Hspd1 encodes Hsp60, the mitochondrial type I (GroEL-family) chaperonin of the mouse. The 573-residue precursor carries a 26-residue matrix-targeting presequence that is removed on import. In the matrix, heptameric Hsp60 rings associate with rings of the co-chaperonin Hsp10 (Hspe1). In an ATP-driven cycle they enclose newly imported or stress-denatured polypeptides and release them folded. In mice the gene is essential: null embryos die shortly after implantation. Tissue-specific deletion in adult cardiomyocytes leaves matrix protein import intact but causes misfolding and accelerated degradation of Hsp60-dependent matrix proteins, followed by respiratory-chain defects, ROS and heart failure. Halving Hsp60 levels impairs folding of MnSOD and assembly of respiratory complex III in neurons and causes a late-onset motor deficit, which models human SPG13 hereditary spastic paraplegia. Loss in intestinal epithelium activates the mitochondrial unfolded protein response. Small pools of Hsp60 occur at the cell surface (including the head of capacitated sperm) and outside cells. Exogenously added Hsp60 binds macrophages and dendritic cells and binds LPS. It enhances antigen-specific T-cell IFN-gamma responses through APC-derived IFN-alpha, independently of TLR4 and MyD88, whereas its apparent induction of IL-6, IL-12 and TNF is attributable to bound endotoxin.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001530 lipopolysaccharide binding | IDA PMID:17164250 Synergistic and differential modulation of immune responses ... | KEEP AS NON CORE | Summary: Lipopolysaccharide binding by extracellular Hsp60 (mouse IDA). Reason: Mouse experiment: Hsp60 specifically binds bacterial LPS and colocalises with CD14 on APC, and the synergy with LPS depends on this binding (PMID:17164250). This is a real property of the exogenous protein, but it is peripheral to the mitochondrial chaperonin role. Supporting Evidence: PMID:17164250 Hsp60 specifically binds bacterial LPS PMID:17164250 Hsp60 bound to the cell surface of APC colocalizes with the LPS co-receptor CD14 and LPS binding sites |
| GO:0001530 lipopolysaccharide binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Lipopolysaccharide binding by extracellular Hsp60 (mouse IDA). Reason: Mouse experiment: Hsp60 specifically binds bacterial LPS and colocalises with CD14 on APC, and the synergy with LPS depends on this binding (PMID:17164250). This is a real property of the exogenous protein, but it is peripheral to the mitochondrial chaperonin role. Supporting Evidence: PMID:17164250 Hsp60 specifically binds bacterial LPS PMID:17164250 Hsp60 bound to the cell surface of APC colocalizes with the LPS co-receptor CD14 and LPS binding sites |
| GO:0001530 lipopolysaccharide binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Lipopolysaccharide binding by extracellular Hsp60 (mouse IDA). Reason: Mouse experiment: Hsp60 specifically binds bacterial LPS and colocalises with CD14 on APC, and the synergy with LPS depends on this binding (PMID:17164250). This is a real property of the exogenous protein, but it is peripheral to the mitochondrial chaperonin role. Supporting Evidence: PMID:17164250 Hsp60 specifically binds bacterial LPS PMID:17164250 Hsp60 bound to the cell surface of APC colocalizes with the LPS co-receptor CD14 and LPS binding sites |
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to hypoxia (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
| GO:0001819 positive regulation of cytokine production | IEA GO_REF:0000117 | MODIFY | Summary: Positive regulation of cytokine production (ARBA). Reason: The term is true but too general for the mouse data. The best-controlled cytokine effect of LPS-free Hsp60 is IFN-alpha induction in APC. LPS-free Hsp60 does not induce IL-6, IL-12 or TNF (PMID:18256040). Proposed replacements: positive regulation of interferon-alpha production Supporting Evidence: PMID:18256040 LPS-free Hsp60 enhances IFN alpha expression in APC PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC |
| GO:0002039 p53 binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: p53 binding (human tumour-cell co-immunoprecipitation, projected). Reason: This interaction was reported in human tumour cells and has not been tested with mouse proteins. It is kept as a non-core inferred interaction. |
| GO:0002039 p53 binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: p53 binding (human tumour-cell co-immunoprecipitation, projected). Reason: This interaction was reported in human tumour cells and has not been tested with mouse proteins. It is kept as a non-core inferred interaction. |
| GO:0002755 MyD88-dependent toll-like receptor signaling pathway | IEA GO_REF:0000107 | REMOVE | Summary: MyD88-dependent toll-like receptor signaling pathway. Reason: Mouse knockout experiments show that the LPS-free Hsp60 effect is independent of TLR4 and MyD88 (PMID:18256040). The TLR4-dependent effects of Hsp60/LPS complexes are attributable to the bound LPS. In addition, an extracellular ligand carrier is not a component of the intracellular signalling pathway. The mouse data contradict the projected claim. Supporting Evidence: PMID:18256040 T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 and the TLR-associated myeloide differentiation factor 88-signaling pathway |
| GO:0002755 MyD88-dependent toll-like receptor signaling pathway | ISO GO_REF:0000119 | REMOVE | Summary: MyD88-dependent toll-like receptor signaling pathway. Reason: Mouse knockout experiments show that the LPS-free Hsp60 effect is independent of TLR4 and MyD88 (PMID:18256040). The TLR4-dependent effects of Hsp60/LPS complexes are attributable to the bound LPS. In addition, an extracellular ligand carrier is not a component of the intracellular signalling pathway. The mouse data contradict the projected claim. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Source claim rests on recombinant Hsp60 whose TLR4/MyD88 dependence mouse data attribute to bound LPS (PMID:18256040). Supporting Evidence: PMID:18256040 T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 and the TLR-associated myeloide differentiation factor 88-signaling pathway |
| GO:0002842 positive regulation of T cell mediated immune response to tumor cell | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of T cell mediated immune response to tumor cell (human data, projected). Reason: This is human-only evidence that tumour-surface Hsp60 contributes to gamma-delta T-cell recognition. It is not tested in mouse and is kept as non-core. |
| GO:0002842 positive regulation of T cell mediated immune response to tumor cell | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Positive regulation of T cell mediated immune response to tumor cell (human data, projected). Reason: This is human-only evidence that tumour-surface Hsp60 contributes to gamma-delta T-cell recognition. It is not tested in mouse and is kept as non-core. |
| GO:0002931 response to ischemia | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to ischemia (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
| GO:0003725 double-stranded RNA binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Double-stranded RNA binding (ISO from PMID:21266579, Raftlin/poly(I:C) study). Reason: The cached full text of PMID:21266579 describes Raftlin-mediated poly(I:C) uptake but does not mention Hsp60 in the accessible text, so the finding is probably in supplementary data. The claim cannot be checked, and no mouse experiment exists. |
| GO:0003725 double-stranded RNA binding | ISO PMID:21266579 Raftlin is involved in the nucleocapture complex to induce p... | UNDECIDED | Summary: Double-stranded RNA binding (ISO from PMID:21266579, Raftlin/poly(I:C) study). Reason: The cached full text of PMID:21266579 describes Raftlin-mediated poly(I:C) uptake but does not mention Hsp60 in the accessible text, so the finding is probably in supplementary data. The claim cannot be checked, and no mouse experiment exists. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P10809 UNRESOLVED Source finding not found in the accessible text of PMID:21266579. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding by the equatorial nucleotide pocket of the chaperonin. Reason: The InterPro chaperonin signatures and the conserved ATP-binding residues (UniProt BINDING 75, 111-115, 440, 520, by similarity to human) support ATP binding. ATP binding is intrinsic to the ATP-dependent folding cycle (PMID:1346131). Supporting Evidence: PMID:1346131 facilitates the formation of catalytically active ribulose-bisphosphate carboxylase from an unfolded state in the presence of K+ and MgATP |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Extracellular region. Reason: Hsp60 is released from cells and acts as an extracellular ligand on APC in mouse experiments (PMID:15371451, PMID:17164250). The release mechanism and the physiological concentrations are unknown. It is kept as non-core. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation |
| GO:0005576 extracellular region | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Extracellular region. Reason: Hsp60 is released from cells and acts as an extracellular ligand on APC in mouse experiments (PMID:15371451, PMID:17164250). The release mechanism and the physiological concentrations are unknown. It is kept as non-core. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation |
| GO:0005576 extracellular region | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Extracellular region. Reason: Hsp60 is released from cells and acts as an extracellular ligand on APC in mouse experiments (PMID:15371451, PMID:17164250). The release mechanism and the physiological concentrations are unknown. It is kept as non-core. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation |
| GO:0005737 cytoplasm | IDA PMID:21874024 The ubiquitin ligase Peli1 negatively regulates T cell activ... | TOO GENERAL | Summary: Cytoplasm. Reason: True, since mitochondria are in the cytoplasm, but uninformative. The mouse IDA (PMID:21874024) used HSP60 as a fractionation and imaging marker. The accepted mitochondrial matrix term entails this location. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | TOO GENERAL | Summary: Cytoplasm. Reason: True, since mitochondria are in the cytoplasm, but uninformative. The mouse IDA (PMID:21874024) used HSP60 as a fractionation and imaging marker. The accepted mitochondrial matrix term entails this location. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005737 cytoplasm | ISO GO_REF:0000119 | TOO GENERAL | Summary: Cytoplasm. Reason: True, since mitochondria are in the cytoplasm, but uninformative. The mouse IDA (PMID:21874024) used HSP60 as a fractionation and imaging marker. The accepted mitochondrial matrix term entails this location. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | HDA PMID:14651853 Integrated analysis of protein composition, tissue diversity... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | HDA PMID:18614015 A mitochondrial protein compendium elucidates complex I dise... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:12931191 BAD and glucokinase reside in a mitochondrial complex that i... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:1516759 Immunocytochemical localization of heat-shock protein 60-rel... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:16959573 SIRT4 inhibits glutamate dehydrogenase and opposes the effec... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:17923681 Mammalian Sir2 homolog SIRT3 regulates global mitochondrial ... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:23976951 Loss of the nuclear receptor corepressor SLIRP compromises m... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:26644517 A keratin scaffold regulates epidermal barrier formation, mi... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:26767982 Nutritional stress exacerbates hepatic steatosis induced by ... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:34048705 Mitocytosis, a migrasome-mediated mitochondrial quality-cont... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:8824711 A family of hsp60-related proteins in pancreatic beta cells ... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:9867803 Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial... | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | ISO GO_REF:0000119 | MODIFY | Summary: Mitochondrion; Hsp60 is detected in mitochondria in many mouse proteomic and imaging studies. Reason: The localisation is correct and well supported in mouse (liver, islet, testis and skin). Several of these studies used Hsp60 only as a mitochondrial marker. The specific supported compartment is the mitochondrial matrix (GO:0005759), which this review accepts from IBA/ISS/ISO rows, so the general term is refined to that descendant. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P10809 SUPPORTS TRANSFER Mitochondrial localisation transfers; the matrix is the specific compartment. Proposed replacements: mitochondrial matrix Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005743 mitochondrial inner membrane | HDA PMID:12865426 Proteomic analysis of the mouse liver mitochondrial inner me... | KEEP AS NON CORE | Summary: Mitochondrial inner membrane; Hsp60 is recovered with mouse liver inner-membrane preparations. Reason: Hsp60 is a soluble matrix chaperonin. Its recovery with the inner membrane (mouse proteomics PMID:12865426; rat immuno-EM; IBA at PTN000143509 seeded by fly, rat and yeast) reflects peripheral association with the matrix face. This is not an integral-membrane location, so it is kept as non-core beside the accepted matrix term. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005743 mitochondrial inner membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane; Hsp60 is recovered with mouse liver inner-membrane preparations. Reason: Hsp60 is a soluble matrix chaperonin. Its recovery with the inner membrane (mouse proteomics PMID:12865426; rat immuno-EM; IBA at PTN000143509 seeded by fly, rat and yeast) reflects peripheral association with the matrix face. This is not an integral-membrane location, so it is kept as non-core beside the accepted matrix term. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane; Hsp60 is recovered with mouse liver inner-membrane preparations. Reason: Hsp60 is a soluble matrix chaperonin. Its recovery with the inner membrane (mouse proteomics PMID:12865426; rat immuno-EM; IBA at PTN000143509 seeded by fly, rat and yeast) reflects peripheral association with the matrix face. This is not an integral-membrane location, so it is kept as non-core beside the accepted matrix term. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005743 mitochondrial inner membrane | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane; Hsp60 is recovered with mouse liver inner-membrane preparations. Reason: Hsp60 is a soluble matrix chaperonin. Its recovery with the inner membrane (mouse proteomics PMID:12865426; rat immuno-EM; IBA at PTN000143509 seeded by fly, rat and yeast) reflects peripheral association with the matrix face. This is not an integral-membrane location, so it is kept as non-core beside the accepted matrix term. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial matrix, the compartment in which the chaperonin acts. Reason: The matrix is the specific site of Hsp60 action. The IBA at PTN000143509 rests on matrix localisation of yeast, fission yeast, zebrafish and human orthologs. In mouse, the transit peptide (1-26) was confirmed by N-terminal protein sequencing (UniProt FT TRANSIT, ECO:0000269 PubMed:7523108). In mouse cardiomyocyte mitochondria the protein acts after import of matrix proteins (PMID:31209364). Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix PMID:31209364 suggesting that mitochondrial protein import was not affected by deletion of HSP60 |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrial matrix, the compartment in which the chaperonin acts. Reason: The matrix is the specific site of Hsp60 action. The IBA at PTN000143509 rests on matrix localisation of yeast, fission yeast, zebrafish and human orthologs. In mouse, the transit peptide (1-26) was confirmed by N-terminal protein sequencing (UniProt FT TRANSIT, ECO:0000269 PubMed:7523108). In mouse cardiomyocyte mitochondria the protein acts after import of matrix proteins (PMID:31209364). Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix PMID:31209364 suggesting that mitochondrial protein import was not affected by deletion of HSP60 |
| GO:0005759 mitochondrial matrix | ISO GO_REF:0000119 | ACCEPT | Summary: Mitochondrial matrix, the compartment in which the chaperonin acts. Reason: The matrix is the specific site of Hsp60 action. The IBA at PTN000143509 rests on matrix localisation of yeast, fission yeast, zebrafish and human orthologs. In mouse, the transit peptide (1-26) was confirmed by N-terminal protein sequencing (UniProt FT TRANSIT, ECO:0000269 PubMed:7523108). In mouse cardiomyocyte mitochondria the protein acts after import of matrix proteins (PMID:31209364). Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix PMID:31209364 suggesting that mitochondrial protein import was not affected by deletion of HSP60 |
| GO:0005759 mitochondrial matrix | ISO GO_REF:0000119 | ACCEPT | Summary: Mitochondrial matrix, the compartment in which the chaperonin acts. Reason: The matrix is the specific site of Hsp60 action. The IBA at PTN000143509 rests on matrix localisation of yeast, fission yeast, zebrafish and human orthologs. In mouse, the transit peptide (1-26) was confirmed by N-terminal protein sequencing (UniProt FT TRANSIT, ECO:0000269 PubMed:7523108). In mouse cardiomyocyte mitochondria the protein acts after import of matrix proteins (PMID:31209364). Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix PMID:31209364 suggesting that mitochondrial protein import was not affected by deletion of HSP60 |
| GO:0005759 mitochondrial matrix | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial matrix, the compartment in which the chaperonin acts. Reason: The matrix is the specific site of Hsp60 action. The IBA at PTN000143509 rests on matrix localisation of yeast, fission yeast, zebrafish and human orthologs. In mouse, the transit peptide (1-26) was confirmed by N-terminal protein sequencing (UniProt FT TRANSIT, ECO:0000269 PubMed:7523108). In mouse cardiomyocyte mitochondria the protein acts after import of matrix proteins (PMID:31209364). Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix PMID:31209364 suggesting that mitochondrial protein import was not affected by deletion of HSP60 |
| GO:0005769 early endosome | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Early endosome (human data on internalised recombinant Hsp60, projected). Reason: The human source followed exogenous recombinant Hsp60 being endocytosed by dendritic cells. That describes the route of a ligand in a recipient cell, not a compartment where endogenous Hspd1 resides. |
| GO:0005769 early endosome | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Early endosome (human data on internalised recombinant Hsp60, projected). Reason: The human source followed exogenous recombinant Hsp60 being endocytosed by dendritic cells. That describes the route of a ligand in a recipient cell, not a compartment where endogenous Hspd1 resides. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Source followed internalised exogenous recombinant Hsp60 in dendritic cells, not endogenous protein. |
| GO:0005782 peroxisomal matrix | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Peroxisomal matrix (rat immuno-EM, projected). Reason: This location comes from rat immunogold labelling with anti-Hsp60 antibodies. Hsp60 has no peroxisomal targeting signal, and the mouse protein carries a mitochondrial presequence confirmed by protein sequencing. It is not supported in mouse. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005782 peroxisomal matrix | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Peroxisomal matrix (rat immuno-EM, projected). Reason: This location comes from rat immunogold labelling with anti-Hsp60 antibodies. Hsp60 has no peroxisomal targeting signal, and the mouse protein carries a mitochondrial presequence confirmed by protein sequencing. It is not supported in mouse. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: RGD:621314 SOURCE WEAK OR INFERRED Rat immunogold labelling with anti-Hsp60 antibodies; no peroxisomal targeting signal. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005829 cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytosol (human data, projected). Reason: A minor cytosolic pool of Hsp60 exists, notably during apoptosis, in human cells. It is not the site of the core function and is kept as non-core. |
| GO:0005829 cytosol | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Cytosol (human data, projected). Reason: A minor cytosolic pool of Hsp60 exists, notably during apoptosis, in human cells. It is not the site of the core function and is kept as non-core. |
| GO:0005886 plasma membrane | IDA PMID:15252132 Tyrosine phosphorylation activates surface chaperones facili... | KEEP AS NON CORE | Summary: Plasma membrane (surface Hsp60 on capacitated mouse sperm). Reason: Mouse IDA: Hsp60 localises to the surface of the sperm head region involved in zona recognition (PMID:15252132). Surface pools are also reported on other cells (PMID:15371451). This is a real but minor extra-mitochondrial location. Supporting Evidence: PMID:15252132 immunofluorescence localised these proteins to the precise region of the sperm head that participates in zona recognition |
| GO:0005886 plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Plasma membrane (surface Hsp60 on capacitated mouse sperm). Reason: Mouse IDA: Hsp60 localises to the surface of the sperm head region involved in zona recognition (PMID:15252132). Surface pools are also reported on other cells (PMID:15371451). This is a real but minor extra-mitochondrial location. Supporting Evidence: PMID:15252132 immunofluorescence localised these proteins to the precise region of the sperm head that participates in zona recognition |
| GO:0005886 plasma membrane | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Plasma membrane (surface Hsp60 on capacitated mouse sperm). Reason: Mouse IDA: Hsp60 localises to the surface of the sperm head region involved in zona recognition (PMID:15252132). Surface pools are also reported on other cells (PMID:15371451). This is a real but minor extra-mitochondrial location. Supporting Evidence: PMID:15252132 immunofluorescence localised these proteins to the precise region of the sperm head that participates in zona recognition |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Clathrin-coated pit (human data on internalised recombinant Hsp60, projected). Reason: This describes the endocytic route of exogenous recombinant Hsp60 in recipient cells, not a location of endogenous protein. |
| GO:0005905 clathrin-coated pit | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Clathrin-coated pit (human data on internalised recombinant Hsp60, projected). Reason: This describes the endocytic route of exogenous recombinant Hsp60 in recipient cells, not a location of endogenous protein. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Source followed internalised exogenous recombinant Hsp60 in dendritic cells, not endogenous protein. |
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: Protein folding in the mitochondrial matrix, the core process of the Hsp60 chaperonin. Reason: The IBA is placed at the family root node PTN000143677 (GroEL, Cpn60s, yeast HSP60, human HSPD1), and it is backed by mouse-specific genetic evidence. Adult cardiomyocyte deletion reveals mitochondrial proteins that rely on HSP60 for correct folding. Their import is unaffected but their stability after import is reduced (PMID:31209364). Hspd1+/- tissue shows impaired MnSOD folding (PMID:24151936) and defective complex III assembly (PMID:23466696). The null allele is early-embryonic lethal (PMID:20393889). Supporting Evidence: PMID:31209364 revealed a list of mitochondrial-localized proteins that rely on HSP60 (HSP60-dependent) for correctly folding in mitochondria PMID:31209364 protein import was comparable between control and HSP60CKO mitochondria while protein was degraded more rapidly in HSP60CKO mitochondria PMID:24151936 we propose that MnSOD is a substrate of the Hsp60 folding machinery PMID:23466696 a defect in the assembly of the respiratory chain complex III in neuronal tissues PMID:20393889 Our results demonstrate that Hspd1 is an essential gene for early embryonic development in mice |
| GO:0006457 protein folding | IEA GO_REF:0000002 | ACCEPT | Summary: Protein folding in the mitochondrial matrix, the core process of the Hsp60 chaperonin. Reason: The IBA is placed at the family root node PTN000143677 (GroEL, Cpn60s, yeast HSP60, human HSPD1), and it is backed by mouse-specific genetic evidence. Adult cardiomyocyte deletion reveals mitochondrial proteins that rely on HSP60 for correct folding. Their import is unaffected but their stability after import is reduced (PMID:31209364). Hspd1+/- tissue shows impaired MnSOD folding (PMID:24151936) and defective complex III assembly (PMID:23466696). The null allele is early-embryonic lethal (PMID:20393889). Supporting Evidence: PMID:31209364 revealed a list of mitochondrial-localized proteins that rely on HSP60 (HSP60-dependent) for correctly folding in mitochondria PMID:31209364 protein import was comparable between control and HSP60CKO mitochondria while protein was degraded more rapidly in HSP60CKO mitochondria PMID:24151936 we propose that MnSOD is a substrate of the Hsp60 folding machinery PMID:23466696 a defect in the assembly of the respiratory chain complex III in neuronal tissues PMID:20393889 Our results demonstrate that Hspd1 is an essential gene for early embryonic development in mice |
| GO:0006986 response to unfolded protein | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to unfolded protein. Reason: Hsp60 is induced by protein misfolding stress and refolds stress-denatured proteins (PMID:11422376). The annotation is projected from human. It is a stress-responsive, non-core aspect of the chaperone function. Supporting Evidence: PMID:11422376 Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. |
| GO:0006986 response to unfolded protein | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Response to unfolded protein. Reason: Hsp60 is induced by protein misfolding stress and refolds stress-denatured proteins (PMID:11422376). The annotation is projected from human. It is a stress-responsive, non-core aspect of the chaperone function. Supporting Evidence: PMID:11422376 Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. |
| GO:0008035 high-density lipoprotein particle binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: High-density lipoprotein particle binding (human hepatocyte-membrane data, projected). Reason: This comes from a single human study of a cell-surface Hsp60 pool. It is not tested in mouse and is kept as non-core. |
| GO:0008035 high-density lipoprotein particle binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: High-density lipoprotein particle binding (human hepatocyte-membrane data, projected). Reason: This comes from a single human study of a cell-surface Hsp60 pool. It is not tested in mouse and is kept as non-core. |
| GO:0008637 apoptotic mitochondrial changes | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Apoptotic mitochondrial changes. Reason: The IBA at PTN000888030 is seeded by rat Hspd1 (IMP). In mouse, deletion of Hsp60 in the Tie2 lineage lowers mitochondrial membrane potential and increases apoptosis in a partly mPTP-dependent way (PMID:31601784). These are consequences of losing mitochondrial proteostasis, and the role is non-core. Supporting Evidence: PMID:31601784 we demonstrated an essential role of HSP60 in regulating yolk sac cell survival partially via a mPTP-dependent mechanism |
| GO:0008637 apoptotic mitochondrial changes | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Apoptotic mitochondrial changes. Reason: The IBA at PTN000888030 is seeded by rat Hspd1 (IMP). In mouse, deletion of Hsp60 in the Tie2 lineage lowers mitochondrial membrane potential and increases apoptosis in a partly mPTP-dependent way (PMID:31601784). These are consequences of losing mitochondrial proteostasis, and the role is non-core. Supporting Evidence: PMID:31601784 we demonstrated an essential role of HSP60 in regulating yolk sac cell survival partially via a mPTP-dependent mechanism |
| GO:0009409 response to cold | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Response to cold (ISS from chicken Q5ZL72). Reason: This is an expression-level observation in chicken, transferred by sequence similarity. It does not describe a function of mouse Hspd1, and no mouse data support it. |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to xenobiotic stimulus (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
| GO:0009986 cell surface | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cell surface. Reason: Hsp60 expressed on eukaryotic cell surfaces enhances T-cell activation (PMID:15371451), and it localises to the sperm-head surface (PMID:15252132). These are minor extra-mitochondrial pools, so the location is non-core. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation PMID:15252132 immunofluorescence localised these proteins to the precise region of the sperm head that participates in zona recognition |
| GO:0009986 cell surface | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Cell surface. Reason: Hsp60 expressed on eukaryotic cell surfaces enhances T-cell activation (PMID:15371451), and it localises to the sperm-head surface (PMID:15252132). These are minor extra-mitochondrial pools, so the location is non-core. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation PMID:15252132 immunofluorescence localised these proteins to the precise region of the sperm head that participates in zona recognition |
| GO:0009986 cell surface | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Cell surface. Reason: Hsp60 expressed on eukaryotic cell surfaces enhances T-cell activation (PMID:15371451), and it localises to the sperm-head surface (PMID:15252132). These are minor extra-mitochondrial pools, so the location is non-core. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation PMID:15252132 immunofluorescence localised these proteins to the precise region of the sperm head that participates in zona recognition |
| GO:0009986 cell surface | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cell surface. Reason: Hsp60 expressed on eukaryotic cell surfaces enhances T-cell activation (PMID:15371451), and it localises to the sperm-head surface (PMID:15252132). These are minor extra-mitochondrial pools, so the location is non-core. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation PMID:15252132 immunofluorescence localised these proteins to the precise region of the sperm head that participates in zona recognition |
| GO:0014823 response to activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to activity (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
| GO:0016020 membrane | IMP PMID:20080761 Loss of autophagy in erythroid cells leads to defective remo... | TOO GENERAL | Summary: Membrane (Atg7-deficient red-cell membrane proteomics). Reason: In Atg7-deficient erythrocytes, retained mitochondrial proteins appear in membrane preparations (PMID:20080761). Hsp60 here marks retained mitochondria, and the term is uninformative beside the mitochondrial matrix and inner-membrane terms. Supporting Evidence: PMID:20080761 mitochondrial proteins were consistently and preferentially detected in Atg7 −/− samples only |
| GO:0019899 enzyme binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Enzyme binding (human: Listeria adhesion protein LAP binds Hsp60). Reason: LAP is a bacterial enzyme that uses host Hsp60 as an enterocyte receptor in human cells. The binding is real but concerns host-pathogen adhesion, and it is not tested in mouse. |
| GO:0019899 enzyme binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Enzyme binding (human: Listeria adhesion protein LAP binds Hsp60). Reason: LAP is a bacterial enzyme that uses host Hsp60 as an enterocyte receptor in human cells. The binding is real but concerns host-pathogen adhesion, and it is not tested in mouse. |
| GO:0030061 mitochondrial crista | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mitochondrial crista (rat immuno-EM, projected by orthology). Reason: Rat immuno-EM placed Hsp60 at cristae, which fits a matrix chaperonin associated with the inner membrane. It is not tested in mouse and is peripheral to the matrix location. |
| GO:0030061 mitochondrial crista | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Mitochondrial crista (rat immuno-EM, projected by orthology). Reason: Rat immuno-EM placed Hsp60 at cristae, which fits a matrix chaperonin associated with the inner membrane. It is not tested in mouse and is peripheral to the matrix location. |
| GO:0030135 coated vesicle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Coated vesicle (human data on internalised recombinant Hsp60, projected). Reason: This describes the endocytic route of exogenous recombinant Hsp60 in recipient cells, not a location of endogenous protein. |
| GO:0030135 coated vesicle | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Coated vesicle (human data on internalised recombinant Hsp60, projected). Reason: This describes the endocytic route of exogenous recombinant Hsp60 in recipient cells, not a location of endogenous protein. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Source followed internalised exogenous recombinant Hsp60 in dendritic cells, not endogenous protein. |
| GO:0030141 secretory granule | IDA PMID:1516759 Immunocytochemical localization of heat-shock protein 60-rel... | KEEP AS NON CORE | Summary: Secretory granule (immuno-EM of mouse beta cells). Reason: Mouse immuno-EM detected HSP60 immunoreactivity in the insulin core of mature beta-cell granules, and western blotting found a single 62 kDa band (PMID:1516759). A later study reported a family of cross-reactive proteins of several sizes in granules, microvesicles and microtubules (PMID:8824711). So not all granular signal is necessarily Hspd1. It is kept as non-core. Supporting Evidence: PMID:1516759 antibody to mammalian HSP60 cross-reacted with protein(s) located to mitochondria and secretory granules PMID:1516759 HSP60 antibody specifically interacted with a single 62 kDa islet cell protein PMID:8824711 the hsp60 antibody cross-reactive proteins were detected in secretory granules, mitochondria, synaptic-like microvesicles and microtubules of mouse pancreatic beta cells |
| GO:0030141 secretory granule | IDA PMID:8824711 A family of hsp60-related proteins in pancreatic beta cells ... | KEEP AS NON CORE | Summary: Secretory granule (immuno-EM of mouse beta cells). Reason: Mouse immuno-EM detected HSP60 immunoreactivity in the insulin core of mature beta-cell granules, and western blotting found a single 62 kDa band (PMID:1516759). A later study reported a family of cross-reactive proteins of several sizes in granules, microvesicles and microtubules (PMID:8824711). So not all granular signal is necessarily Hspd1. It is kept as non-core. Supporting Evidence: PMID:1516759 antibody to mammalian HSP60 cross-reacted with protein(s) located to mitochondria and secretory granules PMID:1516759 HSP60 antibody specifically interacted with a single 62 kDa islet cell protein PMID:8824711 the hsp60 antibody cross-reactive proteins were detected in secretory granules, mitochondria, synaptic-like microvesicles and microtubules of mouse pancreatic beta cells |
| GO:0030141 secretory granule | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Secretory granule (immuno-EM of mouse beta cells). Reason: Mouse immuno-EM detected HSP60 immunoreactivity in the insulin core of mature beta-cell granules, and western blotting found a single 62 kDa band (PMID:1516759). A later study reported a family of cross-reactive proteins of several sizes in granules, microvesicles and microtubules (PMID:8824711). So not all granular signal is necessarily Hspd1. It is kept as non-core. Supporting Evidence: PMID:1516759 antibody to mammalian HSP60 cross-reacted with protein(s) located to mitochondria and secretory granules PMID:1516759 HSP60 antibody specifically interacted with a single 62 kDa islet cell protein PMID:8824711 the hsp60 antibody cross-reactive proteins were detected in secretory granules, mitochondria, synaptic-like microvesicles and microtubules of mouse pancreatic beta cells |
| GO:0030141 secretory granule | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Secretory granule (immuno-EM of mouse beta cells). Reason: Mouse immuno-EM detected HSP60 immunoreactivity in the insulin core of mature beta-cell granules, and western blotting found a single 62 kDa band (PMID:1516759). A later study reported a family of cross-reactive proteins of several sizes in granules, microvesicles and microtubules (PMID:8824711). So not all granular signal is necessarily Hspd1. It is kept as non-core. Supporting Evidence: PMID:1516759 antibody to mammalian HSP60 cross-reacted with protein(s) located to mitochondria and secretory granules PMID:1516759 HSP60 antibody specifically interacted with a single 62 kDa islet cell protein PMID:8824711 the hsp60 antibody cross-reactive proteins were detected in secretory granules, mitochondria, synaptic-like microvesicles and microtubules of mouse pancreatic beta cells |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ubiquitin protein ligase binding (human Parkin pull-down, projected). Reason: Hsp60 was recovered with Parkin by affinity purification in human cells. It may be a client or a co-purifying matrix protein. It is not tested in mouse and is kept as non-core. |
| GO:0031625 ubiquitin protein ligase binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Ubiquitin protein ligase binding (human Parkin pull-down, projected). Reason: Hsp60 was recovered with Parkin by affinity purification in human cells. It may be a client or a co-purifying matrix protein. It is not tested in mouse and is kept as non-core. |
| GO:0031985 Golgi cisterna | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Golgi cisterna (rat immuno-EM, projected). Reason: This location comes from rat antibody-based immuno-EM. Mouse beta-cell immuno-EM saw very little Golgi signal (PMID:1516759), and cross-reactive hsp60-related proteins confound such studies (PMID:8824711). Supporting Evidence: PMID:8824711 the hsp60 antibody cross-reactive proteins were detected in secretory granules, mitochondria, synaptic-like microvesicles and microtubules of mouse pancreatic beta cells |
| GO:0031985 Golgi cisterna | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Golgi cisterna (rat immuno-EM, projected). Reason: This location comes from rat antibody-based immuno-EM. Mouse beta-cell immuno-EM saw very little Golgi signal (PMID:1516759), and cross-reactive hsp60-related proteins confound such studies (PMID:8824711). Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: RGD:621314 SOURCE WEAK OR INFERRED Rat antibody-based immuno-EM; hsp60-related cross-reactive proteins confound such data (PMID:8824711). Supporting Evidence: PMID:8824711 the hsp60 antibody cross-reactive proteins were detected in secretory granules, mitochondria, synaptic-like microvesicles and microtubules of mouse pancreatic beta cells |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to lipopolysaccharide (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
| GO:0032727 positive regulation of interferon-alpha production | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of interferon-alpha production by exogenous Hsp60 acting on APC. Reason: Mouse experiments show LPS-free Hsp60 induces IFN-alpha in professional APC (PMID:17164250, PMID:18256040). Mouse Hspd1 is a seed of the Euteleostomi PAINT node PTN002900230. This is the best-controlled immune effect of the protein, but it is a property of exogenously added Hsp60 in culture. The physiological role of endogenous extracellular Hsp60 is not established, so it is non-core. Supporting Evidence: PMID:17164250 in contrast to LPS Hsp60 induces IFNalpha production in professional APC PMID:18256040 LPS-free Hsp60 enhances IFN alpha expression in APC |
| GO:0032727 positive regulation of interferon-alpha production | IDA PMID:17164250 Synergistic and differential modulation of immune responses ... | KEEP AS NON CORE | Summary: Positive regulation of interferon-alpha production by exogenous Hsp60 acting on APC. Reason: Mouse experiments show LPS-free Hsp60 induces IFN-alpha in professional APC (PMID:17164250, PMID:18256040). Mouse Hspd1 is a seed of the Euteleostomi PAINT node PTN002900230. This is the best-controlled immune effect of the protein, but it is a property of exogenously added Hsp60 in culture. The physiological role of endogenous extracellular Hsp60 is not established, so it is non-core. Supporting Evidence: PMID:17164250 in contrast to LPS Hsp60 induces IFNalpha production in professional APC PMID:18256040 LPS-free Hsp60 enhances IFN alpha expression in APC |
| GO:0032727 positive regulation of interferon-alpha production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of interferon-alpha production by exogenous Hsp60 acting on APC. Reason: Mouse experiments show LPS-free Hsp60 induces IFN-alpha in professional APC (PMID:17164250, PMID:18256040). Mouse Hspd1 is a seed of the Euteleostomi PAINT node PTN002900230. This is the best-controlled immune effect of the protein, but it is a property of exogenously added Hsp60 in culture. The physiological role of endogenous extracellular Hsp60 is not established, so it is non-core. Supporting Evidence: PMID:17164250 in contrast to LPS Hsp60 induces IFNalpha production in professional APC PMID:18256040 LPS-free Hsp60 enhances IFN alpha expression in APC |
| GO:0032727 positive regulation of interferon-alpha production | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Positive regulation of interferon-alpha production by exogenous Hsp60 acting on APC. Reason: Mouse experiments show LPS-free Hsp60 induces IFN-alpha in professional APC (PMID:17164250, PMID:18256040). Mouse Hspd1 is a seed of the Euteleostomi PAINT node PTN002900230. This is the best-controlled immune effect of the protein, but it is a property of exogenously added Hsp60 in culture. The physiological role of endogenous extracellular Hsp60 is not established, so it is non-core. Supporting Evidence: PMID:17164250 in contrast to LPS Hsp60 induces IFNalpha production in professional APC PMID:18256040 LPS-free Hsp60 enhances IFN alpha expression in APC |
| GO:0032729 positive regulation of type II interferon production | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of type II interferon (IFN-gamma) production in antigen-specific T cells. Reason: Mouse IDA/IGI: Hsp60 enhances antigen-dependent IFN-gamma release. The effect is lost without IFNAR (Ifnar1, IGI) and needs professional APC (PMID:17164250, PMID:15371451). The effect is indirect, via APC-derived IFN-alpha, and comes from added protein. It is kept as non-core. Supporting Evidence: PMID:17164250 Neutralization of IFNalpha as well as the absence of functional IFNalphabeta receptor on APC and T cells interfered with Hsp60-mediated IFNgamma secretion in antigen-dependent T cell activation PMID:15371451 the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination |
| GO:0032729 positive regulation of type II interferon production | IDA PMID:15371451 Lipopolysaccharide-free heat shock protein 60 activates T ce... | KEEP AS NON CORE | Summary: Positive regulation of type II interferon (IFN-gamma) production in antigen-specific T cells. Reason: Mouse IDA/IGI: Hsp60 enhances antigen-dependent IFN-gamma release. The effect is lost without IFNAR (Ifnar1, IGI) and needs professional APC (PMID:17164250, PMID:15371451). The effect is indirect, via APC-derived IFN-alpha, and comes from added protein. It is kept as non-core. Supporting Evidence: PMID:17164250 Neutralization of IFNalpha as well as the absence of functional IFNalphabeta receptor on APC and T cells interfered with Hsp60-mediated IFNgamma secretion in antigen-dependent T cell activation PMID:15371451 the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination |
| GO:0032729 positive regulation of type II interferon production | IDA PMID:17164250 Synergistic and differential modulation of immune responses ... | KEEP AS NON CORE | Summary: Positive regulation of type II interferon (IFN-gamma) production in antigen-specific T cells. Reason: Mouse IDA/IGI: Hsp60 enhances antigen-dependent IFN-gamma release. The effect is lost without IFNAR (Ifnar1, IGI) and needs professional APC (PMID:17164250, PMID:15371451). The effect is indirect, via APC-derived IFN-alpha, and comes from added protein. It is kept as non-core. Supporting Evidence: PMID:17164250 Neutralization of IFNalpha as well as the absence of functional IFNalphabeta receptor on APC and T cells interfered with Hsp60-mediated IFNgamma secretion in antigen-dependent T cell activation PMID:15371451 the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination |
| GO:0032729 positive regulation of type II interferon production | IDA PMID:17164250 Synergistic and differential modulation of immune responses ... | KEEP AS NON CORE | Summary: Positive regulation of type II interferon (IFN-gamma) production in antigen-specific T cells. Reason: Mouse IDA/IGI: Hsp60 enhances antigen-dependent IFN-gamma release. The effect is lost without IFNAR (Ifnar1, IGI) and needs professional APC (PMID:17164250, PMID:15371451). The effect is indirect, via APC-derived IFN-alpha, and comes from added protein. It is kept as non-core. Supporting Evidence: PMID:17164250 Neutralization of IFNalpha as well as the absence of functional IFNalphabeta receptor on APC and T cells interfered with Hsp60-mediated IFNgamma secretion in antigen-dependent T cell activation PMID:15371451 the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination |
| GO:0032729 positive regulation of type II interferon production | IGI PMID:17164250 Synergistic and differential modulation of immune responses ... | KEEP AS NON CORE | Summary: Positive regulation of type II interferon (IFN-gamma) production in antigen-specific T cells. Reason: Mouse IDA/IGI: Hsp60 enhances antigen-dependent IFN-gamma release. The effect is lost without IFNAR (Ifnar1, IGI) and needs professional APC (PMID:17164250, PMID:15371451). The effect is indirect, via APC-derived IFN-alpha, and comes from added protein. It is kept as non-core. Supporting Evidence: PMID:17164250 Neutralization of IFNalpha as well as the absence of functional IFNalphabeta receptor on APC and T cells interfered with Hsp60-mediated IFNgamma secretion in antigen-dependent T cell activation PMID:15371451 the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination |
| GO:0032729 positive regulation of type II interferon production | ISO GO_REF:0000008 | KEEP AS NON CORE | Summary: Positive regulation of type II interferon (IFN-gamma) production in antigen-specific T cells. Reason: Mouse IDA/IGI: Hsp60 enhances antigen-dependent IFN-gamma release. The effect is lost without IFNAR (Ifnar1, IGI) and needs professional APC (PMID:17164250, PMID:15371451). The effect is indirect, via APC-derived IFN-alpha, and comes from added protein. It is kept as non-core. Supporting Evidence: PMID:17164250 Neutralization of IFNalpha as well as the absence of functional IFNalphabeta receptor on APC and T cells interfered with Hsp60-mediated IFNgamma secretion in antigen-dependent T cell activation PMID:15371451 the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination |
| GO:0032729 positive regulation of type II interferon production | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Positive regulation of type II interferon (IFN-gamma) production in antigen-specific T cells. Reason: Mouse IDA/IGI: Hsp60 enhances antigen-dependent IFN-gamma release. The effect is lost without IFNAR (Ifnar1, IGI) and needs professional APC (PMID:17164250, PMID:15371451). The effect is indirect, via APC-derived IFN-alpha, and comes from added protein. It is kept as non-core. Supporting Evidence: PMID:17164250 Neutralization of IFNalpha as well as the absence of functional IFNalphabeta receptor on APC and T cells interfered with Hsp60-mediated IFNgamma secretion in antigen-dependent T cell activation PMID:15371451 the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination |
| GO:0032733 positive regulation of interleukin-10 production | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of interleukin-10 production (human B-cell data, projected). Reason: The human source used recombinant Hsp60 on B cells, and those findings are contested because of endotoxin. In mouse APC, LPS-free Hsp60 does not induce the classic inflammatory cytokines (PMID:18256040). Supporting Evidence: PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC |
| GO:0032733 positive regulation of interleukin-10 production | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Positive regulation of interleukin-10 production (human B-cell data, projected). Reason: The human source used recombinant Hsp60 on B cells, and those findings are contested because of endotoxin. In mouse APC, LPS-free Hsp60 does not induce the classic inflammatory cytokines (PMID:18256040). Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Human recombinant-protein B-cell data, contested because of endotoxin. Supporting Evidence: PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC |
| GO:0032735 positive regulation of interleukin-12 production | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of interleukin-12 production. Reason: In mouse, LPS-free Hsp60 does not induce IL-12 (PMID:18256040). IL-12p40 enhancement is seen only when Hsp60 and LPS are combined, and it depends on LPS binding (PMID:17164250). The protein's own contribution is LPS delivery, which the LPS binding term captures. Supporting Evidence: PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC PMID:17164250 both molecules synergistically enhanced IL-12p40 production in APC and IFNgamma release in antigen-dependent T cell activation |
| GO:0032735 positive regulation of interleukin-12 production | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Positive regulation of interleukin-12 production. Reason: In mouse, LPS-free Hsp60 does not induce IL-12 (PMID:18256040). IL-12p40 enhancement is seen only when Hsp60 and LPS are combined, and it depends on LPS binding (PMID:17164250). The protein's own contribution is LPS delivery, which the LPS binding term captures. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Mouse data show IL-12 induction needs bound LPS (PMID:18256040, PMID:17164250). Supporting Evidence: PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC PMID:17164250 both molecules synergistically enhanced IL-12p40 production in APC and IFNgamma release in antigen-dependent T cell activation |
| GO:0032755 positive regulation of interleukin-6 production | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Positive regulation of interleukin-6 production. Reason: The PAINT node PTN002900230 seeds this term from rat and human, not mouse. In mouse APC, LPS-free Hsp60 did not induce IL-6 (PMID:18256040), and TNF induction by recombinant Hsp60 disappears after endotoxin removal (PMID:15371451). So the IL-6 effect is most likely attributable to bound LPS. The term over-states what the mouse protein does. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: PANTHER:PTN002900230 SOURCE WEAK OR INFERRED Mouse APC data show no IL-6 induction by LPS-free Hsp60 (PMID:18256040). Supporting Evidence: PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC PMID:15371451 The induction of tumor necrosis factor-alpha secretion in mouse macrophages is lost after endotoxin removal and is not mediated by Hsp60 expressed in eukaryotic systems |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Positive regulation of interleukin-6 production. Reason: The PAINT node PTN002900230 seeds this term from rat and human, not mouse. In mouse APC, LPS-free Hsp60 did not induce IL-6 (PMID:18256040), and TNF induction by recombinant Hsp60 disappears after endotoxin removal (PMID:15371451). So the IL-6 effect is most likely attributable to bound LPS. The term over-states what the mouse protein does. Supporting Evidence: PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC PMID:15371451 The induction of tumor necrosis factor-alpha secretion in mouse macrophages is lost after endotoxin removal and is not mediated by Hsp60 expressed in eukaryotic systems |
| GO:0032755 positive regulation of interleukin-6 production | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Positive regulation of interleukin-6 production. Reason: The PAINT node PTN002900230 seeds this term from rat and human, not mouse. In mouse APC, LPS-free Hsp60 did not induce IL-6 (PMID:18256040), and TNF induction by recombinant Hsp60 disappears after endotoxin removal (PMID:15371451). So the IL-6 effect is most likely attributable to bound LPS. The term over-states what the mouse protein does. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Mouse APC data show no IL-6 induction by LPS-free Hsp60 (PMID:18256040). Supporting Evidence: PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC PMID:15371451 The induction of tumor necrosis factor-alpha secretion in mouse macrophages is lost after endotoxin removal and is not mediated by Hsp60 expressed in eukaryotic systems |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of tumor necrosis factor production (rat IMP, projected). Reason: Mouse data directly address this. TNF secretion by mouse macrophages in response to recombinant Hsp60 is lost after endotoxin removal and is not produced by Hsp60 expressed in eukaryotic cells (PMID:15371451, PMID:18256040). The rat observation is not removed, because its source was not examined. Supporting Evidence: PMID:15371451 The induction of tumor necrosis factor-alpha secretion in mouse macrophages is lost after endotoxin removal and is not mediated by Hsp60 expressed in eukaryotic systems PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Protein-containing complex (transferred from human co-purification data). Reason: The human source rows record co-purification of HSPD1 with unrelated bait proteins, many of which are probably chaperonin clients. The informative complex for Hsp60 is the Hsp60-Hsp10 chaperonin, which this generic term does not specify. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt Homoheptamer arranged in a ring structure. |
| GO:0032991 protein-containing complex | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Protein-containing complex (transferred from human co-purification data). Reason: The human source rows record co-purification of HSPD1 with unrelated bait proteins, many of which are probably chaperonin clients. The informative complex for Hsp60 is the Hsp60-Hsp10 chaperonin, which this generic term does not specify. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Source rows are co-purifications with unrelated baits, not a defined complex. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt Homoheptamer arranged in a ring structure. |
| GO:0032991 protein-containing complex | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Protein-containing complex (transferred from human co-purification data). Reason: The human source rows record co-purification of HSPD1 with unrelated bait proteins, many of which are probably chaperonin clients. The informative complex for Hsp60 is the Hsp60-Hsp10 chaperonin, which this generic term does not specify. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Source rows are co-purifications with unrelated baits, not a defined complex. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt Homoheptamer arranged in a ring structure. |
| GO:0033198 response to ATP | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to ATP (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
| GO:0034185 apolipoprotein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Apolipoprotein binding (human data, projected). Reason: This is the same human HDL/apolipoprotein ligand-blotting evidence. It is not tested in mouse and is kept as non-core. |
| GO:0034185 apolipoprotein binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Apolipoprotein binding (human data, projected). Reason: This is the same human HDL/apolipoprotein ligand-blotting evidence. It is not tested in mouse and is kept as non-core. |
| GO:0034186 apolipoprotein A-I binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Apolipoprotein A-I binding (human data, projected). Reason: This is the same human HDL/apoA-I ligand-blotting evidence. It is not tested in mouse and is kept as non-core. |
| GO:0034186 apolipoprotein A-I binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Apolipoprotein A-I binding (human data, projected). Reason: This is the same human HDL/apoA-I ligand-blotting evidence. It is not tested in mouse and is kept as non-core. |
| GO:0034514 mitochondrial unfolded protein response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitochondrial unfolded protein response. Reason: The PAINT IBD at PTN000143510 is seeded by C. elegans hsp-60, the classic UPRmt target. In mouse intestinal epithelium, Hsp60 loss activates the MT-UPR (PMID:27786175). That shows Hsp60 is part of the folding capacity the response monitors and restores, with Hspd1 as an induced effector. This is real but secondary to constitutive folding. Supporting Evidence: PMID:27786175 loss of HSP60, a mitochondrial chaperone, activates the mitochondrial unfolded protein response (MT-UPR) and results in mitochondrial dysfunction |
| GO:0034605 cellular response to heat | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to heat (rat IEP projected by orthology). Reason: Hsp60 is a heat-inducible chaperone, and the rat source is an expression-induction (IEP) observation. Heat-denatured matrix proteins are refolded by the chaperonin (PMID:11422376), which links the induction to the activity. It is kept as non-core. Supporting Evidence: PMID:11422376 Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. |
| GO:0042026 protein refolding | IEA GO_REF:0000120 | ACCEPT | Summary: Refolding of stress-denatured polypeptides by the Hsp60-Hsp10 chaperonin. Reason: Mammalian mitochondrial Cpn60/Cpn10 refolds chemically denatured malate dehydrogenase and Rubisco in an ATP-dependent manner (PMID:11422376, PMID:1346131). These assays used non-mouse mammalian protein, so the transfer rests on 1:1 orthology inside PTN000143509. The UniProt function statement (by similarity) agrees. Supporting Evidence: PMID:11422376 does not inhibit malate dehydrogenase refolding or ATP hydrolysis by mt-cpn60 in the presence of mt-cpn10 PMID:1346131 facilitates the formation of catalytically active ribulose-bisphosphate carboxylase from an unfolded state in the presence of K+ and MgATP PMID:11422376 Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. |
| GO:0042026 protein refolding | ISO GO_REF:0000119 | ACCEPT | Summary: Refolding of stress-denatured polypeptides by the Hsp60-Hsp10 chaperonin. Reason: Mammalian mitochondrial Cpn60/Cpn10 refolds chemically denatured malate dehydrogenase and Rubisco in an ATP-dependent manner (PMID:11422376, PMID:1346131). These assays used non-mouse mammalian protein, so the transfer rests on 1:1 orthology inside PTN000143509. The UniProt function statement (by similarity) agrees. Supporting Evidence: PMID:11422376 does not inhibit malate dehydrogenase refolding or ATP hydrolysis by mt-cpn60 in the presence of mt-cpn10 PMID:1346131 facilitates the formation of catalytically active ribulose-bisphosphate carboxylase from an unfolded state in the presence of K+ and MgATP PMID:11422376 Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. |
| GO:0042100 B cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: B cell proliferation (human recombinant Hsp60 data, projected). Reason: The B-cell findings come from one study with recombinant protein and are contested because of endotoxin. In mouse, Hsp60 binds macrophages and DC but not B lymphocytes, and T-cell stimulation is not mediated by B cells (PMID:17164250). Supporting Evidence: PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes |
| GO:0042100 B cell proliferation | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: B cell proliferation (human recombinant Hsp60 data, projected). Reason: The B-cell findings come from one study with recombinant protein and are contested because of endotoxin. In mouse, Hsp60 binds macrophages and DC but not B lymphocytes, and T-cell stimulation is not mediated by B cells (PMID:17164250). Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Human recombinant-protein B-cell data, contested; mouse Hsp60 does not bind B cells (PMID:17164250). Supporting Evidence: PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes |
| GO:0042110 T cell activation | IBA GO_REF:0000033 | MODIFY | Summary: T cell activation. Reason: Hsp60 is not a component of the T cell's own activation machinery. It binds macrophages and DC, not T cells (PMID:17164250), and enhances T-cell activation through them. 'Positive regulation of T cell activation' (GO:0050870, already annotated by IBA and IDA) describes the supported claim. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002900230 SUPPORTS TRANSFER The costimulatory effect transfers; the correct term is positive regulation of T cell activation. Proposed replacements: positive regulation of T cell activation Supporting Evidence: PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation |
| GO:0042110 T cell activation | IDA PMID:15371451 Lipopolysaccharide-free heat shock protein 60 activates T ce... | MODIFY | Summary: T cell activation. Reason: Hsp60 is not a component of the T cell's own activation machinery. It binds macrophages and DC, not T cells (PMID:17164250), and enhances T-cell activation through them. 'Positive regulation of T cell activation' (GO:0050870, already annotated by IBA and IDA) describes the supported claim. Proposed replacements: positive regulation of T cell activation Supporting Evidence: PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation |
| GO:0042110 T cell activation | IDA PMID:17164250 Synergistic and differential modulation of immune responses ... | MODIFY | Summary: T cell activation. Reason: Hsp60 is not a component of the T cell's own activation machinery. It binds macrophages and DC, not T cells (PMID:17164250), and enhances T-cell activation through them. 'Positive regulation of T cell activation' (GO:0050870, already annotated by IBA and IDA) describes the supported claim. Proposed replacements: positive regulation of T cell activation Supporting Evidence: PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation |
| GO:0042110 T cell activation | IDA PMID:18256040 Hsp60-mediated T cell stimulation is independent of TLR4 and... | MODIFY | Summary: T cell activation. Reason: Hsp60 is not a component of the T cell's own activation machinery. It binds macrophages and DC, not T cells (PMID:17164250), and enhances T-cell activation through them. 'Positive regulation of T cell activation' (GO:0050870, already annotated by IBA and IDA) describes the supported claim. Proposed replacements: positive regulation of T cell activation Supporting Evidence: PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation |
| GO:0042110 T cell activation | IGI PMID:17164250 Synergistic and differential modulation of immune responses ... | MODIFY | Summary: T cell activation. Reason: Hsp60 is not a component of the T cell's own activation machinery. It binds macrophages and DC, not T cells (PMID:17164250), and enhances T-cell activation through them. 'Positive regulation of T cell activation' (GO:0050870, already annotated by IBA and IDA) describes the supported claim. Proposed replacements: positive regulation of T cell activation Supporting Evidence: PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation |
| GO:0042110 T cell activation | ISO GO_REF:0000008 | MODIFY | Summary: T cell activation. Reason: Hsp60 is not a component of the T cell's own activation machinery. It binds macrophages and DC, not T cells (PMID:17164250), and enhances T-cell activation through them. 'Positive regulation of T cell activation' (GO:0050870, already annotated by IBA and IDA) describes the supported claim. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P10809 SUPPORTS TRANSFER The costimulatory effect transfers; the correct term is positive regulation of T cell activation. Proposed replacements: positive regulation of T cell activation Supporting Evidence: PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation |
| GO:0042113 B cell activation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: B cell activation (human recombinant Hsp60 data, projected). Reason: The B-cell findings come from one study with recombinant protein and are contested. In mouse, Hsp60 does not bind B lymphocytes (PMID:17164250). Supporting Evidence: PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes |
| GO:0042113 B cell activation | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: B cell activation (human recombinant Hsp60 data, projected). Reason: The B-cell findings come from one study with recombinant protein and are contested. In mouse, Hsp60 does not bind B lymphocytes (PMID:17164250). Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Human recombinant-protein B-cell data, contested; mouse Hsp60 does not bind B cells (PMID:17164250). Supporting Evidence: PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes |
| GO:0042220 response to cocaine | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to cocaine (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
| GO:0042542 response to hydrogen peroxide | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to hydrogen peroxide (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
| GO:0042588 zymogen granule | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Zymogen granule (rat immuno-EM, projected). Reason: This location comes from rat antibody-based immuno-EM. In mouse beta cells the antibody-reactive granular signal includes several cross-reactive proteins (PMID:8824711). It is not supported by mouse data. Supporting Evidence: PMID:8824711 the hsp60 antibody cross-reactive proteins were detected in secretory granules, mitochondria, synaptic-like microvesicles and microtubules of mouse pancreatic beta cells |
| GO:0042588 zymogen granule | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Zymogen granule (rat immuno-EM, projected). Reason: This location comes from rat antibody-based immuno-EM. In mouse beta cells the antibody-reactive granular signal includes several cross-reactive proteins (PMID:8824711). It is not supported by mouse data. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: RGD:621314 SOURCE WEAK OR INFERRED Rat antibody-based immuno-EM; hsp60-related cross-reactive proteins confound such data (PMID:8824711). Supporting Evidence: PMID:8824711 the hsp60 antibody cross-reactive proteins were detected in secretory granules, mitochondria, synaptic-like microvesicles and microtubules of mouse pancreatic beta cells |
| GO:0043032 positive regulation of macrophage activation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of macrophage activation (human data, projected). Reason: Mouse data show that macrophage activation by recombinant Hsp60 tracks endotoxin contamination (PMID:15371451), and that LPS-free Hsp60 does not induce IL-6, IL-12 or TNF in APC (PMID:18256040). Supporting Evidence: PMID:15371451 The induction of tumor necrosis factor-alpha secretion in mouse macrophages is lost after endotoxin removal and is not mediated by Hsp60 expressed in eukaryotic systems PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC |
| GO:0043032 positive regulation of macrophage activation | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Positive regulation of macrophage activation (human data, projected). Reason: Mouse data show that macrophage activation by recombinant Hsp60 tracks endotoxin contamination (PMID:15371451), and that LPS-free Hsp60 does not induce IL-6, IL-12 or TNF in APC (PMID:18256040). Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Macrophage activation by recombinant Hsp60 tracks endotoxin contamination in mouse (PMID:15371451). Supporting Evidence: PMID:15371451 The induction of tumor necrosis factor-alpha secretion in mouse macrophages is lost after endotoxin removal and is not mediated by Hsp60 expressed in eukaryotic systems PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process. Reason: Human tumour-cell knockdown and rat IMP data support an anti-apoptotic role. In mouse, Hsp60 deletion increases apoptosis of yolk-sac erythrocytes (PMID:31601784). The effect is downstream of mitochondrial folding, so it is kept as non-core. Supporting Evidence: PMID:31601784 we demonstrated an essential role of HSP60 in regulating yolk sac cell survival partially via a mPTP-dependent mechanism |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process. Reason: Human tumour-cell knockdown and rat IMP data support an anti-apoptotic role. In mouse, Hsp60 deletion increases apoptosis of yolk-sac erythrocytes (PMID:31601784). The effect is downstream of mitochondrial folding, so it is kept as non-core. Supporting Evidence: PMID:31601784 we demonstrated an essential role of HSP60 in regulating yolk sac cell survival partially via a mPTP-dependent mechanism |
| GO:0043209 myelin sheath | HDA PMID:17634366 Proteolipid protein is required for transport of sirtuin 2 i... | MARK AS OVER ANNOTATED | Summary: Myelin sheath (CNS myelin proteomics). Reason: Biochemically purified CNS myelin fractions routinely contain mitochondrial proteins from axonal and glial mitochondria. Detection of Hsp60 in such a proteome does not show that it resides in compact myelin. |
| GO:0043524 negative regulation of neuron apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of neuron apoptotic process (rat IMP, projected by Compara). Reason: In mouse, Hspd1 haploinsufficiency causes late neuronal dysfunction through impaired complex III assembly and MnSOD folding (PMID:23466696, PMID:24151936). Neuronal survival is a downstream consequence of the chaperonin's folding function, not a regulatory process the protein carries out. Supporting Evidence: PMID:23466696 a defect in the assembly of the respiratory chain complex III in neuronal tissues |
| GO:0043627 response to estrogen | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to estrogen (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
| GO:0044406 adhesion of symbiont to host | IDA NOT PMID:20633027 Mycobacterium tuberculosis employs Cpn60.2 as an adhesin tha... | KEEP AS NON CORE | Summary: NOT adhesion of symbiont to host. Reason: Mouse and human Hsp60, unlike M. tuberculosis Cpn60.2 and E. coli GroEL, do not competitively inhibit mycobacterial binding to macrophages (PMID:20633027). The negative statement is supported and is kept. Supporting Evidence: PMID:20633027 shared by the Escherichia coli homologue, GroEL, but not by the mouse and human Hsp60 homologues |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Protein-containing complex binding (rat IPI PMID:16579988, projected). Reason: The rat source paper is not cached and the partner complex is unclear. The claim cannot be assessed for mouse. |
| GO:0044877 protein-containing complex binding | ISO GO_REF:0000096 | UNDECIDED | Summary: Protein-containing complex binding (rat IPI PMID:16579988, projected). Reason: The rat source paper is not cached and the partner complex is unclear. The claim cannot be assessed for mouse. Propagation Review Root cause: UNRESOLVED Sources checked: RGD:621314 UNRESOLVED Rat IPI source (PMID:16579988) not cached; partner complex unclear. |
| GO:0045041 protein import into mitochondrial intermembrane space | IBA GO_REF:0000033 | UNDECIDED | Summary: Protein import into mitochondrial intermembrane space (IBA seeded only by yeast HSP60). Reason: PAINT placed this at PTN000143510 using only yeast HSP60, where matrix Hsp60 was proposed to hold imported cytochrome b2 before re-export to the IMS. That route was disputed even in yeast. Mouse is inside the clade, so the transfer is not phylogenetically wrong. But no mammalian experiment addresses IMS sorting, and import of matrix proteins into Hsp60-deleted mouse heart mitochondria is normal (PMID:31209364). The mouse data neither confirm nor refute the IMS claim. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000143510 UNRESOLVED Node seeded only by yeast HSP60; IMS sorting role disputed in yeast and untested in mammals. Supporting Evidence: PMID:31209364 suggesting that mitochondrial protein import was not affected by deletion of HSP60 |
| GO:0046696 lipopolysaccharide receptor complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Lipopolysaccharide receptor complex. Reason: Hsp60 bound at the APC surface colocalises with CD14 and binds LPS (PMID:17164250). That makes it an LPS-binding extracellular protein, not an established subunit of the CD14/TLR4/MD-2 receptor complex. LPS binding (GO:0001530) captures the supported claim. Supporting Evidence: PMID:17164250 Hsp60 bound to the cell surface of APC colocalizes with the LPS co-receptor CD14 and LPS binding sites |
| GO:0046696 lipopolysaccharide receptor complex | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Lipopolysaccharide receptor complex. Reason: Hsp60 bound at the APC surface colocalises with CD14 and binds LPS (PMID:17164250). That makes it an LPS-binding extracellular protein, not an established subunit of the CD14/TLR4/MD-2 receptor complex. LPS binding (GO:0001530) captures the supported claim. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:P10809 SOURCE WEAK OR INFERRED Colocalisation with CD14 and LPS binding do not make Hsp60 a receptor-complex subunit. Supporting Evidence: PMID:17164250 Hsp60 bound to the cell surface of APC colocalizes with the LPS co-receptor CD14 and LPS binding sites |
| GO:0048291 isotype switching to IgG isotypes | IEA GO_REF:0000107 | UNDECIDED | Summary: Isotype switching to IgG isotypes (human data, projected). Reason: The source study's isotype-switching experiment is not in the accessible abstract, and its B-cell findings are contested. The claim cannot be assessed for mouse. |
| GO:0048291 isotype switching to IgG isotypes | ISO GO_REF:0000119 | UNDECIDED | Summary: Isotype switching to IgG isotypes (human data, projected). Reason: The source study's isotype-switching experiment is not in the accessible abstract, and its B-cell findings are contested. The claim cannot be assessed for mouse. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P10809 UNRESOLVED Isotype-switching experiment not visible in the accessible source abstract. |
| GO:0050821 protein stabilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein stabilization. Reason: The source is human tumour-cell survivin/p53 data. Mouse cardiomyocyte data show that imported SIRT3 is degraded faster in Hsp60-deleted mitochondria (PMID:31209364). Stabilisation is therefore a consequence of chaperonin folding, and it is kept as non-core. Supporting Evidence: PMID:31209364 protein import was comparable between control and HSP60CKO mitochondria while protein was degraded more rapidly in HSP60CKO mitochondria |
| GO:0050821 protein stabilization | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Protein stabilization. Reason: The source is human tumour-cell survivin/p53 data. Mouse cardiomyocyte data show that imported SIRT3 is degraded faster in Hsp60-deleted mitochondria (PMID:31209364). Stabilisation is therefore a consequence of chaperonin folding, and it is kept as non-core. Supporting Evidence: PMID:31209364 protein import was comparable between control and HSP60CKO mitochondria while protein was degraded more rapidly in HSP60CKO mitochondria |
| GO:0050870 positive regulation of T cell activation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of T cell activation (costimulation via APC). Reason: Exogenous or cell-surface Hsp60 enhances antigen-specific T-cell activation in mouse cultures independently of endotoxin (PMID:15371451, PMID:17164250, PMID:18256040). It does so through APC, so 'positive regulation' is the right relation. It is not a core function of the mitochondrial chaperonin. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation PMID:18256040 T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 and the TLR-associated myeloide differentiation factor 88-signaling pathway PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes |
| GO:0050870 positive regulation of T cell activation | IDA PMID:17164250 Synergistic and differential modulation of immune responses ... | KEEP AS NON CORE | Summary: Positive regulation of T cell activation (costimulation via APC). Reason: Exogenous or cell-surface Hsp60 enhances antigen-specific T-cell activation in mouse cultures independently of endotoxin (PMID:15371451, PMID:17164250, PMID:18256040). It does so through APC, so 'positive regulation' is the right relation. It is not a core function of the mitochondrial chaperonin. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation PMID:18256040 T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 and the TLR-associated myeloide differentiation factor 88-signaling pathway PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes |
| GO:0050870 positive regulation of T cell activation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of T cell activation (costimulation via APC). Reason: Exogenous or cell-surface Hsp60 enhances antigen-specific T-cell activation in mouse cultures independently of endotoxin (PMID:15371451, PMID:17164250, PMID:18256040). It does so through APC, so 'positive regulation' is the right relation. It is not a core function of the mitochondrial chaperonin. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation PMID:18256040 T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 and the TLR-associated myeloide differentiation factor 88-signaling pathway PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes |
| GO:0050870 positive regulation of T cell activation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Positive regulation of T cell activation (costimulation via APC). Reason: Exogenous or cell-surface Hsp60 enhances antigen-specific T-cell activation in mouse cultures independently of endotoxin (PMID:15371451, PMID:17164250, PMID:18256040). It does so through APC, so 'positive regulation' is the right relation. It is not a core function of the mitochondrial chaperonin. Supporting Evidence: PMID:15371451 Hsp60 that is expressed on the surface of different eukaryotic cell lines increases the activation of T cells in primary stimulation PMID:18256040 T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 and the TLR-associated myeloide differentiation factor 88-signaling pathway PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes |
| GO:0051087 protein-folding chaperone binding | IBA GO_REF:0000033 | ACCEPT | Summary: Binding of the co-chaperonin Hsp10 (Hspe1), which caps the Hsp60 ring during the folding cycle. Reason: The IBA at the mitochondrial Hsp60 node PTN000143509 is seeded by yeast HSP60 and human HSPD1. Human Hsp60 works specifically with Hsp10 and not with GroES (PMID:11050098), and the structures show the Hsp60-Hsp10 football complex (PMID:32317635). In mouse, the Hspe1 gene is co-regulated with Hspd1 in Hspd1 gene-trap mice (PMID:20393889). The binding itself has not been measured biochemically with mouse protein. Supporting Evidence: PMID:11050098 its human homologue, Hsp60 functions specifically with its co-chaperonin partner, Hsp10 PMID:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins PMID:20393889 Together with its co-chaperonin Hsp10, Hsp60 forms a large multisubunit complex that is one of the most important factors in the facilitation of the proper folding and assembly of proteins in the mitochondrial matrix. |
| GO:0051087 protein-folding chaperone binding | IEA GO_REF:0000107 | ACCEPT | Summary: Binding of the co-chaperonin Hsp10 (Hspe1), which caps the Hsp60 ring during the folding cycle. Reason: The IBA at the mitochondrial Hsp60 node PTN000143509 is seeded by yeast HSP60 and human HSPD1. Human Hsp60 works specifically with Hsp10 and not with GroES (PMID:11050098), and the structures show the Hsp60-Hsp10 football complex (PMID:32317635). In mouse, the Hspe1 gene is co-regulated with Hspd1 in Hspd1 gene-trap mice (PMID:20393889). The binding itself has not been measured biochemically with mouse protein. Supporting Evidence: PMID:11050098 its human homologue, Hsp60 functions specifically with its co-chaperonin partner, Hsp10 PMID:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins PMID:20393889 Together with its co-chaperonin Hsp10, Hsp60 forms a large multisubunit complex that is one of the most important factors in the facilitation of the proper folding and assembly of proteins in the mitochondrial matrix. |
| GO:0051087 protein-folding chaperone binding | ISO GO_REF:0000119 | ACCEPT | Summary: Binding of the co-chaperonin Hsp10 (Hspe1), which caps the Hsp60 ring during the folding cycle. Reason: The IBA at the mitochondrial Hsp60 node PTN000143509 is seeded by yeast HSP60 and human HSPD1. Human Hsp60 works specifically with Hsp10 and not with GroES (PMID:11050098), and the structures show the Hsp60-Hsp10 football complex (PMID:32317635). In mouse, the Hspe1 gene is co-regulated with Hspd1 in Hspd1 gene-trap mice (PMID:20393889). The binding itself has not been measured biochemically with mouse protein. Supporting Evidence: PMID:11050098 its human homologue, Hsp60 functions specifically with its co-chaperonin partner, Hsp10 PMID:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins PMID:20393889 Together with its co-chaperonin Hsp10, Hsp60 forms a large multisubunit complex that is one of the most important factors in the facilitation of the proper folding and assembly of proteins in the mitochondrial matrix. |
| GO:0051384 response to glucocorticoid | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to glucocorticoid (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
| GO:0051702 biological process involved in interaction with symbiont | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Biological process involved in interaction with symbiont (human Listeria adhesion data, projected). Reason: Host Hsp60 acts as a receptor for Listeria LAP in human intestinal cells. It is not tested in mouse. Mouse Hsp60 does not mediate the M. tuberculosis Cpn60.2 interaction (PMID:20633027), so the role is pathogen-specific. It is kept as non-core. Supporting Evidence: PMID:20633027 shared by the Escherichia coli homologue, GroEL, but not by the mouse and human Hsp60 homologues |
| GO:0051702 biological process involved in interaction with symbiont | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Biological process involved in interaction with symbiont (human Listeria adhesion data, projected). Reason: Host Hsp60 acts as a receptor for Listeria LAP in human intestinal cells. It is not tested in mouse. Mouse Hsp60 does not mediate the M. tuberculosis Cpn60.2 interaction (PMID:20633027), so the role is pathogen-specific. It is kept as non-core. Supporting Evidence: PMID:20633027 shared by the Escherichia coli homologue, GroEL, but not by the mouse and human Hsp60 homologues |
| GO:0070062 extracellular exosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Extracellular exosome (human proteomics, projected). Reason: Hsp60 is commonly found in extracellular vesicle proteomes, but this is not tested in mouse. It is kept as non-core. |
| GO:0070062 extracellular exosome | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Extracellular exosome (human proteomics, projected). Reason: Hsp60 is commonly found in extracellular vesicle proteomes, but this is not tested in mouse. It is kept as non-core. |
| GO:0071866 negative regulation of apoptotic process in bone marrow cell | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of apoptotic process in bone marrow cell (rat IMP, projected). Reason: This is a cell-type-specific survival phenotype from a single rat study. As with the other survival rows, it is a consequence of loss of mitochondrial proteostasis and is an over-specific annotation for mouse. |
| GO:0097225 sperm midpiece | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sperm midpiece (human data, projected). Reason: The sperm midpiece is the mitochondria-rich segment of the flagellum, so this location follows from mitochondrial residence. It is kept as non-core. |
| GO:0098761 cellular response to interleukin-7 | IDA PMID:29581031 IL-7-induced phosphorylation of the adaptor Crk-like and oth... | MARK AS OVER ANNOTATED | Summary: Cellular response to interleukin-7 (phosphoproteomics, PMID:29581031). Reason: This study profiled tyrosine-phosphorylated proteins in an IL-7-dependent mouse cell line, and the abstract does not mention Hsp60. At best the evidence is a phosphorylation change after IL-7 stimulation. That does not show Hsp60 carries out part of the IL-7 response. |
| GO:0140030 modification-dependent protein binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Modification-dependent protein binding (rat IPI PMID:9811814, projected). Reason: The rat source paper is not cached, and the modification and partner cannot be identified. The claim cannot be assessed for mouse. |
| GO:0140030 modification-dependent protein binding | ISO GO_REF:0000096 | UNDECIDED | Summary: Modification-dependent protein binding (rat IPI PMID:9811814, projected). Reason: The rat source paper is not cached, and the modification and partner cannot be identified. The claim cannot be assessed for mouse. Propagation Review Root cause: UNRESOLVED Sources checked: RGD:621314 UNRESOLVED Rat IPI source (PMID:9811814) not cached; modification and partner unclear. |
| GO:0140494 migrasome | IDA PMID:34048705 Mitocytosis, a migrasome-mediated mitochondrial quality-cont... | KEEP AS NON CORE | Summary: Migrasome (mitocytosis study). Reason: Damaged mitochondria are transported into migrasomes and expelled (PMID:34048705). Hsp60 is detected there as part of the cargo mitochondria. The location is real but incidental to function. Supporting Evidence: PMID:34048705 damaged mitochondria are transported into migrasomes |
| GO:0140608 cysteine-type endopeptidase activator activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cysteine-type endopeptidase activator activity (procaspase-3 activation, human data). Reason: Human Hsp60/Hsp10 accelerates cytochrome c/dATP-dependent procaspase-3 activation in vitro. The orthology transfer is plausible, but the activity is not tested in mouse and is not the core function. |
| GO:0140608 cysteine-type endopeptidase activator activity | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Cysteine-type endopeptidase activator activity (procaspase-3 activation, human data). Reason: Human Hsp60/Hsp10 accelerates cytochrome c/dATP-dependent procaspase-3 activation in vitro. The orthology transfer is plausible, but the activity is not tested in mouse and is not the core function. |
| GO:0140662 ATP-dependent protein folding chaperone | IEA GO_REF:0000120 | ACCEPT | Summary: ATP-dependent folding chaperone activity of the mitochondrial Hsp60-Hsp10 chaperonin. Reason: This is the core molecular function of Hsp60. Mouse Hspd1 is a one-to-one ortholog of human HSPD1 in the mitochondrial Hsp60 PAINT clade (PTN000143509, PANTHER PTHR45633). The ATP-dependent refolding activity has been measured biochemically on recombinant mammalian mitochondrial Cpn60 with Cpn10 (PMID:1346131, PMID:11422376), not on the mouse protein specifically. In mouse, in vivo evidence shows that the protein is needed for matrix proteins to fold. Cardiomyocyte deletion leaves import intact, but imported HSP60-dependent proteins misfold and are degraded (PMID:31209364). MnSOD requires Hsp60 to fold (PMID:24151936). The activity is therefore inferred for the mouse protein by orthology and supported by mouse genetics. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt Together with Hsp10, facilitates the correct folding of imported proteins. PMID:1346131 facilitates the formation of catalytically active ribulose-bisphosphate carboxylase from an unfolded state in the presence of K+ and MgATP PMID:11422376 does not inhibit malate dehydrogenase refolding or ATP hydrolysis by mt-cpn60 in the presence of mt-cpn10 PMID:31209364 revealed a list of mitochondrial-localized proteins that rely on HSP60 (HSP60-dependent) for correctly folding in mitochondria PMID:24151936 we propose that MnSOD is a substrate of the Hsp60 folding machinery |
| GO:0140662 ATP-dependent protein folding chaperone | ISO GO_REF:0000119 | ACCEPT | Summary: ATP-dependent folding chaperone activity of the mitochondrial Hsp60-Hsp10 chaperonin. Reason: This is the core molecular function of Hsp60. Mouse Hspd1 is a one-to-one ortholog of human HSPD1 in the mitochondrial Hsp60 PAINT clade (PTN000143509, PANTHER PTHR45633). The ATP-dependent refolding activity has been measured biochemically on recombinant mammalian mitochondrial Cpn60 with Cpn10 (PMID:1346131, PMID:11422376), not on the mouse protein specifically. In mouse, in vivo evidence shows that the protein is needed for matrix proteins to fold. Cardiomyocyte deletion leaves import intact, but imported HSP60-dependent proteins misfold and are degraded (PMID:31209364). MnSOD requires Hsp60 to fold (PMID:24151936). The activity is therefore inferred for the mouse protein by orthology and supported by mouse genetics. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt Together with Hsp10, facilitates the correct folding of imported proteins. PMID:1346131 facilitates the formation of catalytically active ribulose-bisphosphate carboxylase from an unfolded state in the presence of K+ and MgATP PMID:11422376 does not inhibit malate dehydrogenase refolding or ATP hydrolysis by mt-cpn60 in the presence of mt-cpn10 PMID:31209364 revealed a list of mitochondrial-localized proteins that rely on HSP60 (HSP60-dependent) for correctly folding in mitochondria PMID:24151936 we propose that MnSOD is a substrate of the Hsp60 folding machinery |
| GO:0140662 ATP-dependent protein folding chaperone | ISS GO_REF:0000024 | ACCEPT | Summary: ATP-dependent folding chaperone activity of the mitochondrial Hsp60-Hsp10 chaperonin. Reason: This is the core molecular function of Hsp60. Mouse Hspd1 is a one-to-one ortholog of human HSPD1 in the mitochondrial Hsp60 PAINT clade (PTN000143509, PANTHER PTHR45633). The ATP-dependent refolding activity has been measured biochemically on recombinant mammalian mitochondrial Cpn60 with Cpn10 (PMID:1346131, PMID:11422376), not on the mouse protein specifically. In mouse, in vivo evidence shows that the protein is needed for matrix proteins to fold. Cardiomyocyte deletion leaves import intact, but imported HSP60-dependent proteins misfold and are degraded (PMID:31209364). MnSOD requires Hsp60 to fold (PMID:24151936). The activity is therefore inferred for the mouse protein by orthology and supported by mouse genetics. Supporting Evidence: file:mouse/Hspd1/Hspd1-uniprot.txt Together with Hsp10, facilitates the correct folding of imported proteins. PMID:1346131 facilitates the formation of catalytically active ribulose-bisphosphate carboxylase from an unfolded state in the presence of K+ and MgATP PMID:11422376 does not inhibit malate dehydrogenase refolding or ATP hydrolysis by mt-cpn60 in the presence of mt-cpn10 PMID:31209364 revealed a list of mitochondrial-localized proteins that rely on HSP60 (HSP60-dependent) for correctly folding in mitochondria PMID:24151936 we propose that MnSOD is a substrate of the Hsp60 folding machinery |
| GO:1900118 negative regulation of execution phase of apoptosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of execution phase of apoptosis (human cell-line data, projected). Reason: This is human-only evidence: HSP60 knockdown promotes death with some apoptotic inducers. It is context-dependent and not tested in mouse, so it is kept as non-core. |
| GO:1900118 negative regulation of execution phase of apoptosis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Negative regulation of execution phase of apoptosis (human cell-line data, projected). Reason: This is human-only evidence: HSP60 knockdown promotes death with some apoptotic inducers. It is context-dependent and not tested in mouse, so it is kept as non-core. |
| GO:1900119 positive regulation of execution phase of apoptosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of execution phase of apoptosis (human cell-line data, projected). Reason: This is human-only evidence: cytosolic HSP60 promotes caspase-3 maturation with BMD188. The opposite-direction row reflects a different inducer. Both are context-dependent and not tested in mouse, so this is kept as non-core. |
| GO:1900119 positive regulation of execution phase of apoptosis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Positive regulation of execution phase of apoptosis (human cell-line data, projected). Reason: This is human-only evidence: cytosolic HSP60 promotes caspase-3 maturation with BMD188. The opposite-direction row reflects a different inducer. Both are context-dependent and not tested in mouse, so this is kept as non-core. |
| GO:1903427 negative regulation of reactive oxygen species biosynthetic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of reactive oxygen species biosynthetic process (rat IMP, projected). Reason: Mouse data explain the ROS increase in Hsp60-deficient tissue as impaired folding of MnSOD and respiratory-chain defects (PMID:24151936, PMID:31209364). Hsp60 is not a regulator of ROS biosynthesis. The ROS change is a downstream consequence of the folding defect. Supporting Evidence: PMID:24151936 the increase of ROS is, at least in part, due to impaired folding of the manganese superoxide dismutase (MnSOD) PMID:31209364 HSP60 deletion in adult mouse hearts altered mitochondrial complex activity, mitochondrial membrane potential, and ROS production |
| GO:1904638 response to resveratrol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to resveratrol (rat IEP, projected by Ensembl Compara). Reason: The rat source annotation is an expression-change (IEP) observation for a stress-inducible chaperone. Projected to mouse, it says nothing about what Hspd1 does, and no mouse study shows the protein takes part in this response. |
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Download this section (compressed HTML)Q: Which mouse matrix proteins are obligate Hsp60 clients, as opposed to proteins that are destabilised secondarily when respiration fails? The cardiomyocyte proteome (PMID:31209364) lists Hsp60-dependent proteins, but trapping or crosslinking experiments would be needed to separate direct clients from downstream losses.
Q: Does endogenous extracellular Hsp60 reach concentrations in vivo at which the IFN-alpha-dependent T-cell costimulation seen with added protein (PMID:17164250, 18256040) occurs, and by what route is it released?
Q: Should PAINT node PTN002900230 keep 'positive regulation of interleukin-6 production', given that mouse experiments with LPS-free Hsp60 found no IL-6 induction (PMID:18256040)?
Q: Does mammalian Hsp60 take part in sorting of intermembrane-space proteins, as the yeast-seeded IBA for GO:0045041 implies? No mammalian experiment has tested this.
Experiment: Purify recombinant mouse Hsp60 and Hspe1 and measure ATPase activity, ring state and refolding of denatured malate dehydrogenase and MnSOD, alongside human HSPD1 as a reference.
Hypothesis: Mouse Hsp60 is an ATP-dependent folding chaperone with the same single/double-ring behaviour as the human protein.
Type: biochemistry
Experiment: In inducible cardiomyocyte Hspd1 knockouts, combine pulse-chase import of tagged candidate clients with crosslinking or substrate-trap Hsp60 variants to identify proteins captured inside the chaperonin before degradation.
Hypothesis: A defined set of mouse matrix proteins depends directly on Hsp60 for folding in vivo.
Type: cell biology
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