id: P61221
gene_symbol: ABCE1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ABCE1 is a highly conserved cytosolic Fe-S ABC-family ATPase that drives
  eukaryotic ribosome recycling. After canonical termination, or after PELO/HBS1L
  recognition of stalled or vacant ribosomes, ABCE1 uses ATP hydrolysis to split
  80S ribosomes into 60S and 40S subunits, thereby coupling translational
  termination, ribosome-associated quality control, and re-use of ribosomal
  subunits. ABCE1 contains an N-terminal 4Fe-4S cluster binding region and two
  ABC nucleotide-binding domains. It was originally identified as RNase L
  inhibitor/RLI and can inhibit the 2-5A/RNASEL pathway, but current biochemical
  and genetic evidence supports ribosome recycling as its core conserved
  function.
existing_annotations:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ABCE1 is a conserved cytosolic ribosome-recycling ATPase. Cytosolic
      localization is consistent with the experimentally supported cytoplasmic
      localization and its activity on cytosolic 80S ribosomes.
    action: ACCEPT
    reason: >-
      The annotation captures the main compartment where ABCE1 carries out its
      core function on cytosolic ribosomes.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        ABCE1 dissociates post-TCs into free 60S subunits and mRNA- and
        tRNA-bound 40S subunits.
- term:
    id: GO:0006415
    label: translational termination
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ABCE1 acts at the post-termination stage of translation, after release
      factor action, to recycle post-termination ribosomes.
    action: ACCEPT
    reason: >-
      Although the most precise process term for ABCE1 is ribosome disassembly,
      post-termination ribosome recycling is mechanistically part of the
      termination-to-reinitiation transition and is well supported for ABCE1.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        After termination, eukaryotic 80S ribosomes remain associated with
        mRNA, P-site deacylated tRNA, and release factor eRF1 and must be
        recycled by dissociating these ligands and separating ribosomes into
        subunits.
- term:
    id: GO:0005506
    label: iron ion binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ABCE1 contains a conserved N-terminal iron-sulfur cluster binding region.
      The generic "iron ion binding" term is directionally correct but less
      precise than the 4Fe-4S cluster binding term.
    action: MODIFY
    reason: >-
      UniProt and the deep research report both describe an N-terminal Fe-S
      domain required for ABCE1 function. The more informative GO term is
      4 iron, 4 sulfur cluster binding.
    proposed_replacement_terms:
    - id: GO:0051539
      label: 4 iron, 4 sulfur cluster binding
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        ABCE1 comprises an N-terminal domain harboring two [4Fe-4S] clusters
        that is structurally related to bacterial-type ferredoxins, followed by
        two NBDs arranged by a hinge domain (Karcher et al., 2008).
    - reference_id: file:human/ABCE1/ABCE1-deep-research-falcon.md
      supporting_text: >-
        ABCE1 (ATP-binding cassette subfamily E member 1; also historically
        **RNase L inhibitor/RLI**) is an essential, highly conserved **Fe–S
        ABC-family ATPase** that acts as the principal **eukaryotic ribosome
        recycling (splitting) factor**.
    - reference_id: file:human/ABCE1/ABCE1-bioinformatics/RESULTS.md
      supporting_text: >-
        The N-terminal region (residues 1-80) contains nine cysteines arranged
        across the two UniProt-annotated 4Fe-4S ferredoxin-type domains (7-37
        and 46-75), consistent with coordination of two [4Fe-4S] clusters
        rather than mononuclear iron.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ABCE1 has two ABC nucleotide-binding domains with predicted ATP-binding
      sites and experimentally supported ATP-dependent ribosome recycling.
    action: ACCEPT
    reason: >-
      ATP binding is an integral molecular property of the ABCE1 ATPase cycle
      that drives ribosome splitting.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        NTP hydrolysis by ABCE1 is stimulated by post-TCs and is required for
        its recycling activity.
- term:
    id: GO:0006413
    label: translational initiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ABCE1 promotes ribosome recycling, which enables ribosomal subunits to be
      reused for subsequent initiation, but it is not itself a canonical
      translation initiation factor.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The evidence supports an indirect effect on initiation through ribosome
      recycling and 40S reuse. Ribosome disassembly and rescue of stalled
      cytosolic ribosomes are more accurate process annotations for ABCE1.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        ABCE1 dissociates post-TCs into free 60S subunits and mRNA- and
        tRNA-bound 40S subunits.
- term:
    id: GO:0043024
    label: ribosomal small subunit binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      ABCE1 associates with ribosomal subunits during recycling and is reported
      to remain with the 40S subunit after splitting in structural and pathway
      models.
    action: ACCEPT
    reason: >-
      Small ribosomal subunit binding is consistent with ABCE1's core
      ribosome-recycling mechanism.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        we observed that in the AMPPNP-bound form, ABCE1 efficiently associated
        with 40S subunits and 43S complexes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16275648
  review:
    summary: >-
      This annotation reflects interaction with HIV-1 Gag during viral capsid
      assembly.
    action: REMOVE
    reason: >-
      Protein binding is too generic to represent ABCE1 function, and the
      specific viral Gag interaction is a host-virus interaction rather than a
      core human gene-product function.
    supported_by:
    - reference_id: PMID:16275648
      supporting_text: >-
        In primate cells, ABCE1 associates with Gag polypeptides present in
        immature capsid assembly intermediates.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25944354
  review:
    summary: >-
      This annotation reflects a Chandipura virus matrix protein interaction
      from a host-interactor screen.
    action: REMOVE
    reason: >-
      Generic protein binding is not informative for ABCE1's molecular
      function, and a viral matrix protein interaction should not drive the core
      GO molecular-function model for human ABCE1.
    supported_by:
    - reference_id: PMID:25944354
      supporting_text: >-
        The present study aims to screen the human fetal brain cDNA library for
        interactors of CHPV M protein using yeast two-hybrid system.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: >-
      This high-throughput binary interactome annotation reports protein
      interaction evidence but does not specify an ABCE1 molecular function.
    action: REMOVE
    reason: >-
      The term "protein binding" is too broad for curation and does not improve
      the ABCE1 functional model beyond the specific ribosome-recycling and
      RNase L inhibitor annotations.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: >-
        The dataset, versioned HI-III-20 (Human Interactome obtained from
        screening Space III, published in 2020), contains 52,569 verified PPIs
        involving 8,275 proteins (Supplementary Table 9).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: >-
      This annotation comes from a high-throughput endogenous tagging and
      cellular organization resource.
    action: REMOVE
    reason: >-
      Generic protein binding is not an informative molecular function for
      ABCE1. Specific activities and process terms better represent the
      supported biology.
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: >-
        We combined genome engineering, confocal live-cell imaging, mass
        spectrometry, and data science to systematically map the localization
        and interactions of human proteins.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      InterPro-based ATP binding is consistent with the two ABC
      nucleotide-binding domains and the experimentally supported ATPase
      function of ABCE1.
    action: ACCEPT
    reason: >-
      ATP binding is a required component of ABCE1's ATP hydrolysis-driven
      ribosome recycling mechanism.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        It can hydrolyze ATP, GTP, UTP, and CTP.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Cytoplasmic localization is supported by UniProt and by ABCE1's activity
      on cytosolic ribosomes.
    action: ACCEPT
    reason: >-
      The annotation is broad but correct; more specific cytosol and cytosolic
      ribosome annotations are also present.
    supported_by:
    - reference_id: Reactome:R-HSA-8985201
      supporting_text: >-
        ATP-binding cassette sub-family E member 1 (ABCE1, aka RNase L
        inhibitor, RLI) is a member of the ATP-binding cassette transporters
        which express in the cytoplasm and the nuclear membrane.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      A mitochondrial fraction of ABCE1/RLI has been reported, and later work
      links ABCE1 to mitochondrial outer membrane-associated translation quality
      control under damage conditions.
    action: KEEP_AS_NON_CORE
    reason: >-
      Mitochondrial association is supported but is not the dominant core
      function of ABCE1; the core conserved function is cytosolic ribosome
      recycling.
    supported_by:
    - reference_id: PMID:11585831
      supporting_text: >-
        We found that a fraction of cellular RNase L and RLI is localized in
        the mitochondria.
    - reference_id: PMID:29861391
      supporting_text: >-
        Mitochondrial damage causes stalled translation of complex-I 30 kDa
        subunit (C-I30) mRNA on MOM, triggering the recruitment of
        co-translational quality control factors Pelo, ABCE1, and NOT4 to the
        ribosome/mRNA-ribonucleoprotein complex.
- term:
    id: GO:0006412
    label: translation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      ABCE1 is clearly involved in translation, but this broad term obscures
      the supported mechanism: ATP-driven recycling and splitting of
      post-termination or stalled cytosolic ribosomes.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The annotation is not wrong, but ribosome disassembly, translational
      termination, and rescue of stalled cytosolic ribosome are more precise and
      already present.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        Consistently, we found that silencing of ABCE1 in HeLa cells impaired
        ribosomal recycling.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      InterPro-based ATPase prediction agrees with direct biochemical evidence
      that ABCE1 hydrolyzes ATP and requires NTP hydrolysis for recycling.
    action: ACCEPT
    reason: >-
      ATP hydrolysis is the core molecular activity that powers ABCE1-mediated
      ribosome splitting.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        NTP hydrolysis by ABCE1 is stimulated by post-TCs and is required for
        its recycling activity.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      HPA immunofluorescence supports cytosolic localization, consistent with
      ABCE1's cytosolic ribosome-recycling role.
    action: ACCEPT
    reason: >-
      This directly supports the main compartment for ABCE1 function.
    supported_by:
    - reference_id: Reactome:R-HSA-8985201
      supporting_text: >-
        ATP-binding cassette sub-family E member 1 (ABCE1, aka RNase L
        inhibitor, RLI) is a member of the ATP-binding cassette transporters
        which express in the cytoplasm and the nuclear membrane.
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948299
  review:
    summary: >-
      Reactome places ABCE1 downstream of PELO/HBS1L in rescue of non-stop or
      stalled cytosolic ribosomes, where ABCE1 hydrolyzes ATP to split the 80S
      ribosome.
    action: ACCEPT
    reason: >-
      This is a core ABCE1 process in ribosome-associated quality control.
    supported_by:
    - reference_id: Reactome:R-HSA-9948299
      supporting_text: >-
        HBS1L hydrolyzes GTP and dissociates from PELO and the ribosome,
        exposing a site on PELO to which ABCE1 binds.
    - reference_id: PMID:21448132
      supporting_text: >-
        Pelota/Hbs1 also induced dissociation of ECs and release of
        peptidyl-tRNA, but only in the presence of ABCE1.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9955731
  review:
    summary: >-
      Reactome explicitly describes ABCE1 hydrolyzing ATP while bound with PELO
      to split a stalled 80S ribosome.
    action: ACCEPT
    reason: >-
      ATP hydrolysis is the mechanistic molecular activity driving ABCE1's core
      ribosome-splitting function.
    supported_by:
    - reference_id: Reactome:R-HSA-9955731
      supporting_text: >-
        ABCE1 bound to PELO near the P site of the 80S ribosome hydrolyzes ATP,
        causing dissociation of the 80S ribosome into 40S and 60S ribosomal
        subunits
- term:
    id: GO:0006415
    label: translational termination
  evidence_type: IDA
  original_reference_id: PMID:20122402
  review:
    summary: >-
      ABCE1 acts on post-termination ribosomal complexes after eRF-mediated
      peptide release and promotes their recycling.
    action: ACCEPT
    reason: >-
      Direct biochemical evidence supports ABCE1 function at the
      termination/recycling stage of translation. Ribosome disassembly is the
      most precise process term, but this termination annotation is defensible.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        ABCE1 dissociates post-TCs into free 60S subunits and mRNA- and
        tRNA-bound 40S subunits.
- term:
    id: GO:0017111
    label: ribonucleoside triphosphate phosphatase activity
  evidence_type: IDA
  original_reference_id: PMID:20122402
  review:
    summary: >-
      ABCE1 was directly shown to hydrolyze ATP, GTP, UTP and CTP in vitro.
    action: ACCEPT
    reason: >-
      This broad NTPase activity is experimentally supported. For the core
      cellular mechanism, ATP hydrolysis activity is the more specific and more
      central molecular function.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        It can hydrolyze ATP, GTP, UTP, and CTP.
- term:
    id: GO:0022626
    label: cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:20122402
  review:
    summary: >-
      ABCE1 acts directly on eukaryotic cytosolic 80S ribosomal complexes and
      their post-recycling subunits.
    action: ACCEPT
    reason: >-
      The cytosolic ribosome is the active site of ABCE1's core function.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        ABCE1 dissociates post-TCs into free 60S subunits and mRNA- and
        tRNA-bound 40S subunits.
- term:
    id: GO:0022626
    label: cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:21448132
  review:
    summary: >-
      Mammalian ABCE1 functions on vacant and stalled 80S ribosomes with
      Pelota/Hbs1.
    action: ACCEPT
    reason: >-
      This annotation accurately captures the ribosomal location of ABCE1's
      stalled-ribosome rescue function.
    supported_by:
    - reference_id: PMID:21448132
      supporting_text: >-
        Pelota/Hbs1 also induced dissociation of ECs and release of
        peptidyl-tRNA, but only in the presence of ABCE1.
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IDA
  original_reference_id: PMID:20122402
  review:
    summary: >-
      ABCE1 hydrolyzed GTP in vitro in the same biochemical study that
      established its NTPase activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      The direct assay supports GTP hydrolysis, but the primary cellular
      ribosome-recycling mechanism is best represented by ATP hydrolysis
      activity.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        It can hydrolyze ATP, GTP, UTP, and CTP.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:20122402
  review:
    summary: >-
      ABCE1 directly hydrolyzes ATP, and NTP hydrolysis is required for
      ribosome recycling.
    action: ACCEPT
    reason: >-
      ATP hydrolysis is the core ABCE1 molecular function that powers 80S
      ribosome splitting.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        NTP hydrolysis by ABCE1 is stimulated by post-TCs and is required for
        its recycling activity.
- term:
    id: GO:0032790
    label: ribosome disassembly
  evidence_type: IDA
  original_reference_id: PMID:20122402
  review:
    summary: >-
      ABCE1 dissociates post-termination ribosomes into 60S and 40S subunits in
      a reconstituted eukaryotic system.
    action: ACCEPT
    reason: >-
      This is the most precise core biological-process annotation for ABCE1's
      canonical function.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        ABCE1, a conserved and essential member of the ATP-binding cassette
        (ABC) family of proteins, promotes eukaryotic ribosomal recycling over
        a wide range of Mg(2+) concentrations.
- term:
    id: GO:0032790
    label: ribosome disassembly
  evidence_type: IDA
  original_reference_id: PMID:21448132
  review:
    summary: >-
      ABCE1, with Pelota and Hbs1, dissociates mammalian vacant 80S ribosomes
      and stalled elongation complexes.
    action: ACCEPT
    reason: >-
      This annotation captures ABCE1's ribosome-splitting role in quality
      control as well as in recycling.
    supported_by:
    - reference_id: PMID:21448132
      supporting_text: >-
        Pelota/Hbs1 also induced dissociation of ECs and release of
        peptidyl-tRNA, but only in the presence of ABCE1.
- term:
    id: GO:0043273
    label: CTPase activity
  evidence_type: IDA
  original_reference_id: PMID:20122402
  review:
    summary: >-
      ABCE1 hydrolyzed CTP in vitro in the biochemical study that characterized
      its broad NTPase activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      The assay supports CTP hydrolysis, but current evidence for ABCE1's
      physiological core function points to ATP-driven ribosome recycling.
    supported_by:
    - reference_id: PMID:20122402
      supporting_text: >-
        It can hydrolyze ATP, GTP, UTP, and CTP.
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:21448132
  review:
    summary: >-
      Mammalian ABCE1 is essential with Pelota, and Hbs1 is stimulatory, for
      dissociation of stalled elongation complexes in vitro.
    action: ACCEPT
    reason: >-
      This is a core quality-control role for ABCE1 that follows directly from
      the experimental evidence.
    supported_by:
    - reference_id: PMID:21448132
      supporting_text: >-
        Whereas Pelota and ABCE1 were essential, Hbs1 had a stimulatory effect.
- term:
    id: GO:0006515
    label: protein quality control for misfolded or incompletely synthesized proteins
  evidence_type: IC
  original_reference_id: PMID:21448132
  supporting_entities:
  - GO:0072344
  review:
    summary: >-
      NEW annotation supported by ribosome-associated quality-control pathway
      context and by direct evidence that mammalian ABCE1, with Pelota/Hbs1,
      dissociates stalled elongation complexes and releases peptidyl-tRNA.
    action: NEW
    reason: >-
      This broad protein-quality-control term is appropriate as a parent/context
      process for ABCE1's stalled-ribosome rescue role. It should not replace
      the more precise core annotations to rescue of stalled cytosolic ribosome
      and ribosome disassembly.
    supported_by:
    - reference_id: PMID:21448132
      supporting_text: >-
        Pelota/Hbs1 also induced dissociation of ECs and release of
        peptidyl-tRNA, but only in the presence of ABCE1.
    - reference_id: PMID:21448132
      supporting_text: >-
        Whereas Pelota and ABCE1 were essential, Hbs1 had a stimulatory effect.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8985201
  review:
    summary: >-
      Reactome's RNASEL binding event places ABCE1/RLI in the cytoplasm and
      describes its RNase L inhibitory role.
    action: ACCEPT
    reason: >-
      Cytosolic localization is supported and consistent with ABCE1's core
      ribosome function and non-core RNASEL inhibition function.
    supported_by:
    - reference_id: Reactome:R-HSA-8985201
      supporting_text: >-
        ATP-binding cassette sub-family E member 1 (ABCE1, aka RNase L
        inhibitor, RLI) is a member of the ATP-binding cassette transporters
        which express in the cytoplasm and the nuclear membrane.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9954919
  review:
    summary: >-
      Reactome describes the cytosolic stalled-ribosome rescue pathway in which
      HBS1L dissociation exposes PELO for ABCE1 binding.
    action: ACCEPT
    reason: >-
      This is consistent with ABCE1's cytosolic ribosome-associated function.
    supported_by:
    - reference_id: Reactome:R-HSA-9954919
      supporting_text: >-
        The dissociation exposes a surface on PELO for ABCE1 to bind and allows
        the central domain of PELO to move towards the peptidyl-tRNA in P site
        of the 80S ribosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9955731
  review:
    summary: >-
      Reactome describes ABCE1-bound PELO hydrolyzing ATP to dissociate a
      stalled cytosolic 80S ribosome.
    action: ACCEPT
    reason: >-
      The pathway event is cytosolic and mechanistically aligned with ABCE1's
      core function.
    supported_by:
    - reference_id: Reactome:R-HSA-9955731
      supporting_text: >-
        ABCE1 bound to PELO near the P site of the 80S ribosome hydrolyzes ATP,
        causing dissociation of the 80S ribosome into 40S and 60S ribosomal
        subunits
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:7539425
  review:
    summary: >-
      This annotation reflects ABCE1/RLI association with RNase L.
    action: REMOVE
    reason: >-
      The RNase L interaction is real, but generic protein binding is not
      informative. The same evidence is better captured by the specific
      endoribonuclease inhibitor activity and negative regulation of
      endoribonuclease activity annotations.
    supported_by:
    - reference_id: PMID:7539425
      supporting_text: >-
        Its expression in reticulocyte extracts antagonizes the 2-5A binding
        ability and the nuclease activity of endogenous RNase L or the cloned
        2DR polypeptide.
- term:
    id: GO:0060698
    label: endoribonuclease inhibitor activity
  evidence_type: IDA
  original_reference_id: PMID:7539425
  review:
    summary: >-
      ABCE1/RLI directly inhibits RNase L activity in the 2-5A/RNase L pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a specific, experimentally supported molecular activity, but it
      appears secondary to ABCE1's conserved core role in ribosome recycling.
    supported_by:
    - reference_id: PMID:7539425
      supporting_text: >-
        Its expression in reticulocyte extracts antagonizes the 2-5A binding
        ability and the nuclease activity of endogenous RNase L or the cloned
        2DR polypeptide.
    - reference_id: Reactome:R-HSA-5223305
      supporting_text: >-
        ATP-binding cassette sub-family E member 1 (ABCE1, aka RNase L
        inhibitor, RLI) directly interacts with RNASEL and inhibits its
        endoribonuclease activity
- term:
    id: GO:0060702
    label: negative regulation of endoribonuclease activity
  evidence_type: IDA
  original_reference_id: PMID:7539425
  review:
    summary: >-
      ABCE1/RLI negatively regulates RNase L endoribonuclease activity in the
      interferon-regulated 2-5A pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      This regulation is supported experimentally, but it is not the main
      conserved ABCE1 function relative to ATP-driven ribosome recycling.
    supported_by:
    - reference_id: PMID:7539425
      supporting_text: >-
        The overexpression of RLI in stably transfected HeLa cells inhibits the
        antiviral activity of IFN on encephalomyocarditis virus but not on
        vesicular stomatitis virus.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  review:
    summary: >-
      This high-throughput NK cell membrane-proteome study identified many
      proteins, including species likely to be transiently or indirectly
      associated with membranes.
    action: REMOVE
    reason: >-
      ABCE1 lacks a transmembrane region and its core function is soluble
      cytosolic ribosome recycling. This broad membrane annotation is weak and
      likely reflects fractionation or transient association rather than a
      defining localization.
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: >-
        The remaining species were largely involved in cellular processes and
        molecular functions that could be predicted to be transiently associated
        with membranes.
    - reference_id: file:human/ABCE1/ABCE1-bioinformatics/RESULTS.md
      supporting_text: >-
        The curated UniProt feature table for P61221 lists zero TRANSMEM
        features, and an independent Kyte-Doolittle scan (window 19) finds no
        window reaching the 1.6 transmembrane-helix threshold (global maximum
        1.54 at residue 64), confirming ABCE1 has no transmembrane region and
        is a soluble cytosolic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5223305
  review:
    summary: >-
      Mitochondrial association of ABCE1/RLI is supported, but the more specific
      mitochondrial matrix location is not clearly justified by the cited
      RNASEL inhibition event.
    action: MODIFY
    reason: >-
      The available evidence supports mitochondrion-level association, not a
      confidently matrix-specific localization. Use the broader mitochondrion
      term.
    proposed_replacement_terms:
    - id: GO:0005739
      label: mitochondrion
    supported_by:
    - reference_id: PMID:11585831
      supporting_text: >-
        We found that a fraction of cellular RNase L and RLI is localized in
        the mitochondria.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:11585831
  review:
    summary: >-
      The interferon/RNase L study supports cellular ABCE1/RLI localization in
      cytoplasm with an additional mitochondrial fraction.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is well aligned with ABCE1's ribosome-recycling
      role and with its RNase L inhibitor role.
    supported_by:
    - reference_id: Reactome:R-HSA-8985201
      supporting_text: >-
        ATP-binding cassette sub-family E member 1 (ABCE1, aka RNase L
        inhibitor, RLI) is a member of the ATP-binding cassette transporters
        which express in the cytoplasm and the nuclear membrane.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:11585831
  review:
    summary: >-
      A mitochondrial fraction of ABCE1/RLI was reported in the context of
      interferon-induced regulation of mitochondrial mRNA stability.
    action: KEEP_AS_NON_CORE
    reason: >-
      The localization is supported, but current evidence indicates ABCE1's
      core conserved function is cytosolic ribosome recycling rather than a
      primary mitochondrial matrix function.
    supported_by:
    - reference_id: PMID:11585831
      supporting_text: >-
        We found that a fraction of cellular RNase L and RLI is localized in
        the mitochondria.
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
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11585831
  title: "The 2-5A/RNase L/RNase L inhibitor (RLI) [correction of (RNI)] pathway regulates mitochondrial mRNAs stability in interferon alpha-treated H9 cells."
  findings:
  - statement: A fraction of RNase L and ABCE1/RLI localizes to mitochondria.
    supporting_text: >-
      We found that a fraction of cellular RNase L and RLI is localized in the
      mitochondria.
  - statement: RNase L/RLI activity contributes to interferon-dependent mitochondrial mRNA regulation.
    supporting_text: >-
      These results demonstrate that IFNalpha exerts its antiproliferative
      effect on H9 cells at least in part via the degradation of mitochondrial
      mRNAs by RNase L.
- id: PMID:16275648
  title: "Basic residues in the nucleocapsid domain of Gag are required for interaction of HIV-1 gag with ABCE1 (HP68), a cellular protein important for HIV-1 capsid assembly."
  findings:
  - statement: HIV-1 Gag interacts with ABCE1/HP68 during immature capsid assembly.
    supporting_text: >-
      In primate cells, ABCE1 associates with Gag polypeptides present in
      immature capsid assembly intermediates.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings:
  - statement: The membrane fraction proteome includes many non-integral proteins.
    supporting_text: >-
      The remaining species were largely involved in cellular processes and
      molecular functions that could be predicted to be transiently associated
      with membranes.
- id: PMID:20122402
  title: The role of ABCE1 in eukaryotic posttermination ribosomal recycling.
  findings:
  - statement: ABCE1 dissociates eukaryotic post-termination ribosomal complexes.
    supporting_text: >-
      ABCE1 dissociates post-TCs into free 60S subunits and mRNA- and tRNA-bound
      40S subunits.
  - statement: ABCE1 is an NTPase whose hydrolysis activity is required for recycling.
    supporting_text: >-
      It can hydrolyze ATP, GTP, UTP, and CTP. NTP hydrolysis by ABCE1 is
      stimulated by post-TCs and is required for its recycling activity.
- id: PMID:21448132
  title: Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes.
  findings:
  - statement: ABCE1 and Pelota are required for mammalian stalled-ribosome dissociation.
    supporting_text: >-
      Pelota/Hbs1 also induced dissociation of ECs and release of peptidyl-tRNA,
      but only in the presence of ABCE1.
  - statement: ABCE1 also participates in recycling vacant 80S ribosomes.
    supporting_text: >-
      ABCE1/Pelota/Hbs1 also dissociated vacant 80S ribosomes, which stimulated
      48S complex formation, suggesting that Pelota/Hbs1 have an additional role
      outside of NGD.
- id: PMID:25944354
  title: Host interactions of Chandipura virus matrix protein.
  findings:
  - statement: ABCE1 was identified as a host interactor of Chandipura virus matrix protein.
    supporting_text: >-
      The present study aims to screen the human fetal brain cDNA library for
      interactors of CHPV M protein using yeast two-hybrid system.
- id: PMID:29861391
  title: Ubiquitination of ABCE1 by NOT4 in Response to Mitochondrial Damage Links Co-translational Quality Control to PINK1-Directed Mitophagy.
  findings:
  - statement: Mitochondrial damage recruits ABCE1 to mitochondrial outer membrane-associated mRNP quality-control complexes.
    supporting_text: >-
      Mitochondrial damage causes stalled translation of complex-I 30 kDa
      subunit (C-I30) mRNA on MOM, triggering the recruitment of
      co-translational quality control factors Pelo, ABCE1, and NOT4 to the
      ribosome/mRNA-ribonucleoprotein complex.
  - statement: NOT4-mediated ubiquitination of ABCE1 contributes to mitophagy signaling.
    supporting_text: >-
      Damage-induced ubiquitination of ABCE1 by NOT4 generates poly-ubiquitin
      signals that attract autophagy receptors to MOM to initiate mitophagy.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings:
  - statement: High-throughput interactome evidence reports ABCE1 protein interactions.
    supporting_text: >-
      The dataset, versioned HI-III-20 (Human Interactome obtained from
      screening Space III, published in 2020), contains 52,569 verified PPIs
      involving 8,275 proteins
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings:
  - statement: OpenCell provides high-throughput localization and interaction context for human proteins.
    supporting_text: >-
      We combined genome engineering, confocal live-cell imaging, mass
      spectrometry and data science to systematically map the localization and
      interactions of human proteins.
- id: PMID:7539425
  title: Cloning and characterization of a RNase L inhibitor. A new component of the interferon-regulated 2-5A pathway.
  findings:
  - statement: ABCE1/RLI inhibits RNase L activity.
    supporting_text: >-
      Its expression in reticulocyte extracts antagonizes the 2-5A binding
      ability and the nuclease activity of endogenous RNase L or the cloned 2DR
      polypeptide.
  - statement: ABCE1/RLI can suppress an interferon antiviral effect mediated through RNase L.
    supporting_text: >-
      The overexpression of RLI in stably transfected HeLa cells inhibits the
      antiviral activity of IFN on encephalomyocarditis virus but not on
      vesicular stomatitis virus.
- id: Reactome:R-HSA-5223305
  title: ABCE1 binds RNASEL, inhibiting it
  findings:
  - statement: ABCE1 directly interacts with RNASEL and inhibits its endoribonuclease activity.
    supporting_text: >-
      ATP-binding cassette sub-family E member 1 (ABCE1, aka RNase L inhibitor,
      RLI) directly interacts with RNASEL and inhibits its endoribonuclease
      activity
- id: Reactome:R-HSA-8985201
  title: ABCE1 binds RNASEL
  findings:
  - statement: ABCE1/RLI binds RNase L and inhibits the 2-5A/RNase L pathway.
    supporting_text: >-
      ABCE1 (RLI) was shown to associate with RNase L inhibiting the
      endoribonuclease activity of RNase L
- id: Reactome:R-HSA-9948299
  title: Ribosome-associated quality control
  findings:
  - statement: ABCE1 splits non-stop or stalled cytosolic ribosomes after PELO/HBS1L action.
    supporting_text: >-
      HBS1L hydrolyzes GTP and dissociates from PELO and the ribosome, exposing
      a site on PELO to which ABCE1 binds.
- id: Reactome:R-HSA-9954919
  title: ABCE1:ATP binds PELO:HBS1L-1:GTP:80S ribosome:non-stop mRNA:peptidyl-tRNA with nascent peptide and HBS1L-1:GDP is released
  findings:
  - statement: HBS1L dissociation permits ABCE1 binding to a PELO-containing stalled ribosome.
    supporting_text: >-
      The dissociation exposes a surface on PELO for ABCE1 to bind and allows
      the central domain of PELO to move towards the peptidyl-tRNA in P site of
      the 80S ribosome
- id: Reactome:R-HSA-9955731
  title: ABCE1:PELO:80S Ribosome:non-stop mRNA:peptidyl-tRNA with elongating peptide dissociates yielding ABCE1:40S ribosomal subunit, PELO, and 60S ribosomal subunit:peptidyl-tRNA
  findings:
  - statement: ABCE1 hydrolyzes ATP to split a PELO-bound stalled 80S ribosome.
    supporting_text: >-
      ABCE1 bound to PELO near the P site of the 80S ribosome hydrolyzes ATP,
      causing dissociation of the 80S ribosome into 40S and 60S ribosomal
      subunits
- id: file:human/ABCE1/ABCE1-deep-research-falcon.md
  title: Deep research on ABCE1 function
  findings:
  - statement: ABCE1 is a conserved Fe-S ABC ATPase whose core function is ATP-driven eukaryotic ribosome recycling.
  - statement: ABCE1 functions with eRF1/eRF3 in canonical post-termination recycling and with PELO/HBS1L in stalled-ribosome rescue.
  - statement: RNase L inhibition and mitochondrial stress-associated relocalization are supported but are not the central conserved function.
- id: file:human/ABCE1/ABCE1-bioinformatics/RESULTS.md
  title: Sequence-level bioinformatics analysis of ABCE1 (transmembrane, NBD, and Fe-S architecture)
  findings:
  - statement: ABCE1 has no transmembrane region (0 UniProt TRANSMEM features; Kyte-Doolittle max 19-residue window 1.54, below the 1.6 TM-helix threshold), consistent with a soluble cytosolic ATPase rather than a membrane transporter.
    supporting_text: >-
      The curated UniProt feature table for P61221 lists zero TRANSMEM
      features, and an independent Kyte-Doolittle scan (window 19) finds no
      window reaching the 1.6 transmembrane-helix threshold (global maximum
      1.54 at residue 64), confirming ABCE1 has no transmembrane region and is
      a soluble cytosolic protein.
  - statement: Two Walker A P-loop motifs map to the UniProt ATP-binding sites (110-117 and 379-386), confirming two nucleotide-binding domains.
  - statement: The N-terminal region carries nine cysteines across the two UniProt-annotated ferredoxin-type domains, consistent with coordination of two [4Fe-4S] clusters.
core_functions:
- molecular_function:
    id: GO:0016887
    label: ATP hydrolysis activity
  description: >-
    ABCE1 hydrolyzes ATP through its ABC nucleotide-binding domains to drive
    splitting of eukaryotic 80S ribosomes after canonical termination and during
    PELO/HBS1L-mediated rescue of stalled or vacant cytosolic ribosomes. This
    ATPase-driven ribosome disassembly is the core conserved function of ABCE1.
    The N-terminal 4Fe-4S cluster binding domain is a key mechanistic feature of
    the protein, while RNase L inhibition and mitochondrial damage-associated
    quality-control signaling are supported but secondary contexts.
  directly_involved_in:
  - id: GO:0032790
    label: ribosome disassembly
  - id: GO:0006415
    label: translational termination
  - id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  - id: GO:0006515
    label: protein quality control for misfolded or incompletely synthesized proteins
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0022626
    label: cytosolic ribosome
  supported_by:
  - reference_id: PMID:20122402
    supporting_text: >-
      ABCE1 dissociates post-TCs into free 60S subunits and mRNA- and tRNA-bound
      40S subunits.
  - reference_id: PMID:21448132
    supporting_text: >-
      Pelota/Hbs1 also induced dissociation of ECs and release of peptidyl-tRNA,
      but only in the presence of ABCE1.
  - reference_id: Reactome:R-HSA-9955731
    supporting_text: >-
      ABCE1 bound to PELO near the P site of the 80S ribosome hydrolyzes ATP,
      causing dissociation of the 80S ribosome into 40S and 60S ribosomal
      subunits
proposed_new_terms: []
suggested_questions:
- question: >-
    Does ABCE1's experimentally observed GTPase, CTPase and UTPase activity
    have physiological roles, or is ATP hydrolysis the only relevant nucleotide
    cycle in cells?
- question: >-
    What is the precise mitochondrial compartment and context for ABCE1
    association: soluble mitochondrial fraction, matrix, mitochondrial outer
    membrane-associated translation quality control, or stress-induced
    relocalization?
- question: >-
    How does the N-terminal 4Fe-4S cluster domain mechanistically couple the ABC
    ATPase cycle to ribosome splitting?
suggested_experiments:
- description: >-
    Reconstitute human ABCE1 with mammalian eRF1/eRF3 and PELO/HBS1L ribosomal
    complexes using nucleotide-specific ATP, GTP, CTP and UTP conditions, then
    compare subunit splitting and factor-release kinetics.
  hypothesis: >-
    ATP hydrolysis is the physiologically relevant nucleotide cycle for ABCE1
    ribosome splitting, while GTP and CTP hydrolysis reflect broader in vitro
    substrate tolerance.
- description: >-
    Use endogenous tagging plus protease protection, carbonate extraction and
    purified mitochondrial subfractionation before and after mitochondrial
    damage to distinguish matrix localization from outer membrane-associated
    ribosome quality-control recruitment.
  hypothesis: >-
    Most mitochondrial ABCE1 signal reflects stress- or translation-associated
    recruitment to mitochondrial outer membrane mRNP/ribosome complexes rather
    than stable matrix localization.
- description: >-
    Compare wild-type ABCE1 with Fe-S cluster-disrupting mutants in human
    ribosome splitting assays and cryo-EM of termination and PELO/HBS1L rescue
    complexes.
  hypothesis: >-
    The 4Fe-4S domain is required to position or allosterically activate ABCE1
    for productive ATP-driven ribosome disassembly.