id: Q9Y450 gene_symbol: HBS1L product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: HBS1L (HBS1-like translational GTPase) is a cytoplasmic GTPase of the TRAFAC-class translation-factor superfamily, in the eEF1A/eRF3/Hbs1 group. It is the GTP-binding subunit of the Pelota-HBS1L complex (also called the Dom34-Hbs1 complex), partnering the eRF1-like factor PELO. The complex recognizes ribosomes stalled at the 3' end of an mRNA (truncated, non-stop, or no-go messages); HBS1L delivers PELO to the ribosomal A site and, through its GTPase activity, licenses PELO- and ABCE1-mediated splitting of the stalled 80S ribosome into subunits, thereby rescuing the ribosome and initiating no-go decay (NGD) and non-stop decay (NSD). Although phylogenetically related to the translation-termination factor eRF3, HBS1L does not possess eRF3 (peptide-release) activity. A short alternatively spliced isoform (HBS1LV3) instead scaffolds the cytoplasmic SKI complex and exosome via direct SKIC2 and EXOSC3 binding, coupling mRNA extraction to 3'-5' degradation. alternative_products: - name: 1 (HBS1LV1 {ECO:0000303|PubMed:28204585}) id: Q9Y450-1 - name: 2 (HBS1LV3 {ECO:0000303|PubMed:28204585}) id: Q9Y450-2 sequence_note: VSP_013624 - name: '3' id: Q9Y450-4 sequence_note: VSP_041068 existing_annotations: - term: id: GO:0072344 label: rescue of stalled cytosolic ribosome evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Rescue of stalled ribosomes is the core biological role of HBS1L as the GTPase of the Pelota-HBS1L complex. IBA inference matches direct evidence. action: ACCEPT reason: Core process; conserved across yeast Hbs1 and human HBS1L and supported by direct mammalian biochemistry. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: GTPase component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway - term: id: GO:0003924 label: GTPase activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: HBS1L is a translational GTPase; GTP hydrolysis drives delivery of PELO and licensing of ribosome splitting. Core molecular function. action: ACCEPT reason: GTPase activity is the defining catalytic function of HBS1L, supported by family membership and the UniProt catalytic activity record. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: GTPase component of the Pelota-HBS1L complex - term: id: GO:0006412 label: translation evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: HBS1L is associated with the translation apparatus, but its specific role is ribosome rescue/surveillance rather than productive protein synthesis. action: KEEP_AS_NON_CORE reason: Broad parent process; the informative role is rescue of stalled ribosomes, captured by more specific terms. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: GTPase component of the Pelota-HBS1L complex - term: id: GO:0003924 label: GTPase activity evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: Electronic transfer of GTPase activity, consistent with the experimentally and phylogenetically supported function. action: ACCEPT reason: Correct core molecular function; redundant with IBA/ISS annotations. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: GTPase component of the Pelota-HBS1L complex - term: id: GO:0005525 label: GTP binding evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: HBS1L binds GTP as a translational GTPase; necessary for its catalytic cycle. action: ACCEPT reason: GTP binding is a well-supported molecular function underlying GTPase activity. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: GTPase component of the Pelota-HBS1L complex - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Electronic cytoplasmic localization, consistent with the documented and experimentally supported cytoplasmic site of action. action: ACCEPT reason: Correct compartment, corroborated by experimental (EXP) cytoplasm evidence. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0010629 label: negative regulation of gene expression evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: Very broad process transferred electronically; HBS1L's effect on gene expression is indirect, via mRNA surveillance, and is better captured by the specific mRNA-decay terms. action: MARK_AS_OVER_ANNOTATED reason: Generic and indirect; the mechanistic role is ribosome rescue / no-go and non-stop mRNA decay, not transcriptional/general gene-expression regulation. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: triggers the No-Go Decay (NGD) pathway - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20531386 qualifier: enables review: summary: Interaction with the human exosome captured in this study; for HBS1L this reflects the isoform-2 (HBS1LV3) link between SKI and the cytoplasmic exosome. action: KEEP_AS_NON_CORE reason: Real interaction underlying the isoform-specific SKI/exosome scaffolding role; bare protein binding term is uninformative. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: Associates with the exosome complex; the interaction with EXOSC3 is direct - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: Yeast two-hybrid interactome capturing the HBS1L-PELO interaction (the defining partner). Bare protein binding term. action: KEEP_AS_NON_CORE reason: The PELO interaction is core but is already captured by the complex term; the generic protein binding term itself is non-core. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: composed of PELO and HBS1L - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables review: summary: Interactome screen capturing HBS1L interactions including PELO. Bare protein binding. action: KEEP_AS_NON_CORE reason: Generic term; the relevant PELO interaction is captured elsewhere. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: composed of PELO and HBS1L - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: Binary interactome map; HBS1L-PELO plus other partners. Bare protein binding. action: KEEP_AS_NON_CORE reason: Generic term; PELO is the functionally meaningful partner. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: composed of PELO and HBS1L - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: BioPlex affinity-purification interactome capturing HBS1L interactions. Bare protein binding. action: KEEP_AS_NON_CORE reason: Records physical interactions but the generic term is uninformative for core function. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: composed of PELO and HBS1L - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:40205054 qualifier: enables review: summary: Multimodal cell-maps interactome capturing HBS1L interactions. Bare protein binding. action: KEEP_AS_NON_CORE reason: Generic term; non-core. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: composed of PELO and HBS1L - 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: Reactome curated ribosome-rescue role of HBS1L. Core process. action: ACCEPT reason: Curated TAS annotation consistent with the experimentally supported core function. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: triggers the No-Go Decay (NGD) pathway - term: id: GO:0003924 label: GTPase activity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: Sequence-similarity transfer of GTPase activity; consistent with family and direct evidence. action: ACCEPT reason: Correct core molecular function. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: GTPase component of the Pelota-HBS1L complex - term: id: GO:0005737 label: cytoplasm evidence_type: EXP original_reference_id: PMID:28204585 qualifier: located_in review: summary: Experimental cytoplasmic localization, consistent with HBS1L's site of action. action: ACCEPT reason: Experimentally supported localization to the cytoplasm. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0003924 label: GTPase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-9954919 qualifier: enables review: summary: Reactome curated GTPase activity in the ribosome-rescue pathway. action: ACCEPT reason: Curated TAS consistent with the core molecular function. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: GTPase component of the Pelota-HBS1L complex - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9954730 qualifier: located_in review: summary: Reactome curated cytosolic localization, consistent with site of action. action: KEEP_AS_NON_CORE reason: Correct but generic localization. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9954919 qualifier: located_in review: summary: Reactome curated cytosolic localization (duplicate context). action: KEEP_AS_NON_CORE reason: Correct but generic localization. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0003924 label: GTPase activity evidence_type: ISS original_reference_id: PMID:20947765 qualifier: enables review: summary: Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off; HBS1L GTPase activity inferred by similarity to characterized yeast Hbs1. action: ACCEPT reason: Core molecular function supported by orthology and mechanistic studies of the Dom34:Hbs1 complex. supported_by: - reference_id: PMID:20947765 supporting_text: 'Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay' - term: id: GO:0022626 label: cytosolic ribosome evidence_type: IDA original_reference_id: PMID:27863242 qualifier: is_active_in review: summary: Direct cryo-EM evidence places HBS1L on the stalled cytosolic 80S ribosome. action: ACCEPT reason: Strong direct structural evidence for HBS1L acting on the cytosolic ribosome. supported_by: - reference_id: PMID:27863242 supporting_text: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes - term: id: GO:0032790 label: ribosome disassembly evidence_type: IDA original_reference_id: PMID:21448132 qualifier: involved_in review: summary: With PELO and ABCE1, HBS1L drives dissociation of 80S ribosomes into subunits (in vitro reconstitution). action: ACCEPT reason: Directly demonstrated; subunit dissociation is the mechanistic output of the complex. supported_by: - reference_id: PMID:21448132 supporting_text: Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes - term: id: GO:0070966 label: nuclear-transcribed mRNA catabolic process, no-go decay evidence_type: IDA original_reference_id: PMID:23667253 qualifier: involved_in review: summary: HBS1L (Hbs1-Dom34 complex) functions in no-go/non-stop mRNA decay in mammalian cells. action: ACCEPT reason: Directly demonstrated mRNA-decay role. supported_by: - reference_id: PMID:23667253 supporting_text: The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells - term: id: GO:0070966 label: nuclear-transcribed mRNA catabolic process, no-go decay evidence_type: IDA original_reference_id: PMID:27863242 qualifier: involved_in review: summary: Structural study supporting the complex's role in recognizing stalled ribosomes that triggers no-go decay. action: ACCEPT reason: Direct evidence for the recognition step that triggers NGD. supported_by: - reference_id: PMID:27863242 supporting_text: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes - term: id: GO:0072344 label: rescue of stalled cytosolic ribosome evidence_type: IDA original_reference_id: PMID:21448132 qualifier: involved_in review: summary: In vitro reconstitution shows HBS1L (with PELO/ABCE1) rescues stalled elongation complexes. action: ACCEPT reason: Directly demonstrated core biological process. supported_by: - reference_id: PMID:21448132 supporting_text: Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes - term: id: GO:0072344 label: rescue of stalled cytosolic ribosome evidence_type: IDA original_reference_id: PMID:27863242 qualifier: involved_in review: summary: Structural demonstration of HBS1L engaging stalled ribosomes for rescue. action: ACCEPT reason: Direct structural evidence for the rescue process. supported_by: - reference_id: PMID:27863242 supporting_text: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes - term: id: GO:1990533 label: Dom34-Hbs1 complex evidence_type: IDA original_reference_id: PMID:27863242 qualifier: part_of review: summary: HBS1L directly identified as a component of the Pelota-HBS1L (Dom34-Hbs1) complex by cryo-EM. action: ACCEPT reason: Direct evidence for HBS1L as a complex subunit. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: Component of the Pelota-HBS1L complex, also named Dom34-Hbs1 complex, composed of PELO and HBS1L - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-430028 qualifier: located_in review: summary: Reactome curated cytosolic localization. action: KEEP_AS_NON_CORE reason: Correct but generic localization. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0016020 label: membrane evidence_type: HDA original_reference_id: PMID:19946888 qualifier: located_in review: summary: High-throughput NK-cell membrane proteome detection. Not the functional site for this cytoplasmic GTPase. action: MARK_AS_OVER_ANNOTATED reason: Mass-spectrometry catalog localization that conflicts with the documented cytoplasmic site of action; likely co-purification. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: High-throughput extracellular-vesicle proteome detection. Not the functional compartment. action: MARK_AS_OVER_ANNOTATED reason: Proteomic catalog localization unrelated to HBS1L's cytoplasmic ribosome-rescue function. supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm' - term: id: GO:0005525 label: GTP binding evidence_type: TAS original_reference_id: PMID:9872408 qualifier: enables review: summary: Original characterization showing HBS1L is a GTP-binding protein phylogenetically related to eRF3 but lacking eRF3 release activity. action: ACCEPT reason: Author-curated GTP binding, consistent with the core GTPase function. supported_by: - reference_id: PMID:9872408 supporting_text: is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3-like activity - term: id: GO:0006412 label: translation evidence_type: TAS original_reference_id: PMID:9872408 qualifier: involved_in review: summary: HBS1L was assigned to translation as a translation-factor-related GTPase; its specific role is ribosome rescue/surveillance. action: KEEP_AS_NON_CORE reason: Broad process; the informative function is rescue of stalled ribosomes. supported_by: - reference_id: PMID:9872408 supporting_text: is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3-like activity - term: id: GO:0007165 label: signal transduction evidence_type: TAS original_reference_id: PMID:9872408 qualifier: involved_in review: summary: Generic signal-transduction assignment in the original cloning paper; not supported by any subsequent mechanistic role for HBS1L. action: MARK_AS_OVER_ANNOTATED reason: Overly broad and not corroborated; HBS1L is a ribosome-rescue GTPase, not a signal-transduction component. supported_by: - reference_id: PMID:9872408 supporting_text: is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3-like activity references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000024 title: Manual transfer of annotations from one model organism to another based on sequence orthology findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees 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:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. findings: [] - id: PMID:19946888 title: Defining the membrane proteome of NK cells. findings: [] - id: PMID:20531386 title: 'The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L.' findings: - statement: HBS1L (via its short isoform) bridges the cytoplasmic exosome and SKI complex. reference_section_type: RESULTS - id: PMID:20947765 title: 'Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay.' findings: - statement: The Dom34:Hbs1 complex promotes ribosomal subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay. reference_section_type: RESULTS - id: PMID:21448132 title: Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes. reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Cached publications/PMID_21448132.md title matches; anchored to GOA as the IDA source for GO:0072344 (rescue of stalled cytosolic ribosome) and GO:0032790 (ribosome disassembly). Directly establishes the Pelota-HBS1L-ABCE1 ribosome-splitting/rescue core function. Cited in core_functions supported_by." findings: - statement: Pelota, Hbs1 and ABCE1 together dissociate vacant 80S ribosomes and stalled elongation complexes into subunits. reference_section_type: RESULTS - id: PMID:23667253 title: The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells. findings: - statement: The mammalian Hbs1-Dom34 complex functions in non-stop mRNA decay. reference_section_type: RESULTS - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:27863242 title: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes. reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Cached publications/PMID_27863242.md title matches; anchored to GOA as the IDA source for GO:1990533 (Dom34-Hbs1 complex), GO:0072344 (rescue of stalled cytosolic ribosome), GO:0022626 (cytosolic ribosome) and GO:0070966 (no-go decay). Cryo-EM defines HBS1L as the GTPase subunit of the PELO-HBS1L rescue complex." findings: - statement: Cryo-EM of the PELO-HBS1L complex on stalled ribosomes defines HBS1L as the GTPase subunit. reference_section_type: RESULTS - id: PMID:28204585 title: A short splicing isoform of HBS1L links the cytoplasmic exosome and SKI complexes in humans. reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Cached publications/PMID_28204585.md title matches; anchored to GOA as the EXP source for GO:0005737 (cytoplasm). Establishes the distinct short-isoform scaffolding function bridging the cytoplasmic exosome and SKI complex, a separable HBS1L role from the PELO-rescue complex." findings: - statement: A short HBS1L splice isoform links the cytoplasmic exosome and SKI complexes via direct SKIC2 and EXOSC3 binding. reference_section_type: RESULTS - id: PMID:31515488 title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:40205054 title: Multimodal cell maps as a foundation for structural and functional genomics. findings: [] - id: PMID:9872408 title: The product of the mammalian orthologue of the Saccharomyces cerevisiae HBS1 gene is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3-like activity. reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: "Cached publications/PMID_9872408.md title matches; anchored to GOA as the TAS source for GO:0005525 (GTP binding) and GO:0006412 (translation). Original characterization establishing HBS1L as an eRF3-related GTP-binding protein without release activity; foundational but not the mechanistic rescue function." findings: - statement: HBS1L is a GTP-binding protein phylogenetically related to eRF3 but lacking eRF3-like (peptide-release) activity. reference_section_type: RESULTS - id: Reactome:R-HSA-430028 title: Reactome cytosol localization (HBS1L) findings: [] - id: Reactome:R-HSA-9948299 title: Reactome ribosome rescue reaction (HBS1L) findings: [] - id: Reactome:R-HSA-9954730 title: Reactome cytosol localization (HBS1L) findings: [] - id: Reactome:R-HSA-9954919 title: Reactome ribosome rescue reaction (HBS1L) findings: [] core_functions: - description: Translational GTPase subunit of the Pelota-HBS1L (Dom34-Hbs1) complex that delivers the eRF1-like factor PELO to the A site of stalled ribosomes and, via GTP hydrolysis, licenses PELO/ABCE1-mediated subunit dissociation, rescuing stalled ribosomes and initiating no-go and non-stop mRNA decay. molecular_function: id: GO:0003924 label: GTPase activity in_complex: id: GO:1990533 label: Dom34-Hbs1 complex locations: - id: GO:0022626 label: cytosolic ribosome supported_by: - reference_id: file:human/HBS1L/HBS1L-uniprot.txt supporting_text: GTPase component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway - reference_id: PMID:21448132 supporting_text: Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes proposed_new_terms: [] suggested_questions: - question: How does HBS1L GTP hydrolysis kinetically couple PELO A-site engagement to ABCE1-driven subunit splitting? - question: To what extent does the short HBS1LV3 isoform's SKI/exosome scaffolding role function independently of the canonical Pelota-HBS1L rescue complex? suggested_experiments: - description: Reconstituted GTPase assays comparing wild-type and GTPase-dead HBS1L in PELO-dependent ribosome splitting to define the catalytic requirement for rescue. - description: Isoform-resolved interactome and rescue-activity profiling (HBS1LV1 vs HBS1LV3) to separate the ribosome-rescue and SKI/exosome scaffolding functions.