review:
    summary: >-
      Involvement in proton transmembrane transport as part of the F0F1-ATP synthase, which
      couples proton flux to ATP synthesis. Reasonable for OSCP as a subunit, though OSCP
      itself is in the peripheral stalk rather than the proton channel.
    action: ACCEPT
    reason: >-
      The ATP synthase complex couples proton translocation across the inner membrane to
      ATP synthesis; OSCP is a required structural subunit of this proton-transporting
      complex. The annotation is appropriate at the complex level.
    supported_by:
    - reference_id: PMID:17851741
      supporting_text: >-
        OSCP and beta subunits of F(0)F(1)ATPsynthase in HepG2 cells
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:12110673
  qualifier: located_in
  review:
    summary: >-
      Direct mitochondrial localization from immunocapture of human F1Fo ATP synthase from
      heart and fibroblasts. General but correct.
    action: ACCEPT
    reason: >-
      OSCP was co-purified with the intact mitochondrial ATP synthase complex, confirming
      mitochondrial localization.
    supported_by:
    - reference_id: PMID:12110673
      supporting_text: >-
        The immunoprecipitated F(1)F(0) contained a full complement of
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:17851741
  qualifier: located_in
  review:
    summary: >-
      Direct mitochondrial localization of OSCP in HepG2 cells. General but correct.
    action: ACCEPT
    reason: >-
      OSCP is detected in mitochondria as an F0F1-ATP synthase subunit; the bulk pool is
      mitochondrial.
    supported_by:
    - reference_id: PMID:17851741
      supporting_text: >-
        OSCP and beta subunits of F(0)F(1)ATPsynthase in HepG2 cells
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:17851741
  qualifier: located_in
  review:
    summary: >-
      Plasma-membrane detection of OSCP as part of an ecto-F0F1-ATP synthase pool on HepG2
      hepatocytes. A genuine but minor, non-canonical surface localization distinct from the
      core mitochondrial-inner-membrane role.
    action: KEEP_AS_NON_CORE
    reason: >-
      The study reports OSCP associated with the plasma membrane as part of the reported
      cell-surface (ecto) ATP synthase; this is a minor surface pool and not the core
      inner-membrane function of OSCP.
    supported_by:
    - reference_id: PMID:17851741
      supporting_text: >-
        associated to the plasma membrane
core_functions:
- description: >-
    Structural (stator) subunit of the mitochondrial F1Fo ATP synthase peripheral stalk:
    OSCP caps the F1 catalytic head and, with the b, d and F6 subunits, holds the
    alpha3beta3 hexamer static against the rotating central stalk, coupling proton flow
    through Fo to ATP synthesis and conferring oligomycin sensitivity.
  molecular_function:
    id: GO:0005198
    label: structural molecule activity
  directly_involved_in:
  - id: GO:0042776
    label: proton motive force-driven mitochondrial ATP synthesis
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  in_complex:
    id: GO:0045259
    label: proton-transporting ATP synthase complex
  supported_by:
  - reference_id: PMID:7490082
    supporting_text: >-
      This ATP5O subunit is a key structural component of the stalk of the mitochondrial
      respiratory chain
  - reference_id: file:human/ATP5PO/ATP5PO-uniprot.txt
    supporting_text: >-
      a stationary peripheral stalk (subunits F6, b, d, and
proposed_new_terms: []
suggested_questions:
- question: >-
    Beyond its structural stator role, does OSCP acetylation at Lys-162 (regulated by
    SIRT3) or its interaction with cyclophilin D directly modulate ATP synthase output or
    permeability transition pore opening in vivo?
suggested_experiments:
- description: >-
    Structure-guided mutagenesis of the OSCP F1-binding interface to quantify effects on
    coupling efficiency and oligomycin sensitivity in reconstituted human ATP synthase.
- description: >-
    Test whether the reported cell-surface (ecto) pool of OSCP reflects a genuine
    plasma-membrane targeting mechanism or mitochondrial contamination, using surface
    biotinylation combined with strict mitochondrial-contamination controls.
references:
- 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:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  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: file:human/ATP5PO/ATP5PO-uniprot.txt
  title: UniProtKB entry P48047 (ATPO_HUMAN), ATP synthase peripheral stalk subunit OSCP
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      UniProt curated record establishing OSCP as the peripheral (stator) stalk subunit of
      Complex V; FUNCTION and SUBUNIT sections quoted verbatim.
- id: PMID:12110673
  title: A functionally active human F1F0 ATPase can be purified by immunocapture
    from heart tissue and fibroblast cell lines. Subunit structure and activity studies.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Immunocapture of intact human F1Fo ATP synthase; OSCP identified as a subunit;
      complex showed oligomycin-sensitive activity.
- id: PMID:15850986
  title: Identification and validation of the mitochondrial F1F0-ATPase as the molecular
    target of the immunomodulatory benzodiazepine Bz-423.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Identifies OSCP as the direct binding target of the F1Fo-ATPase inhibitor Bz-423 and
      uses OSCP RNAi; functionally anchors OSCP to ATP synthase activity.
- id: PMID:17851741
  title: IF(1) distribution in HepG2 cells in relation to ecto-F(0)F (1)ATPsynthase
    and calmodulin.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reports OSCP in mitochondria and in a plasma-membrane (ecto-ATP synthase) pool;
      supports the non-core surface localization.
- id: PMID:20833797
  title: Phosphoproteome analysis of functional mitochondria isolated from resting
    human muscle reveals extensive phosphorylation of inner membrane protein complexes
    and enzymes.
  findings: []
- id: PMID:21516116
  title: Next-generation sequencing to generate interactome datasets.
  findings: []
- id: PMID:21630459
  title: Proteomic characterization of the human sperm nucleus.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Sperm-nucleus proteomics; nuclear detection of OSCP most likely reflects
      mitochondrial contamination.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:26297831
  title: Assembly of human mitochondrial ATP synthase through two separate intermediates,
    F1-c-ring and b-e-g complex.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      ComplexPortal source; describes ATP synthase as a motor enzyme with a peripheral
      stator stalk, of which OSCP is a component.
- id: PMID:27499296
  title: Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory
    Chain Function.
  findings: []
- id: PMID:30021884
  title: Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry
    in Intact Cell Nuclei.
  findings: []
- id: PMID:30266287
  title: Cyclophilin D deficiency attenuates mitochondrial F1Fo ATP synthase dysfunction
    via OSCP in Alzheimer's disease.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Documents the OSCP-cyclophilin D interaction linking OSCP to F1Fo ATP synthase
      dysfunction and permeability transition in Alzheimer's disease.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- 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: >-
      High-confidence human mitochondrial proteome; supports mitochondrial localization of
      OSCP.
- id: PMID:37244256
  title: Structure of the human ATP synthase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Cryo-EM structure of human ATP synthase resolving OSCP (chain O, residues 24-213)
      within the peripheral stalk; primary structural evidence for OSCP function and
      complex membership.
- id: PMID:34954817
  title: Variants in Mitochondrial ATP Synthase Cause Variable Neurologic Phenotypes.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reports biallelic ATP5PO variants causing mitochondrial complex V deficiency nuclear
      type 7 (MC5DN7); establishes an essential in-vivo role for OSCP in Complex V (from
      UniProt DISEASE annotation; full text not cached).
- id: PMID:7490082
  title: Cloning of the cDNA for the human ATP synthase OSCP subunit (ATP5O) by exon
    trapping and mapping to chromosome 21q22.1-q22.2.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Original cloning of human ATP5O/OSCP; explicitly describes it as a key structural
      component of the ATP synthase stalk.
- id: Reactome:R-HSA-164832
  title: ATPase synthesizes ATP
  findings: []
- id: Reactome:R-HSA-164834
  title: Enzyme-bound ATP is released
  findings: []
- id: Reactome:R-HSA-164840
  title: ADP and Pi bind to ATPase
  findings: []
- id: Reactome:R-HSA-8949580
  title: F1Fo ATP synthase dimerizes
  findings: []
- id: Reactome:R-HSA-9837978
  title: LONP1 binds mitochondrial inner membrane proteins
  findings: []
- id: Reactome:R-HSA-9838004
  title: LONP1 degrades mitochondrial inner membrane proteins
  findings: []