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). The cached text does not name GTPBP6, so assignment to the MitoCoP set defers to the curator.
Supporting Evidence:
PMID:34800366
We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP).
PMID:34135319
the GTPases GTPBP5, GTPBP6, GTPBP7, and GTPBP10 mediate mtLSU maturation
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

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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)

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Pn Notes

(GTPBP6-pn-notes.md)

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