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.