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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0072344 rescue of stalled cytosolic ribosome | IBA GO_REF:0000033 | ACCEPT | 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. Reason: Core process; conserved across yeast Hbs1 and human HBS1L and supported by direct mammalian biochemistry. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt GTPase component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway |
| GO:0003924 GTPase activity | IBA GO_REF:0000033 | ACCEPT | Summary: HBS1L is a translational GTPase; GTP hydrolysis drives delivery of PELO and licensing of ribosome splitting. Core molecular function. Reason: GTPase activity is the defining catalytic function of HBS1L, supported by family membership and the UniProt catalytic activity record. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt GTPase component of the Pelota-HBS1L complex |
| GO:0006412 translation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: HBS1L is associated with the translation apparatus, but its specific role is ribosome rescue/surveillance rather than productive protein synthesis. Reason: Broad parent process; the informative role is rescue of stalled ribosomes, captured by more specific terms. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt GTPase component of the Pelota-HBS1L complex |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic transfer of GTPase activity, consistent with the experimentally and phylogenetically supported function. Reason: Correct core molecular function; redundant with IBA/ISS annotations. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt GTPase component of the Pelota-HBS1L complex |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: HBS1L binds GTP as a translational GTPase; necessary for its catalytic cycle. Reason: GTP binding is a well-supported molecular function underlying GTPase activity. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt GTPase component of the Pelota-HBS1L complex |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic cytoplasmic localization, consistent with the documented and experimentally supported cytoplasmic site of action. Reason: Correct compartment, corroborated by experimental (EXP) cytoplasm evidence. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | 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. Reason: Generic and indirect; the mechanistic role is ribosome rescue / no-go and non-stop mRNA decay, not transcriptional/general gene-expression regulation. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt triggers the No-Go Decay (NGD) pathway |
| GO:0005515 protein binding | IPI PMID:20531386 The human core exosome interacts with differentially localiz... | KEEP AS NON CORE | 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. Reason: Real interaction underlying the isoform-specific SKI/exosome scaffolding role; bare protein binding term is uninformative. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt Associates with the exosome complex; the interaction with EXOSC3 is direct |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Yeast two-hybrid interactome capturing the HBS1L-PELO interaction (the defining partner). Bare protein binding term. Reason: The PELO interaction is core but is already captured by the complex term; the generic protein binding term itself is non-core. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt composed of PELO and HBS1L |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Interactome screen capturing HBS1L interactions including PELO. Bare protein binding. Reason: Generic term; the relevant PELO interaction is captured elsewhere. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt composed of PELO and HBS1L |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary interactome map; HBS1L-PELO plus other partners. Bare protein binding. Reason: Generic term; PELO is the functionally meaningful partner. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt composed of PELO and HBS1L |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex affinity-purification interactome capturing HBS1L interactions. Bare protein binding. Reason: Records physical interactions but the generic term is uninformative for core function. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt composed of PELO and HBS1L |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Multimodal cell-maps interactome capturing HBS1L interactions. Bare protein binding. Reason: Generic term; non-core. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt composed of PELO and HBS1L |
| GO:0072344 rescue of stalled cytosolic ribosome | TAS Reactome:R-HSA-9948299 | ACCEPT | Summary: Reactome curated ribosome-rescue role of HBS1L. Core process. Reason: Curated TAS annotation consistent with the experimentally supported core function. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt triggers the No-Go Decay (NGD) pathway |
| GO:0003924 GTPase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of GTPase activity; consistent with family and direct evidence. Reason: Correct core molecular function. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt GTPase component of the Pelota-HBS1L complex |
| GO:0005737 cytoplasm | EXP PMID:28204585 A short splicing isoform of HBS1L links the cytoplasmic exos... | ACCEPT | Summary: Experimental cytoplasmic localization, consistent with HBS1L's site of action. Reason: Experimentally supported localization to the cytoplasm. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0003924 GTPase activity | TAS Reactome:R-HSA-9954919 | ACCEPT | Summary: Reactome curated GTPase activity in the ribosome-rescue pathway. Reason: Curated TAS consistent with the core molecular function. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt GTPase component of the Pelota-HBS1L complex |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9954730 | KEEP AS NON CORE | Summary: Reactome curated cytosolic localization, consistent with site of action. Reason: Correct but generic localization. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9954919 | KEEP AS NON CORE | Summary: Reactome curated cytosolic localization (duplicate context). Reason: Correct but generic localization. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0003924 GTPase activity | ISS PMID:20947765 Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA d... | ACCEPT | Summary: Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off; HBS1L GTPase activity inferred by similarity to characterized yeast Hbs1. Reason: Core molecular function supported by orthology and mechanistic studies of the Dom34:Hbs1 complex. Supporting Evidence: PMID:20947765 Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay |
| GO:0022626 cytosolic ribosome | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: Direct cryo-EM evidence places HBS1L on the stalled cytosolic 80S ribosome. Reason: Strong direct structural evidence for HBS1L acting on the cytosolic ribosome. Supporting Evidence: PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes |
| GO:0032790 ribosome disassembly | IDA PMID:21448132 Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 8... | ACCEPT | Summary: With PELO and ABCE1, HBS1L drives dissociation of 80S ribosomes into subunits (in vitro reconstitution). Reason: Directly demonstrated; subunit dissociation is the mechanistic output of the complex. Supporting Evidence: PMID:21448132 Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes |
| GO:0070966 nuclear-transcribed mRNA catabolic process, no-go decay | IDA PMID:23667253 The Hbs1-Dom34 protein complex functions in non-stop mRNA de... | ACCEPT | Summary: HBS1L (Hbs1-Dom34 complex) functions in no-go/non-stop mRNA decay in mammalian cells. Reason: Directly demonstrated mRNA-decay role. Supporting Evidence: PMID:23667253 The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells |
| GO:0070966 nuclear-transcribed mRNA catabolic process, no-go decay | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: Structural study supporting the complex's role in recognizing stalled ribosomes that triggers no-go decay. Reason: Direct evidence for the recognition step that triggers NGD. Supporting Evidence: PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:21448132 Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 8... | ACCEPT | Summary: In vitro reconstitution shows HBS1L (with PELO/ABCE1) rescues stalled elongation complexes. Reason: Directly demonstrated core biological process. Supporting Evidence: PMID:21448132 Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: Structural demonstration of HBS1L engaging stalled ribosomes for rescue. Reason: Direct structural evidence for the rescue process. Supporting Evidence: PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes |
| GO:1990533 Dom34-Hbs1 complex | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: HBS1L directly identified as a component of the Pelota-HBS1L (Dom34-Hbs1) complex by cryo-EM. Reason: Direct evidence for HBS1L as a complex subunit. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt Component of the Pelota-HBS1L complex, also named Dom34-Hbs1 complex, composed of PELO and HBS1L |
| GO:0005829 cytosol | TAS Reactome:R-HSA-430028 | KEEP AS NON CORE | Summary: Reactome curated cytosolic localization. Reason: Correct but generic localization. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: High-throughput NK-cell membrane proteome detection. Not the functional site for this cytoplasmic GTPase. Reason: Mass-spectrometry catalog localization that conflicts with the documented cytoplasmic site of action; likely co-purification. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: High-throughput extracellular-vesicle proteome detection. Not the functional compartment. Reason: Proteomic catalog localization unrelated to HBS1L's cytoplasmic ribosome-rescue function. Supporting Evidence: file:human/HBS1L/HBS1L-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005525 GTP binding | TAS PMID:9872408 The product of the mammalian orthologue of the Saccharomyces... | ACCEPT | Summary: Original characterization showing HBS1L is a GTP-binding protein phylogenetically related to eRF3 but lacking eRF3 release activity. Reason: Author-curated GTP binding, consistent with the core GTPase function. Supporting Evidence: PMID:9872408 is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3-like activity |
| GO:0006412 translation | TAS PMID:9872408 The product of the mammalian orthologue of the Saccharomyces... | KEEP AS NON CORE | Summary: HBS1L was assigned to translation as a translation-factor-related GTPase; its specific role is ribosome rescue/surveillance. Reason: Broad process; the informative function is rescue of stalled ribosomes. Supporting Evidence: PMID:9872408 is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3-like activity |
| GO:0007165 signal transduction | TAS PMID:9872408 The product of the mammalian orthologue of the Saccharomyces... | MARK AS OVER ANNOTATED | Summary: Generic signal-transduction assignment in the original cloning paper; not supported by any subsequent mechanistic role for HBS1L. Reason: Overly broad and not corroborated; HBS1L is a ribosome-rescue GTPase, not a signal-transduction component. Supporting Evidence: PMID:9872408 is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3-like activity |
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Download this section (compressed HTML)Q: How does HBS1L GTP hydrolysis kinetically couple PELO A-site engagement to ABCE1-driven subunit splitting?
Q: To what extent does the short HBS1LV3 isoform's SKI/exosome scaffolding role function independently of the canonical Pelota-HBS1L rescue complex?
Experiment: Reconstituted GTPase assays comparing wild-type and GTPase-dead HBS1L in PELO-dependent ribosome splitting to define the catalytic requirement for rescue.
Experiment: Isoform-resolved interactome and rescue-activity profiling (HBS1LV1 vs HBS1LV3) to separate the ribosome-rescue and SKI/exosome scaffolding functions.
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