id: O14949
gene_symbol: UQCRQ
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  UQCRQ (cytochrome b-c1 complex subunit 8, also called complex III subunit VIII,
  ubiquinol-cytochrome c reductase complex ubiquinone-binding protein QP-C, or QCR8)
  is a small (82 aa) non-catalytic structural subunit of mitochondrial respiratory
  Complex III (ubiquinol-cytochrome c oxidoreductase / cytochrome b-c1 complex),
  one of the six low-molecular-weight subunits of the 11-subunit enzyme. Complex III
  is an obligate dimer embedded in the mitochondrial inner membrane that catalyzes
  electron transfer from ubiquinol to cytochrome c, coupling this redox reaction to
  proton translocation across the inner membrane (the protonmotive Q cycle) as part
  of the oxidative-phosphorylation electron transport chain. The catalytic redox
  centres reside in cytochrome b, the Rieske iron-sulfur protein (UQCRFS1) and
  cytochrome c1; UQCRQ itself is non-catalytic and was historically identified as the
  ubiquinone-binding protein QP-C, contributing to the ubiquinone-binding environment
  and to complex integrity/assembly. It is a single-pass inner-membrane protein
  (matrix N-terminus, one transmembrane helix, intermembrane-space C-terminus). A
  homozygous Ser45->Phe missense variant causes mitochondrial complex III deficiency,
  nuclear type 4 (MC3DN4), a severe neurological disorder with mitochondrial
  encephalopathy, psychomotor retardation, ataxia and failure to thrive.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  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: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 of the human respiratory megacomplex I2III2IV2 (PDB 5XTE/5XTH/5XTI); places UQCRQ as a subunit within the CIII dimer and underpins its inner-membrane topology features. Cached entry is abstract-only."
- 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-throughput MitoCoP proteomics; supports mitochondrial localization of UQCRQ as a member of the >1,100-protein high-confidence mitochondrial proteome (not a UQCRQ-specific functional study)."
- id: Reactome:R-HSA-164651
  title: Electron transfer from ubiquinol to cytochrome c of complex III
  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: []
- id: Reactome:R-HSA-9906017
  title: Unknown peptidase cleaves UQCRFS1 subunit
  findings: []
- id: Reactome:R-HSA-9906042
  title: TTC19 clears UQCRFS1 fragments from Complex III
  findings: []
- id: file:human/UQCRQ/UQCRQ-uniprot.txt
  title: UniProtKB O14949 (QCR8_HUMAN) Cytochrome b-c1 complex subunit 8
  findings: []
existing_annotations:
- term:
    id: GO:0045275
    label: respiratory chain complex III
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      UQCRQ is a bona fide structural subunit of respiratory chain complex III.
      Phylogenetically-inferred (IBA) complex membership is fully consistent with
      UniProt, ComplexPortal (CPX-560) and cryo-EM structural data, and represents a
      core cellular-component annotation.
    action: ACCEPT
    reason: >-
      UQCRQ/QCR8 is one of the six low-molecular-weight subunits of the 11-subunit
      cytochrome b-c1 complex; membership is conserved across eukaryotes, so the IBA
      call is well-founded.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8,"
- term:
    id: GO:0006122
    label: mitochondrial electron transport, ubiquinol to cytochrome c
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      As a subunit of Complex III, UQCRQ participates in mitochondrial electron
      transport from ubiquinol to cytochrome c. This is the core biological process
      of the complex and the appropriate BP term; the IBA inference is well supported.
    action: ACCEPT
    reason: >-
      Complex III catalyzes electron transfer from ubiquinol to cytochrome c; UQCRQ is
      an integral structural subunit contributing to this process. Correct level of
      specificity for the gene's core role.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "The cytochrome b-c1 complex catalyzes electron"
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: >-
      Electronic annotation to the mitochondrial inner membrane, consistent with
      UniProt subcellular location and the protein's single transmembrane helix.
      Correct core localization.
    action: ACCEPT
    reason: >-
      UQCRQ is an integral single-pass protein of the mitochondrial inner membrane;
      the IEA localization agrees with experimental (IDA/ISS/TAS) evidence in the same
      GOA and with UniProt.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Mitochondrion inner membrane"
- term:
    id: GO:0006122
    label: mitochondrial electron transport, ubiquinol to cytochrome c
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      InterPro2GO electronic annotation mapping the UcrQ/cytochrome b-c1 subunit 8
      domain (IPR004205/IPR036642) to the ubiquinol-to-cytochrome-c electron transport
      process. Consistent with the manually curated and IBA annotations.
    action: ACCEPT
    reason: >-
      The domain-to-process mapping correctly captures the core process of the complex
      that this subunit belongs to; duplicates the IBA/NAS BP call at the right level.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "The cytochrome b-c1 complex catalyzes electron"
- term:
    id: GO:0045275
    label: respiratory chain complex III
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: >-
      Electronic complex-membership annotation, redundant with the IBA and IPI
      annotations to the same term. Correct core cellular-component annotation.
    action: ACCEPT
    reason: >-
      Consistent with all other lines of evidence for UQCRQ as a Complex III subunit.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8,"
- term:
    id: GO:0021539
    label: subthalamus development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic Ensembl-Compara transfer from a mouse ortholog annotation
      (ECO:0000265), reflecting the ortholog's developmental expression/phenotype
      rather than a UQCRQ-specific developmental function. UQCRQ is a ubiquitously
      required housekeeping respiratory-chain subunit; specific brain-region
      development is not its core evolved function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is an over-annotation: the gene is broadly required for oxidative
      phosphorylation and its loss (MC3DN4) has neurological consequences, but that
      does not make discrete subthalamus development a molecular function of UQCRQ.
      The BP is better captured by mitochondrial electron transport / cellular
      respiration. Not removed because the annotation stems from a phenotype-based
      ortholog transfer rather than a demonstrably wrong domain mapping.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Component of the ubiquinol-cytochrome c oxidoreductase, a"
- term:
    id: GO:0021548
    label: pons development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic Ensembl-Compara ortholog transfer (ECO:0000265) capturing the mouse
      ortholog's developmental expression/phenotype, not a UQCRQ-specific pons
      development function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Over-annotation of a housekeeping respiratory subunit; core role is oxidative
      phosphorylation electron transport, not region-specific hindbrain development.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Component of the ubiquinol-cytochrome c oxidoreductase, a"
- term:
    id: GO:0021680
    label: cerebellar Purkinje cell layer development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic Ensembl-Compara ortholog transfer (ECO:0000265); reflects ortholog
      developmental expression/phenotype rather than a UQCRQ-specific function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Over-annotation; UQCRQ's core evolved function is as a structural subunit of
      Complex III in mitochondrial electron transport, not Purkinje cell layer
      development.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Component of the ubiquinol-cytochrome c oxidoreductase, a"
- term:
    id: GO:0021766
    label: hippocampus development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic Ensembl-Compara ortholog transfer (ECO:0000265) reflecting ortholog
      developmental expression/phenotype, not a UQCRQ-specific hippocampus development
      function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Over-annotation of a ubiquitous respiratory subunit; core BP is electron
      transport / cellular respiration.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Component of the ubiquinol-cytochrome c oxidoreductase, a"
- term:
    id: GO:0021794
    label: thalamus development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic Ensembl-Compara ortholog transfer (ECO:0000265); captures the mouse
      ortholog's developmental expression/phenotype rather than a UQCRQ-specific
      thalamus development function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Over-annotation; the gene's core function is Complex III-mediated electron
      transport, not region-specific brain development.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Component of the ubiquinol-cytochrome c oxidoreductase, a"
- term:
    id: GO:0021854
    label: hypothalamus development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic Ensembl-Compara ortholog transfer (ECO:0000265) reflecting ortholog
      developmental expression/phenotype, not a UQCRQ-specific hypothalamus
      development function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Over-annotation of a housekeeping respiratory-chain subunit; core BP is
      mitochondrial electron transport / cellular respiration.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Component of the ubiquinol-cytochrome c oxidoreductase, a"
- term:
    id: GO:0021860
    label: pyramidal neuron development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic Ensembl-Compara ortholog transfer (ECO:0000265); reflects ortholog
      developmental expression/phenotype rather than a UQCRQ-specific neuronal
      development function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Over-annotation; core evolved function is as a Complex III structural subunit in
      oxidative phosphorylation, not pyramidal neuron development.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Component of the ubiquinol-cytochrome c oxidoreductase, a"
- term:
    id: GO:0030901
    label: midbrain development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Automatic Ensembl-Compara ortholog transfer (ECO:0000265) reflecting the mouse
      ortholog's developmental expression/phenotype, not a UQCRQ-specific midbrain
      development function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Over-annotation of a ubiquitous respiratory subunit; core BP is mitochondrial
      electron transport / cellular respiration.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Component of the ubiquinol-cytochrome c oxidoreductase, a"
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      HPA immunofluorescence IDA localizing UQCRQ to the mitochondrion. Correct but
      less specific than the inner-membrane annotations; retained as a valid,
      experimentally supported (if general) localization.
    action: ACCEPT
    reason: >-
      Mitochondrial localization is correct and experimentally supported; the more
      specific inner-membrane annotations refine it but do not contradict it.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Mitochondrion inner membrane"
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IDA
  original_reference_id: PMID:28844695
  qualifier: located_in
  review:
    summary: >-
      ComplexPortal IDA localizing UQCRQ to the mitochondrial inner membrane, backed
      by the cryo-EM megacomplex structure in which UQCRQ is assigned as a CIII
      subunit with a defined matrix/transmembrane/intermembrane topology. Core
      localization annotation.
    action: ACCEPT
    reason: >-
      Directly supported by the structural study and consistent with the single-pass
      inner-membrane topology recorded in UniProt.
    supported_by:
    - reference_id: PMID:28844695
      supporting_text: "the precise assignment of individual subunits of"
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Single-pass membrane protein"
- term:
    id: GO:0006122
    label: mitochondrial electron transport, ubiquinol to cytochrome c
  evidence_type: NAS
  original_reference_id: PMID:28844695
  qualifier: involved_in
  review:
    summary: >-
      ComplexPortal NAS annotation of UQCRQ to the ubiquinol-to-cytochrome-c electron
      transport process, the core biological process of Complex III. Consistent with
      IBA and InterPro2GO calls to the same term.
    action: ACCEPT
    reason: >-
      Correct core BP; UQCRQ is a structural subunit of the complex that mediates this
      electron transfer.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "The cytochrome b-c1 complex catalyzes electron"
- term:
    id: GO:0045275
    label: respiratory chain complex III
  evidence_type: IPI
  original_reference_id: PMID:28844695
  qualifier: part_of
  review:
    summary: >-
      ComplexPortal IPI complex-membership annotation (CPX-560) placing UQCRQ in
      respiratory chain complex III, supported by the cryo-EM structure that assigns
      UQCRQ within the CIII dimer. This is a core, well-evidenced annotation.
    action: ACCEPT
    reason: >-
      Complex III subunit membership is directly demonstrated structurally and by
      biochemical purification; the appropriate specific cellular-component term.
    supported_by:
    - reference_id: PMID:28844695
      supporting_text: "the precise assignment of individual subunits of"
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8,"
- term:
    id: GO:0045333
    label: cellular respiration
  evidence_type: NAS
  original_reference_id: PMID:28844695
  qualifier: involved_in
  review:
    summary: >-
      ComplexPortal NAS annotation to cellular respiration. This is a correct broader
      BP that encompasses the electron-transport role of Complex III; retained as a
      valid (if more general) process annotation.
    action: ACCEPT
    reason: >-
      Cellular respiration is a correct parent process for UQCRQ's role; not
      contradicted by any evidence. The more specific GO:0006122 is the preferred core
      term, but this broader term is legitimate.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "part of the mitochondrial"
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: >-
      High-throughput proteomics (MitoCoP) placing UQCRQ within the high-confidence
      human mitochondrial proteome. Supports mitochondrial localization; less specific
      than the inner-membrane annotations but consistent with them.
    action: ACCEPT
    reason: >-
      Correct, experimentally derived (high-throughput) mitochondrial localization,
      corroborating the more specific inner-membrane annotations.
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: "mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)"
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Sequence-similarity localization to the mitochondrial inner membrane, transferred
      from the bovine ortholog (UniProtKB:P08525). Consistent with the experimental
      IDA/TAS annotations and UniProt.
    action: ACCEPT
    reason: >-
      Correct core localization; agrees with independent experimental evidence in the
      same GOA.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Mitochondrion inner membrane"
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-164651
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS localization to the mitochondrial inner membrane, from the pathway
      "Electron transfer from ubiquinol to cytochrome c of complex III". Correct core
      localization for a CIII subunit.
    action: ACCEPT
    reason: >-
      Consistent with all other localization evidence; UQCRQ acts within the inner
      membrane as part of Complex III's Q cycle.
    supported_by:
    - reference_id: Reactome:R-HSA-164651
      supporting_text: "complex III transfers electrons from ubiquinol to cytochrome c"
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9837978
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS localization to the mitochondrial inner membrane, from a
      mitochondrial-protein-degradation reaction (LONP1 binding inner-membrane
      proteins). Correct localization annotation.
    action: ACCEPT
    reason: >-
      The inner-membrane localization is correct and consistent with all other
      evidence for UQCRQ.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Mitochondrion 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 TAS localization to the mitochondrial inner membrane, from a
      mitochondrial-protein-degradation reaction (LONP1 degrading inner-membrane
      proteins). Correct localization annotation.
    action: ACCEPT
    reason: >-
      Consistent with the experimentally supported inner-membrane localization.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Mitochondrion inner membrane"
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9906017
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS localization to the mitochondrial inner membrane, from a Complex III
      assembly/maturation reaction (cleavage of the UQCRFS1 subunit). Correct
      localization for a CIII subunit.
    action: ACCEPT
    reason: >-
      Consistent with all other inner-membrane localization evidence.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Mitochondrion inner membrane"
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9906042
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS localization to the mitochondrial inner membrane, from a Complex III
      maturation reaction (TTC19 clearing UQCRFS1 fragments). Correct localization.
    action: ACCEPT
    reason: >-
      Consistent with the well-supported inner-membrane localization of this CIII
      subunit.
    supported_by:
    - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
      supporting_text: "Mitochondrion inner membrane"
core_functions:
- description: >-
    Non-catalytic structural subunit of mitochondrial respiratory Complex III
    (ubiquinol-cytochrome c oxidoreductase / cytochrome b-c1 complex) in the
    mitochondrial inner membrane. UQCRQ contributes to the structural integrity of
    the complex and to its ubiquinone-binding environment (historically the QP-C
    ubiquinone-binding protein); it does not itself carry a catalytic redox centre.
    Through the complex, it participates in electron transfer from ubiquinol to
    cytochrome c during oxidative phosphorylation.
  molecular_function:
    id: GO:0005198
    label: structural molecule activity
  contributes_to_molecular_function:
    id: GO:0009055
    label: electron transfer activity
  directly_involved_in:
  - id: GO:0006122
    label: mitochondrial electron transport, ubiquinol to cytochrome c
  - id: GO:0045333
    label: cellular respiration
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  in_complex:
    id: GO:0045275
    label: respiratory chain complex III
  supported_by:
  - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
    supporting_text: "Ubiquinol-cytochrome c reductase complex ubiquinone-binding protein QP-C"
  - reference_id: file:human/UQCRQ/UQCRQ-uniprot.txt
    supporting_text: "The cytochrome b-c1 complex catalyzes electron"