HSPD1 (Hsp60, mitochondrial chaperonin 60) is the mitochondrial member of the type I (GroEL-like) chaperonin family. In mammals it is imported into the mitochondrial matrix via an N-terminal transit peptide and assembles into heptameric rings that, with the HSPE1/Hsp10 co-chaperonin, form ATP-driven folding chambers that fold newly imported and stress-denatured matrix proteins. Each subunit has an equatorial ATP-binding domain, an intermediate hinge domain that couples nucleotide state to movement, and an apical substrate- and Hsp10-binding domain. The horse HSPD1 gene on chromosome 18 encodes this chaperonin; this UniProt entry (F6Z587, 541 aa) is an alternative gene model that skips one 96-bp coding exon and so lacks 32 residues of the intermediate hinge domain (human P10809 residues 171-202), while keeping the transit peptide, the equatorial ATP-binding residues and the apical domain. Whether a product of this model can cycle as a chaperonin is untested. The full-length horse product is represented by A0A9L0S8L8.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding by the equatorial domain; the equatorial nucleotide-binding residues are all retained in this exon-skipped model. Reason: Nucleotide binding is a conserved property of the whole Cpn60/GroEL family (PTHR45633; InterPro IPR001844) and is carried by the equatorial domain (mature residues 1-137 and 411-526 in the human structure, PMID:32317635). The 32-residue deletion in F6Z587 falls entirely inside the intermediate hinge domain (mature 145-176), and every human ATP-binding position maps to an identical horse residue. ATP binding is a narrower claim than ATP-dependent folding, and it does not depend on the hinge region. Accepted; the folding activity itself is judged separately below. Supporting Evidence: file:HORSE/HSPD1/HSPD1-bioinformatics/RESULTS.md | BINDING | 111–115 | 111,112,113,114,115 | 5/5 | 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) file:HORSE/HSPD1/HSPD1-bioinformatics/RESULTS-rereview.md 171-202 (32 aa, mature 145-176, intermediate) |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrial matrix is the compartment of the HSPD1 chaperonin, and F6Z587 keeps the N-terminal transit peptide. Reason: Mitochondrial matrix is a PAINT IBD at PTN000143509 (seeded by human P10809, yeast HSP60, S. pombe mcp60 and zebrafish hspd1), a node from which mammalian HSPD1 descends. The human protein folds proteins in the matrix (curated UniProt function, PubMed:11422376, PubMed:1346131). F6Z587 begins with the same MLRLP start as human P10809, and the 26-residue transit peptide region aligns with 20/26 identities, so targeting does not depend on the skipped exon. Supporting Evidence: file:human/HSPD1/HSPD1-uniprot.txt under stress conditions in the mitochondrial matrix (PubMed:11422376, file:interpro/panther/PTHR45633/PTHR45633-paint.tsv PomBase:SPAC12G12.04|SGD:S000004249|UniProtKB:P10809|ZFIN:ZDB-GENE-021206-1 file:HORSE/HSPD1/HSPD1-bioinformatics/RESULTS.md | TRANSIT | 1–26 | |
| GO:0005832 chaperonin-containing T-complex | IEA GO_REF:0000117 | REMOVE | Summary: Wrong complex. HSPD1 is a type I (GroEL-like) chaperonin; the chaperonin-containing T-complex (CCT/TRiC) is the cytosolic type II chaperonin built from TCP-1 subunits. Reason: The ARBA rule conflates the two chaperonin types because both share the Cpn60/TCP-1 fold signature (InterPro IPR002423, IPR017998). HSPD1 belongs to PTHR45633 (Cpn60/GroEL), not to the TCP-1 family that makes up CCT, and it acts in the mitochondrial matrix with Hsp10, not in the cytosol. No member of PTHR45633 carries this complex in the PAINT data, and the human structure defines the HSPD1 assembly as the type I Hsp60-Hsp10 system. The exon skip in F6Z587 does not bear on this. Supporting Evidence: PMID:25918392 Human mitochondria harbor a single type I chaperonin system file:human/HSPD1/HSPD1-uniprot.txt Belongs to the chaperonin (HSP60) family |
| GO:0006457 protein folding | IEA GO_REF:0000002 | UNDECIDED | Summary: Protein folding is the function of the horse HSPD1 gene, but this exon-skipped product lacks part of the hinge domain on which the folding cycle depends. Reason: Protein folding is a PAINT IBD at the family root node PTN000143677 (seeded by E. coli GroEL, M. tuberculosis GroEL1/2, yeast HSP60 and human P10809), so it is the ancestral function of the gene. The full-length horse product A0A9L0S8L8 has every human residue and inherits this IBA. F6Z587, however, omits 32 of the 54 residues of the first segment of the intermediate hinge domain (mature 138-191; PMID:32317635). The hinge couples ATP binding in the equatorial domain to the apical-domain movement that encapsulates substrate. Even single substitutions elsewhere in mammalian Hsp60 (D3G, V72I) destabilise the complex in the presence of nucleotide and abolish folding (PMID:31444388). No evidence was found that the exon-skipped transcript is expressed or that its product oligomerises. The gene-level function is not in doubt; whether this particular product performs it is unknown, so the row is left undecided rather than accepted or removed. Supporting Evidence: file:interpro/panther/PTHR45633/PTHR45633-paint.tsv SGD:S000004249|UniProtKB:P0A6F5|UniProtKB:P10809|UniProtKB:P9WPE7|UniProtKB:P9WPE9 PMID:1346131 facilitates the formation of catalytically active ribulose-bisphosphate carboxylase from an unfolded state in the presence of K+ and MgATP. PMID:31444388 and DLS results suggest that the D3G and V72I complexes fall apart when treated file:HORSE/HSPD1/HSPD1-bioinformatics/RESULTS-rereview.md 171-202 (32 aa, mature 145-176, intermediate) |
| GO:0009409 response to cold | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from chicken HSPD1, whose Hsp60 mRNA rises in cold-stressed heart; a stress-induction observation, kept as non-core. Reason: The ISS donor Q5ZL72 is chicken HSPD1, a member of the same PANTHER family (PTHR45633) and a vertebrate ortholog of horse HSPD1. The source study measured increased Hsp60 mRNA in chicken hearts under cold stress. That is induction of the gene as part of a general stress response, which is consistent with the stress-inducible chaperonin role but does not show a cold-specific mechanism. The claim concerns the gene's regulation rather than the activity of this specific protein model, so the exon skip does not affect it. Kept as a peripheral annotation, matching the human HSPD1 review of the same transfer. Supporting Evidence: PMID:23636703 the mRNA levels of Hsps (70, 60, 40, and 27) increased significantly |
| GO:0042026 protein refolding | IEA GO_REF:0000002 | UNDECIDED | Summary: Refolding of stress-denatured proteins is a gene-level function of HSPD1, but the competence of this hinge-deleted product is untested. Reason: Purified mammalian Hsp60 with Hsp10 refolds denatured substrates in an ATP-dependent reaction (PMID:1346131; PMID:31444388 for client refolding by wild-type and its failure in disease variants). For F6Z587 the same reasoning applies as for protein folding above; 32 residues of the intermediate hinge domain are missing, and refolding requires the full ATP-driven conformational cycle. Left undecided for this product; the canonical model A0A9L0S8L8 carries the full sequence. Supporting Evidence: PMID:1346131 facilitates the formation of catalytically active ribulose-bisphosphate carboxylase from an unfolded state in the presence of K+ and MgATP. file:HORSE/HSPD1/HSPD1-bioinformatics/RESULTS-rereview.md 171-202 (32 aa, mature 145-176, intermediate) |
| GO:0140662 ATP-dependent protein folding chaperone | IEA GO_REF:0000002 | UNDECIDED | Summary: The core activity of the HSPD1 gene, but not established for a product lacking part of the hinge domain. Reason: ATP-dependent folding with Hsp10 is the defining activity of mitochondrial Hsp60 (curated human function, PubMed:11422376, PubMed:1346131), and the human structural work shows the domain organisation through which the ATP cycle drives encapsulation (PMID:32317635). F6Z587 keeps the equatorial ATP site and the apical domain but lacks mature residues 145-176 of the intermediate hinge domain, which transmits the nucleotide-driven movement. ATP turnover and productive folding are separable readouts, and nucleotide-triggered disassembly abolishes folding even for point variants (PMID:31444388). Without expression or biochemical data for this model, the activity cannot be accepted for this accession, and there is no basis to remove it either. Supporting Evidence: file:human/HSPD1/HSPD1-uniprot.txt Together with Hsp10, facilitates the correct 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:31444388 and DLS results suggest that the D3G and V72I complexes fall apart when treated |
Loading supporting content…
Download this section (compressed HTML)Q: Is the horse HSPD1 transcript that skips the 96-bp exon at chr18:72882811-72882906 (ENSECAT00000009419, UniProt F6Z587) supported by RNA-seq junction reads, or is it a gene-build artefact?
Q: Is the 14-residue N-terminal extension (MKAHLTKRNSASSE) of the Ensembl canonical horse model A0A9L0S8L8 real, given that human and F6Z587 both start at MLRLP?
Experiment: Express the F6Z587 product (lacking mature residues 145-176) alongside the full-length horse Hsp60 and test tetradecamer assembly, Hsp10 binding and ATP-dependent refolding of malate dehydrogenase or rhodanese in vitro.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)