PTCD3 encodes mS39, a pentatricopeptide repeat (PPR) protein that is an integral, mitochondria-specific component of the 28S small subunit of the 55S mitochondrial ribosome. It associates with 12S mt-rRNA and, together with mS31, forms the mRNA entry corridor of the small subunit, where mitochondrial mRNAs are delivered by the LRPPRC-SLIRP complex for translation initiation. PTCD3 is required for mitochondrial protein synthesis; knockdown reduces translation and respiratory complex III and IV activity without changing mt-mRNA levels, and biallelic PTCD3 variants cause loss of small-subunit proteins, generalized mitochondrial translation defects and combined oxidative phosphorylation deficiency 51 (Leigh/Leigh-like syndrome).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | ACCEPT | Summary: mRNA interactome capture detected PTCD3 among RNA-crosslinked proteins. Reason: PTCD3 is a pentatricopeptide-repeat (PPR) protein of the mitoribosomal small subunit that associates with 12S rRNA and lies at the mRNA entry corridor where mRNA is handed over by LRPPRC-SLIRP; generic RNA binding is correct, although the more informative activities are rRNA binding and structural constituent of ribosome. Supporting Evidence: PMID:39134711 Here, the mRNA is handed to mS31–mS39, consistent with a translation initiation complex |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: mRNA interactome capture detected PTCD3 among RNA-crosslinked proteins. Reason: PTCD3 is a pentatricopeptide-repeat (PPR) protein of the mitoribosomal small subunit that associates with 12S rRNA and lies at the mRNA entry corridor where mRNA is handed over by LRPPRC-SLIRP; generic RNA binding is correct, although the more informative activities are rRNA binding and structural constituent of ribosome. Supporting Evidence: PMID:39134711 Here, the mRNA is handed to mS31–mS39, consistent with a translation initiation complex |
| GO:0005515 protein binding | IPI PMID:19427859 Pentatricopeptide repeat domain protein 3 associates with th... | MODIFY | Summary: PTCD3 co-immunoprecipitates with the small-subunit protein MRPS15 and co-sediments with the 28S subunit. Reason: protein binding is uninformative. The association with MRPS15 reflects PTCD3 being an integral protein of the mitochondrial small ribosomal subunit (mS39), so the informative molecular function is structural constituent of ribosome. Proposed replacements: structural constituent of ribosome Supporting Evidence: PMID:19427859 showed that it is a mitochondrial protein that associates with the small subunit of mitochondrial ribosomes PMID:30607703 PTCD3, a member of the pentatricopeptide repeat domain protein family, is a component of the small mitoribosomal subunit |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | REMOVE | Summary: Generic protein binding from high-throughput screens (Y2H with LNX2; BioPlex AP-MS with MRPS15; pestivirus Npro host-factor pulldown). Reason: protein binding (GO:0005515) is uninformative. The LNX2 and viral Npro interactions have no established role in PTCD3 function, and the MRPS15 association is a co-subunit relationship already represented by the mitochondrial small ribosomal subunit annotation. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:24965446 Host factors that interact with the pestivirus N-terminal pr... | REMOVE | Summary: Generic protein binding from high-throughput screens (Y2H with LNX2; BioPlex AP-MS with MRPS15; pestivirus Npro host-factor pulldown). Reason: protein binding (GO:0005515) is uninformative. The LNX2 and viral Npro interactions have no established role in PTCD3 function, and the MRPS15 association is a co-subunit relationship already represented by the mitochondrial small ribosomal subunit annotation. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: Generic protein binding from high-throughput screens (Y2H with LNX2; BioPlex AP-MS with MRPS15; pestivirus Npro host-factor pulldown). Reason: protein binding (GO:0005515) is uninformative. The LNX2 and viral Npro interactions have no established role in PTCD3 function, and the MRPS15 association is a co-subunit relationship already represented by the mitochondrial small ribosomal subunit annotation. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Generic protein binding from high-throughput screens (Y2H with LNX2; BioPlex AP-MS with MRPS15; pestivirus Npro host-factor pulldown). Reason: protein binding (GO:0005515) is uninformative. The LNX2 and viral Npro interactions have no established role in PTCD3 function, and the MRPS15 association is a co-subunit relationship already represented by the mitochondrial small ribosomal subunit annotation. Removal does not imply the interactions are false. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding from high-throughput screens (Y2H with LNX2; BioPlex AP-MS with MRPS15; pestivirus Npro host-factor pulldown). Reason: protein binding (GO:0005515) is uninformative. The LNX2 and viral Npro interactions have no established role in PTCD3 function, and the MRPS15 association is a co-subunit relationship already represented by the mitochondrial small ribosomal subunit annotation. Removal does not imply the interactions are false. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Detected in the high-confidence human mitochondrial proteome (MitoCoP). Reason: Consistent with targeted studies. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial localization (IBA, HPA immunofluorescence, combined IEA). Reason: Consistent with experimental data placing PTCD3 in the mitoribosome. Supporting Evidence: PMID:19427859 showed that it is a mitochondrial protein that associates with the small subunit of mitochondrial ribosomes |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Mitochondrial localization (IBA, HPA immunofluorescence, combined IEA). Reason: Consistent with experimental data placing PTCD3 in the mitoribosome. Supporting Evidence: PMID:19427859 showed that it is a mitochondrial protein that associates with the small subunit of mitochondrial ribosomes |
| GO:0005739 mitochondrion | IDA PMID:19427859 Pentatricopeptide repeat domain protein 3 associates with th... | ACCEPT | Summary: PTCD3 was shown to be a mitochondrial protein associated with the small mitoribosomal subunit. Reason: Direct experimental localization. Supporting Evidence: PMID:19427859 showed that it is a mitochondrial protein that associates with the small subunit of mitochondrial ribosomes |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrial localization (IBA, HPA immunofluorescence, combined IEA). Reason: Consistent with experimental data placing PTCD3 in the mitoribosome. Supporting Evidence: PMID:19427859 showed that it is a mitochondrial protein that associates with the small subunit of mitochondrial ribosomes |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | NAS PMID:27023846 Structure and Function of the Mitochondrial Ribosome. | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419261 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419264 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419271 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419273 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419277 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-5419281 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9937394 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9937412 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9937415 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9937719 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-9937724 | KEEP AS NON CORE | Summary: Inner-membrane localization asserted from Reactome mitochondrial translation events, a mitoribosome review, and ARBA. Reason: The mitoribosome is peripherally associated with the matrix face of the inner membrane through its large subunit; PTCD3/mS39 is a soluble small-subunit protein at the mRNA entry site, not a membrane protein. Kept as non-core, reflecting the whole-particle association. Supporting Evidence: PMID:27023846 mitoribosomes have become functionally specialized for synthesizing mitochondrial membrane proteins |
| GO:0005759 mitochondrial matrix | IDA PMID:23275553 Alternative translation initiation augments the human mitoch... | ACCEPT | Summary: Localization to the mitochondrial matrix (alternative translation initiation / mitochondrial proteome study). Reason: Consistent with PTCD3 being a protein of the matrix-resident mitoribosome. The cached abstract does not name PTCD3, so the specific data are deferred to the curator who read the full text. |
| GO:0005763 mitochondrial small ribosomal subunit | NAS PMID:25838379 Ribosome. The structure of the human mitochondrial ribosome. | ACCEPT | Summary: PTCD3 (mS39) is a component of the 28S small subunit of the human mitoribosome. Reason: Core cellular component, supported by co-sedimentation, the human mitoribosome structures and loss of small-subunit proteins in patient cells. Supporting Evidence: PMID:30607703 PTCD3, a member of the pentatricopeptide repeat domain protein family, is a component of the small mitoribosomal subunit PMID:30607703 Quantitative proteomic analysis revealed decreased levels of the small mitoribosomal subunits |
| GO:0019843 rRNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: PTCD3 associates with 12S mt-rRNA as part of the small subunit (IDA), also inferred by IBA and InterPro. Reason: Accepted; UniProt records association with 12S mt-rRNA from this study, and the curator read the full text (abstract only cached here). Supporting Evidence: PMID:19427859 showed that it is a mitochondrial protein that associates with the small subunit of mitochondrial ribosomes |
| GO:0019843 rRNA binding | IDA PMID:19427859 Pentatricopeptide repeat domain protein 3 associates with th... | ACCEPT | Summary: PTCD3 associates with 12S mt-rRNA as part of the small subunit (IDA), also inferred by IBA and InterPro. Reason: Accepted; UniProt records association with 12S mt-rRNA from this study, and the curator read the full text (abstract only cached here). Supporting Evidence: PMID:19427859 showed that it is a mitochondrial protein that associates with the small subunit of mitochondrial ribosomes |
| GO:0019843 rRNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: PTCD3 associates with 12S mt-rRNA as part of the small subunit (IDA), also inferred by IBA and InterPro. Reason: Accepted; UniProt records association with 12S mt-rRNA from this study, and the curator read the full text (abstract only cached here). Supporting Evidence: PMID:19427859 showed that it is a mitochondrial protein that associates with the small subunit of mitochondrial ribosomes |
| GO:0032543 mitochondrial translation | IBA GO_REF:0000033 | ACCEPT | Summary: PTCD3 knockdown decreases mitochondrial protein synthesis, and biallelic PTCD3 variants cause generalized mitochondrial translation defects. Reason: Core biological process; PTCD3 is an integral protein of the translating mitoribosome. Supporting Evidence: PMID:19427859 lowering PTCD3 in 143B osteosarcoma cells decreased mitochondrial protein synthesis PMID:30607703 generalized mitochondrial translation defects in fibroblasts |
| GO:0032543 mitochondrial translation | IEA GO_REF:0000002 | ACCEPT | Summary: PTCD3 knockdown decreases mitochondrial protein synthesis, and biallelic PTCD3 variants cause generalized mitochondrial translation defects. Reason: Core biological process; PTCD3 is an integral protein of the translating mitoribosome. Supporting Evidence: PMID:19427859 lowering PTCD3 in 143B osteosarcoma cells decreased mitochondrial protein synthesis PMID:30607703 generalized mitochondrial translation defects in fibroblasts |
| GO:0032543 mitochondrial translation | IMP PMID:19427859 Pentatricopeptide repeat domain protein 3 associates with th... | ACCEPT | Summary: PTCD3 knockdown decreases mitochondrial protein synthesis, and biallelic PTCD3 variants cause generalized mitochondrial translation defects. Reason: Core biological process; PTCD3 is an integral protein of the translating mitoribosome. Supporting Evidence: PMID:19427859 lowering PTCD3 in 143B osteosarcoma cells decreased mitochondrial protein synthesis PMID:30607703 generalized mitochondrial translation defects in fibroblasts |
| GO:0032543 mitochondrial translation | NAS PMID:27023846 Structure and Function of the Mitochondrial Ribosome. | ACCEPT | Summary: PTCD3 knockdown decreases mitochondrial protein synthesis, and biallelic PTCD3 variants cause generalized mitochondrial translation defects. Reason: Core biological process; PTCD3 is an integral protein of the translating mitoribosome. Supporting Evidence: PMID:19427859 lowering PTCD3 in 143B osteosarcoma cells decreased mitochondrial protein synthesis PMID:30607703 generalized mitochondrial translation defects in fibroblasts |
| GO:0043024 ribosomal small subunit binding | IBA GO_REF:0000033 | MODIFY | Summary: Ribosomal small subunit binding, from the original observation that PTCD3 co-sediments with the 28S subunit (IDA) and propagated by IBA/InterPro. Reason: PTCD3 was first described as a protein that associates with the small subunit, but it is now established as an integral mitoribosomal protein (mS39), resolved in cryo-EM structures where its PPR domain forms part of the mRNA entry site. For a ribosomal protein, structural constituent of ribosome is the appropriate molecular function rather than binding to the subunit it belongs to. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN000417987 SUPPORTS TRANSFER mS39 family node; the inherited association with the small subunit is correct, but for an integral mitoribosomal protein it is better expressed as structural constituent of ribosome than as binding to the subunit. UniProtKB:Q96EY7 SUPPORTS TRANSFER Human PTCD3 itself, whose IDA (PMID:19427859) seeds the node; expected self-appearance, not circular. Proposed replacements: structural constituent of ribosome Supporting Evidence: PMID:30607703 PTCD3, a member of the pentatricopeptide repeat domain protein family, is a component of the small mitoribosomal subunit PMID:32812867 Hence, the human mitoribosome evolved a specialized mechanism involving auxiliary factors and linker PPR protein mS39 for regulation and alignment of the transcripts |
| GO:0043024 ribosomal small subunit binding | IDA PMID:19427859 Pentatricopeptide repeat domain protein 3 associates with th... | MODIFY | Summary: Ribosomal small subunit binding, from the original observation that PTCD3 co-sediments with the 28S subunit (IDA) and propagated by IBA/InterPro. Reason: PTCD3 was first described as a protein that associates with the small subunit, but it is now established as an integral mitoribosomal protein (mS39), resolved in cryo-EM structures where its PPR domain forms part of the mRNA entry site. For a ribosomal protein, structural constituent of ribosome is the appropriate molecular function rather than binding to the subunit it belongs to. Proposed replacements: structural constituent of ribosome Supporting Evidence: PMID:30607703 PTCD3, a member of the pentatricopeptide repeat domain protein family, is a component of the small mitoribosomal subunit PMID:32812867 Hence, the human mitoribosome evolved a specialized mechanism involving auxiliary factors and linker PPR protein mS39 for regulation and alignment of the transcripts |
| GO:0043024 ribosomal small subunit binding | IEA GO_REF:0000002 | MODIFY | Summary: Ribosomal small subunit binding, from the original observation that PTCD3 co-sediments with the 28S subunit (IDA) and propagated by IBA/InterPro. Reason: PTCD3 was first described as a protein that associates with the small subunit, but it is now established as an integral mitoribosomal protein (mS39), resolved in cryo-EM structures where its PPR domain forms part of the mRNA entry site. For a ribosomal protein, structural constituent of ribosome is the appropriate molecular function rather than binding to the subunit it belongs to. Proposed replacements: structural constituent of ribosome Supporting Evidence: PMID:30607703 PTCD3, a member of the pentatricopeptide repeat domain protein family, is a component of the small mitoribosomal subunit PMID:32812867 Hence, the human mitoribosome evolved a specialized mechanism involving auxiliary factors and linker PPR protein mS39 for regulation and alignment of the transcripts |
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Download this section (compressed HTML)Q: Do the PPR motifs of mS39 contact mitochondrial mRNA directly, and with any sequence preference, or does mS39 act only as a docking platform for LRPPRC-SLIRP?
Q: Does PTCD3 contribute to translation of all mt-mRNAs equally, or preferentially to LRPPRC-dependent transcripts such as MT-CO1 and MT-CO2?
Experiment: Mitoribosome profiling and transcript-resolved metabolic labelling in PTCD3-knockout cells complemented with PPR-motif mutants, to test whether mS39 RNA contacts are needed for mRNA recruitment.
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