HBS1L

UniProt ID: Q9Y450
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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.

Existing Annotations Review

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

Core Functions

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:
GTPase activity
Cellular Locations:
cytosolic ribosome
In Complex:
Dom34-Hbs1 complex
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
  • PMID:21448132
    Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of annotations from one model organism to another based on sequence orthology
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exosomes.
PMID:19946888
Defining the membrane proteome of NK cells.
PMID:20531386
The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L.
  • HBS1L (via its short isoform) bridges the cytoplasmic exosome and SKI complex.
PMID:20947765
Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay.
  • The Dom34:Hbs1 complex promotes ribosomal subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay.
PMID:21448132
Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes.
  • Pelota, Hbs1 and ABCE1 together dissociate vacant 80S ribosomes and stalled elongation complexes into subunits.
PMID:23667253
The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells.
  • The mammalian Hbs1-Dom34 complex functions in non-stop mRNA decay.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:27863242
Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes.
  • Cryo-EM of the PELO-HBS1L complex on stalled ribosomes defines HBS1L as the GTPase subunit.
PMID:28204585
A short splicing isoform of HBS1L links the cytoplasmic exosome and SKI complexes in humans.
  • A short HBS1L splice isoform links the cytoplasmic exosome and SKI complexes via direct SKIC2 and EXOSC3 binding.
PMID:31515488
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
PMID:9872408
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.
  • HBS1L is a GTP-binding protein phylogenetically related to eRF3 but lacking eRF3-like (peptide-release) activity.
Reactome:R-HSA-430028
Reactome cytosol localization (HBS1L)
Reactome:R-HSA-9948299
Reactome ribosome rescue reaction (HBS1L)
Reactome:R-HSA-9954730
Reactome cytosol localization (HBS1L)
Reactome:R-HSA-9954919
Reactome ribosome rescue reaction (HBS1L)

Suggested Questions for Experts

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?

Suggested Experiments

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.

📚 Additional Documentation

Notes

(HBS1L-notes.md)

HBS1L — research notes

UniProt: Q9Y450. TRAFAC-class translation-factor GTPase, eEF1A/eRF3/Hbs1 group. Cytoplasmic.

Core function

HBS1L is the GTPase subunit of the Pelota-HBS1L (Dom34-Hbs1) complex. It delivers PELO
(eRF1-like) to the A site of stalled ribosomes and, via GTP hydrolysis, licenses PELO/ABCE1-driven
subunit dissociation (ribosome disassembly) in no-go and non-stop decay.

  • [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"]
  • [file:human/HBS1L/HBS1L-uniprot.txt "Component of the Pelota-HBS1L complex, also named Dom34-Hbs1 complex, composed of PELO and HBS1L"]
  • PMID:21448132 dissociation of stalled complexes by Pelota/Hbs1/ABCE1.
  • PMID:27863242 cryo-EM defines the complex on stalled ribosomes.
  • PMID:23667253 Hbs1-Dom34 in non-stop mRNA decay.
  • PMID:9872408 — original characterization: GTP-binding, translation-related, eRF3-like but NO eRF3 (release) activity. NOTE: this paper's TAS annotations for GTP binding / translation / signal transduction are coarse.

Isoforms

  • Isoform 2 (Q9Y450-2, "HBS1LV3", short splice form) links the SKI complex and the cytoplasmic exosome (direct SKIC2 and EXOSC3 binding) [PMID:28204585; PMID:20531386 (human exosome interactions)]. This is a distinct, isoform-specific scaffolding role.

Other / non-core

  • Bare protein binding IPI rows: PELO (Q9BRX2) is the meaningful partner; others are HT noise.
  • HDA membrane (PMID:19946888 NK-cell membrane proteome) and extracellular exosome (PMID:19056867) localizations are mass-spec catalog hits, not the functional site.
  • GO:0010629 negative regulation of gene expression (IEA, GO_REF:0000117) and GO:0007165 signal transduction (TAS, PMID:9872408) are overly broad / weakly supported.

Action plan

  • Core MF: GO:0003924 GTPase activity (with GTP binding). Core BP: GO:0072344 rescue; GO:0032790 disassembly; no-go/non-stop decay. Core CC: GO:1990533 Dom34-Hbs1 complex.
  • GO:0006412 translation: KEEP_AS_NON_CORE (broad; specific role is rescue).
  • signal transduction, neg reg gene expression, membrane, exosome localization: MARK_AS_OVER_ANNOTATED or KEEP_AS_NON_CORE.

Pn Notes

(HBS1L-pn-notes.md)

HBS1L PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9Y450
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07c
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • 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.
  • Existing/core annotation action counts: ACCEPT: 18; KEEP_AS_NON_CORE: 11; MARK_AS_OVER_ANNOTATED: 4

PN Consistency Summary

  • Consistency: Fully consistent. Deep research, review, and PN all describe HBS1L as the GTPase subunit of the Pelota-HBS1L (Dom34-Hbs1) complex that licenses PELO/ABCE1 ribosome splitting and triggers no-go/non-stop decay. The review is rich and well-aligned (multiple IDA GO:0072344, GO:0032790 ribosome disassembly, GO:0070966 no-go decay, GO:1990533 Dom34-Hbs1 complex). The isoform-2 (HBS1LV3) SKI/exosome scaffolding role is an added reviewer dimension outside the PN frame, not a contradiction.
  • PN story / NEW pressure: No NEW pressure. PN's rescue story (GO:0072344) is already in GOA exact and richly ACCEPTED in the review (IBA + 2×IDA + TAS). The group-level GO:0006515 is a broad parent already entailed by the specific rescue/RQC terms HBS1L carries. Conclusion: already captured (more specifically than the PN projection).
  • Evidence alignment: PN lists no reference titles. Review cites the canonical mechanistic set: PMID:21448132 (Pelota/Hbs1/ABCE1 dissociation), PMID:27863242 (cryo-EM), PMID:23667253 (non-stop decay), PMID:20947765 (Dom34:Hbs1 yeast), PMID:9872408 (original eRF3-related characterization), PMID:28204585 (short-isoform SKI/exosome). No citation conflict; PN simply carries no PMIDs.
  • Verdict: Fully consistent; PN rescue story already captured (more specifically) — no NEW pressure. Recommended edits: none warranted; treat group-node GO:0006515 as context-only/entailed for HBS1L (do not add as a separate annotation) [MAP].

Full Consistency Review

  • UniProt: Q9Y450 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
  • PN placement: Translation|Cytosolic translation|Ribosome-associated QC|Ribosomal rescue ; PN-node mapping: type Ribosomal rescue=mapped→GO:0072344 rescue of stalled cytosolic ribosome (already_in_goa_exact); group Ribosome-associated QC=mapped→GO:0006515 protein quality control (new_to_goa); class/branch=context_only.
  • Consistency: Fully consistent. Deep research, review, and PN all describe HBS1L as the GTPase subunit of the Pelota-HBS1L (Dom34-Hbs1) complex that licenses PELO/ABCE1 ribosome splitting and triggers no-go/non-stop decay. The review is rich and well-aligned (multiple IDA GO:0072344, GO:0032790 ribosome disassembly, GO:0070966 no-go decay, GO:1990533 Dom34-Hbs1 complex). The isoform-2 (HBS1LV3) SKI/exosome scaffolding role is an added reviewer dimension outside the PN frame, not a contradiction.
  • PN story / NEW pressure: No NEW pressure. PN's rescue story (GO:0072344) is already in GOA exact and richly ACCEPTED in the review (IBA + 2×IDA + TAS). The group-level GO:0006515 is a broad parent already entailed by the specific rescue/RQC terms HBS1L carries. Conclusion: already captured (more specifically than the PN projection).
  • Mapping strategy: Mapping matches precedent correctly — type-node GO:0072344 is exact and already in GOA; group-node GO:0006515 is a broader parent and should be treated as entailed/context, not separately propagated (would duplicate the more specific rescue/no-go terms). No node change driven by this gene.
  • Evidence alignment: PN lists no reference titles. Review cites the canonical mechanistic set: PMID:21448132 (Pelota/Hbs1/ABCE1 dissociation), PMID:27863242 (cryo-EM), PMID:23667253 (non-stop decay), PMID:20947765 (Dom34:Hbs1 yeast), PMID:9872408 (original eRF3-related characterization), PMID:28204585 (short-isoform SKI/exosome). No citation conflict; PN simply carries no PMIDs.
  • Verdict: Fully consistent; PN rescue story already captured (more specifically) — no NEW pressure. Recommended edits: none warranted; treat group-node GO:0006515 as context-only/entailed for HBS1L (do not add as a separate annotation) [MAP].

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/HBS1L/HBS1L-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Translation | Cytosolic translation | Ribosome-associated QC | Ribosomal rescue

  • UniProt: Q9Y450
  • In branches: TR
  • PN-node mapping records (path + ancestors):
    • [type] Translation|Cytosolic translation|Ribosome-associated QC|Ribosomal rescue
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0072344 rescue of stalled cytosolic ribosome]
      rationale: This PN RQC type denotes rescue of stalled cytosolic ribosomes. The matching GO process term is the direct target.
    • [group] Translation|Cytosolic translation|Ribosome-associated QC
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0006515 protein quality control for misfolded or incompletely synthesized proteins]
      rationale: The PN ribosome-associated quality-control group covers surveillance and disposal of stalled or defective nascent-chain translation products. GO lacks a dedicated ribosome-associated QC term in the local cache, so the broader protein-quality-control process is the best supported target.
    • [class] Translation|Cytosolic translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
      rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
    • [branch] Translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
      rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

Projected GO annotations (2)

  • GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome-associated QC
  • GO:0072344 rescue of stalled cytosolic ribosome | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Translation|Cytosolic translation|Ribosome-associated QC|Ribosomal rescue

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
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.