Hspa8 (UniProt P63018; HSP7C_RAT) encodes the rat Heat shock cognate 71 kDa protein, the constitutively expressed cytosolic HSP70-family chaperone known as HSC70/HSC73. Unlike the stress-inducible Hspa1a/Hspa1b (HSP70) paralogs, HSC70 is expressed under basal conditions and is the housekeeping HSP70. Its core molecular function is an ATP-dependent (EC 3.6.4.10) protein-folding chaperone activity built on the canonical HSP70 architecture: an N-terminal nucleotide-binding/ATPase domain and a C-terminal substrate-binding domain with a helical lid, whose nucleotide state (ATP = low affinity/fast client exchange; ADP = high affinity) governs cyclic binding and release of unfolded/misfolded client polypeptides. The ATPase cycle is driven by J-domain (HSP40/DNAJ) co-chaperones that stimulate ATP hydrolysis and reset by nucleotide-exchange factors. Three best-supported, mechanistically distinct roles emerge: (1) general proteostasis - protein folding, refolding, unfolding and disassembly of protein complexes; (2) clathrin-coated vesicle uncoating - the clathrin-uncoating ATPase activity in which the J-domain co-chaperone auxilin (DNAJC6) recruits HSC70 to clathrin-coated vesicles and stimulates its ATPase to disassemble clathrin coats, central to clathrin-mediated endocytosis and synaptic vesicle recycling; and (3) chaperone-mediated autophagy (CMA) - cytosolic HSC70 recognizes KFERQ-like pentapeptide motifs in soluble client proteins and delivers them to LAMP-2A at the lysosomal membrane, with lysosomal HSC70 supporting translocation into the lysosomal lumen for degradation. HSC70 acts predominantly in the cytosol, with additional functional pools at the lysosomal membrane/lumen and at endocytic/synaptic trafficking structures. It is a highly pleiotropic protein; many of its annotated processes and locations reflect this pleiotropy rather than its evolved core function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Manual review: HSC70 has documented nuclear/nucleolar pools (e.g. nuclear import roles), but the nucleus is not the site of its core chaperone, clathrin-uncoating, or CMA functions. Reason: Valid localization but peripheral to the evolved cytosolic chaperone function. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Manual review: cytoplasm is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Manual review: plasma membrane is not the site of the core chaperone function of HSC70, which acts in the cytosol; surface/extracellular pools are context-specific (e.g. exosomal/cell-surface) and do not represent the evolved function. Reason: Localization over-annotation; the core HSC70 function is cytosolic, not at the plasma membrane. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN002500132 · PANTHER:PTN002500132 SOURCE STALE OR MISSING The GOA WITH/FROM names this node with mostly fungal (Candida) cell-surface members as seeds, but no IBD for GO:0005886 remains anywhere in the current PTHR19375 PAINT slice (snapshot rows dated through 2026-08-28); the node now carries only nucleus (GO:0005634) and cytosol (GO:0005829). PAINT has therefore withdrawn or re-scoped the plasma-membrane assertion, which confirms the corrective call here: the compartment reflected fungal cell-surface and moonlighting contexts, whereas the core HSC70 chaperone cycle is cytosolic. |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: Manual review: ATP hydrolysis activity underpins the ATP-dependent chaperone cycle of Hspa8/HSC70, in which the nucleotide state controls client affinity and is regulated by J-domain co-chaperones. Reason: Retained as supporting the core ATP-driven chaperone cycle, corroborated by falcon deep research. Supporting Evidence: file:rat/Hspa8/Hspa8-deep-research-falcon.md nucleotide state controls substrate affinity (ATP-bound low affinity/fast exchange; ADP-bound high affinity/slow exchange) |
| GO:0031072 heat shock protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: Manual review: heat shock protein binding is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0044183 protein folding chaperone | IBA GO_REF:0000033 | ACCEPT | Summary: Manual review: protein folding chaperone is the core molecular function of Hspa8/HSC70; the constitutive HSP70-family ATP-dependent chaperone that assists folding, refolding, unfolding and complex disassembly of client proteins. Reason: Retained as the core molecular function, corroborated by falcon deep research. Supporting Evidence: file:rat/Hspa8/Hspa8-deep-research-falcon.md Hspa8/HSC70 is a **constitutive** HSP70-family **ATPase chaperone** that supports proteostasis by assisting **protein folding/refolding**, **unfolding**, and **disassembly of protein complexes** |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0072318 clathrin coat disassembly | IBA GO_REF:0000033 | ACCEPT | Summary: Manual review: clathrin coat disassembly is a core process for Hspa8/HSC70; the auxilin (DNAJC6)-recruited HSC70 ATPase disassembles clathrin coats from clathrin-coated vesicles. Reason: Retained as a core process, corroborated by falcon deep research. Supporting Evidence: file:rat/Hspa8/Hspa8-deep-research-falcon.md the **J-domain co-chaperone auxilin (DNAJC6)** recruits HSC70 to CCVs and **stimulates HSC70 ATPase activity** to disassemble clathrin coats |
| GO:0042026 protein refolding | IBA GO_REF:0000033 | ACCEPT | Summary: Manual review: protein refolding is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0007165 signal transduction | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Manual review: signal transduction is an over-broad inter-ontology IEA inference; HSC70 is a chaperone and does not act as a signal transducer. This generic term over-annotates the gene. Reason: Over-broad IEA inference that does not reflect the evolved chaperone function of HSC70. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: Manual review: nucleotide binding is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0001916 positive regulation of T cell mediated cytotoxicity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Manual review: positive regulation of T cell mediated cytotoxicity may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: Manual review: ATP binding is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005681 spliceosomal complex | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Manual review: spliceosomal complex may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Manual review: nucleolus may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Manual review: cytoplasm is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Manual review: the lysosomal membrane is a functional location of the core chaperone-mediated autophagy role of HSC70, where the chaperone-substrate complex engages LAMP-2A; this electronic annotation is consistent with the experimentally supported IDA annotations to the same term. Reason: Lysosomal membrane is a bona fide functional location for the core CMA role of HSC70 (experimentally supported by PMID:18644871 and PMID:9038169); accepted for consistency with those IDA annotations. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Manual review: plasma membrane is not the site of the core chaperone function of HSC70; surface/extracellular pools are context-specific and do not represent the evolved function. Reason: Localization over-annotation; the core HSC70 function is cytosolic, not at the plasma membrane. |
| GO:0006397 mRNA processing | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Manual review: mRNA processing may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0006914 autophagy | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Manual review: autophagy may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0008289 lipid binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Manual review: lipid binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0008380 RNA splicing | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Manual review: RNA splicing may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Manual review: HSC70 is indeed a hydrolase (an ATPase, EC 3.6.4.10), so GO:0016787 is not factually wrong, but it is an over-broad parent term. The more specific GO:0016887 (ATP hydrolysis activity) is already ACCEPTed and captures the actual catalytic function. Reason: GO:0016887 (ATP hydrolysis activity) is already ACCEPTed and is more specific; GO:0016787 (hydrolase activity) is the over-broad parent and is redundant. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: Manual review: ATP hydrolysis activity is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0042470 melanosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Manual review: melanosome may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Manual review: negative regulation of apoptotic process may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043168 anion binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Manual review: anion binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0001786 phosphatidylserine binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: phosphatidylserine binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005770 late endosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: late endosome may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0030674 protein-macromolecule adaptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Manual review: protein-macromolecule adaptor activity is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0035651 AP-3 adaptor complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: AP-3 adaptor complex binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0044788 host-mediated perturbation of viral process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: host-mediated perturbation of viral process may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0044829 host-mediated activation of viral genome replication | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: host-mediated activation of viral genome replication may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: perinuclear region of cytoplasm may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000120 | MODIFY | Summary: Manual review: unfolded protein binding is better represented by a more specific replacement term for Hspa8. Reason: Modified to align with current curation guidance and improve term specificity. Proposed replacements: protein folding chaperone |
| GO:0061684 chaperone-mediated autophagy | IEA GO_REF:0000107 | ACCEPT | Summary: Manual review: chaperone-mediated autophagy is a core process for Hspa8/HSC70, which selects KFERQ-motif clients and delivers them to LAMP-2A for lysosomal degradation. Reason: Retained as a core process, corroborated by falcon deep research. Supporting Evidence: file:rat/Hspa8/Hspa8-deep-research-falcon.md recognition of KFERQ-like pentapeptide motifs** in client proteins targeted for **chaperone-mediated autophagy (CMA)** |
| GO:0061738 late endosomal microautophagy | IEA GO_REF:0000107 | ACCEPT | Summary: Manual review: late endosomal microautophagy is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0070062 extracellular exosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: extracellular exosome may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0072318 clathrin coat disassembly | IEA GO_REF:0000120 | ACCEPT | Summary: Manual review: clathrin coat disassembly is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0098684 photoreceptor ribbon synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: photoreceptor ribbon synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098690 glycinergic synapse | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Manual review: glycinergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098793 presynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: presynapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: glutamatergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0099175 regulation of postsynapse organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: regulation of postsynapse organization may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0099634 postsynaptic specialization membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: postsynaptic specialization membrane may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0160020 positive regulation of ferroptosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Manual review: positive regulation of ferroptosis may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0030674 protein-macromolecule adaptor activity | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: protein-macromolecule adaptor activity is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0061684 chaperone-mediated autophagy | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: chaperone-mediated autophagy is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0160020 positive regulation of ferroptosis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: positive regulation of ferroptosis may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: cytoplasm is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0101031 protein folding chaperone complex | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: protein folding chaperone complex is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005615 extracellular space | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: extracellular space may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0030335 positive regulation of cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: positive regulation of cell migration may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0048018 receptor ligand activity | ISO GO_REF:0000121 | REMOVE | Summary: Manual review: receptor ligand activity is not sufficiently supported as a direct function of Hspa8. Reason: Removed due weak mechanistic support or likely misannotation for this gene. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P11142 · human HSPA8 SOURCE WEAK OR INFERRED Human HSPA8 donor claim of receptor-ligand activity has weak mechanistic support and is a likely misannotation; nothing robust transfers to rat. |
| GO:0006457 protein folding | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: protein folding is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0014069 postsynaptic density | IEP PMID:11230095 Presence of both constitutive and inducible forms of heat sh... | KEEP AS NON CORE | Summary: Manual review: postsynaptic density may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0014069 postsynaptic density | IDA PMID:11230095 Presence of both constitutive and inducible forms of heat sh... | KEEP AS NON CORE | Summary: Manual review: postsynaptic density may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0014069 postsynaptic density | IDA PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: postsynaptic density may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098684 photoreceptor ribbon synapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: photoreceptor ribbon synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098690 glycinergic synapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: glycinergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098690 glycinergic synapse | IDA PMID:21209184 Heat shock cognate protein 70 regulates gephyrin clustering. | KEEP AS NON CORE | Summary: Manual review: glycinergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098690 glycinergic synapse | EXP PMID:21209184 Heat shock cognate protein 70 regulates gephyrin clustering. | KEEP AS NON CORE | Summary: Manual review: glycinergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098690 glycinergic synapse | IMP PMID:21209184 Heat shock cognate protein 70 regulates gephyrin clustering. | KEEP AS NON CORE | Summary: Manual review: glycinergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098793 presynapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: presynapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098793 presynapse | IEP PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: presynapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098793 presynapse | IDA PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: presynapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098794 postsynapse | IEP PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: postsynapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098794 postsynapse | IDA PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: postsynapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098880 maintenance of postsynaptic specialization structure | IDA PMID:21209184 Heat shock cognate protein 70 regulates gephyrin clustering. | KEEP AS NON CORE | Summary: Manual review: maintenance of postsynaptic specialization structure may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098880 maintenance of postsynaptic specialization structure | EXP PMID:21209184 Heat shock cognate protein 70 regulates gephyrin clustering. | KEEP AS NON CORE | Summary: Manual review: maintenance of postsynaptic specialization structure may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098880 maintenance of postsynaptic specialization structure | IMP PMID:21209184 Heat shock cognate protein 70 regulates gephyrin clustering. | KEEP AS NON CORE | Summary: Manual review: maintenance of postsynaptic specialization structure may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098978 glutamatergic synapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: glutamatergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098978 glutamatergic synapse | IEP PMID:11230095 Presence of both constitutive and inducible forms of heat sh... | KEEP AS NON CORE | Summary: Manual review: glutamatergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098978 glutamatergic synapse | IDA PMID:11230095 Presence of both constitutive and inducible forms of heat sh... | KEEP AS NON CORE | Summary: Manual review: glutamatergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098978 glutamatergic synapse | IEP PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: glutamatergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0098978 glutamatergic synapse | IDA PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: glutamatergic synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0099175 regulation of postsynapse organization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: regulation of postsynapse organization may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0099634 postsynaptic specialization membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: postsynaptic specialization membrane may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0072318 clathrin coat disassembly | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: clathrin coat disassembly is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0072318 clathrin coat disassembly | IDA PMID:8524399 Role of auxilin in uncoating clathrin-coated vesicles. | ACCEPT | Summary: Manual review: clathrin coat disassembly is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005765 lysosomal membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: the lysosomal membrane is a functional location of the core chaperone-mediated autophagy role of HSC70; this orthology-based annotation is consistent with the experimentally supported IDA annotations to the same term. Reason: Lysosomal membrane is a bona fide functional location for the core CMA role of HSC70 (experimentally supported by PMID:18644871 and PMID:9038169); accepted for consistency with those IDA annotations. |
| GO:0030674 protein-macromolecule adaptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: Manual review: protein-macromolecule adaptor activity is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy | ISS GO_REF:0000024 | ACCEPT | Summary: Manual review: protein targeting to lysosome in CMA is a core process for Hspa8/HSC70; cytosolic HSC70 recognizes KFERQ-like motifs and delivers clients to LAMP-2A, and lysosomal HSC70 supports translocation into the lysosomal lumen. Reason: Retained as a core CMA process, corroborated by falcon deep research. Supporting Evidence: file:rat/Hspa8/Hspa8-deep-research-falcon.md recognition of KFERQ-like pentapeptide motifs** in client proteins targeted for **chaperone-mediated autophagy (CMA)** file:rat/Hspa8/Hspa8-deep-research-falcon.md Lysosomal HSC70 (Lys‑HSC70)** facilitates **substrate translocation** into the lysosome lumen |
| GO:1900226 negative regulation of NLRP3 inflammasome complex assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: negative regulation of NLRP3 inflammasome complex assembly may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0001786 phosphatidylserine binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: phosphatidylserine binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0061635 regulation of protein complex stability | IDA PMID:18644871 The chaperone-mediated autophagy receptor organizes in dynam... | KEEP AS NON CORE | Summary: Manual review: regulation of protein complex stability may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0140545 ATP-dependent protein disaggregase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: ATP-dependent protein disaggregase activity is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0061684 chaperone-mediated autophagy | IGI PMID:18644871 The chaperone-mediated autophagy receptor organizes in dynam... | ACCEPT | Summary: Manual review: chaperone-mediated autophagy is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0043202 lysosomal lumen | TAS Reactome:R-RNO-9625160 | KEEP AS NON CORE | Summary: Manual review: lysosomal lumen may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043202 lysosomal lumen | TAS Reactome:R-RNO-9625173 | KEEP AS NON CORE | Summary: Manual review: lysosomal lumen may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043202 lysosomal lumen | TAS Reactome:R-RNO-9626028 | KEEP AS NON CORE | Summary: Manual review: lysosomal lumen may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0048471 perinuclear region of cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: perinuclear region of cytoplasm may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005829 cytosol | TAS Reactome:R-RNO-9613356 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005829 cytosol | TAS Reactome:R-RNO-9615712 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005829 cytosol | TAS Reactome:R-RNO-9620205 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005829 cytosol | TAS Reactome:R-RNO-9622832 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005829 cytosol | TAS Reactome:R-RNO-9626236 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005829 cytosol | TAS Reactome:R-RNO-9626239 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005829 cytosol | TAS Reactome:R-RNO-9626254 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0043195 terminal bouton | HDA PMID:24876496 Composition of isolated synaptic boutons reveals the amounts... | KEEP AS NON CORE | Summary: Manual review: terminal bouton may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0031625 ubiquitin protein ligase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: ubiquitin protein ligase binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0051087 protein-folding chaperone binding | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: protein-folding chaperone binding is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005515 protein binding | IPI PMID:15708368 Small glutamine-rich tetratricopeptide repeat-containing pro... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for Hspa8. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0030425 dendrite | IDA PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: dendrite may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0044309 neuron spine | IDA PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: neuron spine may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: protein targeting to lysosome involved in chaperone-mediated autophagy is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0044788 host-mediated perturbation of viral process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: host-mediated perturbation of viral process may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0044829 host-mediated activation of viral genome replication | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: host-mediated activation of viral genome replication may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005765 lysosomal membrane | IDA PMID:18644871 The chaperone-mediated autophagy receptor organizes in dynam... | ACCEPT | Summary: Manual review: this IDA derives from a key CMA mechanistic paper showing HSC70 organizes in dynamic protein complexes with LAMP-2A at the lysosomal membrane. The lysosomal membrane is a functional location of the core CMA role of HSC70 (also listed in the CMA core_function), so this experimental annotation is accepted as core. Reason: The lysosomal membrane is a bona fide functional location for the core chaperone-mediated autophagy role of HSC70, directly demonstrated experimentally in PMID:18644871. Falcon corroboration is captured in the references findings block. |
| GO:0032984 protein-containing complex disassembly | IMP PMID:18644871 The chaperone-mediated autophagy receptor organizes in dynam... | KEEP AS NON CORE | Summary: Manual review: protein-containing complex disassembly may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:1990836 lysosomal matrix | IDA PMID:18644871 The chaperone-mediated autophagy receptor organizes in dynam... | KEEP AS NON CORE | Summary: Manual review: lysosomal matrix may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005770 late endosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: late endosome may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0061738 late endosomal microautophagy | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: late endosomal microautophagy is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:20060297 Chaperone-assisted selective autophagy is essential for musc... | ACCEPT | Summary: Manual review: ATP hydrolysis activity is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:1904764 chaperone-mediated autophagy translocation complex disassembly | IDA PMID:18644871 The chaperone-mediated autophagy receptor organizes in dynam... | KEEP AS NON CORE | Summary: Manual review: chaperone-mediated autophagy translocation complex disassembly may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0042026 protein refolding | ISS GO_REF:0000024 | ACCEPT | Summary: Manual review: protein refolding is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0061684 chaperone-mediated autophagy | IDA PMID:18644871 The chaperone-mediated autophagy receptor organizes in dynam... | ACCEPT | Summary: Manual review: chaperone-mediated autophagy is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0031647 regulation of protein stability | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: regulation of protein stability may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0097214 positive regulation of lysosomal membrane permeability | IMP PMID:9038169 A population of rat liver lysosomes responsible for the sele... | KEEP AS NON CORE | Summary: Manual review: positive regulation of lysosomal membrane permeability may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:1990832 slow axonal transport | IEP PMID:11933046 Slow axonal transport of the cytosolic chaperonin CCT with H... | KEEP AS NON CORE | Summary: Manual review: slow axonal transport may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:1990833 clathrin-uncoating ATPase activity | IDA PMID:8363588 High-level expression of soluble rat hsc70 in Escherichia co... | ACCEPT | Summary: Manual review: clathrin-uncoating ATPase activity is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:1990834 response to odorant | IEP PMID:11268007 Odorants as cell-type specific activators of a heat shock re... | KEEP AS NON CORE | Summary: Manual review: response to odorant may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0000082 G1/S transition of mitotic cell cycle | IEP PMID:10198213 73-kDa heat shock cognate protein interacts directly with P2... | KEEP AS NON CORE | Summary: Manual review: G1/S transition of mitotic cell cycle may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0070301 cellular response to hydrogen peroxide | IEP PMID:10329212 A physiologically relevant hyperthermia selectively activate... | KEEP AS NON CORE | Summary: Manual review: cellular response to hydrogen peroxide may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:1904593 prostaglandin binding | IPI PMID:21445266 Proteomic identification of protein targets for 15-deoxy-Δ(1... | REMOVE | Summary: Manual review: prostaglandin binding is not sufficiently supported as a direct function of Hspa8. Reason: Removed due weak mechanistic support or likely misannotation for this gene. |
| GO:0001916 positive regulation of T cell mediated cytotoxicity | IMP PMID:8871636 Involvement of peptide antigens in the cytotoxicity between ... | KEEP AS NON CORE | Summary: Manual review: positive regulation of T cell mediated cytotoxicity may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005776 autophagosome | IDA PMID:20392947 Essential role of the redox-sensitive kinase p66shc in deter... | KEEP AS NON CORE | Summary: Manual review: autophagosome may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005874 microtubule | IDA PMID:2527848 Beta-internexin is a microtubule-associated protein identica... | KEEP AS NON CORE | Summary: Manual review: microtubule may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005882 intermediate filament | IDA PMID:7721954 Integrity of intermediate filaments is associated with the d... | KEEP AS NON CORE | Summary: Manual review: intermediate filament may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0009986 cell surface | IDA PMID:8228242 70 kDa heat shock cognate protein is a transformation-associ... | KEEP AS NON CORE | Summary: Manual review: cell surface may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0010628 positive regulation of gene expression | IMP PMID:8734434 Antisense oligonucleotide to the 70-kDa heat shock cognate p... | KEEP AS NON CORE | Summary: Manual review: positive regulation of gene expression may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0032279 asymmetric synapse | IDA PMID:11230095 Presence of both constitutive and inducible forms of heat sh... | KEEP AS NON CORE | Summary: Manual review: asymmetric synapse may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043197 dendritic spine | IDA PMID:11230095 Presence of both constitutive and inducible forms of heat sh... | KEEP AS NON CORE | Summary: Manual review: dendritic spine may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043198 dendritic shaft | IDA PMID:11230095 Presence of both constitutive and inducible forms of heat sh... | KEEP AS NON CORE | Summary: Manual review: dendritic shaft may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043204 perikaryon | IDA PMID:11230095 Presence of both constitutive and inducible forms of heat sh... | KEEP AS NON CORE | Summary: Manual review: perikaryon may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0045471 response to ethanol | IEP PMID:12170112 Stress response caused by chronic alcohol intake in aged rat... | KEEP AS NON CORE | Summary: Manual review: response to ethanol may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0050766 positive regulation of phagocytosis | IMP PMID:9886410 Clathrin-coated pit-associated proteins are required for alv... | KEEP AS NON CORE | Summary: Manual review: positive regulation of phagocytosis may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:1904592 positive regulation of protein refolding | IDA PMID:11360998 The effect of mutating arginine-469 on the substrate binding... | KEEP AS NON CORE | Summary: Manual review: positive regulation of protein refolding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0001822 kidney development | IEP PMID:9764759 Constitutive expression of heat shock proteins Hsp90, Hsc70,... | KEEP AS NON CORE | Summary: Manual review: kidney development may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0001917 photoreceptor inner segment | IDA PMID:10549657 Constitutive and inducible heat shock protein 70 immunoreact... | KEEP AS NON CORE | Summary: Manual review: photoreceptor inner segment may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005765 lysosomal membrane | IDA PMID:9038169 A population of rat liver lysosomes responsible for the sele... | ACCEPT | Summary: Manual review: PMID:9038169 (Cuervo, Dice & Knecht 1997) is a foundational CMA paper showing lysosomal hsc73 mediates selective uptake/degradation of cytosolic substrates in rat liver lysosomes. The lysosomal membrane is a functional location of the core CMA role of HSC70. Reason: The lysosomal membrane is a bona fide functional location for the core chaperone-mediated autophagy role of HSC70, directly demonstrated experimentally in PMID:9038169. |
| GO:0006606 protein import into nucleus | IMP PMID:8892974 Evidence for the existence of a novel mechanism for the nucl... | KEEP AS NON CORE | Summary: Manual review: protein import into nucleus may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0007519 skeletal muscle tissue development | IEP PMID:12909603 Endogenous expression and developmental changes of HSP72 in ... | KEEP AS NON CORE | Summary: Manual review: skeletal muscle tissue development may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0008088 axo-dendritic transport | IEP PMID:11933046 Slow axonal transport of the cytosolic chaperonin CCT with H... | KEEP AS NON CORE | Summary: Manual review: axo-dendritic transport may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:10425221 Identification of a novel splice variant of heat shock cogna... | KEEP AS NON CORE | Summary: Manual review: response to xenobiotic stimulus may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0014823 response to activity | IEP PMID:10606824 The effects of exercise duration on adrenal HSP72/73 inducti... | KEEP AS NON CORE | Summary: Manual review: response to activity may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0021549 cerebellum development | IEP PMID:9764759 Constitutive expression of heat shock proteins Hsp90, Hsc70,... | KEEP AS NON CORE | Summary: Manual review: cerebellum development may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0034605 cellular response to heat | IEP PMID:8955942 Differential expression of heat shock 70 proteins in primary... | KEEP AS NON CORE | Summary: Manual review: cellular response to heat may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0042277 peptide binding | IDA PMID:8363588 High-level expression of soluble rat hsc70 in Escherichia co... | KEEP AS NON CORE | Summary: Manual review: peptide binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0042594 response to starvation | IEP PMID:9038169 A population of rat liver lysosomes responsible for the sele... | KEEP AS NON CORE | Summary: Manual review: response to starvation may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0044743 protein transmembrane import into intracellular organelle | IEP PMID:9038169 A population of rat liver lysosomes responsible for the sele... | KEEP AS NON CORE | Summary: Manual review: protein transmembrane import into intracellular organelle may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0045862 positive regulation of proteolysis | IDA PMID:9987077 Direct lysosomal uptake of alpha 2-microglobulin contributes... | KEEP AS NON CORE | Summary: Manual review: positive regulation of proteolysis may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0046777 protein autophosphorylation | IDA PMID:8420978 Aspartyl residue 10 is essential for ATPase activity of rat ... | REMOVE | Summary: Manual review: PMID:8420978 (Huang et al. 1993, "Aspartyl residue 10 is essential for ATPase activity of rat hsc70") studies the ATPase activity of HSC70, not protein autophosphorylation. The annotation appears to be a database error. Reason: Misannotation: PMID:8420978 reports ATPase activity (the catalytic mechanism of HSC70), not protein autophosphorylation; there is no evidence in this reference that HSC70 autophosphorylates. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:10549657 Constitutive and inducible heat shock protein 70 immunoreact... | KEEP AS NON CORE | Summary: Manual review: perinuclear region of cytoplasm may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0071276 cellular response to cadmium ion | IEP PMID:9736451 Involvement of heat shock elements and basal transcription e... | KEEP AS NON CORE | Summary: Manual review: cellular response to cadmium ion may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0072318 clathrin coat disassembly | IDA PMID:8363588 High-level expression of soluble rat hsc70 in Escherichia co... | ACCEPT | Summary: Manual review: clathrin coat disassembly is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:1990836 lysosomal matrix | IDA PMID:9038169 A population of rat liver lysosomes responsible for the sele... | KEEP AS NON CORE | Summary: Manual review: lysosomal matrix may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0010045 response to nickel cation | IEP PMID:15736156 Effects of nickel poisoning on expression pattern of the 72/... | KEEP AS NON CORE | Summary: Manual review: response to nickel cation may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0010667 negative regulation of cardiac muscle cell apoptotic process | IMP PMID:21958194 Constitutive heat shock protein 70 interacts with α-enolase ... | KEEP AS NON CORE | Summary: Manual review: negative regulation of cardiac muscle cell apoptotic process may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0019899 enzyme binding | IPI PMID:21958194 Constitutive heat shock protein 70 interacts with α-enolase ... | KEEP AS NON CORE | Summary: Manual review: enzyme binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0030424 axon | IDA PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: axon may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0030900 forebrain development | IEP PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: forebrain development may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0031686 A1 adenosine receptor binding | IPI PMID:10866672 The heat shock cognate protein hsc73 assembles with A(1) ade... | KEEP AS NON CORE | Summary: Manual review: PMID:10866672 documents a direct, specific rat hsc73-A1 adenosine receptor interaction (Kd ~0.5 nM by surface plasmon resonance, plus affinity chromatography, co-immunoprecipitation and confocal colocalization). This is a genuine documented interaction but is peripheral to the evolved core chaperone function. Reason: Well-supported experimental rat interaction (PMID:10866672) but peripheral to the core HSC70 chaperone, clathrin-uncoating, and CMA functions; retained as non-core rather than removed. |
| GO:0032355 response to estradiol | IEP PMID:9990085 The 70-kDa heat shock cognate protein (Hsc73) gene is enhanc... | KEEP AS NON CORE | Summary: Manual review: response to estradiol may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0032570 response to progesterone | IEP PMID:9990085 The 70-kDa heat shock cognate protein (Hsc73) gene is enhanc... | KEEP AS NON CORE | Summary: Manual review: response to progesterone may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043025 neuronal cell body | IDA PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: neuronal cell body may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043085 positive regulation of catalytic activity | IMP PMID:21958194 Constitutive heat shock protein 70 interacts with α-enolase ... | KEEP AS NON CORE | Summary: Manual review: positive regulation of catalytic activity may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043195 terminal bouton | IDA PMID:9878698 Presence of molecular chaperones, heat shock cognate (Hsc) 7... | KEEP AS NON CORE | Summary: Manual review: terminal bouton may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0044849 estrous cycle | IEP PMID:9990085 The 70-kDa heat shock cognate protein (Hsc73) gene is enhanc... | KEEP AS NON CORE | Summary: Manual review: estrous cycle may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0032991 protein-containing complex | IDA PMID:20596529 Molecular composition of staufen2-containing ribonucleoprote... | KEEP AS NON CORE | Summary: Manual review: protein-containing complex may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0003723 RNA binding | IDA PMID:23159318 Identification in the rat brain of a set of nuclear proteins... | KEEP AS NON CORE | Summary: Manual review: RNA binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005515 protein binding | IPI PMID:23159318 Identification in the rat brain of a set of nuclear proteins... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for Hspa8. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0046034 ATP metabolic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: ATP metabolic process may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0055131 C3HC4-type RING finger domain binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: C3HC4-type RING finger domain binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0048026 positive regulation of mRNA splicing, via spliceosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: positive regulation of mRNA splicing, via spliceosome may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0001664 G protein-coupled receptor binding | ISO GO_REF:0000121 | REMOVE | Summary: Manual review: G protein-coupled receptor binding is not sufficiently supported as a direct function of Hspa8. Reason: Removed due weak mechanistic support or likely misannotation for this gene. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P11142 · human HSPA8 SOURCE WEAK OR INFERRED Human HSPA8 donor claim of G protein-coupled receptor binding has weak mechanistic support (likely misannotation) and does not warrant transfer. |
| GO:0070062 extracellular exosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: extracellular exosome may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005515 protein binding | IPI PMID:18307834 Cathepsin C propeptide interacts with intestinal alkaline ph... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for Hspa8. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005524 ATP binding | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: ATP binding is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0019899 enzyme binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: enzyme binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0031072 heat shock protein binding | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: heat shock protein binding is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:1902904 negative regulation of supramolecular fiber organization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: negative regulation of supramolecular fiber organization may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005829 cytosol | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: cytosol is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0042026 protein refolding | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: protein refolding is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0051082 unfolded protein binding | ISO GO_REF:0000121 | MODIFY | Summary: Manual review: unfolded protein binding is better represented by a more specific replacement term for Hspa8. Reason: Modified to align with current curation guidance and improve term specificity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P11142 · human HSPA8 SUPPORTS SOURCE BUT NOT TARGET Human donor evidence for unfolded-protein binding is sound; the target-side issue is term choice -- protein folding chaperone (GO:0044183) better captures the Hsc70 activity. MGI:MGI:105384 · mouse Hspa8 SUPPORTS SOURCE BUT NOT TARGET Mouse Hspa8 donor likewise supports client-protein binding; folded into the same MODIFY to GO:0044183 protein folding chaperone. Proposed replacements: protein folding chaperone |
| GO:0000974 Prp19 complex | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Manual review: Prp19 complex may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0000974 Prp19 complex | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: Prp19 complex may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Manual review: HSC70 has documented nuclear/nucleolar pools, but the nucleus is not the site of its core chaperone, clathrin-uncoating, or CMA functions. Reason: Valid localization but peripheral to the evolved cytosolic chaperone function. |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: HSC70 has documented nuclear/nucleolar pools, but the nucleus is not the site of its core chaperone, clathrin-uncoating, or CMA functions. Reason: Valid localization but peripheral to the evolved cytosolic chaperone function. |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Manual review: negative regulation of DNA-templated transcription may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005515 protein binding | IPI PMID:19457116 The molecular chaperone Hsc70 interacts with the vesicular m... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for Hspa8. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0008021 synaptic vesicle | IDA PMID:19457116 The molecular chaperone Hsc70 interacts with the vesicular m... | KEEP AS NON CORE | Summary: Manual review: synaptic vesicle may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0043025 neuronal cell body | IDA PMID:19457116 The molecular chaperone Hsc70 interacts with the vesicular m... | KEEP AS NON CORE | Summary: Manual review: neuronal cell body may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0045892 negative regulation of DNA-templated transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: negative regulation of DNA-templated transcription may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005515 protein binding | IPI PMID:17877381 Increased striatal mRNA and protein levels of the immunophil... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for Hspa8. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:9528774 The carboxy-terminal domain of Hsc70 provides binding sites ... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for Hspa8. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:9528774 The carboxy-terminal domain of Hsc70 provides binding sites ... | ACCEPT | Summary: Manual review: ATP hydrolysis activity is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0032991 protein-containing complex | IDA PMID:9528774 The carboxy-terminal domain of Hsc70 provides binding sites ... | KEEP AS NON CORE | Summary: Manual review: protein-containing complex may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005102 signaling receptor binding | IPI PMID:11133993 Characteristics of the interaction between Hsc70 and the tra... | KEEP AS NON CORE | Summary: Manual review: signaling receptor binding may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005515 protein binding | IPI PMID:10198213 73-kDa heat shock cognate protein interacts directly with P2... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for Hspa8. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0032991 protein-containing complex | IDA PMID:10198213 73-kDa heat shock cognate protein interacts directly with P2... | KEEP AS NON CORE | Summary: Manual review: protein-containing complex may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0051082 unfolded protein binding | IDA PMID:11133993 Characteristics of the interaction between Hsc70 and the tra... | MODIFY | Summary: Manual review: unfolded protein binding is better represented by a more specific replacement term for Hspa8. Reason: Modified to align with current curation guidance and improve term specificity. Proposed replacements: protein folding chaperone |
| GO:1990904 ribonucleoprotein complex | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Manual review: ribonucleoprotein complex may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:1990904 ribonucleoprotein complex | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: ribonucleoprotein complex may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005515 protein binding | IPI PMID:12514190 Cloning and characterization of a novel GRP78-binding protei... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for Hspa8. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0016887 ATP hydrolysis activity | ISO GO_REF:0000121 | ACCEPT | Summary: Manual review: ATP hydrolysis activity is consistent with known biology of Hspa8. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0051726 regulation of cell cycle | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Manual review: regulation of cell cycle may be context-dependent or peripheral for Hspa8. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
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