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.
| 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 |
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Download this section (compressed HTML)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?
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.
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