id: Q8N3C0
gene_symbol: ASCC3
product_type: PROTEIN
aliases:
- HELIC1
- RQT2
- ASC1p200
status: COMPLETE
description: 'ASCC3 encodes a large ATP-dependent superfamily II helicase that functions in distinct ASCC-containing
  complexes. In the nucleus, ASCC3 is the catalytic helicase subunit of the ALKBH3-associated ASCC DNA
  dealkylation repair complex, where it helps unwind alkylated duplex DNA and is recruited to alkylation-induced
  nuclear foci. In the cytosol, ASCC3/RQT2 is the ATPase subunit of the human ribosome quality control
  trigger complex with ASCC2 and TRIP4, where it promotes splitting of K63-ubiquitinated collided ribosomes
  to initiate ribosome-associated quality control. ASCC3 was also originally identified as a component
  of the ASC-1 transcription coactivator complex, but its best-supported mechanistic roles are DNA alkylation
  repair and stalled ribosome rescue.'
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
alternative_products:
- name: '1'
  id: Q8N3C0-1
- name: '2'
  id: Q8N3C0-3
  sequence_note: VSP_042955, VSP_042956
- name: '3'
  id: Q8N3C0-4
  sequence_note: VSP_042957, VSP_042958
references:
- id: file:human/ASCC3/ASCC3-notes.md
  title: ASCC3 review notes
  findings:
  - statement: ASCC3 has separable nuclear DNA alkylation repair and cytosolic hRQT ribosome-rescue 
      roles, and the PN GO:0006515 projection was not added because more specific RQC terms are 
      already present.
    supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not
      add a new ASCC3 annotation to `GO:0006515`.'
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  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:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:12077347
  title: Novel transcription coactivator complex containing activating signal cointegrator 1.
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:22055184
  title: DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and 
    cancer cell proliferation.
  findings:
  - statement: ASCC3 helicase activity provides single-stranded substrate for ALKBH3-mediated DNA 
      repair.
    supporting_text: ASCC3 unwinds DNA to generate the single-stranded substrate needed for 
      ALKBH3-mediated DNA repair
- id: PMID:22681889
  title: The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:28757607
  title: Ubiquitination of stalled ribosome triggers ribosome-associated quality control.
  findings: []
- id: PMID:29144457
  title: A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair.
  findings:
  - statement: ASCC3 is recruited to alkylation-induced nuclear foci in the ASCC dealkylation repair
      pathway.
    supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
      alkylating agent
- id: PMID:29997253
  title: RNA ligase-like domain in activating signal cointegrator 1 complex subunit 1 (ASCC1) 
    regulates ASCC complex function during alkylation damage.
  findings:
  - statement: ASCC1 regulates ASCC complex function by interacting through ASCC3 during alkylation 
      damage signaling.
    supporting_text: ASCC1 interacts with the ASCC complex through the ASCC3 helicase subunit
- id: PMID:32099016
  title: Identification of a novel trigger complex that facilitates ribosome-associated quality 
    control in mammalian cells.
  findings:
  - statement: The human RQT complex contains ASCC3, ASCC2, and TRIP4 and triggers RQC.
    supporting_text: The hRQT complex is composed of ASCC3, ASCC2, and TRIP4
- id: PMID:32579943
  title: The ASC-1 Complex Disassembles Collided Ribosomes.
  findings:
  - statement: ASCC disassembles ubiquitinated collided ribosomes, defining ASCC3 as a core RQC 
      ribosome-rescue factor.
    supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
      lead ribosome
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:36302773
  title: A distinct mammalian disome collision interface harbors K63-linked polyubiquitination of 
    uS10 to trigger hRQT-mediated subunit dissociation.
  findings:
  - statement: K63-linked uS10 polyubiquitination triggers hRQT-mediated subunit dissociation.
    supporting_text: the trimeric hRQT complex-mediated subunit dissociation
- id: PMID:37019967
  title: Extended DNA threading through a dual-engine motor module of the activating signal
    co-integrator 1 complex.
  full_text_unavailable: true
  findings:
  - statement: ASCC3 contains two tandem Ski2-like NTPase/helicase cassettes that cooperate to thread
      substrate through both cassettes, and TRIP4 docks via a zinc-finger domain to position an ASCH
      domain next to the C-terminal cassette and stimulate the helicase.
  - statement: TRIP4 and the dealkylase ALKBH3 bind ASCC3 in a mutually exclusive manner, providing a
      mechanism that directs ASCC3 toward distinct cellular processes.
- id: PMID:37092320
  title: The ASC-1 complex promotes translation initiation by scanning ribosomes.
  full_text_unavailable: true
  findings:
  - statement: ASCC3 associates with scanning ribosomes and localizes predominantly to 5'
      untranslated regions, and its knockdown impairs 43S preinitiation complex loading and scanning
      dynamics, reducing translation efficiency for a subset of transcripts.
- id: PMID:38148115
  title: ASCC3 promotes the immunosuppression and progression of non-small cell lung cancer by
    impairing the type I interferon response via CAND1-mediated ubiquitination inhibition of STAT3.
  full_text_unavailable: true
  findings:
  - statement: In non-small cell lung cancer ASCC3 is upregulated and reported to stabilize STAT3 by
      recruiting CAND1 to inhibit STAT3 ubiquitination, impairing the type I interferon response and
      promoting an immunosuppressive tumor microenvironment.
- id: PMID:38366554
  title: Ribosomal collision is not a prerequisite for ZNF598-mediated ribosome ubiquitination and
    disassembly of ribosomal complexes by ASCC.
  full_text_unavailable: true
  findings:
  - statement: After ZNF598-dependent K63-polyubiquitination of uS10, ASCC efficiently disassembles
      polysomal, monosomal, 80S elongation and 48S initiation complexes without a strict requirement
      for ribosomal collision, provided at least ~30-35 nucleotides of 3' mRNA remain downstream of
      the P site.
- id: PMID:39286456
  title: 'Case report: Second report of neuromuscular syndrome caused by biallelic variants in ASCC3.'
  full_text_unavailable: true
  findings:
  - statement: Biallelic loss-of-function variants in ASCC3 cause an autosomal-recessive
      neurodevelopmental and neuromuscular syndrome (MIM:620700) featuring global developmental delay,
      intellectual disability, reduced muscle tone and motor and language impairment.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: Reactome:R-HSA-112123
  title: Oxidative demethylation of 1-meA damaged DNA By ALKBH3
  findings: []
- id: Reactome:R-HSA-112124
  title: Oxidative demethylation of 3-meC damaged DNA By ALKBH3
  findings: []
- id: Reactome:R-HSA-112125
  title: Oxidative dealkylation of 1-EtA damaged DNA by ABH3
  findings: []
- id: Reactome:R-HSA-5657617
  title: ALKBH3 associated with ASCC1:ASCC2:ASCC3 binds alkylated dsDNA containing 3-meC
  findings: []
- id: Reactome:R-HSA-5657637
  title: ALKBH3 associated with ASCC1:ASCC2:ASCC3 binds alkylated dsDNA containing 1-meA
  findings: []
- id: Reactome:R-HSA-5657642
  title: ALKBH3 in complex with ASCC1:ASCC2:ASCC3 binds alkylated DNA containing 1-etA
  findings: []
- id: Reactome:R-HSA-9948291
  title: RQT complex binds K63polyUb-80S ribosome:no-go mRNA:peptidyl-tRNA with nascent peptide
  findings: []
- id: Reactome:R-HSA-9948299
  title: Ribosome-associated quality control
  findings: []
- id: Reactome:R-HSA-9948300
  title: RQT complex:K63polyUb-80S ribosome dissociates yielding K63polyUb-40S subunit and 60S 
    subunit:peptidyl-tRNA with nascent peptide
  findings: []
existing_annotations:
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: RNA binding is plausible for ASCC3 but is less specific than its characterized 
      helicase/RQT roles.
    action: KEEP_AS_NON_CORE
    reason: ASCC3 contacts nucleic acids in both the DNA repair and ribosome-rescue settings, and 
      purified ASCC3 can bind ssRNA in vitro, but RNA binding alone does not capture the core 
      ATP-dependent activities. Keep the annotation as contextual rather than using it as the main 
      MF.
    additional_reference_ids:
    - PMID:29144457
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: Purified ASCC3 bound to ssRNA in vitro
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role.
    action: ACCEPT
    reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later 
      shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a 
      core location for the DNA repair arm of ASCC3 biology.
    additional_reference_ids:
    - PMID:29144457
    - PMID:12077347
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: PMID:12077347
      supporting_text: ASC-1 exists as a steady-state complex associated with three polypeptides, 
        P200, P100, and P50, in HeLa nuclei
- term:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: ASCC3 3'-5' DNA helicase activity is directly supported and central to ALKBH3-coupled 
      dealkylation repair.
    action: ACCEPT
    reason: The ALKBH3-ASCC paper demonstrates that ASCC3 unwinds duplex DNA to produce the 
      single-stranded substrate preferred by ALKBH3. This is the most specific molecular-function 
      term for the nuclear DNA repair activity.
    additional_reference_ids:
    - PMID:22055184
    - PMID:29144457
    supported_by:
    - reference_id: PMID:22055184
      supporting_text: ASCC3 unwinds DNA to generate the single-stranded substrate needed for 
        ALKBH3-mediated DNA repair
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: ASCC3 is a large ATP-dependent SF2 helicase with two well-supported 
        functional contexts.
- term:
    id: GO:0003676
    label: nucleic acid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: The broad nucleic-acid binding annotation is directionally true but should be replaced 
      by the specific DNA helicase activity.
    action: MODIFY
    reason: ASCC3 is a nucleic-acid-dependent ATPase/helicase, but the InterPro-derived term is too 
      general. Direct evidence supports 3'-5' DNA helicase activity in ALKBH3-mediated repair.
    proposed_replacement_terms:
    - id: GO:0043138
      label: 3'-5' DNA helicase activity
    additional_reference_ids:
    - PMID:22055184
    supported_by:
    - reference_id: PMID:22055184
      supporting_text: ASCC3 unwinds DNA to generate the single-stranded substrate needed for 
        ALKBH3-mediated DNA repair
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: ASCC3 is a large ATP-dependent SF2 helicase with two well-supported 
        functional contexts.
- term:
    id: GO:0004386
    label: helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: Generic helicase activity should be refined to ASCC3-specific DNA helicase and ATPase 
      terms.
    action: MODIFY
    reason: ASCC3 is a helicase-family ATPase, but GOA already has stronger, more specific 
      annotations for 3'-5' DNA helicase activity and ATP hydrolysis activity. The generic helicase 
      term should not be the preferred assertion.
    proposed_replacement_terms:
    - id: GO:0043138
      label: 3'-5' DNA helicase activity
    - id: GO:0016887
      label: ATP hydrolysis activity
    additional_reference_ids:
    - PMID:22055184
    - PMID:32579943
    supported_by:
    - reference_id: PMID:22055184
      supporting_text: ASCC3 unwinds DNA to generate the single-stranded substrate needed for 
        ALKBH3-mediated DNA repair
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: ASCC3 is a large ATP-dependent SF2 helicase with two well-supported 
        functional contexts.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: ATP binding is consistent with ASCC3 helicase/ATPase function but is not the most 
      informative MF annotation.
    action: KEEP_AS_NON_CORE
    reason: ASCC3 uses ATP-dependent helicase activity in both DNA repair and hRQT ribosome 
      splitting. ATP binding is true as a supporting property, but ATP hydrolysis activity and the 
      specific biological processes carry the core functional meaning.
    additional_reference_ids:
    - PMID:32579943
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: its loss phenocopies the loss of ZNF598. This activity of ASCC3 is dependent 
        on its ATP-dependent helicase activities
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role.
    action: ACCEPT
    reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later 
      shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a 
      core location for the DNA repair arm of ASCC3 biology.
    additional_reference_ids:
    - PMID:29144457
    - PMID:12077347
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: PMID:12077347
      supporting_text: ASC-1 exists as a steady-state complex associated with three polypeptides, 
        P200, P100, and P50, in HeLa nuclei
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cytosolic localization is supported by the ribosome-associated quality-control role.
    action: ACCEPT
    reason: ASCC3 acts on cytosolic collided ribosomes as part of hRQT. Cytosol annotations are 
      appropriate for the RQC arm of ASCC3, while nuclear annotations remain appropriate for the DNA
      repair arm.
    additional_reference_ids:
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do
        not add a new ASCC3 annotation to `GO:0006515`.'
- term:
    id: GO:0016607
    label: nuclear speck
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Nuclear speckle/foci localization is supported in the alkylation damage response 
      context.
    action: ACCEPT
    reason: ASCC3 and ASCC complex foci are linked to RNA polymerase II/splicing-associated nuclear 
      regions after alkylation damage, and ASCC1 is described at nuclear speckle foci before damage.
      This is a supported subnuclear context for the repair complex rather than a separate enzymatic
      function.
    additional_reference_ids:
    - PMID:29144457
    - PMID:29997253
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: ASCC foci co-localized with elongating (Ser2 phosphorylated) RNA polymerase 
        II
    - reference_id: PMID:29997253
      supporting_text: ASCC1 is present at nuclear speckle foci prior to damage
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: ATP hydrolysis activity is directly tied to ASCC3 helicase-dependent DNA repair and 
      hRQT ribosome splitting.
    action: ACCEPT
    reason: ASCC3 is an ATP-dependent helicase; RQC studies show ASCC3 ATPase activity is required 
      for hRQT-mediated ribosome rescue, and DNA repair studies show ATP-dependent helicase activity
      in ASCC3. This is an informative core MF annotation.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: This activity of ASCC3 is dependent on its ATP-dependent helicase activities
    - reference_id: PMID:32099016
      supporting_text: The ATPase activity of ASCC3 and the ubiquitin-binding activity of ASCC2 are 
        crucial for triggering
- term:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: ASCC3 3'-5' DNA helicase activity is directly supported and central to ALKBH3-coupled 
      dealkylation repair.
    action: ACCEPT
    reason: The ALKBH3-ASCC paper demonstrates that ASCC3 unwinds duplex DNA to produce the 
      single-stranded substrate preferred by ALKBH3. This is the most specific molecular-function 
      term for the nuclear DNA repair activity.
    additional_reference_ids:
    - PMID:22055184
    - PMID:29144457
    supported_by:
    - reference_id: PMID:22055184
      supporting_text: ASCC3 unwinds DNA to generate the single-stranded substrate needed for 
        ALKBH3-mediated DNA repair
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: ASCC3 is a large ATP-dependent SF2 helicase with two well-supported 
        functional contexts.
- term:
    id: GO:0180022
    label: RQC-trigger complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: part_of
  review:
    summary: ASCC3 is a core subunit of the human RQC-trigger/hRQT complex.
    action: ACCEPT
    reason: The original ASC-1 complex paper supports ASCC3/p200 complex membership, and later RQC 
      papers establish the ASCC3-ASCC2-TRIP4 hRQT complex as the ribosome quality-control trigger. 
      The term is therefore biologically correct, even when the older original reference alone is 
      not sufficient for the modern RQC label.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32099016
      supporting_text: The hRQT complex is composed of ASCC3, ASCC2, and TRIP4
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: The interaction evidence is real but generic protein binding is not an informative 
      ASCC3 molecular-function annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: These rows reflect physical associations from targeted or large-scale interaction data. 
      They are useful as support for ASCC/ALKBH3/hRQT complex biology when specific partners are 
      considered, but the generic GO protein binding term should not be retained as a core MF for 
      ASCC3.
    supported_by:
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: Treat generic binding annotations conservatively. `protein binding` rows are 
        interaction evidence but not informative molecular-function curation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29997253
  qualifier: enables
  review:
    summary: The interaction evidence is real but generic protein binding is not an informative 
      ASCC3 molecular-function annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: These rows reflect physical associations from targeted or large-scale interaction data. 
      They are useful as support for ASCC/ALKBH3/hRQT complex biology when specific partners are 
      considered, but the generic GO protein binding term should not be retained as a core MF for 
      ASCC3.
    supported_by:
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: Treat generic binding annotations conservatively. `protein binding` rows are 
        interaction evidence but not informative molecular-function curation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: The interaction evidence is real but generic protein binding is not an informative 
      ASCC3 molecular-function annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: These rows reflect physical associations from targeted or large-scale interaction data. 
      They are useful as support for ASCC/ALKBH3/hRQT complex biology when specific partners are 
      considered, but the generic GO protein binding term should not be retained as a core MF for 
      ASCC3.
    supported_by:
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: Treat generic binding annotations conservatively. `protein binding` rows are 
        interaction evidence but not informative molecular-function curation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: The interaction evidence is real but generic protein binding is not an informative 
      ASCC3 molecular-function annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: These rows reflect physical associations from targeted or large-scale interaction data. 
      They are useful as support for ASCC/ALKBH3/hRQT complex biology when specific partners are 
      considered, but the generic GO protein binding term should not be retained as a core MF for 
      ASCC3.
    supported_by:
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: Treat generic binding annotations conservatively. `protein binding` rows are 
        interaction evidence but not informative molecular-function curation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Cytosolic localization is supported by the ribosome-associated quality-control role.
    action: ACCEPT
    reason: ASCC3 acts on cytosolic collided ribosomes as part of hRQT. Cytosol annotations are 
      appropriate for the RQC arm of ASCC3, while nuclear annotations remain appropriate for the DNA
      repair arm.
    additional_reference_ids:
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do
        not add a new ASCC3 annotation to `GO:0006515`.'
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948299
  qualifier: involved_in
  review:
    summary: Rescue of stalled cytosolic ribosomes is the PN-relevant core process for ASCC3/hRQT.
    action: ACCEPT
    reason: ASCC3 acts in the hRQT/RQC-trigger complex to split ubiquitinated collided ribosomes, 
      allowing downstream RQC. This exact GO term is the conservative PN projection target and is 
      already present in GOA.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    - Reactome:R-HSA-9948299
    - Reactome:R-HSA-9948300
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do
        not add a new ASCC3 annotation to `GO:0006515`.'
    - reference_id: Reactome:R-HSA-9948300
      supporting_text: splits stalled 80S K63-polyubiquitinated ribosomes into 60S subunits and 
        K63-polyubiquitinated 40S subunits
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:29144457
  qualifier: located_in
  review:
    summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role.
    action: ACCEPT
    reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later 
      shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a 
      core location for the DNA repair arm of ASCC3 biology.
    additional_reference_ids:
    - PMID:29144457
    - PMID:12077347
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: PMID:12077347
      supporting_text: ASC-1 exists as a steady-state complex associated with three polypeptides, 
        P200, P100, and P50, in HeLa nuclei
- term:
    id: GO:0016607
    label: nuclear speck
  evidence_type: EXP
  original_reference_id: PMID:29144457
  qualifier: located_in
  review:
    summary: Nuclear speckle/foci localization is supported in the alkylation damage response 
      context.
    action: ACCEPT
    reason: ASCC3 and ASCC complex foci are linked to RNA polymerase II/splicing-associated nuclear 
      regions after alkylation damage, and ASCC1 is described at nuclear speckle foci before damage.
      This is a supported subnuclear context for the repair complex rather than a separate enzymatic
      function.
    additional_reference_ids:
    - PMID:29144457
    - PMID:29997253
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: ASCC foci co-localized with elongating (Ser2 phosphorylated) RNA polymerase 
        II
    - reference_id: PMID:29997253
      supporting_text: ASCC1 is present at nuclear speckle foci prior to damage
- term:
    id: GO:0016607
    label: nuclear speck
  evidence_type: EXP
  original_reference_id: PMID:29997253
  qualifier: located_in
  review:
    summary: Nuclear speckle/foci localization is supported in the alkylation damage response 
      context.
    action: ACCEPT
    reason: ASCC3 and ASCC complex foci are linked to RNA polymerase II/splicing-associated nuclear 
      regions after alkylation damage, and ASCC1 is described at nuclear speckle foci before damage.
      This is a supported subnuclear context for the repair complex rather than a separate enzymatic
      function.
    additional_reference_ids:
    - PMID:29144457
    - PMID:29997253
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: ASCC foci co-localized with elongating (Ser2 phosphorylated) RNA polymerase 
        II
    - reference_id: PMID:29997253
      supporting_text: ASCC1 is present at nuclear speckle foci prior to damage
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948300
  qualifier: enables
  review:
    summary: ATP hydrolysis activity is directly tied to ASCC3 helicase-dependent DNA repair and 
      hRQT ribosome splitting.
    action: ACCEPT
    reason: ASCC3 is an ATP-dependent helicase; RQC studies show ASCC3 ATPase activity is required 
      for hRQT-mediated ribosome rescue, and DNA repair studies show ATP-dependent helicase activity
      in ASCC3. This is an informative core MF annotation.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: This activity of ASCC3 is dependent on its ATP-dependent helicase activities
    - reference_id: PMID:32099016
      supporting_text: The ATPase activity of ASCC3 and the ubiquitin-binding activity of ASCC2 are 
        crucial for triggering
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948291
  qualifier: located_in
  review:
    summary: Cytosolic localization is supported by the ribosome-associated quality-control role.
    action: ACCEPT
    reason: ASCC3 acts on cytosolic collided ribosomes as part of hRQT. Cytosol annotations are 
      appropriate for the RQC arm of ASCC3, while nuclear annotations remain appropriate for the DNA
      repair arm.
    additional_reference_ids:
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do
        not add a new ASCC3 annotation to `GO:0006515`.'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948300
  qualifier: located_in
  review:
    summary: Cytosolic localization is supported by the ribosome-associated quality-control role.
    action: ACCEPT
    reason: ASCC3 acts on cytosolic collided ribosomes as part of hRQT. Cytosol annotations are 
      appropriate for the RQC arm of ASCC3, while nuclear annotations remain appropriate for the DNA
      repair arm.
    additional_reference_ids:
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do
        not add a new ASCC3 annotation to `GO:0006515`.'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:29997253
  qualifier: located_in
  review:
    summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role.
    action: ACCEPT
    reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later 
      shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a 
      core location for the DNA repair arm of ASCC3 biology.
    additional_reference_ids:
    - PMID:29144457
    - PMID:12077347
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: PMID:12077347
      supporting_text: ASC-1 exists as a steady-state complex associated with three polypeptides, 
        P200, P100, and P50, in HeLa nuclei
- term:
    id: GO:0006260
    label: DNA replication
  evidence_type: NAS
  original_reference_id: PMID:29997253
  qualifier: involved_in
  review:
    summary: The cited ASCC damage-response evidence does not support a general DNA replication role
      for ASCC3.
    action: REMOVE
    reason: ASCC3 participates in ALKBH3-mediated alkylation repair and forms repair foci in 
      cell-cycle contexts, but the cited ASCC1/ASCC paper supports repair-complex regulation rather 
      than DNA replication. This annotation appears to overinterpret ComplexPortal context.
    additional_reference_ids:
    - PMID:29144457
    - PMID:29997253
    supported_by:
    - reference_id: PMID:29997253
      supporting_text: ASCC1 interacts with the ASCC complex through the ASCC3 helicase subunit
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
- term:
    id: GO:0006307
    label: DNA alkylation repair
  evidence_type: NAS
  original_reference_id: PMID:29997253
  qualifier: involved_in
  review:
    summary: DNA alkylation repair is a directly supported core ASCC3 function.
    action: ACCEPT
    reason: ASCC3 unwinds alkylated duplex DNA and supports ALKBH3-dependent DNA dealkylation 
      repair. Later studies show alkylation-specific nuclear recruitment of the ASCC repair complex.
    additional_reference_ids:
    - PMID:22055184
    - PMID:29144457
    - PMID:29997253
    supported_by:
    - reference_id: PMID:22055184
      supporting_text: ASCC3 unwinds DNA to generate the single-stranded substrate needed for 
        ALKBH3-mediated DNA repair
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: ASCC3 is a large ATP-dependent SF2 helicase with two well-supported 
        functional contexts.
- term:
    id: GO:0032790
    label: ribosome disassembly
  evidence_type: NAS
  original_reference_id: PMID:32099016
  qualifier: involved_in
  review:
    summary: Ribosome disassembly is directly supported by hRQT/ASCC biochemical and cell-based 
      studies.
    action: ACCEPT
    reason: ASCC3-containing ASCC/hRQT disassembles ubiquitinated collided ribosomes in an 
      ATP-dependent reaction, which is the mechanistic core of ASCC3 in RQC.
    additional_reference_ids:
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: hRQT-driven splitting of ribosomes collided on endogenous XBP1u and poly(A) 
        staller mRNAs
- term:
    id: GO:1990116
    label: ribosome-associated ubiquitin-dependent protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:32099016
  qualifier: involved_in
  review:
    summary: ASCC3 is upstream in ribosome-associated ubiquitin-dependent nascent-chain quality 
      control.
    action: ACCEPT
    reason: ASCC3/hRQT splits stalled, ubiquitinated ribosomes and thereby produces the 
      subunit/nascent-chain intermediates that enter RQC-associated ubiquitin-dependent protein 
      degradation. The term is broader than the immediate splitting event but is supported as the 
      pathway context.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32099016
      supporting_text: Ribosome stalling triggers the ribosome-associated quality control (RQC) 
        pathway
    - reference_id: PMID:32579943
      supporting_text: 60S-peptidyl-tRNAs are substrates for RQC factors that trigger nascent 
        polypeptide ubiquitination and degradation
- term:
    id: GO:1990391
    label: DNA repair complex
  evidence_type: IPI
  original_reference_id: PMID:29997253
  qualifier: part_of
  review:
    summary: ASCC3 is a subunit of the ASCC DNA alkylation repair complex.
    action: ACCEPT
    reason: The ASCC1/ASCC2/ASCC3 complex is repeatedly supported in the alkylation repair 
      literature and is recruited with ALKBH3 to alkylation-induced nuclear foci.
    additional_reference_ids:
    - PMID:29144457
    - PMID:29997253
    - PMID:22055184
    supported_by:
    - reference_id: PMID:29997253
      supporting_text: ASCC1 interacts with the ASCC complex through the ASCC3 helicase subunit
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:32579943
  qualifier: enables
  review:
    summary: ATP hydrolysis activity is directly tied to ASCC3 helicase-dependent DNA repair and 
      hRQT ribosome splitting.
    action: ACCEPT
    reason: ASCC3 is an ATP-dependent helicase; RQC studies show ASCC3 ATPase activity is required 
      for hRQT-mediated ribosome rescue, and DNA repair studies show ATP-dependent helicase activity
      in ASCC3. This is an informative core MF annotation.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: This activity of ASCC3 is dependent on its ATP-dependent helicase activities
    - reference_id: PMID:32099016
      supporting_text: The ATPase activity of ASCC3 and the ubiquitin-binding activity of ASCC2 are 
        crucial for triggering
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:36302773
  qualifier: enables
  review:
    summary: ATP hydrolysis activity is directly tied to ASCC3 helicase-dependent DNA repair and 
      hRQT ribosome splitting.
    action: ACCEPT
    reason: ASCC3 is an ATP-dependent helicase; RQC studies show ASCC3 ATPase activity is required 
      for hRQT-mediated ribosome rescue, and DNA repair studies show ATP-dependent helicase activity
      in ASCC3. This is an informative core MF annotation.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: This activity of ASCC3 is dependent on its ATP-dependent helicase activities
    - reference_id: PMID:32099016
      supporting_text: The ATPase activity of ASCC3 and the ubiquitin-binding activity of ASCC2 are 
        crucial for triggering
- term:
    id: GO:0022626
    label: cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:36302773
  qualifier: is_active_in
  review:
    summary: ASCC3 is active on cytosolic ribosomes during hRQT-mediated RQC initiation.
    action: ACCEPT
    reason: The RQC studies directly place ASCC3/hRQT on collided cytosolic ribosomes and show that 
      ASCC3 ATPase activity drives subunit dissociation.
    additional_reference_ids:
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do
        not add a new ASCC3 annotation to `GO:0006515`.'
- term:
    id: GO:0032790
    label: ribosome disassembly
  evidence_type: IDA
  original_reference_id: PMID:32579943
  qualifier: involved_in
  review:
    summary: Ribosome disassembly is directly supported by hRQT/ASCC biochemical and cell-based 
      studies.
    action: ACCEPT
    reason: ASCC3-containing ASCC/hRQT disassembles ubiquitinated collided ribosomes in an 
      ATP-dependent reaction, which is the mechanistic core of ASCC3 in RQC.
    additional_reference_ids:
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: hRQT-driven splitting of ribosomes collided on endogenous XBP1u and poly(A) 
        staller mRNAs
- term:
    id: GO:0032790
    label: ribosome disassembly
  evidence_type: IDA
  original_reference_id: PMID:36302773
  qualifier: involved_in
  review:
    summary: Ribosome disassembly is directly supported by hRQT/ASCC biochemical and cell-based 
      studies.
    action: ACCEPT
    reason: ASCC3-containing ASCC/hRQT disassembles ubiquitinated collided ribosomes in an 
      ATP-dependent reaction, which is the mechanistic core of ASCC3 in RQC.
    additional_reference_ids:
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: hRQT-driven splitting of ribosomes collided on endogenous XBP1u and poly(A) 
        staller mRNAs
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:32579943
  qualifier: involved_in
  review:
    summary: Rescue of stalled cytosolic ribosomes is the PN-relevant core process for ASCC3/hRQT.
    action: ACCEPT
    reason: ASCC3 acts in the hRQT/RQC-trigger complex to split ubiquitinated collided ribosomes, 
      allowing downstream RQC. This exact GO term is the conservative PN projection target and is 
      already present in GOA.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    - Reactome:R-HSA-9948299
    - Reactome:R-HSA-9948300
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do
        not add a new ASCC3 annotation to `GO:0006515`.'
    - reference_id: Reactome:R-HSA-9948300
      supporting_text: splits stalled 80S K63-polyubiquitinated ribosomes into 60S subunits and 
        K63-polyubiquitinated 40S subunits
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:36302773
  qualifier: involved_in
  review:
    summary: Rescue of stalled cytosolic ribosomes is the PN-relevant core process for ASCC3/hRQT.
    action: ACCEPT
    reason: ASCC3 acts in the hRQT/RQC-trigger complex to split ubiquitinated collided ribosomes, 
      allowing downstream RQC. This exact GO term is the conservative PN projection target and is 
      already present in GOA.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    - Reactome:R-HSA-9948299
    - Reactome:R-HSA-9948300
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do
        not add a new ASCC3 annotation to `GO:0006515`.'
    - reference_id: Reactome:R-HSA-9948300
      supporting_text: splits stalled 80S K63-polyubiquitinated ribosomes into 60S subunits and 
        K63-polyubiquitinated 40S subunits
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IMP
  original_reference_id: PMID:32099016
  qualifier: involved_in
  review:
    summary: Rescue of stalled cytosolic ribosomes is the PN-relevant core process for ASCC3/hRQT.
    action: ACCEPT
    reason: ASCC3 acts in the hRQT/RQC-trigger complex to split ubiquitinated collided ribosomes, 
      allowing downstream RQC. This exact GO term is the conservative PN projection target and is 
      already present in GOA.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    - Reactome:R-HSA-9948299
    - Reactome:R-HSA-9948300
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do
        not add a new ASCC3 annotation to `GO:0006515`.'
    - reference_id: Reactome:R-HSA-9948300
      supporting_text: splits stalled 80S K63-polyubiquitinated ribosomes into 60S subunits and 
        K63-polyubiquitinated 40S subunits
- term:
    id: GO:1990116
    label: ribosome-associated ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:32099016
  qualifier: involved_in
  review:
    summary: ASCC3 is upstream in ribosome-associated ubiquitin-dependent nascent-chain quality 
      control.
    action: ACCEPT
    reason: ASCC3/hRQT splits stalled, ubiquitinated ribosomes and thereby produces the 
      subunit/nascent-chain intermediates that enter RQC-associated ubiquitin-dependent protein 
      degradation. The term is broader than the immediate splitting event but is supported as the 
      pathway context.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32099016
      supporting_text: Ribosome stalling triggers the ribosome-associated quality control (RQC) 
        pathway
    - reference_id: PMID:32579943
      supporting_text: 60S-peptidyl-tRNAs are substrates for RQC factors that trigger nascent 
        polypeptide ubiquitination and degradation
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:28757607
  qualifier: located_in
  review:
    summary: Cytosolic localization is supported by the ribosome-associated quality-control role.
    action: ACCEPT
    reason: ASCC3 acts on cytosolic collided ribosomes as part of hRQT. Cytosol annotations are 
      appropriate for the RQC arm of ASCC3, while nuclear annotations remain appropriate for the DNA
      repair arm.
    additional_reference_ids:
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32579943
      supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
        lead ribosome
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do
        not add a new ASCC3 annotation to `GO:0006515`.'
- term:
    id: GO:0180022
    label: RQC-trigger complex
  evidence_type: IDA
  original_reference_id: PMID:12077347
  qualifier: part_of
  review:
    summary: ASCC3 is a core subunit of the human RQC-trigger/hRQT complex.
    action: ACCEPT
    reason: The original ASC-1 complex paper supports ASCC3/p200 complex membership, and later RQC 
      papers establish the ASCC3-ASCC2-TRIP4 hRQT complex as the ribosome quality-control trigger. 
      The term is therefore biologically correct, even when the older original reference alone is 
      not sufficient for the modern RQC label.
    additional_reference_ids:
    - PMID:32099016
    - PMID:32579943
    - PMID:36302773
    supported_by:
    - reference_id: PMID:32099016
      supporting_text: The hRQT complex is composed of ASCC3, ASCC2, and TRIP4
    - reference_id: PMID:36302773
      supporting_text: the trimeric hRQT complex-mediated subunit dissociation
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12077347
  qualifier: located_in
  review:
    summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role.
    action: ACCEPT
    reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later 
      shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a 
      core location for the DNA repair arm of ASCC3 biology.
    additional_reference_ids:
    - PMID:29144457
    - PMID:12077347
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: PMID:12077347
      supporting_text: ASC-1 exists as a steady-state complex associated with three polypeptides, 
        P200, P100, and P50, in HeLa nuclei
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-112123
  qualifier: located_in
  review:
    summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 
      nuclear DNA repair function.
    action: ACCEPT
    reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex
      in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci 
      evidence.
    additional_reference_ids:
    - PMID:29144457
    supported_by:
    - reference_id: Reactome:R-HSA-112123
      supporting_text: The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of
        DNA helicase ASCC3
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-112124
  qualifier: located_in
  review:
    summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 
      nuclear DNA repair function.
    action: ACCEPT
    reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex
      in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci 
      evidence.
    additional_reference_ids:
    - PMID:29144457
    supported_by:
    - reference_id: Reactome:R-HSA-112123
      supporting_text: The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of
        DNA helicase ASCC3
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-112125
  qualifier: located_in
  review:
    summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 
      nuclear DNA repair function.
    action: ACCEPT
    reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex
      in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci 
      evidence.
    additional_reference_ids:
    - PMID:29144457
    supported_by:
    - reference_id: Reactome:R-HSA-112123
      supporting_text: The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of
        DNA helicase ASCC3
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5657617
  qualifier: located_in
  review:
    summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 
      nuclear DNA repair function.
    action: ACCEPT
    reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex
      in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci 
      evidence.
    additional_reference_ids:
    - PMID:29144457
    supported_by:
    - reference_id: Reactome:R-HSA-112123
      supporting_text: The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of
        DNA helicase ASCC3
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5657637
  qualifier: located_in
  review:
    summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 
      nuclear DNA repair function.
    action: ACCEPT
    reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex
      in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci 
      evidence.
    additional_reference_ids:
    - PMID:29144457
    supported_by:
    - reference_id: Reactome:R-HSA-112123
      supporting_text: The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of
        DNA helicase ASCC3
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5657642
  qualifier: located_in
  review:
    summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 
      nuclear DNA repair function.
    action: ACCEPT
    reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex
      in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci 
      evidence.
    additional_reference_ids:
    - PMID:29144457
    supported_by:
    - reference_id: Reactome:R-HSA-112123
      supporting_text: The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of
        DNA helicase ASCC3
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: The high-throughput membrane localization is not consistent with the curated ASCC3 
      functional picture.
    action: REMOVE
    reason: ASCC3 is a soluble nuclear/cytosolic helicase in ASCC and hRQT complexes and lacks a 
      compelling membrane-associated core role. The membrane-proteome HDA row is likely a peripheral
      or proteomics-carryover signal and should not be retained.
    supported_by:
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: 'Remove the high-throughput `membrane` localization: ASCC3 is a soluble nuclear/cytosolic
        protein with no transmembrane-domain basis'
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  qualifier: enables
  review:
    summary: RNA binding is plausible for ASCC3 but is less specific than its characterized 
      helicase/RQT roles.
    action: KEEP_AS_NON_CORE
    reason: ASCC3 contacts nucleic acids in both the DNA repair and ribosome-rescue settings, and 
      purified ASCC3 can bind ssRNA in vitro, but RNA binding alone does not capture the core 
      ATP-dependent activities. Keep the annotation as contextual rather than using it as the main 
      MF.
    additional_reference_ids:
    - PMID:29144457
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: Purified ASCC3 bound to ssRNA in vitro
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22055184
  qualifier: enables
  review:
    summary: The interaction evidence is real but generic protein binding is not an informative 
      ASCC3 molecular-function annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: These rows reflect physical associations from targeted or large-scale interaction data. 
      They are useful as support for ASCC/ALKBH3/hRQT complex biology when specific partners are 
      considered, but the generic GO protein binding term should not be retained as a core MF for 
      ASCC3.
    supported_by:
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: Treat generic binding annotations conservatively. `protein binding` rows are 
        interaction evidence but not informative molecular-function curation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:22055184
  qualifier: located_in
  review:
    summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role.
    action: ACCEPT
    reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later 
      shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a 
      core location for the DNA repair arm of ASCC3 biology.
    additional_reference_ids:
    - PMID:29144457
    - PMID:12077347
    supported_by:
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: PMID:12077347
      supporting_text: ASC-1 exists as a steady-state complex associated with three polypeptides, 
        P200, P100, and P50, in HeLa nuclei
- term:
    id: GO:0006307
    label: DNA alkylation repair
  evidence_type: IDA
  original_reference_id: PMID:22055184
  qualifier: involved_in
  review:
    summary: DNA alkylation repair is a directly supported core ASCC3 function.
    action: ACCEPT
    reason: ASCC3 unwinds alkylated duplex DNA and supports ALKBH3-dependent DNA dealkylation 
      repair. Later studies show alkylation-specific nuclear recruitment of the ASCC repair complex.
    additional_reference_ids:
    - PMID:22055184
    - PMID:29144457
    - PMID:29997253
    supported_by:
    - reference_id: PMID:22055184
      supporting_text: ASCC3 unwinds DNA to generate the single-stranded substrate needed for 
        ALKBH3-mediated DNA repair
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: ASCC3 is a large ATP-dependent SF2 helicase with two well-supported 
        functional contexts.
- term:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:22055184
  qualifier: enables
  review:
    summary: ASCC3 3'-5' DNA helicase activity is directly supported and central to ALKBH3-coupled 
      dealkylation repair.
    action: ACCEPT
    reason: The ALKBH3-ASCC paper demonstrates that ASCC3 unwinds duplex DNA to produce the 
      single-stranded substrate preferred by ALKBH3. This is the most specific molecular-function 
      term for the nuclear DNA repair activity.
    additional_reference_ids:
    - PMID:22055184
    - PMID:29144457
    supported_by:
    - reference_id: PMID:22055184
      supporting_text: ASCC3 unwinds DNA to generate the single-stranded substrate needed for 
        ALKBH3-mediated DNA repair
    - reference_id: PMID:29144457
      supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
        alkylating agent
    - reference_id: file:human/ASCC3/ASCC3-notes.md
      supporting_text: ASCC3 is a large ATP-dependent SF2 helicase with two well-supported 
        functional contexts.
core_functions:
- description: ASCC3 is the catalytic 3'-5' DNA helicase of the nuclear ASCC-ALKBH3 dealkylation 
    repair complex. It unwinds alkylated duplex DNA to expose single-stranded substrates for ALKBH3 
    and is recruited to alkylation-induced nuclear foci.
  molecular_function:
    id: GO:0043138
    label: 3'-5' DNA helicase activity
  directly_involved_in:
  - id: GO:0006307
    label: DNA alkylation repair
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005654
    label: nucleoplasm
  - id: GO:0016607
    label: nuclear speck
  in_complex:
    id: GO:1990391
    label: DNA repair complex
  supported_by:
  - reference_id: PMID:22055184
    supporting_text: ASCC3 unwinds DNA to generate the single-stranded substrate needed for 
      ALKBH3-mediated DNA repair
  - reference_id: PMID:29144457
    supporting_text: Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the 
      alkylating agent
  - reference_id: file:human/ASCC3/ASCC3-notes.md
    supporting_text: ASCC3 is a large ATP-dependent SF2 helicase with two well-supported functional 
      contexts.
  - reference_id: PMID:29997253
    supporting_text: ASCC1 interacts with the ASCC complex through the ASCC3 helicase subunit
- description: ASCC3/RQT2 is the ATPase subunit of the cytosolic hRQT/RQC-trigger complex. Together 
    with ASCC2 and TRIP4, it acts on K63-ubiquitinated collided ribosomes and promotes ribosomal 
    subunit dissociation, enabling downstream ribosome-associated quality control of stalled nascent
    chains.
  molecular_function:
    id: GO:0016887
    label: ATP hydrolysis activity
  directly_involved_in:
  - id: GO:0032790
    label: ribosome disassembly
  - id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  - id: GO:1990116
    label: ribosome-associated ubiquitin-dependent protein catabolic process
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0022626
    label: cytosolic ribosome
  in_complex:
    id: GO:0180022
    label: RQC-trigger complex
  supported_by:
  - reference_id: PMID:32579943
    supporting_text: ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the 
      lead ribosome
  - reference_id: PMID:36302773
    supporting_text: the trimeric hRQT complex-mediated subunit dissociation
  - reference_id: file:human/ASCC3/ASCC3-notes.md
    supporting_text: 'Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not
      add a new ASCC3 annotation to `GO:0006515`.'
  - reference_id: PMID:32099016
    supporting_text: The hRQT complex is composed of ASCC3, ASCC2, and TRIP4
proposed_new_terms: []
suggested_questions:
- question: Should PN ribosome-associated QC mappings continue to project the broad GO:0006515 term 
    to genes like ASCC3 when more specific ribosome-rescue and RQC catabolic-process terms are 
    already present?
- question: Which endogenous mammalian stall substrates, beyond XBP1u and poly(A)-based reporters, 
    depend most strongly on ASCC3/hRQT for ribosome rescue?
- question: Can ASCC3 disease-associated variants be separated into nuclear DNA-repair defects,
    cytosolic RQC defects, or combined helicase-loss mechanisms?
- question: Does the ASCC3/ASC-1 complex role in promoting translation initiation by scanning
    ribosomes at 5'-UTRs (Kito et al. 2023) warrant a distinct molecular-function or
    biological-process annotation separate from its collided-ribosome rescue activity?
- question: Are the neurodevelopmental/neuromuscular phenotypes of biallelic ASCC3 loss-of-function
    variants driven primarily by impaired ribosome-associated quality control, impaired DNA
    alkylation repair, impaired translation initiation, or a combination?
- question: Is the reported STAT3/CAND1-stabilizing, interferon-dampening activity of ASCC3 in NSCLC
    a direct helicase-dependent function or an indirect consequence of altered proteostasis or
    translation, and should it be curated as a molecular function?
suggested_experiments:
- description: Use acute ASCC3 depletion or degron tagging with wild-type and ATPase-dead rescue 
    constructs, then quantify endogenous collided-ribosome clearance by disome profiling and 
    nascent-chain ubiquitination/degradation assays.
  experiment_type: cell biology and ribosome profiling
  hypothesis: ASCC3 ATPase activity is required for clearance of endogenous mammalian collided 
    ribosomes, not only engineered stalling reporters.
- description: Engineer complex-selective ASCC3 separation-of-function variants or 
    localization-restricted rescue constructs to compare MMS-induced ALKBH3 repair foci with 
    hRQT-mediated poly(A)/XBP1u ribosome rescue.
  experiment_type: separation-of-function rescue
  hypothesis: The nuclear dealkylation repair and cytosolic hRQT roles can be genetically decoupled.
- description: Test ASCC3 patient variants in parallel assays for ALKBH3-dependent alkylation damage
    resistance and hRQT-dependent stalled-ribosome splitting.
  experiment_type: variant functional assay
  hypothesis: Some ASCC3 variants impair one functional context more strongly than the other.