HSPD1 encodes Hsp60, the mitochondrial type I (GroEL-like) chaperonin. This entry (A0A9L0S8L8, 587 aa) is the canonical horse product: it contains every residue of human Hsp60 (P10809), 97.6% identical, plus a 14-residue N-terminal extension ahead of the conserved matrix-targeting presequence. Each subunit has an equatorial ATP-binding domain, an intermediate hinge domain and an apical substrate- and Hsp10-binding domain. In mammals, Hsp60 is imported into the mitochondrial matrix, where heptameric rings associate with the HSPE1/Hsp10 co-chaperonin to form ATP-driven folding chambers. These enclose newly imported and stress-denatured matrix proteins and release them folded. Smaller pools of mammalian Hsp60 are reported in the cytosol, at the cell surface and in extracellular fluids, with context-dependent effects on apoptosis and on antigen-presenting cells. Horse Hsp60 has not been characterised biochemically; its functions are inferred from human, rodent, yeast and bacterial members of the same chaperonin family.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001530 lipopolysaccharide binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Lipopolysaccharide binding; multi-source IEA from human/mouse orthologs. Reason: Recombinant human Hsp60 binds bacterial LPS, and some of its immune effects depend on that binding. Secondary to the chaperonin role; kept as non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:17164250 Hsp60 specifically binds bacterial LPS PMID:17164250 This effect was Hsp60-specific and dependent on LPS-binding by Hsp60. |
| GO:0001819 positive regulation of cytokine production | IEA GO_REF:0000117 | MODIFY | Summary: Positive regulation of cytokine production; ARBA machine-learning IEA. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. The general term is better represented by the specific, LPS-independent effect: induction of IFN-alpha by antigen-presenting cells (GO:0032727), which the gene already carries. Matches the human review. Proposed replacements: positive regulation of interferon-alpha production 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:0002039 p53 binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: p53 binding; IEA from human ortholog. Reason: In human tumour cells Hsp60 holds p53 in a complex, and knockdown releases it. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:18086682 This response involves disruption of an Hsp60-p53 complex |
| GO:0002755 MyD88-dependent toll-like receptor signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: MyD88-dependent toll-like receptor signaling pathway; IEA from human ortholog. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. TLR4/MyD88 dependence of Hsp60 effects is the signature expected of LPS contamination; LPS-free Hsp60 acts independently of TLR4. Over-annotated. Supporting Evidence: PMID:16148103 The effects of HSP60 were found to be largely dependent on TLR4 and MyD88 signaling PMID:18256040 T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 |
| 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; IEA from human ortholog. Reason: Surface Hsp60 on human oesophageal tumour cells is recognised by gamma-delta T cells, and antibodies to it block lysis. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:10663613 Anti-hsp60 and anti-hsp70 mAb significantly inhibited the cytotoxicity of gammadelta T cells to both autologous and allogenic oesophageal tumours PMID:10663613 Surface expression of hsp60 and hsp70 on oesophageal tumours and Daudi cells was demonstrated by flow cytometry |
| GO:0003725 double-stranded RNA binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Double-stranded RNA binding; IEA from human ortholog. Reason: The human source annotation (PMID:21266579, Raftlin and poly(I:C) uptake) was left UNDECIDED in the human review because the paper does not clearly show dsRNA binding by Hsp60. The transfer inherits that uncertainty. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding by the equatorial domain of the Hsp60 chaperonin; InterPro-based IEA. Reason: Horse A0A9L0S8L8 is the canonical (Ensembl ENSECAT00000137290) product of HSPD1, a 1:1 ortholog of human P10809 in PANTHER PTHR45633 with every human residue present (559/573 identical) plus a 14-residue N-terminal extension. ATP binding and hydrolysis in the equatorial domain drive the chaperonin cycle. The horse product retains the complete equatorial domain and matches the Cpn60/GroEL and GroEL family signatures. Inferred, not measured, in horse. Supporting Evidence: file:HORSE/HSPD1__A0A9L0S8L8/HSPD1__A0A9L0S8L8-uniprot.txt InterPro; IPR001844; Cpn60/GroEL. file:HORSE/HSPD1__A0A9L0S8L8/HSPD1__A0A9L0S8L8-uniprot.txt NCBIfam; TIGR02348; GroEL; 1. PMID:32317635 an equatorial ATP-binding domain (residues 1–137, 411–526), an intermediate hinge domain (residues 138–191, 375–411), and an apical domain (residues 192–374) 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:0000107 | KEEP AS NON CORE | Summary: Extracellular region; IEA from human ortholog. Reason: Circulating Hsp60 is detected in human plasma. Secondary location. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:18229457 Mass spectrometric analysis of circulating immunoreactive Hsp60 reveal that it is predominantly the intact protein with no mitochondrial import peptide |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | TOO GENERAL | Summary: Cytoplasm; IEA from human/mouse orthologs. Reason: True but uninformative: the more specific mitochondrial matrix and cytosol terms are already on this gene. Matches the human review. Supporting Evidence: PMID:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | MODIFY | Summary: Mitochondrion; multi-source IEA from human/mouse orthologs. Reason: Correct but less specific than mitochondrial matrix (GO:0005759), which this gene already carries by IBA and IEA. Replace with the matrix term, as for human HSPD1. Proposed replacements: mitochondrial matrix Supporting Evidence: PMID:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins PMID:11422376 Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. |
| GO:0005743 mitochondrial inner membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane; IBA from PTN000143509 (fly, rat and yeast seeds). Reason: PAINT placed inner-membrane association at the mitochondrial Hsp60 clade from several seeds. Hsp60 is a soluble matrix chaperonin; inner-membrane association is peripheral to its function. Kept as non-core, in line with the human review. Supporting Evidence: PMID:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins |
| GO:0005759 mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial matrix; IBA from PTN000143509 (seeded by yeast, fission yeast, zebrafish and human Hsp60). Reason: Mitochondrial matrix is the primary location of the Hsp60-Hsp10 chaperonin. The IBD at PTN000143509 has several independent experimental seeds, and the horse product retains the N-terminal matrix-targeting presequence region (the extra 14 residues lie upstream of the conserved MLRLP start). No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins PMID:25918392 Human mitochondria harbor a single type I chaperonin system file:HORSE/HSPD1__A0A9L0S8L8/HSPD1__A0A9L0S8L8-uniprot.txt PANTHER; PTHR45633; 60 KDA HEAT SHOCK PROTEIN, MITOCHONDRIAL; 1. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrial matrix; multi-source IEA (human ortholog plus UniProt SubCell mapping). Reason: Horse A0A9L0S8L8 is the canonical (Ensembl ENSECAT00000137290) product of HSPD1, a 1:1 ortholog of human P10809 in PANTHER PTHR45633 with every human residue present (559/573 identical) plus a 14-residue N-terminal extension. Consistent with the IBA row; the matrix is where the folding cycle occurs. Supporting Evidence: PMID:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins PMID:11422376 Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. |
| GO:0005769 early endosome | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Early endosome; IEA from human ortholog. Reason: The human source (PMID:11807771) studies uptake of exogenous Hsp60 by dendritic-cell receptors; the endosomal signal is internalised extracellular protein, not an endogenous location. Over-annotated in human and therefore in the transfer. Supporting Evidence: PMID:11807771 (hu)hsp60 share the same receptors on (hu)monocyte-derived DC |
| GO:0005829 cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytosol; IEA from human ortholog. Reason: Horse A0A9L0S8L8 is the canonical (Ensembl ENSECAT00000137290) product of HSPD1, a 1:1 ortholog of human P10809 in PANTHER PTHR45633 with every human residue present (559/573 identical) plus a 14-residue N-terminal extension. In human cells a cytosolic pool of Hsp60 accumulates during apoptosis. This is a secondary location. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:17823127 in numerous apoptotic systems HSP60 protein accumulates in the cytosol |
| GO:0005832 chaperonin-containing T-complex | IEA GO_REF:0000117 | REMOVE | Summary: Chaperonin-containing T-complex; ARBA machine-learning IEA. Reason: CCT/TRiC is the cytosolic type II chaperonin built from TCP-1 family subunits. Hsp60 is the mitochondrial type I (GroEL-like) chaperonin in a different family (PTHR45633). No PAINT node propagates CCT to this family. The ARBA rule confuses the two chaperonin types. Supporting Evidence: PMID:25918392 Human mitochondria harbor a single type I chaperonin system file:HORSE/HSPD1__A0A9L0S8L8/HSPD1__A0A9L0S8L8-uniprot.txt PANTHER; PTHR45633; 60 KDA HEAT SHOCK PROTEIN, MITOCHONDRIAL; 1. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Plasma membrane; multi-source IEA from human/mouse orthologs. Reason: Human Hsp60 was found in plasma membrane preparations as an HDL-binding protein. Minor pool, non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:11027668 A new 55-kDa HDL/apolipoprotein binding protein was demonstrated in plasma membrane preparations of the human cell lines and primary cultured hepatocytes. PMID:11027668 Internal microprotein sequencing of the 55-kDa protein band revealed the binding protein as being heat shock protein 60 |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Clathrin-coated pit; IEA from human ortholog. Reason: Same source as the early endosome row: endocytosis of added Hsp60 by dendritic cells. Over-annotated. Supporting Evidence: PMID:11807771 (hu)hsp60 share the same receptors on (hu)monocyte-derived DC |
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: Protein folding; IBA from PAINT node PTN000143677 (GroEL, M. tuberculosis GroEL1/2, yeast Hsp60, human Hsp60). Reason: The PAINT IBD for protein folding sits at the root-level node PTN000143677, seeded by experimental annotations of E. coli GroEL, both M. tuberculosis GroEL paralogs, yeast HSP60 and human HSPD1. Horse HSPD1 descends from that node, and nothing in its sequence suggests loss of function. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins PMID:11422376 Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. file:HORSE/HSPD1__A0A9L0S8L8/HSPD1__A0A9L0S8L8-uniprot.txt PANTHER; PTHR45633; 60 KDA HEAT SHOCK PROTEIN, MITOCHONDRIAL; 1. |
| GO:0006457 protein folding | IEA GO_REF:0000002 | ACCEPT | Summary: Protein folding; InterPro2GO IEA for the Cpn60 signature. Reason: Horse A0A9L0S8L8 is the canonical (Ensembl ENSECAT00000137290) product of HSPD1, a 1:1 ortholog of human P10809 in PANTHER PTHR45633 with every human residue present (559/573 identical) plus a 14-residue N-terminal extension. Protein folding in the mitochondrial matrix is the core process of Hsp60. Supported by the family signature and by the PAINT IBD at PTN000143677 (row below). Supporting Evidence: file:HORSE/HSPD1__A0A9L0S8L8/HSPD1__A0A9L0S8L8-uniprot.txt InterPro; IPR001844; Cpn60/GroEL. PMID:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins PMID:11422376 Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. |
| GO:0006986 response to unfolded protein | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to unfolded protein; IEA from human ortholog. Reason: Horse A0A9L0S8L8 is the canonical (Ensembl ENSECAT00000137290) product of HSPD1, a 1:1 ortholog of human P10809 in PANTHER PTHR45633 with every human residue present (559/573 identical) plus a 14-residue N-terminal extension. Hsp60 is induced by and acts on unfolded proteins; this is a response-level description of the core folding function. Kept as non-core, as in human. Supporting Evidence: PMID:11422376 Mitochondrial chaperonins are necessary for the folding of newly imported and stress-denatured mitochondrial proteins. PMID:11050098 its human homologue, Hsp60 functions specifically with its co-chaperonin partner, Hsp10 |
| GO:0008035 high-density lipoprotein particle binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: High-density lipoprotein particle binding; IEA from human ortholog. Reason: Human Hsp60 was identified as a high-affinity HDL-binding protein on cell membranes. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:11027668 Internal microprotein sequencing of the 55-kDa protein band revealed the binding protein as being heat shock protein 60 PMID:11027668 A new 55-kDa HDL/apolipoprotein binding protein was demonstrated in plasma membrane preparations of the human cell lines and primary cultured hepatocytes. |
| GO:0008637 apoptotic mitochondrial changes | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Apoptotic mitochondrial changes; IBA from PTN000888030 seeded by rat Hspd1. Reason: Hsp60 forms a complex with pro-caspase-3 in mitochondria and can accumulate in the cytosol during apoptosis. These are context-dependent roles secondary to folding. Kept as non-core, as for human. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:10205158 pro-caspase-3 is present in the mitochondrial fraction of Jurkat T cells in a complex with the chaperone proteins Hsp60 and Hsp10 PMID:17823127 in numerous apoptotic systems HSP60 protein accumulates in the cytosol |
| GO:0009986 cell surface | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cell surface; IEA from human ortholog. Reason: Cell-surface Hsp60 is reported repeatedly on stressed or transformed human cells. Minor pool, non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:15784682 we found clear evidence for the occurrence of HSP60 on the surface of stressed HUVECs PMID:10663613 Surface expression of hsp60 and hsp70 on oesophageal tumours and Daudi cells was demonstrated by flow cytometry |
| GO:0016020 membrane | IEA GO_REF:0000107 | TOO GENERAL | Summary: Membrane; IEA from mouse ortholog. Reason: True but uninformative; mitochondrial inner membrane and plasma membrane are already annotated. Supporting Evidence: PMID:11027668 A new 55-kDa HDL/apolipoprotein binding protein was demonstrated in plasma membrane preparations of the human cell lines and primary cultured hepatocytes. |
| GO:0019899 enzyme binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Enzyme binding; IEA from human ortholog. Reason: The human source shows the Listeria adhesin LAP (an alcohol acetaldehyde dehydrogenase) binding Hsp60 on host cells. A host-pathogen interaction, non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:20507888 interacts with host-cell receptor Hsp60 to promote bacterial adhesion PMID:20507888 displayed strong binding affinity (K(D) 2-31 nM) towards Hsp60 |
| GO:0030135 coated vesicle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Coated vesicle; IEA from human ortholog. Reason: Same source as the early endosome row: endocytosis of added Hsp60 by dendritic cells. Over-annotated. Supporting Evidence: PMID:11807771 (hu)hsp60 share the same receptors on (hu)monocyte-derived DC |
| GO:0030141 secretory granule | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Secretory granule; IEA from mouse ortholog. Reason: Transferred from mouse; a minor non-mitochondrial pool, kept as non-core as in the human review. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ubiquitin protein ligase binding; IEA from human ortholog. Reason: HSPD1 co-purifies with Parkin in human cells. A plausible chaperone-client contact, non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:19725078 Tandem affinity purification/MS revealed 14 potential interactants of Parkin; CKB, DBT, HSPD1 |
| GO:0032727 positive regulation of interferon-alpha production | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of interferon-alpha production; IBA from PTN002900230 (Euteleostomi; human and mouse seeds). Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. IFN-alpha induction persists with LPS-free Hsp60, so it is the best-supported immune effect. The PAINT node covers Euteleostomi, so horse is in the clade. Non-core relative to folding. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. 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; IEA from human ortholog. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. IFN-alpha induction persists with LPS-free Hsp60, so it is the best-supported immune effect. The PAINT node covers Euteleostomi, so horse is in the clade. Non-core relative to folding. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. 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 production; IBA from PTN002900230 (human and mouse seeds). Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. Same claim as the IEA row; the Euteleostomi node includes horse. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:17164250 both, Hsp60 and LPS, increase antigen-specific interferon (IFN) gamma release in T cells 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 | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of type II interferon production; IEA from mouse ortholog. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. Hsp60 increases antigen-specific IFN-gamma release by T cells via APC. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:17164250 both, Hsp60 and LPS, increase antigen-specific interferon (IFN) gamma release in T cells 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; IEA from human ortholog. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. From the contested B-cell study; Hsp60 does not bind B cells in an independent study. Over-annotated. Supporting Evidence: PMID:16148103 human HSP60 (but not the Escherichia coli GroEL or the Mycobacterial HSP65 molecules) induced naive mouse B cells to proliferate PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes |
| GO:0032735 positive regulation of interleukin-12 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of interleukin-12 production; IEA from human ortholog. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. The IL-12 effect depended on LPS binding by Hsp60, and LPS-free Hsp60 does not induce IL-12. Kept as non-core to match the human review. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:17164250 This effect was Hsp60-specific and dependent on LPS-binding by Hsp60. PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC |
| GO:0032755 positive regulation of interleukin-6 production | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Positive regulation of interleukin-6 production; IBA from PTN002900230 (rat and human seeds). Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. LPS-free Hsp60 does not induce IL-6, and the original B-cell effect was TLR4/MyD88-dependent, consistent with LPS contamination. Over-annotated, as in the human review, despite the PAINT placement. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: PANTHER:PTN002900230 · PTN002900230 SOURCE WEAK OR INFERRED Euteleostomi node seeded by rat Hspd1 and human HSPD1; the human IL-6 evidence used recombinant Hsp60 and is not reproduced with LPS-free protein (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:16148103 The effects of HSP60 were found to be largely dependent on TLR4 and MyD88 signaling |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of interleukin-6 production; IEA from human ortholog. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. LPS-free Hsp60 does not induce IL-6, and the original B-cell effect was TLR4/MyD88-dependent, consistent with LPS contamination. Over-annotated, as in the human review, despite the PAINT placement. Supporting Evidence: PMID:18256040 LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC PMID:16148103 The effects of HSP60 were found to be largely dependent on TLR4 and MyD88 signaling |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Protein-containing complex; IEA from human ortholog. Reason: The human sources are interaction reports (ZNF703, lysine methyltransferases). The generic term adds nothing; the chaperonin complex itself has no specific GO CC term used here. Over-annotated, as in human. Supporting Evidence: PMID:21328542 HSP60 was only present in the cytoplasm and may interact with the cytoplasmic form of ZNF703 PMID:23349634 chaperonins HSPD1 and CCT (see METTL18, CAMKMT, METTL20, and METTL21B) |
| GO:0034185 apolipoprotein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Apolipoprotein binding; IEA from human ortholog. Reason: Same human study as the HDL row. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:11027668 Internal microprotein sequencing of the 55-kDa protein band revealed the binding protein as being heat shock protein 60 |
| GO:0034186 apolipoprotein A-I binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Apolipoprotein A-I binding; IEA from human ortholog. Reason: Same human study as the HDL row. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:11027668 Internal microprotein sequencing of the 55-kDa protein band revealed the binding protein as being heat shock protein 60 |
| GO:0034514 mitochondrial unfolded protein response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitochondrial unfolded protein response; IBA from PTN000143510 (Opisthokonta), seeded by C. elegans hsp-60. Reason: Hsp60 is a major chaperone output of the mitochondrial UPR and does folding work during it. The IBD node PTN000143510 covers Opisthokonta, so horse is in the clade. Mammalian UPRmt signalling differs in detail from worms, so this is kept as non-core rather than core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. 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: Protein refolding; multi-source IEA from the human ortholog and Cpn60 signature. Reason: Horse A0A9L0S8L8 is the canonical (Ensembl ENSECAT00000137290) product of HSPD1, a 1:1 ortholog of human P10809 in PANTHER PTHR45633 with every human residue present (559/573 identical) plus a 14-residue N-terminal extension. Refolding of stress-denatured substrates (e.g. malate dehydrogenase) by mt-cpn60/mt-cpn10 is shown for the mammalian chaperonin (PMID:11422376) and is part of the same core activity. Supporting Evidence: PMID:11422376 does not inhibit malate dehydrogenase refolding or ATP hydrolysis by mt-cpn60 in the presence of mt-cpn10 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; IEA from human ortholog. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. Single contested study; Hsp60 did not bind B cells in another study. Over-annotated. Supporting Evidence: PMID:16148103 human HSP60 (but not the Escherichia coli GroEL or the Mycobacterial HSP65 molecules) induced naive mouse B cells to proliferate 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; IBA from PTN002900230. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. Hsp60 does not itself activate T cells; it costimulates them via APCs. The regulation term positive regulation of T cell activation (GO:0050870), already on this gene, is the correct one. Matches the human review. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002900230 · PTN002900230 SUPPORTS TRANSFER Horse is inside this Euteleostomi node; the seeds show costimulation of T cells via APCs, which GO:0050870 describes better than T cell activation itself. Proposed replacements: positive regulation of T cell activation Supporting Evidence: PMID:15371451 the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination PMID:18256040 T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 |
| GO:0042113 B cell activation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: B cell activation; IEA from human ortholog. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. Same contested B-cell study. Over-annotated. Supporting Evidence: PMID:16148103 human HSP60 (but not the Escherichia coli GroEL or the Mycobacterial HSP65 molecules) induced naive mouse B cells to proliferate PMID:17164250 Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes |
| GO:0043032 positive regulation of macrophage activation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of macrophage activation; IEA from human ortholog. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. Macrophage TNF induction is lost after endotoxin removal. Over-annotated. Supporting Evidence: PMID:15371451 The induction of tumor necrosis factor-alpha secretion in mouse macrophages is lost after endotoxin removal 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:0000107 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process; IEA from human ortholog. Reason: Hsp60 knockdown triggers apoptosis in human tumour cells by destabilising survivin and releasing p53. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:18086682 Acute ablation of Hsp60 by small interfering RNA destabilizes the mitochondrial pool of survivin PMID:18086682 This response involves disruption of an Hsp60-p53 complex |
| GO:0045041 protein import into mitochondrial intermembrane space | IBA GO_REF:0000033 | UNDECIDED | Summary: Protein import into mitochondrial intermembrane space; IBA from PTN000143510, seeded only by yeast HSP60. Reason: In yeast, matrix Hsp60 arrests folding of some proteins that are re-exported to the intermembrane space (PMID:1347713), but other IMS-sorted fusion proteins never meet Hsp60 (PMID:7911803). There is no mammalian evidence for this route, so whether the Opisthokonta-level placement holds in mammals is unclear. Left undecided, matching the human HSPD1 review. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000143510 · PTN000143510 UNRESOLVED Opisthokonta node seeded only by yeast HSP60; no mammalian test of Hsp60-dependent intermembrane-space sorting. Supporting Evidence: PMID:1347713 While in the matrix, the protein interacts with hsp60, which arrests its folding prior to export. PMID:7911803 the cytochrome b2 presequence arrests import through the inner membrane, with the result that the attached passenger protein is never exposed to hsp60. |
| GO:0046696 lipopolysaccharide receptor complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Lipopolysaccharide receptor complex; IEA from human ortholog. Reason: The human evidence is colocalisation of exogenous Hsp60 with CD14 on APCs, not membership of the receptor complex. Over-annotated, as in the human review. Supporting Evidence: PMID:17164250 Hsp60 bound to the cell surface of APC colocalizes with the LPS co-receptor CD14 PMID:17164250 Hsp60 specifically binds bacterial LPS |
| GO:0048291 isotype switching to IgG isotypes | IEA GO_REF:0000107 | UNDECIDED | Summary: Isotype switching to IgG isotypes; IEA from human ortholog. Reason: The human source (PMID:16148103) was left UNDECIDED in the human review because the isotype-switching experiment is not in the available abstract and the B-cell findings are contested. The transfer inherits that uncertainty. |
| GO:0050821 protein stabilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein stabilization; IEA from human ortholog. Reason: Hsp60 stabilises the mitochondrial pool of survivin in human tumour cells; a chaperone-client effect. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:18086682 Acute ablation of Hsp60 by small interfering RNA destabilizes the mitochondrial pool of survivin |
| GO:0050870 positive regulation of T cell activation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of T cell activation; IBA from PTN002900230 (human and mouse seeds). Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. LPS-free Hsp60 enhances antigen-specific T-cell activation independently of TLR4. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:15371451 the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination PMID:18256040 T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 |
| GO:0050870 positive regulation of T cell activation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Positive regulation of T cell activation; multi-source IEA from human/mouse orthologs. Reason: These rows come from studies that add recombinant (mostly human) Hsp60 to human or mouse immune cells; they describe effects of extracellular protein, some attributable to bound LPS. LPS-free Hsp60 enhances antigen-specific T-cell activation independently of TLR4. Non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:15371451 the Hsp60-mediated enhancement of antigen-specific T cell activation does not correlate with endotoxin contamination PMID:18256040 T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 |
| GO:0051087 protein-folding chaperone binding | IBA GO_REF:0000033 | ACCEPT | Summary: Protein-folding chaperone binding; IBA from PTN000143509 (seeded by yeast HSP60 and human HSPD1). Reason: The IBD is placed at PTN000143509, the eukaryotic mitochondrial Hsp60 clade, seeded by yeast and human Hsp60. Horse HSPD1 is inside that clade. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:11050098 its human homologue, Hsp60 functions specifically with its co-chaperonin partner, Hsp10 file:HORSE/HSPD1__A0A9L0S8L8/HSPD1__A0A9L0S8L8-uniprot.txt PANTHER; PTHR45633; 60 KDA HEAT SHOCK PROTEIN, MITOCHONDRIAL; 1. |
| GO:0051087 protein-folding chaperone binding | IEA GO_REF:0000107 | ACCEPT | Summary: Protein-folding chaperone binding (Hsp10 co-chaperonin); IEA from human ortholog. Reason: Horse A0A9L0S8L8 is the canonical (Ensembl ENSECAT00000137290) product of HSPD1, a 1:1 ortholog of human P10809 in PANTHER PTHR45633 with every human residue present (559/573 identical) plus a 14-residue N-terminal extension. Binding of the HSPE1/Hsp10 co-chaperonin caps the folding chamber and is required for the cycle; human Hsp60 works specifically with Hsp10 (PMID:11050098). Core to the folding function. Supporting Evidence: PMID:11050098 its human homologue, Hsp60 functions specifically with its co-chaperonin partner, Hsp10 PMID:10205158 pro-caspase-3 is present in the mitochondrial fraction of Jurkat T cells in a complex with the chaperone proteins Hsp60 and Hsp10 |
| 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; IEA from human ortholog. Reason: Human Hsp60 on enterocyte-like cells is a receptor for the Listeria adhesin LAP. A host-pathogen role; non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:20507888 interacts with host-cell receptor Hsp60 to promote bacterial adhesion |
| GO:0070062 extracellular exosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Extracellular exosome; IEA from human ortholog. Reason: HSPD1 recurs in human exosome proteomes without a demonstrated vesicle-specific role; kept as non-core location, matching human. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. |
| GO:0097225 sperm midpiece | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sperm midpiece; IEA from human ortholog. Reason: The human source used Hsp60 staining as a marker of the mitochondrial sheath of the sperm midpiece. The location is a cell-type rendering of the mitochondrial location; non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. |
| GO:0140494 migrasome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Migrasome; IEA from mouse ortholog. Reason: Transferred from a mouse Hspd1 migrasome observation; a vesicle location without demonstrated role. Kept as non-core, matching human. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. |
| GO:0140608 cysteine-type endopeptidase activator activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cysteine-type endopeptidase activator activity; IEA from human ortholog. Reason: Recombinant Hsp60/Hsp10 accelerate pro-caspase-3 activation in an ATP-dependent manner, and cytosolic Hsp60 promotes caspase-3 maturation in some apoptotic systems. Context-dependent; non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:10205158 recombinant Hsp60 and Hsp10 accelerated the activation of pro-caspase-3 by cytochrome c and dATP in an ATP-dependent manner PMID:17823127 HSP60 has a pro-death function and that the pro-death role of HSP60 seems to involve caspase-3 maturation and activation in the cytosol |
| GO:0140662 ATP-dependent protein folding chaperone | IEA GO_REF:0000120 | ACCEPT | Summary: ATP-dependent protein folding chaperone; the core activity of the Hsp60-Hsp10 chaperonin. Multi-source IEA (InterPro plus human ortholog). Reason: Horse A0A9L0S8L8 is the canonical (Ensembl ENSECAT00000137290) product of HSPD1, a 1:1 ortholog of human P10809 in PANTHER PTHR45633 with every human residue present (559/573 identical) plus a 14-residue N-terminal extension. Mammalian mitochondrial chaperonin 60 folds unfolded substrates in an MgATP-dependent reaction with Hsp10 (PMID:1346131, PMID:11422376), and human structures show Hsp60-Hsp10 folding matrix proteins (PMID:32317635). The horse product is full length, with all three domains, so the activity transfers. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: 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:32317635 mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins file:HORSE/HSPD1__A0A9L0S8L8/HSPD1__A0A9L0S8L8-uniprot.txt InterPro; IPR001844; Cpn60/GroEL. file:HORSE/HSPD1/HSPD1-bioinformatics/RESULTS-rereview.md | A0A9L0S8L8 | 587 | 559/573 (97.6%) | none | 1-14 MKAHLTKRNSASSE | |
| 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; IEA from human ortholog. Reason: Human Hsp60 has pro-survival effects in some apoptotic systems. Context-dependent; non-core. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:17823127 HSP60 appears to play a pro-survival role in other apoptotic systems |
| 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; IEA from human ortholog. Reason: Human Hsp60 has pro-death effects via caspase-3 in other systems. Context-dependent; non-core. Both signs are reported in the same human study. No experiment on horse Hsp60 underlies this row; it is a transfer from human/mouse data. Supporting Evidence: PMID:17823127 HSP60 has a pro-death function and that the pro-death role of HSP60 seems to involve caspase-3 maturation and activation in the cytosol |
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Download this section (compressed HTML)Q: Is the 14-residue N-terminal extension (MKAHLTKRNSASSE) of A0A9L0S8L8 translated in horse tissues, or does translation start at the conserved MLRLP methionine as in human?
Q: Should A0A9L0S8L8 or F6Z587 be the PANTHER/UniProt representative for horse HSPD1, given that F6Z587 lacks a hinge-domain exon?
Experiment: N-terminal proteomics or ribosome profiling of horse tissue to determine the translation start and the mature N-terminus of matrix Hsp60.
Type: proteomics
Experiment: Reconstitute recombinant horse Hsp60 with Hsp10 and measure ATP-dependent refolding of a model substrate (e.g. malate dehydrogenase) to confirm the inferred core activity.
Type: biochemical assay
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