GTPBP6

UniProt ID: O43824
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

GTPBP6 (Putative GTP-binding protein 6, PGPL) is a TRAFAC-class OBG-HflX-like GTPase encoded by a pseudoautosomal gene near the Xp/Yp telomere. It functions in mitochondria as one of several conserved GTPases (alongside GTPBP5, GTPBP7 and GTPBP10) that drive late maturation of the mitochondrial large ribosomal subunit (mtLSU). GTPBP6 acts at a final step of mtLSU biogenesis, triggering a molecular switch that drives progression to a near-mature peptidyl transferase centre (PTC), and additionally has a role in recycling/dissociation of mature mitochondrial ribosomes, giving it a dual role in mitoribosome biogenesis and recycling. Its activity is GTP-dependent, consistent with the conserved G-domain motifs of the OBG-HflX-like family.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0043022 ribosome binding
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Phylogenetic transfer of ribosome binding from bacterial ObgE/CgtA-like orthologs. GTPBP6 does bind the ribosome, but in human cells the relevant substrate is the mitochondrial large ribosomal subunit rather than the cytoplasmic ribosome.
Reason: Ribosome binding is correct at the family level, but the specific, experimentally supported activity is binding the mitochondrial large ribosomal subunit (captured by the IDA GO:0043023 annotation). Retained as a non-core general term.
Supporting Evidence:
PMID:34135319
the GTPases GTPBP5, GTPBP6, GTPBP7, and GTPBP10 mediate mtLSU maturation
GO:0005737 cytoplasm
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: Phylogenetic transfer of cytoplasmic localization from bacterial orthologs. The experimentally characterized human GTPBP6 acts in the mitochondrion on the mitoribosome, so this generic cytoplasmic localization is misleading.
Reason: GTPBP6 localizes to and acts in mitochondria (HTP mitochondrion; mtLSU biogenesis), not the general cytoplasm; the IBA cytoplasm transfer from bacterial orthologs does not reflect the human protein's compartment.
Supporting Evidence:
PMID:34135319
the GTPases GTPBP5, GTPBP6, GTPBP7, and GTPBP10 mediate mtLSU maturation
GO:0005525 GTP binding
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro-based assignment of GTP binding, consistent with the conserved G-domain motifs of the OBG-HflX-like GTPase family.
Reason: GTPBP6 is a GTPase with canonical G-domain motifs; GTP binding is a core molecular function that underlies its role as a maturation/recycling GTPase.
Supporting Evidence:
file:human/GTPBP6/GTPBP6-uniprot.txt
Belongs to the TRAFAC class OBG-HflX-like GTPase
GO:0043023 ribosomal large subunit binding
IDA
PMID:34135319
Structural basis of GTPase-mediated mitochondrial ribosome b... 		ACCEPT
Summary: Direct evidence (cryo-EM, in vitro reconstitution) that GTPBP6 binds the mitochondrial large ribosomal subunit during late mtLSU maturation and recycling.
Reason: Direct experimental support for GTPBP6 binding the large (mito)ribosomal subunit; this is a core molecular function.
Supporting Evidence:
PMID:34135319
Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state
GO:1902775 mitochondrial large ribosomal subunit assembly
IDA
PMID:34135319
Structural basis of GTPase-mediated mitochondrial ribosome b... 		ACCEPT
Summary: Direct evidence that GTPBP6 is required for and drives late assembly/maturation of the mitochondrial large ribosomal subunit (PTC folding), with GTPBP6-deficient cells accumulating late mtLSU intermediates.
Reason: Direct experimental support for GTPBP6's core biological process; this is its principal characterized function.
Supporting Evidence:
PMID:34135319
Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding
GO:0005739 mitochondrion
HTP
PMID:34800366
Quantitative high-confidence human mitochondrial proteome an... 		ACCEPT
Summary: High-throughput proteomic evidence that GTPBP6 localizes to mitochondria, consistent with its role in mitoribosome biogenesis.
Reason: Mitochondrial localization is the correct compartment for GTPBP6 and is consistent with the mtLSU-maturation function; this should be regarded as the core localization (in preference to the IBA cytoplasm transfer).
Supporting Evidence:
file:human/GTPBP6/GTPBP6-goa.tsv
GO:0005739 mitochondrion cellular_component ECO:0006056 HTP PMID:34800366
GO:0005525 GTP binding
TAS
PMID:9466997
A novel pseudoautosomal gene encoding a putative GTP-binding... 		ACCEPT
Summary: The original cloning paper reported the GTP-binding protein domain motifs of PGPL/GTPBP6.
Reason: Author-stated GTP-binding consensus motifs, consistent with the InterPro assignment and the protein's GTPase family; supports the core MF.
Supporting Evidence:
PMID:9466997
shows the consensus sequences of a series of motifs of the GTP-binding protein domain

Core Functions

Mitochondrial OBG-HflX-like GTPase that binds the mitochondrial large ribosomal subunit and uses GTP to drive a late maturation step (PTC folding) of mtLSU biogenesis, and to promote recycling of mature mitochondrial ribosomes.

Molecular Function:
ribosomal large subunit binding
Cellular Locations:
mitochondrion
Supporting Evidence:
  • PMID:34135319
    Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state
  • PMID:34135319
    the GTPases GTPBP5, GTPBP6, GTPBP7, and GTPBP10 mediate mtLSU maturation

GTP-binding/GTPase activity of the OBG-HflX-like G-domain that powers GTPBP6's role as a mitoribosome maturation/recycling factor.

Molecular Function:
GTP binding
Cellular Locations:
mitochondrion
Supporting Evidence:
  • file:human/GTPBP6/GTPBP6-uniprot.txt
    Belongs to the TRAFAC class OBG-HflX-like GTPase
  • PMID:9466997
    shows the consensus sequences of a series of motifs of the GTP-binding protein domain

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
PMID:34135319
Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling.
  • GTPBP6 (with GTPBP5, GTPBP7, GTPBP10) mediates late maturation of the mitochondrial large ribosomal subunit; recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and triggers progression to a near-mature PTC state.
  • GTPBP6 has a dual role in mitochondrial ribosome biogenesis and recycling.
PMID:34800366
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
  • GTPBP6 is detected as a component of the human mitochondrial proteome.
PMID:9466997
A novel pseudoautosomal gene encoding a putative GTP-binding protein resides in the vicinity of the Xp/Yp telomere.
  • PGPL (GTPBP6) is a pseudoautosomal gene encoding a 442-aa protein with consensus GTP-binding protein domain motifs; it escapes X inactivation and has a Y-chromosome homologue.

Suggested Questions for Experts

Q: Does human GTPBP6 have any role on cytoplasmic ribosomes, or is its function exclusively mitochondrial (the IBA cytoplasm transfer derives from bacterial orthologs)?

Q: What is the precise GTPase cycle (activating factors, GAP) that couples GTPBP6 nucleotide state to the molecular switch driving PTC maturation?

Suggested Experiments

Experiment: Subcellular fractionation and high-resolution imaging of endogenous GTPBP6 to definitively establish mitochondrial localization and exclude a cytoplasmic ribosome-associated pool.

Experiment: GTPase-dead (G-domain mutant) GTPBP6 rescue experiments in GTPBP6-knockout cells to test whether GTP hydrolysis is required for mtLSU maturation versus ribosome recycling.

📚 Additional Documentation

Notes

(GTPBP6-notes.md)

GTPBP6 (Putative GTP-binding protein 6, PGPL) — research notes

UniProt O43824. TRAFAC-class OBG-HflX-like GTPase. Pseudoautosomal gene (Xp/Yp telomere), escapes X-inactivation, Y homologue PMID:9466997.

Function — mitochondrial ribosome biogenesis & recycling

Despite being annotated by some IBA pipelines (from bacterial ObgE/CgtA ortholog P25519) as cytoplasmic ribosome-binding, the experimentally characterized human function is in MITOCHONDRIA:
- PMID:34135319
- PMID:34135319
- PMID:34135319
- PMID:34800366 mito proteome — GTPBP6 localizes to mitochondrion (HTP).

So: localization = mitochondrion (mitochondrial matrix/mitoribosome), NOT cytoplasm. MF = GTP binding + ribosomal large subunit binding (the mtLSU). BP = mitochondrial large ribosomal subunit assembly + (mitochondrial) ribosome recycling.

Decisions

  • ribosome binding (IBA, from bacterial ortholog) — the real binding is to the mtLSU; MODIFY/keep general or KEEP_AS_NON_CORE; the specific ribosomal large subunit binding (IDA 34135319) is core.
  • cytoplasm (IBA is_active_in, from bacterial ortholog P25519) — the human protein acts in the mitochondrion; this IBA mislocalizes; MARK_AS_OVER_ANNOTATED / flag. Mitochondrion (HTP 34800366) is correct.
  • GTP binding (IEA InterPro, TAS 9466997) — ACCEPT (G-domain motifs; core MF support).
  • ribosomal large subunit binding (IDA 34135319) — ACCEPT core (binds mtLSU).
  • mitochondrial large ribosomal subunit assembly (IDA 34135319) — ACCEPT core BP.
  • mitochondrion (HTP 34800366) — ACCEPT.

Pn Notes

(GTPBP6-pn-notes.md)

GTPBP6 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: O43824
  • 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: GTPBP6 (Putative GTP-binding protein 6, PGPL) is a TRAFAC-class OBG-HflX-like GTPase encoded by a pseudoautosomal gene near the Xp/Yp telomere. It functions in mitochondria as one of several conserved GTPases (alongside GTPBP5, GTPBP7 and GTPBP10) that drive late maturation of the mitochondrial large ribosomal subunit (mtLSU). GTPBP6 acts at a final step of mtLSU biogenesis, triggering a molecular switch that drives progression to a near-mature peptidyl transferase centre (PTC), and additionally has a role in recycling/dissociation of mature mitochondrial ribosomes, giving it a dual role in mitoribosome biogenesis and recycling. Its activity is GTP-dependent, consistent with the conserved G-domain motifs of the OBG-HflX-like family.
  • Existing/core annotation action counts: ACCEPT: 5; KEEP_AS_NON_CORE: 1; MARK_AS_OVER_ANNOTATED: 1

PN Consistency Summary

  • Consistency: Partial mismatch. The review and notes cover ONLY the biogenesis arm (row 1): GO:1902775 mitochondrial large ribosomal subunit assembly (IDA), GO:0043023 mtLSU binding (IDA), mitochondrion, GTP binding. The review description does mention "recycling/dissociation of mature mitochondrial ribosomes ... dual role" (PMID:34135319), which maps to PN row 2's ribosome-rescue/recycling concept — but the review carries NO process annotation for it. PN row 2's GO:7770016 (rescue of stalled mitochondrial ribosome) and GO:0070126 (mitochondrial translational termination) are therefore absent from the review. Note: PN's "39S subunit assembly" maps to GO:0061668 (mito ribosome assembly, parent) whereas the review uses the more specific GO:1902775 (mtLSU assembly) — review is appropriately narrower.
  • PN story / NEW pressure: PN row 2 asserts a stalled-mitoribosome-rescue/termination role not in GTPBP6 GOA and not in the review's annotations. Both projected terms verified real (GO:7770016 def: "freeing the ribosome from the stalled translation complex"; GO:0070126). However the review's recycling claim is dissociation of MATURE mitoribosomes (PMID:34135319), which is ribosome recycling, not stalled-ribosome rescue/termination — so GO:7770016 (stalled) may over-reach relative to the actual evidence; mitochondrial ribosome recycling / GO:0070126 is the better-fitting concept. Conclusion: biogenesis already captured (more specifically); row-2 termination story is over-reaches as "stalled-ribosome rescue" but a recycling term is defensible.
  • Evidence alignment: PN lists no titles. Review anchors on PMID:34135319 (the single key structural paper, supports both biogenesis AND recycling), PMID:34800366 (mito proteome), PMID:9466997 (cloning). PN row 2 cites no PMID to compare.
  • Verdict: Mostly consistent on biogenesis (already captured, review narrower); row-2 stalled-ribosome-rescue projection over-reaches vs the recycling evidence. Recommended edits: keep GO:7770016 as context-only / do not propagate to GTPBP6 unless stalled-ribosome evidence is found [MAP]; optionally add a mitochondrial-ribosome-recycling process annotation (anchored to PMID:34135319 dual-role) to capture row 2 accurately [YAML].

Full Consistency Review

  • UniProt: O43824 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
  • PN placement: TWO rows. Row 1 Translation|Mitochondrial translation|Mitoribosome biogenesis factor|39S subunit assembly (type & group=mapped→GO:0061668 mitochondrial ribosome assembly). Row 2 Translation|Mitochondrial translation|Translation termination|Termination on stalled ribosomes (type=mapped→GO:7770016 rescue of stalled mitochondrial ribosome [new_to_goa]; group=mapped→GO:0070126 mitochondrial translational termination [new_to_goa]). Class/branch=context_only.
  • Consistency: Partial mismatch. The review and notes cover ONLY the biogenesis arm (row 1): GO:1902775 mitochondrial large ribosomal subunit assembly (IDA), GO:0043023 mtLSU binding (IDA), mitochondrion, GTP binding. The review description does mention "recycling/dissociation of mature mitochondrial ribosomes ... dual role" (PMID:34135319), which maps to PN row 2's ribosome-rescue/recycling concept — but the review carries NO process annotation for it. PN row 2's GO:7770016 (rescue of stalled mitochondrial ribosome) and GO:0070126 (mitochondrial translational termination) are therefore absent from the review. Note: PN's "39S subunit assembly" maps to GO:0061668 (mito ribosome assembly, parent) whereas the review uses the more specific GO:1902775 (mtLSU assembly) — review is appropriately narrower.
  • PN story / NEW pressure: PN row 2 asserts a stalled-mitoribosome-rescue/termination role not in GTPBP6 GOA and not in the review's annotations. Both projected terms verified real (GO:7770016 def: "freeing the ribosome from the stalled translation complex"; GO:0070126). However the review's recycling claim is dissociation of MATURE mitoribosomes (PMID:34135319), which is ribosome recycling, not stalled-ribosome rescue/termination — so GO:7770016 (stalled) may over-reach relative to the actual evidence; mitochondrial ribosome recycling / GO:0070126 is the better-fitting concept. Conclusion: biogenesis already captured (more specifically); row-2 termination story is over-reaches as "stalled-ribosome rescue" but a recycling term is defensible.
  • Mapping strategy: Row 1 fine. Row 2 changes nothing in the review and risks projecting a stalled-rescue term onto a recycling function — recommend treating GO:7770016 as context-only for GTPBP6 pending evidence that GTPBP6 acts on STALLED (not mature) mitoribosomes.
  • Evidence alignment: PN lists no titles. Review anchors on PMID:34135319 (the single key structural paper, supports both biogenesis AND recycling), PMID:34800366 (mito proteome), PMID:9466997 (cloning). PN row 2 cites no PMID to compare.
  • Verdict: Mostly consistent on biogenesis (already captured, review narrower); row-2 stalled-ribosome-rescue projection over-reaches vs the recycling evidence. Recommended edits: keep GO:7770016 as context-only / do not propagate to GTPBP6 unless stalled-ribosome evidence is found [MAP]; optionally add a mitochondrial-ribosome-recycling process annotation (anchored to PMID:34135319 dual-role) to capture row 2 accurately [YAML].

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/GTPBP6/GTPBP6-ai-review.yaml
  • PN workbook rows: 2

PN row 1: Translation | Mitochondrial translation | Mitoribosome biogenesis factor | 39S subunit assembly

  • UniProt: O43824
  • In branches: TR
  • PN-node mapping records (path + ancestors):
    • [type] Translation|Mitochondrial translation|Mitoribosome biogenesis factor|39S subunit assembly
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0061668 mitochondrial ribosome assembly]
      rationale: This PN type denotes 39S mitoribosomal subunit assembly factors. Mitochondrial ribosome assembly is the shared process target.
    • [group] Translation|Mitochondrial translation|Mitoribosome biogenesis factor
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0061668 mitochondrial ribosome assembly]
      rationale: This PN group denotes factors for mitoribosome assembly and maturation. Mitochondrial ribosome assembly is the most specific shared process target.
    • [class] Translation|Mitochondrial translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0032543 mitochondrial translation]
      rationale: This PN class is a useful mitochondrial-translation context, but it contains ribosome components, assembly factors, tRNA synthetases, regulatory factors, and translation factors. Direct propagation to mitochondrial translation would over-annotate several adjacent machinery classes, so the relationship is retained as context only.
    • [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.

PN row 2: Translation | Mitochondrial translation | Translation termination | Termination on stalled ribosomes

  • UniProt: O43824
  • In branches: TR
  • PN-node mapping records (path + ancestors):
    • [type] Translation|Mitochondrial translation|Translation termination|Termination on stalled ribosomes
      status=mapped scope=ok_for_propagation_to_go GO=[GO:7770016 rescue of stalled mitochondrial ribosome]
      rationale: This PN type denotes handling of stalled mitochondrial ribosomes. The GO rescue of stalled mitochondrial ribosome process is the best matching target.
    • [group] Translation|Mitochondrial translation|Translation termination
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0070126 mitochondrial translational termination]
      rationale: This PN group denotes mitochondrial translation termination machinery. The matching GO process term is appropriate for propagation.
    • [class] Translation|Mitochondrial translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0032543 mitochondrial translation]
      rationale: This PN class is a useful mitochondrial-translation context, but it contains ribosome components, assembly factors, tRNA synthetases, regulatory factors, and translation factors. Direct propagation to mitochondrial translation would over-annotate several adjacent machinery classes, so the relationship is retained as context only.
    • [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 (4)

  • GO:0061668 mitochondrial ribosome assembly | scope=ok_for_propagation_to_go | goa_status=entailed_by_goa_closure | from=Translation|Mitochondrial translation|Mitoribosome biogenesis factor
  • GO:0061668 mitochondrial ribosome assembly | scope=ok_for_propagation_to_go | goa_status=entailed_by_goa_closure | from=Translation|Mitochondrial translation|Mitoribosome biogenesis factor|39S subunit assembly
  • GO:0070126 mitochondrial translational termination | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Mitochondrial translation|Translation termination
  • GO:7770016 rescue of stalled mitochondrial ribosome | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Mitochondrial translation|Translation termination|Termination on stalled ribosomes

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: O43824
gene_symbol: GTPBP6
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: GTPBP6 (Putative GTP-binding protein 6, PGPL) is a TRAFAC-class OBG-HflX-like
  GTPase encoded by a pseudoautosomal gene near the Xp/Yp telomere. It functions in
  mitochondria as one of several conserved GTPases (alongside GTPBP5, GTPBP7 and GTPBP10)
  that drive late maturation of the mitochondrial large ribosomal subunit (mtLSU). GTPBP6
  acts at a final step of mtLSU biogenesis, triggering a molecular switch that drives
  progression to a near-mature peptidyl transferase centre (PTC), and additionally has
  a role in recycling/dissociation of mature mitochondrial ribosomes, giving it a dual
  role in mitoribosome biogenesis and recycling. Its activity is GTP-dependent, consistent
  with the conserved G-domain motifs of the OBG-HflX-like family.
existing_annotations:
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic transfer of ribosome binding from bacterial ObgE/CgtA-like
      orthologs. GTPBP6 does bind the ribosome, but in human cells the relevant substrate
      is the mitochondrial large ribosomal subunit rather than the cytoplasmic ribosome.
    action: KEEP_AS_NON_CORE
    reason: Ribosome binding is correct at the family level, but the specific, experimentally
      supported activity is binding the mitochondrial large ribosomal subunit (captured
      by the IDA GO:0043023 annotation). Retained as a non-core general term.
    supported_by:
    - reference_id: PMID:34135319
      supporting_text: the GTPases GTPBP5, GTPBP6, GTPBP7, and GTPBP10 mediate mtLSU
        maturation
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic transfer of cytoplasmic localization from bacterial orthologs.
      The experimentally characterized human GTPBP6 acts in the mitochondrion on the
      mitoribosome, so this generic cytoplasmic localization is misleading.
    action: MARK_AS_OVER_ANNOTATED
    reason: GTPBP6 localizes to and acts in mitochondria (HTP mitochondrion; mtLSU
      biogenesis), not the general cytoplasm; the IBA cytoplasm transfer from bacterial
      orthologs does not reflect the human protein's compartment.
    supported_by:
    - reference_id: PMID:34135319
      supporting_text: the GTPases GTPBP5, GTPBP6, GTPBP7, and GTPBP10 mediate mtLSU
        maturation
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based assignment of GTP binding, consistent with the conserved
      G-domain motifs of the OBG-HflX-like GTPase family.
    action: ACCEPT
    reason: GTPBP6 is a GTPase with canonical G-domain motifs; GTP binding is a core
      molecular function that underlies its role as a maturation/recycling GTPase.
    supported_by:
    - reference_id: file:human/GTPBP6/GTPBP6-uniprot.txt
      supporting_text: Belongs to the TRAFAC class OBG-HflX-like GTPase
- term:
    id: GO:0043023
    label: ribosomal large subunit binding
  evidence_type: IDA
  original_reference_id: PMID:34135319
  qualifier: enables
  review:
    summary: Direct evidence (cryo-EM, in vitro reconstitution) that GTPBP6 binds the
      mitochondrial large ribosomal subunit during late mtLSU maturation and recycling.
    action: ACCEPT
    reason: Direct experimental support for GTPBP6 binding the large (mito)ribosomal
      subunit; this is a core molecular function.
    supported_by:
    - reference_id: PMID:34135319
      supporting_text: Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis
        in vitro and shows that GTPBP6 triggers a molecular switch and progression
        to a near-mature PTC state
- term:
    id: GO:1902775
    label: mitochondrial large ribosomal subunit assembly
  evidence_type: IDA
  original_reference_id: PMID:34135319
  qualifier: involved_in
  review:
    summary: Direct evidence that GTPBP6 is required for and drives late assembly/maturation
      of the mitochondrial large ribosomal subunit (PTC folding), with GTPBP6-deficient
      cells accumulating late mtLSU intermediates.
    action: ACCEPT
    reason: Direct experimental support for GTPBP6's core biological process; this
      is its principal characterized function.
    supported_by:
    - reference_id: PMID:34135319
      supporting_text: Structures of transient native mtLSU assembly intermediates
        that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors
        GTPBP5, MTERF4 and NSUN4 facilitate PTC folding
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput proteomic evidence that GTPBP6 localizes to mitochondria,
      consistent with its role in mitoribosome biogenesis.
    action: ACCEPT
    reason: Mitochondrial localization is the correct compartment for GTPBP6 and is
      consistent with the mtLSU-maturation function; this should be regarded as the
      core localization (in preference to the IBA cytoplasm transfer).
    supported_by:
    - reference_id: file:human/GTPBP6/GTPBP6-goa.tsv
      supporting_text: GO:0005739 mitochondrion cellular_component ECO:0006056 HTP
        PMID:34800366
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: TAS
  original_reference_id: PMID:9466997
  qualifier: enables
  review:
    summary: The original cloning paper reported the GTP-binding protein domain motifs
      of PGPL/GTPBP6.
    action: ACCEPT
    reason: Author-stated GTP-binding consensus motifs, consistent with the InterPro
      assignment and the protein's GTPase family; supports the core MF.
    supported_by:
    - reference_id: PMID:9466997
      supporting_text: shows the consensus sequences of a series of motifs of the GTP-binding
        protein domain
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: PMID:34135319
  title: Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and
    recycling.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publications/PMID_34135319.md title matches; anchored to GOA
      as the IDA source for GO:0043023 (ribosomal large subunit binding) and
      GO:1902775 (mtLSU assembly). Recombinant GTPBP6 reconstitutes late mtLSU
      biogenesis in vitro, directly establishing the core function. Cited in
      core_functions supported_by."
  findings:
  - statement: GTPBP6 (with GTPBP5, GTPBP7, GTPBP10) mediates late maturation of the
      mitochondrial large ribosomal subunit; recombinant GTPBP6 reconstitutes late
      mtLSU biogenesis in vitro and triggers progression to a near-mature PTC state.
    reference_section_type: ABSTRACT
  - statement: GTPBP6 has a dual role in mitochondrial ribosome biogenesis and recycling.
    reference_section_type: ABSTRACT
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings:
  - statement: GTPBP6 is detected as a component of the human mitochondrial proteome.
    reference_section_type: RESULTS
- id: PMID:9466997
  title: A novel pseudoautosomal gene encoding a putative GTP-binding protein resides
    in the vicinity of the Xp/Yp telomere.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Cached publications/PMID_9466997.md title matches; anchored to GOA
      as the TAS source for GO:0005525 (GTP binding). Original PGPL/GTPBP6 cloning and
      pseudoautosomal characterization, supporting the G-domain/GTP-binding function
      rather than the mitoribosome-maturation role directly."
  findings:
  - statement: PGPL (GTPBP6) is a pseudoautosomal gene encoding a 442-aa protein with
      consensus GTP-binding protein domain motifs; it escapes X inactivation and has
      a Y-chromosome homologue.
    reference_section_type: ABSTRACT
core_functions:
- description: Mitochondrial OBG-HflX-like GTPase that binds the mitochondrial large
    ribosomal subunit and uses GTP to drive a late maturation step (PTC folding) of
    mtLSU biogenesis, and to promote recycling of mature mitochondrial ribosomes.
  molecular_function:
    id: GO:0043023
    label: ribosomal large subunit binding
  locations:
  - id: GO:0005739
    label: mitochondrion
  supported_by:
  - reference_id: PMID:34135319
    supporting_text: Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis
      in vitro and shows that GTPBP6 triggers a molecular switch and progression to
      a near-mature PTC state
  - reference_id: PMID:34135319
    supporting_text: the GTPases GTPBP5, GTPBP6, GTPBP7, and GTPBP10 mediate mtLSU
      maturation
- description: GTP-binding/GTPase activity of the OBG-HflX-like G-domain that powers
    GTPBP6's role as a mitoribosome maturation/recycling factor.
  molecular_function:
    id: GO:0005525
    label: GTP binding
  locations:
  - id: GO:0005739
    label: mitochondrion
  supported_by:
  - reference_id: file:human/GTPBP6/GTPBP6-uniprot.txt
    supporting_text: Belongs to the TRAFAC class OBG-HflX-like GTPase
  - reference_id: PMID:9466997
    supporting_text: shows the consensus sequences of a series of motifs of the GTP-binding
      protein domain
proposed_new_terms: []
suggested_questions:
- question: Does human GTPBP6 have any role on cytoplasmic ribosomes, or is its function
    exclusively mitochondrial (the IBA cytoplasm transfer derives from bacterial orthologs)?
- question: What is the precise GTPase cycle (activating factors, GAP) that couples
    GTPBP6 nucleotide state to the molecular switch driving PTC maturation?
suggested_experiments:
- description: Subcellular fractionation and high-resolution imaging of endogenous GTPBP6
    to definitively establish mitochondrial localization and exclude a cytoplasmic
    ribosome-associated pool.
- description: GTPase-dead (G-domain mutant) GTPBP6 rescue experiments in GTPBP6-knockout
    cells to test whether GTP hydrolysis is required for mtLSU maturation versus ribosome
    recycling.