HSPA8

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: HSPA8 is found in the nucleus, supported by IBA and confirmed by IDA (PMID:20176811) showing it is a component of the nuclear PRP19-CDC5L spliceosomal complex. Reason: Multiple lines of evidence confirm nuclear localization of HSPA8, including its role in the PRP19-CDC5L complex (PMID:20176811) and stress-induced nuclear accumulation.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: HSPA8 is primarily cytoplasmic as the constitutive HSP70 chaperone, well-established by IBA and multiple experimental studies. Reason: Cytoplasmic localization is a core feature of HSPA8/HSC70, the constitutive cytosolic HSP70 family member.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: HSPA8 localizes to the plasma membrane where it can act as a cell surface receptor for LPS and interacts with IGSF8/EWI-2 on dendritic cells (PMID:11276205, PMID:17785435). Reason: Plasma membrane localization is supported by IBA and experimental evidence showing HSPA8 at the cell surface in dendritic cells and other cell types.
GO:0016887 ATP hydrolysis activity	IBA GO_REF:0000033	ACCEPT	Summary: ATP hydrolysis is a core enzymatic activity of HSPA8 (EC 3.6.4.10), driving the chaperone cycle. J-domain co-chaperones stimulate this ATPase activity over 1000-fold. Reason: ATP hydrolysis activity is the central enzymatic function of HSPA8/HSC70, as confirmed by its EC classification and extensive biochemical characterization (PMID:12526792).
GO:0031072 heat shock protein binding	IBA GO_REF:0000033	ACCEPT	Summary: HSPA8 binds multiple heat shock proteins including HSP90, HSPB8, and various J-domain co-chaperones (DNAJ family members) as part of its chaperone machine. Reason: Heat shock protein binding is a core functional property of HSPA8, which operates in complexes with HSP90, small HSPs, and J-domain proteins.
GO:0044183 protein folding chaperone	IBA GO_REF:0000033	ACCEPT	Summary: Protein folding chaperone activity is the primary molecular function of HSPA8/HSC70. It binds client polypeptides through its substrate-binding domain and assists their folding through ATP-driven conformational cycles. Reason: This is the core molecular function of HSPA8 as a constitutive HSP70 family chaperone, extensively documented in the literature.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: HSPA8 is primarily a cytosolic protein, confirmed by IBA and multiple experimental studies (PMID:21231916). Reason: Cytosol is the primary subcellular location where HSPA8 performs its housekeeping chaperone functions.
GO:0072318 clathrin coat disassembly	IBA GO_REF:0000033	ACCEPT	Summary: HSPA8/HSC70 is essential for clathrin coat disassembly, working with auxilin (DNAJC6) to uncoat clathrin-coated vesicles via ATP-dependent disassembly (PMID:8524399). Reason: Clathrin coat disassembly is a well-established core function of HSPA8, demonstrated by Ungewickell et al. 1995 (PMID:8524399).
GO:0042026 protein refolding	IBA GO_REF:0000033	ACCEPT	Summary: HSPA8 participates in protein refolding, including refolding of heat-denatured substrates, demonstrated experimentally with luciferase refolding assays (PMID:21231916). Reason: Protein refolding is a well-documented core activity of the HSP70 chaperone machine, confirmed by direct assay evidence.
GO:0007165 signal transduction	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Signal transduction is overly broad for HSPA8. While HSPA8 modulates some signaling pathways (e.g., HSF1 regulation, NLRP3 inflammasome), its primary role is as a chaperone, not a signaling molecule. Reason: HSPA8 is a molecular chaperone, not a signaling protein. The IEA annotation to signal transduction is too broad and does not capture the specific mechanistic role of HSPA8.
GO:0000166 nucleotide binding	IEA GO_REF:0000043	ACCEPT	Summary: HSPA8 binds ATP and ADP through its nucleotide-binding domain (NBD), which drives the chaperone conformational cycle. Reason: Nucleotide binding is a core biochemical property of HSPA8, required for its chaperone function. While more general than ATP binding (GO:0005524), it is accurate.
GO:0001664 G protein-coupled receptor binding	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: HSPA8 was reported to interact with CXCR4 in LPS receptor complexes (PMID:11276205). This is a non-core interaction likely related to its cell-surface localization. Reason: While experimentally supported, GPCR binding is not a core function of HSPA8. The IEA annotation captures a peripheral interaction.
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: ATP binding is a core biochemical activity of HSPA8, required for its chaperone cycle. Crystallographic structures confirm the ATP-binding pocket in the NBD. Reason: ATP binding is essential for HSPA8 function, confirmed by crystal structures (PDB entries) and biochemical assays.
GO:0005681 spliceosomal complex	IEA GO_REF:0000043	ACCEPT	Summary: HSPA8 is a component of the PRP19-CDC5L spliceosomal complex, confirmed by IDA (PMID:20176811). Reason: Spliceosomal complex membership is supported by direct experimental evidence (PMID:20176811) showing HSPA8 co-purifies with PRP19-CDC5L.
GO:0005730 nucleolus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Nucleolar localization of HSPA8 from IEA mapping. While HSPA8 is found in the nucleus, nucleolar localization is plausible given HSPA8's role as a broadly distributed chaperone, but not specifically validated as a core localization. Reason: IEA-derived annotation. HSPA8 is found in the nucleus but nucleolar localization is not a primary site of function.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Cytoplasmic localization of HSPA8 is well-established and redundant with the IBA annotation. Reason: Correct annotation, consistent with IBA and experimental evidence.
GO:0005765 lysosomal membrane	IEA GO_REF:0000044	ACCEPT	Summary: HSPA8 associates with the lysosomal membrane during CMA, where it delivers KFERQ-motif substrates to LAMP2A for translocation (PMID:11559757). Reason: Lysosomal membrane localization is a core feature of HSPA8's role in CMA, supported by experimental evidence.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: Plasma membrane localization of HSPA8 is supported by IBA and experimental evidence (PMID:11276205, PMID:17785435). Reason: Consistent with IBA annotation and experimental data showing HSPA8 at cell surface.
GO:0006397 mRNA processing	IEA GO_REF:0000043	ACCEPT	Summary: HSPA8 participates in mRNA processing as a component of the PRP19-CDC5L spliceosomal complex (PMID:20176811, PMID:23742842). Reason: Supported by HSPA8's established role in the PRP19-CDC5L complex involved in splicing.
GO:0006914 autophagy	IEA GO_REF:0000043	ACCEPT	Summary: HSPA8 is central to chaperone-mediated autophagy (CMA), recognizing KFERQ-motif substrates and delivering them to LAMP2A at the lysosomal membrane (PMID:2799391). Reason: Autophagy involvement is a core function of HSPA8 through its essential role in CMA.
GO:0008380 RNA splicing	IEA GO_REF:0000043	ACCEPT	Summary: HSPA8 is involved in RNA splicing as part of the PRP19-CDC5L spliceosomal complex (PMID:20176811). Reason: Supported by HSPA8's established role in the spliceosome.
GO:0009968 negative regulation of signal transduction	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: HSPA8 negatively regulates some signaling pathways, such as repressing HSF1 transcriptional activity (PMID:9499401) and limiting NLRP3 inflammasome activation via CMA (PMID:36586411). Reason: A non-core but documented consequence of HSPA8's chaperone activity, particularly in HSF1 feedback regulation and NLRP3 degradation.
GO:0016787 hydrolase activity	IEA GO_REF:0000043	ACCEPT	Summary: HSPA8 has hydrolase activity (ATP hydrolysis, EC 3.6.4.10). This is a parent term of the more specific GO:0016887 (ATP hydrolysis activity). Reason: Accurate but general; more specific ATP hydrolysis activity terms also annotated. Acceptable as a broader IEA annotation.
GO:0016887 ATP hydrolysis activity	IEA GO_REF:0000002	ACCEPT	Summary: ATP hydrolysis activity is a core enzymatic function of HSPA8, redundant with the IBA annotation. Reason: Correct IEA annotation consistent with the IBA annotation for this core function.
GO:0031072 heat shock protein binding	IEA GO_REF:0000117	ACCEPT	Summary: Heat shock protein binding is well-established for HSPA8, which interacts with HSP90, HSPB8, and multiple DNAJ family members. Reason: Consistent with IBA annotation and extensive experimental evidence for HSP interactions.
GO:0031625 ubiquitin protein ligase binding	IEA GO_REF:0000117	ACCEPT	Summary: HSPA8 binds the E3 ubiquitin ligase CHIP/STUB1, which ubiquitinates Hsc70-bound misfolded substrates to target them for proteasomal degradation (PMID:12150907, PMID:16207813). Reason: Well-established interaction between HSPA8 and CHIP/STUB1 E3 ligase that is central to the chaperone-ubiquitin-proteasome triage pathway.
GO:0031647 regulation of protein stability	IEA GO_REF:0000117	ACCEPT	Summary: HSPA8 regulates protein stability by either promoting correct folding or targeting misfolded proteins for degradation via CHIP-mediated ubiquitination or CMA. Reason: Core consequence of HSPA8's chaperone function in protein quality control.
GO:0033554 cellular response to stress	IEA GO_REF:0000117	ACCEPT	Summary: HSPA8 responds to cellular stress by increasing chaperone activity, though unlike HSPA1A it is constitutively expressed rather than stress-induced. Reason: HSPA8 is a constitutive chaperone that participates in stress responses, including regulating HSF1 during heat shock attenuation (PMID:9499401).
GO:0039531 regulation of cytoplasmic pattern recognition receptor signaling pathway	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: HSPA8 modulates pattern recognition receptor signaling, including NLRP3 inflammasome regulation via CMA-mediated degradation of NLRP3 (PMID:36586411). Reason: A non-core but documented consequence of HSPA8's CMA activity on NLRP3 turnover.
GO:0042026 protein refolding	IEA GO_REF:0000117	ACCEPT	Summary: Protein refolding is a core function of HSPA8, consistent with IBA and IDA evidence. Reason: Redundant with IBA annotation; correct.
GO:0042470 melanosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: HSPA8 was identified in melanosomes by proteomic analysis (PMID:17081065). This likely reflects its role as an abundant chaperone found in many compartments. Reason: IEA-based from subcellular location mapping. HSPA8 is an abundant protein found in many subcellular fractions; melanosome localization is not a core function.
GO:0043254 regulation of protein-containing complex assembly	IEA GO_REF:0000117	ACCEPT	Summary: HSPA8 regulates protein complex assembly, including clathrin lattice disassembly and CMA translocation complex assembly/disassembly. Reason: Consistent with HSPA8's established roles in clathrin uncoating and CMA complex regulation.
GO:0046034 ATP metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: HSPA8 is involved in ATP metabolism through its ATPase cycle that drives chaperone function. Reason: Accurate description of HSPA8's ATP-dependent chaperone mechanism.
GO:0051082 unfolded protein binding	IEA GO_REF:0000117	MODIFY	Summary: GO:0051082 (unfolded protein binding) is being obsoleted. HSPA8 functions as a protein folding chaperone, binding unfolded/misfolded substrates via its SBD to assist their correct folding through ATP-driven conformational cycles. Reason: GO:0051082 is being obsoleted as part of the unfolded protein binding obsoletion project. The correct replacement for HSPA8 is GO:0044183 (protein folding chaperone) since HSPA8/HSC70 binds client polypeptides to assist their folding, not merely to bind unfolded proteins. More specifically, GO:0140662 (ATP-dependent protein folding chaperone) is the most appropriate term. Proposed replacements: protein folding chaperone
GO:0051129 negative regulation of cellular component organization	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: HSPA8 negatively regulates cellular component organization, e.g. through clathrin coat disassembly and prevention of protein aggregation. Reason: A broad annotation capturing indirect consequences of HSPA8's chaperone activities.
GO:0055131 C3HC4-type RING finger domain binding	IEA GO_REF:0000117	ACCEPT	Summary: HSPA8 binds C3HC4-type RING finger domains, consistent with its interaction with CHIP/STUB1 E3 ligase and RNF207 (PMID:25281747). Reason: Reflects the functional interaction between HSPA8 and RING-type E3 ligases.
GO:0071383 cellular response to steroid hormone stimulus	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: HSPA8 participates in steroid hormone receptor chaperoning as part of the HSP70/HSP90 chaperone machine that folds and activates steroid hormone receptors. Reason: A non-core function reflecting HSPA8's role in the HSP90 chaperone cycle for steroid hormone receptors.
GO:0072318 clathrin coat disassembly	IEA GO_REF:0000117	ACCEPT	Summary: Clathrin coat disassembly is a core function of HSPA8, consistent with IBA and IDA evidence (PMID:8524399). Reason: Redundant with IBA annotation; correct.
GO:0140545 ATP-dependent protein disaggregase activity	IEA GO_REF:0000117	ACCEPT	Summary: HSPA8 has ATP-dependent protein disaggregase activity, working with HSP110 (HSPH1) to disaggregate protein aggregates (PMID:22990239, PMID:23921388). Reason: Supported by direct experimental evidence showing HSPA8+HSP110 disaggregase activity.
GO:1902903 regulation of supramolecular fiber organization	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: HSPA8 modulates supramolecular fiber organization, possibly through prevention of amyloid/aggregate formation (PMID:23921388). Reason: A non-core consequence of HSPA8's disaggregase and anti-aggregation chaperone activities.
GO:1904813 ficolin-1-rich granule lumen	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: HSPA8 is found in ficolin-1-rich granule lumen in neutrophils, likely reflecting its presence as an abundant protein in secretory granules. Reason: IEA annotation reflecting proteomic detection in a specialized granule compartment; not a core localization.
GO:1990904 ribonucleoprotein complex	IEA GO_REF:0000117	ACCEPT	Summary: HSPA8 is found in ribonucleoprotein complexes, including IMP1 mRNP granules (PMID:17289661) and the PRP19-CDC5L spliceosomal complex. Reason: Supported by proteomic identification in mRNP granules and the spliceosome.
GO:0005515 protein binding	IPI PMID:14743216 A physical and functional map of the human TNF-alpha/NF-kapp...	REMOVE	Summary: Generic protein binding annotation from PMID:14743216. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:15047060 Analysis of proteins copurifying with the CD4/lck complex us...	REMOVE	Summary: Generic protein binding annotation from PMID:15047060. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:15048123 Abi1 is essential for the formation and activation of a WAVE...	REMOVE	Summary: Generic protein binding annotation from PMID:15048123. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:15657067 Phosphotyrosine signaling networks in epidermal growth facto...	REMOVE	Summary: Generic protein binding annotation from PMID:15657067. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:16049941 A pilot proteomic study of amyloid precursor interactors in ...	REMOVE	Summary: Generic protein binding annotation from PMID:16049941. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:16169070 A human protein-protein interaction network: a resource for ...	REMOVE	Summary: Generic protein binding annotation from PMID:16169070. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	REMOVE	Summary: Generic protein binding annotation from PMID:16189514. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:16275660 Identification of VCP/p97, carboxyl terminus of Hsp70-intera...	REMOVE	Summary: Generic protein binding annotation from PMID:16275660. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:16293251 CHIP interacts with heat shock factor 1 during heat stress.	REMOVE	Summary: Generic protein binding annotation from PMID:16293251. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:17022977 Identification of Hsc70 as an influenza virus matrix protein...	REMOVE	Summary: Generic protein binding annotation from PMID:17022977. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:17332742 Composition and three-dimensional EM structure of double aff...	REMOVE	Summary: Generic protein binding annotation from PMID:17332742. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:17400507 Identification of potential protein interactors of Lrrk2.	REMOVE	Summary: Generic protein binding annotation from PMID:17400507. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:17620599 Functional specialization of beta-arrestin interactions reve...	REMOVE	Summary: Generic protein binding annotation from PMID:17620599. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:18457437 Identification of intracellular proteins associated with the...	REMOVE	Summary: Generic protein binding annotation from PMID:18457437. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:19338310 Streamline proteomic approach for characterizing protein-pro...	REMOVE	Summary: Generic protein binding annotation from PMID:19338310. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:19800331 Short peptides derived from the BAG-1 C-terminus inhibit the...	REMOVE	Summary: Generic protein binding annotation from PMID:19800331. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:20195357 A comprehensive resource of interacting protein regions for ...	REMOVE	Summary: Generic protein binding annotation from PMID:20195357. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:20391533 Proteomic analysis reveals novel binding partners of MIP-T3 ...	REMOVE	Summary: Generic protein binding annotation from PMID:20391533. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:20618441 CHIP participates in protein triage decisions by preferentia...	REMOVE	Summary: Generic protein binding annotation from PMID:20618441. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:22085931 Optimal functional levels of activation-induced deaminase sp...	REMOVE	Summary: Generic protein binding annotation from PMID:22085931. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:22365833 Dynamic protein-protein interaction wiring of the human spli...	REMOVE	Summary: Generic protein binding annotation from PMID:22365833. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:22645275 Identification of novel ATP13A2 interactors and their role i...	REMOVE	Summary: Generic protein binding annotation from PMID:22645275. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:22990239 Metazoan Hsp70 machines use Hsp110 to power protein disaggre...	REMOVE	Summary: Generic protein binding annotation from PMID:22990239. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv...	REMOVE	Summary: Generic protein binding annotation from PMID:23414517. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:23455607 Interplay of LRRK2 with chaperone-mediated autophagy.	REMOVE	Summary: Generic protein binding annotation from PMID:23455607. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:23523103 Lysine-5 acetylation negatively regulates lactate dehydrogen...	REMOVE	Summary: Generic protein binding annotation from PMID:23523103. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:24136289 Identification and comparative analysis of hepatitis C virus...	REMOVE	Summary: Generic protein binding annotation from PMID:24136289. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln...	REMOVE	Summary: Generic protein binding annotation from PMID:24189400. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:24510904 Unbiased screen for interactors of leucine-rich repeat kinas...	REMOVE	Summary: Generic protein binding annotation from PMID:24510904. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ...	REMOVE	Summary: Generic protein binding annotation from PMID:24658140. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:24947832 Differential protein-protein interactions of LRRK1 and LRRK2...	REMOVE	Summary: Generic protein binding annotation from PMID:24947832. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: Generic protein binding annotation from PMID:25416956. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	REMOVE	Summary: Generic protein binding annotation from PMID:25502805. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ...	REMOVE	Summary: Generic protein binding annotation from PMID:25609649. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	REMOVE	Summary: Generic protein binding annotation from PMID:25910212. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:25959826 Quantitative interaction proteomics of neurodegenerative dis...	REMOVE	Summary: Generic protein binding annotation from PMID:25959826. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ...	REMOVE	Summary: Generic protein binding annotation from PMID:26871637. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:27107014 An inter-species protein-protein interaction network across ...	REMOVE	Summary: Generic protein binding annotation from PMID:27107014. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Generic protein binding annotation from PMID:28514442. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:29519959 P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) s...	REMOVE	Summary: Generic protein binding annotation from PMID:29519959. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive...	REMOVE	Summary: Generic protein binding annotation from PMID:29568061. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:29764935 The disorderly conduct of Hsc70 and its interaction with the...	REMOVE	Summary: Generic protein binding annotation from PMID:29764935. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma...	REMOVE	Summary: Generic protein binding annotation from PMID:30021884. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:30827827 A Legionella pneumophila Kinase Phosphorylates the Hsp70 Cha...	REMOVE	Summary: Generic protein binding annotation from PMID:30827827. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:31273097 The heme-regulated inhibitor is a cytosolic sensor of protei...	REMOVE	Summary: Generic protein binding annotation from PMID:31273097. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ...	REMOVE	Summary: Generic protein binding annotation from PMID:31980649. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding annotation from PMID:32296183. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding annotation from PMID:32814053. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Generic protein binding annotation from PMID:33961781. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	REMOVE	Summary: Generic protein binding annotation from PMID:35271311. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	REMOVE	Summary: Generic protein binding annotation from PMID:40205054. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0071383 cellular response to steroid hormone stimulus	TAS Reactome:R-HSA-3371497	KEEP AS NON CORE	Summary: HSPA8 participates in the HSP90 chaperone cycle for steroid hormone receptors (Reactome). This is a non-core chaperoning role. Reason: Well-documented role of HSP70/HSP90 machinery in steroid hormone receptor maturation but not a core defining function of HSPA8.
GO:0061024 membrane organization	TAS Reactome:R-HSA-199991	KEEP AS NON CORE	Summary: HSPA8 is involved in membrane organization through its role in clathrin-mediated vesicle trafficking and uncoating (Reactome:R-HSA-199991). Reason: A broad process annotation capturing the consequence of HSPA8's clathrin uncoating activity.
GO:0000398 mRNA splicing, via spliceosome	NAS PMID:23742842 Splicing and beyond: the many faces of the Prp19 complex.	ACCEPT	Summary: HSPA8 participates in mRNA splicing as a component of the PRP19-CDC5L complex (PMID:20176811, PMID:23742842). Reason: Supported by HSPA8's established membership in the spliceosomal PRP19-CDC5L complex.
GO:0005737 cytoplasm	IDA PMID:17289661 Molecular composition of IMP1 ribonucleoprotein granules.	ACCEPT	Summary: HSPA8 identified in cytoplasmic IMP1 mRNP granules by mass spectrometry (PMID:17289661). Reason: Direct experimental confirmation of cytoplasmic localization.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:40281343 PSAT1 impairs ferroptosis and reduces immunotherapy efficacy...	ACCEPT	Summary: HSPA8 functions as a protein-macromolecule adaptor, connecting substrate proteins to the degradation/autophagy machinery (PMID:40281343). In CMA, it bridges KFERQ-motif substrates to LAMP2A. Reason: Adaptor activity accurately describes HSPA8's role in CMA where it recognizes substrates and delivers them to LAMP2A, and in ERAD where it connects substrates to the ubiquitin-proteasome system.
GO:0061684 chaperone-mediated autophagy	IDA PMID:40281343 PSAT1 impairs ferroptosis and reduces immunotherapy efficacy...	ACCEPT	Summary: CMA function of HSPA8 confirmed by IDA in the context of ferroptosis regulation (PMID:40281343). Reason: Further experimental confirmation of HSPA8's core CMA function.
GO:0160020 positive regulation of ferroptosis	IDA PMID:40281343 PSAT1 impairs ferroptosis and reduces immunotherapy efficacy...	KEEP AS NON CORE	Summary: HSPA8 promotes ferroptosis through CMA-mediated degradation of GPX4 in the context of PSAT1 regulation (PMID:40281343). This is a downstream consequence of CMA activity. Reason: Ferroptosis regulation is a specific downstream outcome of HSPA8's CMA activity, not a core function.
GO:0061684 chaperone-mediated autophagy	TAS PMID:25719862 Modulation of deregulated chaperone-mediated autophagy by a ...	ACCEPT	Summary: CMA is a core function of HSPA8, which recognizes KFERQ-motif substrates and delivers them to LAMP2A. PMID:25719862 demonstrates P140 peptide modulates CMA through HSPA8. Reason: CMA is one of the most well-established and defining functions of HSPA8/HSC70.
GO:0101031 protein folding chaperone complex	IDA PMID:25719862 Modulation of deregulated chaperone-mediated autophagy by a ...	ACCEPT	Summary: HSPA8 forms part of protein folding chaperone complexes, including with HSP90, co-chaperones, and client proteins (PMID:25719862). Reason: Core localization reflecting HSPA8's function in multi-chaperone complexes.
GO:0140662 ATP-dependent protein folding chaperone	TAS PMID:25719862 Modulation of deregulated chaperone-mediated autophagy by a ...	ACCEPT	Summary: HSPA8 is an ATP-dependent protein folding chaperone, the most specific and accurate MF term for its primary molecular function. Reason: GO:0140662 is the ideal MF term for HSPA8, capturing both its ATP-dependent mechanism and chaperone function.
GO:0005515 protein binding	IPI PMID:39225180 ABHD8 antagonizes inflammation by facilitating chaperone-med...	REMOVE	Summary: Generic protein binding annotation from PMID:39225180. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0030335 positive regulation of cell migration	IDA PMID:17785435 EWI-2/CD316 is an inducible receptor of HSPA8 on human dendr...	KEEP AS NON CORE	Summary: Extracellular HSPA8 acts as a ligand for EWI-2/CD316 on dendritic cells, enhancing CCL21-dependent cell migration (PMID:17785435). Reason: A non-core extracellular signaling function of HSPA8 in the immune system. Supporting Evidence: PMID:17785435 The ligation of EWI-2 enhanced the CCL21/SLC-dependent migration of activated mature dendritic cells but attenuated their antigen-specific stimulatory capacities
GO:0048018 receptor ligand activity	IDA PMID:17785435 EWI-2/CD316 is an inducible receptor of HSPA8 on human dendr...	KEEP AS NON CORE	Summary: Extracellular HSPA8 acts as a ligand for the EWI-2/CD316 receptor on dendritic cells (PMID:17785435). Reason: A non-core extracellular function; receptor ligand activity is atypical for a cytosolic chaperone but documented for the extracellular pool of HSPA8. Supporting Evidence: PMID:17785435 human heat shock protein A8 (HSPA8), a member of the hsp70 family, was identified as the ligand for EWI-2
GO:0016887 ATP hydrolysis activity	TAS Reactome:R-HSA-3371422	ACCEPT	Summary: ATP hydrolysis is the core enzymatic activity of HSPA8, driving the chaperone cycle. Reactome pathway confirms this. Reason: Core enzymatic function of HSPA8, well-established.
GO:0016887 ATP hydrolysis activity	TAS Reactome:R-HSA-8868658	ACCEPT	Summary: ATP hydrolysis is the core enzymatic activity of HSPA8, driving the chaperone cycle. Reactome pathway confirms this. Reason: Core enzymatic function of HSPA8, well-established.
GO:0072318 clathrin coat disassembly	IDA PMID:8524399 Role of auxilin in uncoating clathrin-coated vesicles.	ACCEPT	Summary: Seminal paper demonstrating HSPA8/HSC70 mediates clathrin coat disassembly together with auxilin. Auxilin recruits HSC70 to clathrin lattices and the J-domain stimulates ATP-dependent disassembly (PMID:8524399). Reason: Direct experimental demonstration of HSPA8's core role in clathrin uncoating. Supporting Evidence: PMID:8524399 Clathrin-coated vesicles transport selected integral membrane proteins from the cell surface and the trans-Golgi network to the endosomal system
GO:0005515 protein binding	IPI PMID:32671205 A micropeptide encoded by lncRNA MIR155HG suppresses autoimm...	REMOVE	Summary: Generic protein binding annotation from PMID:32671205. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:26775844 Salivary protein histatin 3 regulates cell proliferation by ...	REMOVE	Summary: Generic protein binding annotation from PMID:26775844. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005765 lysosomal membrane	IDA PMID:11559757 A molecular chaperone complex at the lysosomal membrane is r...	ACCEPT	Summary: HSPA8 localizes to the lysosomal membrane as part of the CMA translocation complex (PMID:11559757). Reason: Direct experimental evidence for lysosomal membrane localization in CMA. Supporting Evidence: PMID:11559757 A molecular chaperone complex at the lysosomal membrane is required for protein translocation.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:11559757 A molecular chaperone complex at the lysosomal membrane is r...	ACCEPT	Summary: HSPA8 functions as a protein-macromolecule adaptor, connecting substrate proteins to the degradation/autophagy machinery (PMID:11559757). In CMA, it bridges KFERQ-motif substrates to LAMP2A. Reason: Adaptor activity accurately describes HSPA8's role in CMA where it recognizes substrates and delivers them to LAMP2A, and in ERAD where it connects substrates to the ubiquitin-proteasome system.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:2799391 A role for a 70-kilodalton heat shock protein in lysosomal d...	ACCEPT	Summary: HSPA8 functions as a protein-macromolecule adaptor, connecting substrate proteins to the degradation/autophagy machinery (PMID:2799391). In CMA, it bridges KFERQ-motif substrates to LAMP2A. Reason: Adaptor activity accurately describes HSPA8's role in CMA where it recognizes substrates and delivers them to LAMP2A, and in ERAD where it connects substrates to the ubiquitin-proteasome system.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:36586411 Palmitoylation prevents sustained inflammation by limiting N...	ACCEPT	Summary: HSPA8 functions as a protein-macromolecule adaptor, connecting substrate proteins to the degradation/autophagy machinery (PMID:36586411). In CMA, it bridges KFERQ-motif substrates to LAMP2A. Reason: Adaptor activity accurately describes HSPA8's role in CMA where it recognizes substrates and delivers them to LAMP2A, and in ERAD where it connects substrates to the ubiquitin-proteasome system.
GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy	IDA PMID:11559757 A molecular chaperone complex at the lysosomal membrane is r...	ACCEPT	Summary: HSPA8 targets proteins to lysosomes for CMA-mediated degradation by recognizing KFERQ motifs and delivering substrates to LAMP2A (PMID:11559757). Reason: Core CMA function of HSPA8 demonstrated by direct assay.
GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy	IDA PMID:36586411 Palmitoylation prevents sustained inflammation by limiting N...	ACCEPT	Summary: HSPA8 targets palmitoylated NLRP3 to lysosomes for CMA-mediated degradation, limiting inflammasome activation (PMID:36586411). Reason: Further demonstration of HSPA8's CMA substrate-targeting function.
GO:1900226 negative regulation of NLRP3 inflammasome complex assembly	IDA PMID:36586411 Palmitoylation prevents sustained inflammation by limiting N...	KEEP AS NON CORE	Summary: HSPA8 negatively regulates NLRP3 inflammasome assembly by targeting palmitoylated NLRP3 for CMA-mediated degradation (PMID:36586411). Reason: A specific downstream consequence of HSPA8's CMA activity on a particular substrate (NLRP3), not a core function.
GO:0061635 regulation of protein complex stability	ISS GO_REF:0000024	ACCEPT	Summary: HSPA8 regulates protein complex stability, inferred from sequence similarity. Consistent with its roles in complex assembly/disassembly. Reason: ISS annotation consistent with known functions of HSPA8 in protein complex remodeling.
GO:1904589 regulation of protein import	TAS PMID:20176123 Chaperone-mediated autophagy: molecular mechanisms and physi...	KEEP AS NON CORE	Summary: HSPA8 regulates protein import including delivery of preproteins to Tom70 at the mitochondrial import receptor (PMID:12526792) and CMA substrate import at lysosomes. Reason: Reflects HSPA8's role in protein targeting to mitochondria and lysosomes, but is a broad annotation.
GO:0005515 protein binding	IPI PMID:35044787 Loss-of-function mutations in the co-chaperone protein BAG5 ...	REMOVE	Summary: Generic protein binding annotation from PMID:35044787. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:33857403 DNAJC9 integrates heat shock molecular chaperones into the h...	REMOVE	Summary: Generic protein binding annotation from PMID:33857403. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0140545 ATP-dependent protein disaggregase activity	IDA PMID:23921388 Identification and characterization of a novel human methylt...	ACCEPT	Summary: HSPA8 has ATP-dependent disaggregase activity, working with HSPH1/HSP110 to solubilize protein aggregates (PMID:23921388). Methylation at K561 modulates this activity. Reason: Core chaperone function demonstrated by direct assay. The disaggregase complex (HSPA8+HSPH1+DNAJ) is a mammalian equivalent of the yeast Hsp104 disaggregase.
GO:0005515 protein binding	IPI PMID:18320024 The human TPR protein TTC4 is a putative Hsp90 co-chaperone ...	REMOVE	Summary: Generic protein binding annotation from PMID:18320024. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:23801752 Histone deacetylase 10 promotes autophagy-mediated cell surv...	REMOVE	Summary: Generic protein binding annotation from PMID:23801752. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:29601588 ZMYND10 stabilizes intermediate chain proteins in the cytopl...	REMOVE	Summary: Generic protein binding annotation from PMID:29601588. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:25760597 Structural and functional analysis of Hikeshi, a new nuclear...	REMOVE	Summary: Generic protein binding annotation from PMID:25760597. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0045296 cadherin binding	HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	MARK AS OVER ANNOTATED	Summary: Cadherin binding from high-throughput data (PMID:25468996). HSPA8 is an abundant protein that co-purifies with many complexes. Reason: Likely non-specific; HSPA8's abundance leads to co-purification in many proteomic datasets.
GO:0030674 protein-macromolecule adaptor activity	IPI PMID:16207813 BAG-2 acts as an inhibitor of the chaperone-associated ubiqu...	ACCEPT	Summary: HSPA8 adaptor function demonstrated through interaction data (PMID:16207813). HSPA8 bridges substrates to the CHIP E3 ligase for ubiquitination. Reason: HSPA8 functions as an adaptor connecting client proteins to the ubiquitin-proteasome degradation machinery.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:16207813 BAG-2 acts as an inhibitor of the chaperone-associated ubiqu...	ACCEPT	Summary: HSPA8 binds ubiquitin protein ligases including CHIP/STUB1 and Parkin (PMID:16207813), linking chaperone activity to ubiquitin-dependent degradation. Reason: Core functional interaction between HSPA8 and E3 ligases in protein quality control.
GO:0051087 protein-folding chaperone binding	IPI PMID:16207813 BAG-2 acts as an inhibitor of the chaperone-associated ubiqu...	ACCEPT	Summary: HSPA8 binds other folding chaperones including BAG2, which inhibits the CHIP-HSPA8 complex (PMID:16207813). Reason: Core interaction of HSPA8 with co-chaperones.
GO:0101031 protein folding chaperone complex	IPI PMID:16207813 BAG-2 acts as an inhibitor of the chaperone-associated ubiqu...	ACCEPT	Summary: HSPA8 forms protein folding chaperone complexes with BAG2 and CHIP/STUB1, demonstrated by interaction data (PMID:16207813). Reason: Core complex formation for HSPA8's chaperone-ubiquitin triage function. BAG-2 acts as an inhibitor of the chaperone-associated ubiquitin ligase CHIP.
GO:0005515 protein binding	IPI PMID:24122553 The co-chaperone DNAJC12 binds to Hsc70 and is upregulated b...	REMOVE	Summary: Generic protein binding annotation from PMID:24122553. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:21148293 The endoplasmic reticulum-associated Hsp40 DNAJB12 and Hsc70...	REMOVE	Summary: Generic protein binding annotation from PMID:21148293. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:21150129 A novel ER J-protein DNAJB12 accelerates ER-associated degra...	REMOVE	Summary: Generic protein binding annotation from PMID:21150129. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:27916661 Tetrameric Assembly of K(+) Channels Requires ER-Located Cha...	REMOVE	Summary: Generic protein binding annotation from PMID:27916661. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:27103069 Loss of C9ORF72 impairs autophagy and synergizes with polyQ ...	REMOVE	Summary: Generic protein binding annotation from PMID:27103069. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:24318877 Binding of human nucleotide exchange factors to heat shock p...	REMOVE	Summary: Generic protein binding annotation from PMID:24318877. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:27708256 ARD1-mediated Hsp70 acetylation balances stress-induced prot...	REMOVE	Summary: Generic protein binding annotation from PMID:27708256. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:15708368 Small glutamine-rich tetratricopeptide repeat-containing pro...	REMOVE	Summary: Generic protein binding annotation from PMID:15708368. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:9499401 Molecular chaperones as HSF1-specific transcriptional repres...	REMOVE	Summary: Generic protein binding annotation from PMID:9499401. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:23431407 Distinct roles of molecular chaperones HSP90α and HSP90β in ...	REMOVE	Summary: Generic protein binding annotation from PMID:23431407. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy	IMP PMID:26212789 Chaperone-mediated autophagy prevents apoptosis by degrading...	ACCEPT	Summary: HSPA8's role in CMA-mediated lysosomal targeting demonstrated by mutant phenotype analysis (PMID:26212789). Reason: Mutant phenotype evidence supporting HSPA8's CMA function in targeting BBC3/PUMA for degradation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8932221	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798748	KEEP AS NON CORE	Summary: HSPA8 is found in the extracellular region, including secretory granule contents and ficolin-1-rich granules released by neutrophils. Reason: Extracellular localization of HSPA8 is documented but represents a non-core localization.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6800434	KEEP AS NON CORE	Summary: HSPA8 is found in the extracellular region, including secretory granule contents and ficolin-1-rich granules released by neutrophils. Reason: Extracellular localization of HSPA8 is documented but represents a non-core localization.
GO:0034774 secretory granule lumen	TAS Reactome:R-HSA-6798748	KEEP AS NON CORE	Summary: HSPA8 is found in secretory granule lumen (Reactome). This reflects its presence as a protein released during degranulation. Reason: Not a core localization for HSPA8's primary chaperone functions.
GO:1904813 ficolin-1-rich granule lumen	TAS Reactome:R-HSA-6800434	KEEP AS NON CORE	Summary: HSPA8 is found in ficolin-1-rich granule lumen (Reactome), reflecting its presence in neutrophil granules. Reason: Specialized localization not central to HSPA8's primary functions.
GO:0005515 protein binding	IPI PMID:24787902 Functional and molecular features of the calmodulin-interact...	REMOVE	Summary: Generic protein binding annotation from PMID:24787902. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0009267 cellular response to starvation	TAS PMID:20176123 Chaperone-mediated autophagy: molecular mechanisms and physi...	KEEP AS NON CORE	Summary: CMA is upregulated during starvation, and HSPA8 is the key chaperone recognizing CMA substrates. This indirectly involves HSPA8 in the starvation response. Reason: HSPA8 participates in starvation response through CMA, which is upregulated under nutrient deprivation (PMID:20176123).
GO:0061684 chaperone-mediated autophagy	TAS PMID:20176123 Chaperone-mediated autophagy: molecular mechanisms and physi...	ACCEPT	Summary: CMA is a core function of HSPA8 per the review by Cuervo and Dice (PMID:20176123). Reason: Authoritative review confirming HSPA8's essential role in CMA.
GO:0005765 lysosomal membrane	ISS GO_REF:0000024	ACCEPT	Summary: Lysosomal membrane localization inferred from orthologs, consistent with IDA evidence (PMID:11559757). Reason: Consistent with direct experimental evidence for HSPA8 at lysosomal membrane.
GO:0061684 chaperone-mediated autophagy	ISS GO_REF:0000024	ACCEPT	Summary: CMA involvement inferred from orthologs, consistent with extensive direct evidence for HSPA8 in CMA. Reason: Consistent with HSPA8's well-established role in CMA.
GO:1904764 chaperone-mediated autophagy translocation complex disassembly	ISS GO_REF:0000024	ACCEPT	Summary: HSPA8 participates in disassembly of the CMA translocation complex at the lysosomal membrane, inferred from orthologs. Reason: Consistent with known role of lumenal HSPA8 in CMA complex dynamics.
GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy	TAS PMID:2799391 A role for a 70-kilodalton heat shock protein in lysosomal d...	ACCEPT	Summary: The seminal paper by Chiang et al. 1989 (PMID:2799391) first identified the 70 kDa heat shock protein's role in lysosomal degradation, establishing HSPA8's function in CMA. Reason: Foundational discovery of HSPA8's role in CMA-mediated lysosomal targeting.
GO:0043254 regulation of protein-containing complex assembly	TAS PMID:20176123 Chaperone-mediated autophagy: molecular mechanisms and physi...	ACCEPT	Summary: HSPA8 regulates assembly/disassembly of protein complexes including the CMA translocation complex and clathrin lattices (PMID:20176123). Reason: Core function related to HSPA8's role in complex remodeling.
GO:0098575 lumenal side of lysosomal membrane	TAS PMID:20176123 Chaperone-mediated autophagy: molecular mechanisms and physi...	ACCEPT	Summary: HSPA8 is found on the lumenal side of the lysosomal membrane where it assists in CMA translocation complex disassembly and substrate unfolding (PMID:20176123). Reason: Documented localization of HSPA8 at lysosomal lumen, essential for CMA.
GO:0031647 regulation of protein stability	IMP PMID:26212789 Chaperone-mediated autophagy prevents apoptosis by degrading...	ACCEPT	Summary: HSPA8 regulates protein stability through CMA, as demonstrated by its role in BBC3/PUMA degradation preventing apoptosis (PMID:26212789). Reason: Experimental evidence via mutant phenotype for HSPA8's role in protein stability regulation.
GO:0005515 protein binding	IPI PMID:26212789 Chaperone-mediated autophagy prevents apoptosis by degrading...	REMOVE	Summary: Generic protein binding annotation from PMID:26212789. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:25719862 Modulation of deregulated chaperone-mediated autophagy by a ...	REMOVE	Summary: Generic protein binding annotation from PMID:25719862. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0042026 protein refolding	IDA PMID:25719862 Modulation of deregulated chaperone-mediated autophagy by a ...	ACCEPT	Summary: Direct assay evidence for HSPA8's protein refolding activity (PMID:25719862). HSPA8 assists refolding of heat-denatured substrates. Reason: Core chaperone function of HSPA8 demonstrated experimentally.
GO:0043202 lysosomal lumen	TAS PMID:25719862 Modulation of deregulated chaperone-mediated autophagy by a ...	ACCEPT	Summary: HSPA8 is present in the lysosomal lumen where it participates in CMA substrate unfolding and translocation complex disassembly (PMID:25719862). Reason: Supported by HSPA8's established role in the lumenal side of CMA.
GO:0031072 heat shock protein binding	IPI PMID:17182002 HDJC9, a novel human type C DnaJ/HSP40 member interacts with...	ACCEPT	Summary: HSPA8 binds heat shock proteins including DNAJ family members (PMID:17182002), which are essential co-chaperones. Reason: Core functional interactions with co-chaperones.
GO:0046034 ATP metabolic process	IDA PMID:23921388 Identification and characterization of a novel human methylt...	ACCEPT	Summary: HSPA8 is involved in ATP metabolism through its ATPase activity, confirmed by direct assay (PMID:23921388). Reason: Core metabolic consequence of HSPA8's ATPase activity.
GO:0055131 C3HC4-type RING finger domain binding	IPI PMID:25281747 RING finger protein RNF207, a novel regulator of cardiac exc...	ACCEPT	Summary: HSPA8 binds C3HC4-type RING finger domain of RNF207, a cardiac excitation regulator (PMID:25281747). Reason: Demonstrates HSPA8's interaction with RING-type E3 ligases beyond CHIP.
GO:0005515 protein binding	IPI PMID:14532270 A product of the human gene adjacent to parkin is a componen...	REMOVE	Summary: Generic protein binding annotation from PMID:14532270. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0001664 G protein-coupled receptor binding	IPI PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil...	KEEP AS NON CORE	Summary: HSPA8 binds CXCR4 as part of LPS receptor cluster and interacts with CHIP/Parkin (PMID:12150907). Reason: Non-core interaction; HSPA8 is a chaperone, not primarily a GPCR-binding protein.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil...	ACCEPT	Summary: HSPA8 binds ubiquitin protein ligases including CHIP/STUB1 and Parkin (PMID:12150907), linking chaperone activity to ubiquitin-dependent degradation. Reason: Core functional interaction between HSPA8 and E3 ligases in protein quality control.
GO:0005925 focal adhesion	HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome...	MARK AS OVER ANNOTATED	Summary: Focal adhesion localization from high-throughput proteomics (PMID:21423176). Likely reflects HSPA8's cytoplasmic abundance. Reason: HDA from mass spectrometry; HSPA8 is not known to have specific focal adhesion functions.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: HSPA8 detected in extracellular exosomes by high-throughput proteomics (PMID:23533145). HSPA8 is consistently found in exosome preparations across multiple studies. Reason: Non-core localization. HSPA8 is one of the most frequently identified exosomal proteins.
GO:0070062 extracellular exosome	IDA PMID:21235781 Human saliva, plasma and breast milk exosomes contain RNA: u...	KEEP AS NON CORE	Summary: HSPA8 identified in extracellular exosomes by direct assay (PMID:21235781). HSPA8 is one of the most commonly found proteins in exosome proteomics. Reason: Non-core localization. HSPA8 is abundantly found in exosomes but this reflects its high cellular abundance.
GO:0070062 extracellular exosome	IDA PMID:19028452 Proteomic profiling of human plasma exosomes identifies PPAR...	KEEP AS NON CORE	Summary: HSPA8 identified in extracellular exosomes by direct assay (PMID:19028452). HSPA8 is one of the most commonly found proteins in exosome proteomics. Reason: Non-core localization. HSPA8 is abundantly found in exosomes but this reflects its high cellular abundance.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	ACCEPT	Summary: HSPA8 associates with membranes including lysosomal, plasma, and ER membranes, consistent with its chaperone roles in these compartments. Reason: Broad but accurate annotation for a chaperone with multiple membrane-associated functions.
GO:0005615 extracellular space	HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu...	KEEP AS NON CORE	Summary: HSPA8 detected in extracellular space (colostrum) by proteomics (PMID:16502470). Consistent with extracellular localization. Reason: Non-core localization supported by multiple proteomic studies.
GO:0005515 protein binding	IPI PMID:15936278 HSJ1 is a neuronal shuttling factor for the sorting of chape...	REMOVE	Summary: Generic protein binding annotation from PMID:15936278. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005524 ATP binding	IDA PMID:23921388 Identification and characterization of a novel human methylt...	ACCEPT	Summary: ATP binding by HSPA8 confirmed by direct assay (PMID:23921388). Reason: Core biochemical property of HSPA8.
GO:0019899 enzyme binding	IPI PMID:23921388 Identification and characterization of a novel human methylt...	ACCEPT	Summary: HSPA8 binds enzymes including METTL21A methyltransferase that modulates HSPA8 function (PMID:23921388). Reason: Functional interaction with the enzyme that methylates HSPA8 at K561.
GO:0031072 heat shock protein binding	IPI PMID:23921388 Identification and characterization of a novel human methylt...	ACCEPT	Summary: HSPA8 binds heat shock proteins including DNAJ family members (PMID:23921388), which are essential co-chaperones. Reason: Core functional interactions with co-chaperones.
GO:1902904 negative regulation of supramolecular fiber organization	IDA PMID:23921388 Identification and characterization of a novel human methylt...	KEEP AS NON CORE	Summary: HSPA8 negatively regulates supramolecular fiber organization, preventing aggregation of alpha-synuclein fibrils (PMID:23921388). Reason: Specific consequence of HSPA8's disaggregase activity on amyloid fibrils.
GO:0005829 cytosol	IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist...	ACCEPT	Summary: Cytosolic localization of HSPA8 confirmed by direct assay (PMID:21231916). Reason: Core localization supported by multiple lines of evidence.
GO:0042026 protein refolding	IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist...	ACCEPT	Summary: Direct assay evidence for HSPA8's protein refolding activity (PMID:21231916). HSPA8 assists refolding of heat-denatured substrates. Reason: Core chaperone function of HSPA8 demonstrated experimentally.
GO:0051082 unfolded protein binding	IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist...	MODIFY	Summary: GO:0051082 (unfolded protein binding) is being obsoleted. HSPA8 functions as a protein folding chaperone, binding unfolded/misfolded substrates via its SBD to assist their correct folding through ATP-driven conformational cycles. Reason: GO:0051082 is being obsoleted as part of the unfolded protein binding obsoletion project. The correct replacement for HSPA8 is GO:0044183 (protein folding chaperone) since HSPA8/HSC70 binds client polypeptides to assist their folding, not merely to bind unfolded proteins. More specifically, GO:0140662 (ATP-dependent protein folding chaperone) is the most appropriate term. Proposed replacements: protein folding chaperone
GO:0003723 RNA binding	HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi...	KEEP AS NON CORE	Summary: RNA binding detected by high-throughput methods (PMID:22658674). Consistent with HSPA8's role in mRNP granules and spliceosome. Reason: Non-core function; HSPA8 associates with RNA-containing complexes but is not primarily an RNA-binding protein.
GO:0003723 RNA binding	HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ...	KEEP AS NON CORE	Summary: RNA binding detected by high-throughput methods (PMID:22681889). Consistent with HSPA8's role in mRNP granules and spliceosome. Reason: Non-core function; HSPA8 associates with RNA-containing complexes but is not primarily an RNA-binding protein.
GO:0072562 blood microparticle	HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d...	KEEP AS NON CORE	Summary: HSPA8 detected in blood microparticles by proteomics (PMID:22516433). Reason: Non-core localization reflecting HSPA8's presence in extracellular particles.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3371467	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3371518	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3371554	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5082356	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5082369	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5082384	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9770131	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9770141	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9770145	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9770236	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9770847	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9772351	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9794542	ACCEPT	Summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes. Reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	KEEP AS NON CORE	Summary: HSPA8 detected in extracellular exosomes by high-throughput proteomics (PMID:19199708). HSPA8 is consistently found in exosome preparations across multiple studies. Reason: Non-core localization. HSPA8 is one of the most frequently identified exosomal proteins.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: HSPA8 detected in extracellular exosomes by high-throughput proteomics (PMID:19056867). HSPA8 is consistently found in exosome preparations across multiple studies. Reason: Non-core localization. HSPA8 is one of the most frequently identified exosomal proteins.
GO:0023026 MHC class II protein complex binding	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	KEEP AS NON CORE	Summary: HSPA8 associates with MHC class II complexes in B-cell exosomes (PMID:20458337). May relate to antigen chaperoning. Reason: Non-core interaction potentially relevant to antigen presentation via exosomes.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	KEEP AS NON CORE	Summary: HSPA8 detected in extracellular exosomes by high-throughput proteomics (PMID:20458337). HSPA8 is consistently found in exosome preparations across multiple studies. Reason: Non-core localization. HSPA8 is one of the most frequently identified exosomal proteins.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-888589	ACCEPT	Summary: Plasma membrane localization of HSPA8, supported by its role in clathrin-coated vesicle dynamics at the plasma membrane. Reason: Consistent with HSPA8's role in clathrin coat disassembly at the plasma membrane.
GO:0061202 clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane	TAS Reactome:R-HSA-888589	KEEP AS NON CORE	Summary: HSPA8 is found at clathrin-sculpted GABA transport vesicle membranes (Reactome), reflecting its general role in clathrin-coated vesicle dynamics. Reason: Specific vesicle type annotation from Reactome; reflects general clathrin uncoating function applied to neuronal vesicles.
GO:0061202 clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane	TAS Reactome:R-HSA-917744	KEEP AS NON CORE	Summary: HSPA8 is found at clathrin-sculpted GABA transport vesicle membranes (Reactome), reflecting its general role in clathrin-coated vesicle dynamics. Reason: Specific vesicle type annotation from Reactome; reflects general clathrin uncoating function applied to neuronal vesicles.
GO:0005829 cytosol	TAS Reactome:R-HSA-3371422	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-3371503	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-3371590	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-421836	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-432688	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-450551	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-450580	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-5618085	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-5618098	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-5618105	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-5618107	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-5618110	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-6797269	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-8868658	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-8868660	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0005829 cytosol	TAS Reactome:R-HSA-9835411	ACCEPT	Summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic. Reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
GO:0070062 extracellular exosome	HDA PMID:21362503 Protein profile of exosomes from trabecular meshwork cells.	KEEP AS NON CORE	Summary: HSPA8 detected in extracellular exosomes by high-throughput proteomics (PMID:21362503). HSPA8 is consistently found in exosome preparations across multiple studies. Reason: Non-core localization. HSPA8 is one of the most frequently identified exosomal proteins.
GO:0000974 Prp19 complex	IDA PMID:20176811 Molecular architecture of the human Prp19/CDC5L complex.	ACCEPT	Summary: HSPA8 is a component of the PRP19-CDC5L complex, demonstrated by mass spectrometry and biochemical characterization (PMID:20176811). Reason: Direct experimental evidence for HSPA8 membership in this spliceosomal complex.
GO:0005634 nucleus	IDA PMID:20176811 Molecular architecture of the human Prp19/CDC5L complex.	ACCEPT	Summary: Nuclear localization of HSPA8 demonstrated in the context of the PRP19-CDC5L complex (PMID:20176811). Reason: Confirmed by direct assay in the spliceosome study.
GO:0005515 protein binding	IPI PMID:10954706 Identification of Mrj, a DnaJ/Hsp40 family protein, as a ker...	REMOVE	Summary: Generic protein binding annotation from PMID:10954706. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:10722728 The MSG1 non-DNA-binding transactivator binds to the p300/CB...	REMOVE	Summary: Generic protein binding annotation from PMID:10722728. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0045892 negative regulation of DNA-templated transcription	IDA PMID:10722728 The MSG1 non-DNA-binding transactivator binds to the p300/CB...	KEEP AS NON CORE	Summary: HSPA8 suppresses Smad-mediated transcription by sequestering MSG1/CITED1 (PMID:10722728). This is a non-core regulatory consequence of HSPA8's protein binding activity. Reason: Transcriptional regulation is not a core function of HSPA8 but reflects its ability to modulate transcription factor activity through client binding. Supporting Evidence: PMID:10722728 Hsc70 heat-shock cognate protein also forms complex with MSG1 in vivo, suppressing both binding of MSG1 to p300/CBP and enhancement of Smad-mediated transcription by MSG1.
GO:0005515 protein binding	IPI PMID:9305631 BAG-1 modulates the chaperone activity of Hsp70/Hsc70.	REMOVE	Summary: Generic protein binding annotation from PMID:9305631. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:1990904 ribonucleoprotein complex	IDA PMID:17289661 Molecular composition of IMP1 ribonucleoprotein granules.	ACCEPT	Summary: HSPA8 is found in ribonucleoprotein complexes including IMP1 mRNP granules (PMID:17289661). Reason: Direct experimental identification by mass spectrometry in mRNP granules.
GO:0005515 protein binding	IPI PMID:16531398 Tid1 isoforms are mitochondrial DnaJ-like chaperones with un...	REMOVE	Summary: Generic protein binding annotation from PMID:16531398. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0005515 protein binding	IPI PMID:14557246 AIP is a mitochondrial import mediator that binds to both im...	REMOVE	Summary: Generic protein binding annotation from PMID:14557246. HSP70 chaperones bind many client proteins and co-chaperones; this annotation is uninformative without specifying the nature of the interaction. Reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087 (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor activity) are preferable depending on the specific interaction.
GO:0006986 response to unfolded protein	NAS PMID:11093761 Molecular and functional characterization of HSC54, a novel ...	ACCEPT	Summary: HSPA8 responds to unfolded proteins as a constitutive molecular chaperone. PMID:11093761 characterizes HSC54, a variant of HSPA8. Reason: Core function of HSPA8 as a chaperone that recognizes and responds to unfolded proteins.
GO:0016887 ATP hydrolysis activity	NAS PMID:8530083 Localization of the gene encoding the human heat shock cogna...	ACCEPT	Summary: ATP hydrolysis activity of HSPA8, referenced from PMID:8530083 describing HSP73 gene localization and function. Reason: Core enzymatic activity of HSPA8.
GO:0006457 protein folding	NAS PMID:8530083 Localization of the gene encoding the human heat shock cogna...	ACCEPT	Summary: Protein folding is a core biological process of HSPA8, which assists nascent and misfolded proteins to achieve their native conformations. Reason: Central biological process function of HSPA8 as a molecular chaperone.

📄 View Raw YAML

id: P11142
gene_symbol: HSPA8
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: HSPA8 (also known as HSC70 or HSP73) is a constitutively expressed member of the HSP70 family of molecular chaperones.
  It functions as an ATP-dependent foldase chaperone that uses nucleotide-driven conformational changes to bind and release
  unfolded or misfolded substrate proteins, promoting their correct folding. HSPA8 plays central roles in protein quality
  control, chaperone-mediated autophagy (CMA) where it recognizes KFERQ motifs on substrate proteins for lysosomal degradation,
  clathrin coat disassembly, ER-associated degradation (ERAD), protein disaggregation, and as a component of the spliceosomal
  PRP19-CDC5L complex. Unlike the stress-inducible HSPA1A, HSPA8 is constitutively expressed and is the primary HSP70 family
  member involved in housekeeping chaperone functions.
alternative_products:
- name: '1'
  id: P11142-1
- name: 2 (HSC54)
  id: P11142-2
  sequence_note: VSP_002427
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: HSPA8 is found in the nucleus, supported by IBA and confirmed by IDA (PMID:20176811) showing it is a component
      of the nuclear PRP19-CDC5L spliceosomal complex.
    action: ACCEPT
    reason: Multiple lines of evidence confirm nuclear localization of HSPA8, including its role in the PRP19-CDC5L complex
      (PMID:20176811) and stress-induced nuclear accumulation.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: HSPA8 is primarily cytoplasmic as the constitutive HSP70 chaperone, well-established by IBA and multiple experimental
      studies.
    action: ACCEPT
    reason: Cytoplasmic localization is a core feature of HSPA8/HSC70, the constitutive cytosolic HSP70 family member.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: HSPA8 localizes to the plasma membrane where it can act as a cell surface receptor for LPS and interacts with
      IGSF8/EWI-2 on dendritic cells (PMID:11276205, PMID:17785435).
    action: ACCEPT
    reason: Plasma membrane localization is supported by IBA and experimental evidence showing HSPA8 at the cell surface in
      dendritic cells and other cell types.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ATP hydrolysis is a core enzymatic activity of HSPA8 (EC 3.6.4.10), driving the chaperone cycle. J-domain co-chaperones
      stimulate this ATPase activity over 1000-fold.
    action: ACCEPT
    reason: ATP hydrolysis activity is the central enzymatic function of HSPA8/HSC70, as confirmed by its EC classification
      and extensive biochemical characterization (PMID:12526792).
- term:
    id: GO:0031072
    label: heat shock protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: HSPA8 binds multiple heat shock proteins including HSP90, HSPB8, and various J-domain co-chaperones (DNAJ family
      members) as part of its chaperone machine.
    action: ACCEPT
    reason: Heat shock protein binding is a core functional property of HSPA8, which operates in complexes with HSP90, small
      HSPs, and J-domain proteins.
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Protein folding chaperone activity is the primary molecular function of HSPA8/HSC70. It binds client polypeptides
      through its substrate-binding domain and assists their folding through ATP-driven conformational cycles.
    action: ACCEPT
    reason: This is the core molecular function of HSPA8 as a constitutive HSP70 family chaperone, extensively documented
      in the literature.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: HSPA8 is primarily a cytosolic protein, confirmed by IBA and multiple experimental studies (PMID:21231916).
    action: ACCEPT
    reason: Cytosol is the primary subcellular location where HSPA8 performs its housekeeping chaperone functions.
- term:
    id: GO:0072318
    label: clathrin coat disassembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: HSPA8/HSC70 is essential for clathrin coat disassembly, working with auxilin (DNAJC6) to uncoat clathrin-coated
      vesicles via ATP-dependent disassembly (PMID:8524399).
    action: ACCEPT
    reason: Clathrin coat disassembly is a well-established core function of HSPA8, demonstrated by Ungewickell et al. 1995
      (PMID:8524399).
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: HSPA8 participates in protein refolding, including refolding of heat-denatured substrates, demonstrated experimentally
      with luciferase refolding assays (PMID:21231916).
    action: ACCEPT
    reason: Protein refolding is a well-documented core activity of the HSP70 chaperone machine, confirmed by direct assay
      evidence.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: Signal transduction is overly broad for HSPA8. While HSPA8 modulates some signaling pathways (e.g., HSF1 regulation,
      NLRP3 inflammasome), its primary role is as a chaperone, not a signaling molecule.
    action: MARK_AS_OVER_ANNOTATED
    reason: HSPA8 is a molecular chaperone, not a signaling protein. The IEA annotation to signal transduction is too broad
      and does not capture the specific mechanistic role of HSPA8.
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: HSPA8 binds ATP and ADP through its nucleotide-binding domain (NBD), which drives the chaperone conformational
      cycle.
    action: ACCEPT
    reason: Nucleotide binding is a core biochemical property of HSPA8, required for its chaperone function. While more general
      than ATP binding (GO:0005524), it is accurate.
- term:
    id: GO:0001664
    label: G protein-coupled receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 was reported to interact with CXCR4 in LPS receptor complexes (PMID:11276205). This is a non-core interaction
      likely related to its cell-surface localization.
    action: KEEP_AS_NON_CORE
    reason: While experimentally supported, GPCR binding is not a core function of HSPA8. The IEA annotation captures a peripheral
      interaction.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ATP binding is a core biochemical activity of HSPA8, required for its chaperone cycle. Crystallographic structures
      confirm the ATP-binding pocket in the NBD.
    action: ACCEPT
    reason: ATP binding is essential for HSPA8 function, confirmed by crystal structures (PDB entries) and biochemical assays.
- term:
    id: GO:0005681
    label: spliceosomal complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: HSPA8 is a component of the PRP19-CDC5L spliceosomal complex, confirmed by IDA (PMID:20176811).
    action: ACCEPT
    reason: Spliceosomal complex membership is supported by direct experimental evidence (PMID:20176811) showing HSPA8 co-purifies
      with PRP19-CDC5L.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Nucleolar localization of HSPA8 from IEA mapping. While HSPA8 is found in the nucleus, nucleolar localization
      is plausible given HSPA8's role as a broadly distributed chaperone, but not specifically validated as a core localization.
    action: KEEP_AS_NON_CORE
    reason: IEA-derived annotation. HSPA8 is found in the nucleus but nucleolar localization is not a primary site of function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Cytoplasmic localization of HSPA8 is well-established and redundant with the IBA annotation.
    action: ACCEPT
    reason: Correct annotation, consistent with IBA and experimental evidence.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: HSPA8 associates with the lysosomal membrane during CMA, where it delivers KFERQ-motif substrates to LAMP2A for
      translocation (PMID:11559757).
    action: ACCEPT
    reason: Lysosomal membrane localization is a core feature of HSPA8's role in CMA, supported by experimental evidence.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Plasma membrane localization of HSPA8 is supported by IBA and experimental evidence (PMID:11276205, PMID:17785435).
    action: ACCEPT
    reason: Consistent with IBA annotation and experimental data showing HSPA8 at cell surface.
- term:
    id: GO:0006397
    label: mRNA processing
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: HSPA8 participates in mRNA processing as a component of the PRP19-CDC5L spliceosomal complex (PMID:20176811,
      PMID:23742842).
    action: ACCEPT
    reason: Supported by HSPA8's established role in the PRP19-CDC5L complex involved in splicing.
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: HSPA8 is central to chaperone-mediated autophagy (CMA), recognizing KFERQ-motif substrates and delivering them
      to LAMP2A at the lysosomal membrane (PMID:2799391).
    action: ACCEPT
    reason: Autophagy involvement is a core function of HSPA8 through its essential role in CMA.
- term:
    id: GO:0008380
    label: RNA splicing
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: HSPA8 is involved in RNA splicing as part of the PRP19-CDC5L spliceosomal complex (PMID:20176811).
    action: ACCEPT
    reason: Supported by HSPA8's established role in the spliceosome.
- term:
    id: GO:0009968
    label: negative regulation of signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 negatively regulates some signaling pathways, such as repressing HSF1 transcriptional activity (PMID:9499401)
      and limiting NLRP3 inflammasome activation via CMA (PMID:36586411).
    action: KEEP_AS_NON_CORE
    reason: A non-core but documented consequence of HSPA8's chaperone activity, particularly in HSF1 feedback regulation
      and NLRP3 degradation.
- term:
    id: GO:0016787
    label: hydrolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: HSPA8 has hydrolase activity (ATP hydrolysis, EC 3.6.4.10). This is a parent term of the more specific GO:0016887
      (ATP hydrolysis activity).
    action: ACCEPT
    reason: Accurate but general; more specific ATP hydrolysis activity terms also annotated. Acceptable as a broader IEA
      annotation.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: ATP hydrolysis activity is a core enzymatic function of HSPA8, redundant with the IBA annotation.
    action: ACCEPT
    reason: Correct IEA annotation consistent with the IBA annotation for this core function.
- term:
    id: GO:0031072
    label: heat shock protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Heat shock protein binding is well-established for HSPA8, which interacts with HSP90, HSPB8, and multiple DNAJ
      family members.
    action: ACCEPT
    reason: Consistent with IBA annotation and extensive experimental evidence for HSP interactions.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 binds the E3 ubiquitin ligase CHIP/STUB1, which ubiquitinates Hsc70-bound misfolded substrates to target
      them for proteasomal degradation (PMID:12150907, PMID:16207813).
    action: ACCEPT
    reason: Well-established interaction between HSPA8 and CHIP/STUB1 E3 ligase that is central to the chaperone-ubiquitin-proteasome
      triage pathway.
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 regulates protein stability by either promoting correct folding or targeting misfolded proteins for degradation
      via CHIP-mediated ubiquitination or CMA.
    action: ACCEPT
    reason: Core consequence of HSPA8's chaperone function in protein quality control.
- term:
    id: GO:0033554
    label: cellular response to stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 responds to cellular stress by increasing chaperone activity, though unlike HSPA1A it is constitutively
      expressed rather than stress-induced.
    action: ACCEPT
    reason: HSPA8 is a constitutive chaperone that participates in stress responses, including regulating HSF1 during heat
      shock attenuation (PMID:9499401).
- term:
    id: GO:0039531
    label: regulation of cytoplasmic pattern recognition receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 modulates pattern recognition receptor signaling, including NLRP3 inflammasome regulation via CMA-mediated
      degradation of NLRP3 (PMID:36586411).
    action: KEEP_AS_NON_CORE
    reason: A non-core but documented consequence of HSPA8's CMA activity on NLRP3 turnover.
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Protein refolding is a core function of HSPA8, consistent with IBA and IDA evidence.
    action: ACCEPT
    reason: Redundant with IBA annotation; correct.
- term:
    id: GO:0042470
    label: melanosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: HSPA8 was identified in melanosomes by proteomic analysis (PMID:17081065). This likely reflects its role as an
      abundant chaperone found in many compartments.
    action: KEEP_AS_NON_CORE
    reason: IEA-based from subcellular location mapping. HSPA8 is an abundant protein found in many subcellular fractions;
      melanosome localization is not a core function.
- term:
    id: GO:0043254
    label: regulation of protein-containing complex assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 regulates protein complex assembly, including clathrin lattice disassembly and CMA translocation complex
      assembly/disassembly.
    action: ACCEPT
    reason: Consistent with HSPA8's established roles in clathrin uncoating and CMA complex regulation.
- term:
    id: GO:0046034
    label: ATP metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 is involved in ATP metabolism through its ATPase cycle that drives chaperone function.
    action: ACCEPT
    reason: Accurate description of HSPA8's ATP-dependent chaperone mechanism.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: GO:0051082 (unfolded protein binding) is being obsoleted. HSPA8 functions as a protein folding chaperone, binding
      unfolded/misfolded substrates via its SBD to assist their correct folding through ATP-driven conformational cycles.
    action: MODIFY
    reason: GO:0051082 is being obsoleted as part of the unfolded protein binding obsoletion project. The correct replacement
      for HSPA8 is GO:0044183 (protein folding chaperone) since HSPA8/HSC70 binds client polypeptides to assist their folding,
      not merely to bind unfolded proteins. More specifically, GO:0140662 (ATP-dependent protein folding chaperone) is the
      most appropriate term.
    proposed_replacement_terms:
    - id: GO:0044183
      label: protein folding chaperone
- term:
    id: GO:0051129
    label: negative regulation of cellular component organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 negatively regulates cellular component organization, e.g. through clathrin coat disassembly and prevention
      of protein aggregation.
    action: KEEP_AS_NON_CORE
    reason: A broad annotation capturing indirect consequences of HSPA8's chaperone activities.
- term:
    id: GO:0055131
    label: C3HC4-type RING finger domain binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 binds C3HC4-type RING finger domains, consistent with its interaction with CHIP/STUB1 E3 ligase and RNF207
      (PMID:25281747).
    action: ACCEPT
    reason: Reflects the functional interaction between HSPA8 and RING-type E3 ligases.
- term:
    id: GO:0071383
    label: cellular response to steroid hormone stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 participates in steroid hormone receptor chaperoning as part of the HSP70/HSP90 chaperone machine that
      folds and activates steroid hormone receptors.
    action: KEEP_AS_NON_CORE
    reason: A non-core function reflecting HSPA8's role in the HSP90 chaperone cycle for steroid hormone receptors.
- term:
    id: GO:0072318
    label: clathrin coat disassembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Clathrin coat disassembly is a core function of HSPA8, consistent with IBA and IDA evidence (PMID:8524399).
    action: ACCEPT
    reason: Redundant with IBA annotation; correct.
- term:
    id: GO:0140545
    label: ATP-dependent protein disaggregase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 has ATP-dependent protein disaggregase activity, working with HSP110 (HSPH1) to disaggregate protein aggregates
      (PMID:22990239, PMID:23921388).
    action: ACCEPT
    reason: Supported by direct experimental evidence showing HSPA8+HSP110 disaggregase activity.
- term:
    id: GO:1902903
    label: regulation of supramolecular fiber organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 modulates supramolecular fiber organization, possibly through prevention of amyloid/aggregate formation
      (PMID:23921388).
    action: KEEP_AS_NON_CORE
    reason: A non-core consequence of HSPA8's disaggregase and anti-aggregation chaperone activities.
- term:
    id: GO:1904813
    label: ficolin-1-rich granule lumen
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 is found in ficolin-1-rich granule lumen in neutrophils, likely reflecting its presence as an abundant
      protein in secretory granules.
    action: KEEP_AS_NON_CORE
    reason: IEA annotation reflecting proteomic detection in a specialized granule compartment; not a core localization.
- term:
    id: GO:1990904
    label: ribonucleoprotein complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: HSPA8 is found in ribonucleoprotein complexes, including IMP1 mRNP granules (PMID:17289661) and the PRP19-CDC5L
      spliceosomal complex.
    action: ACCEPT
    reason: Supported by proteomic identification in mRNP granules and the spliceosome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14743216
  review:
    summary: Generic protein binding annotation from PMID:14743216. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15047060
  review:
    summary: Generic protein binding annotation from PMID:15047060. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15048123
  review:
    summary: Generic protein binding annotation from PMID:15048123. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15657067
  review:
    summary: Generic protein binding annotation from PMID:15657067. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16049941
  review:
    summary: Generic protein binding annotation from PMID:16049941. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16169070
  review:
    summary: Generic protein binding annotation from PMID:16169070. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  review:
    summary: Generic protein binding annotation from PMID:16189514. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16275660
  review:
    summary: Generic protein binding annotation from PMID:16275660. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16293251
  review:
    summary: Generic protein binding annotation from PMID:16293251. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17022977
  review:
    summary: Generic protein binding annotation from PMID:17022977. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17332742
  review:
    summary: Generic protein binding annotation from PMID:17332742. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17400507
  review:
    summary: Generic protein binding annotation from PMID:17400507. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17620599
  review:
    summary: Generic protein binding annotation from PMID:17620599. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18457437
  review:
    summary: Generic protein binding annotation from PMID:18457437. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19338310
  review:
    summary: Generic protein binding annotation from PMID:19338310. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19800331
  review:
    summary: Generic protein binding annotation from PMID:19800331. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20195357
  review:
    summary: Generic protein binding annotation from PMID:20195357. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20391533
  review:
    summary: Generic protein binding annotation from PMID:20391533. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20618441
  review:
    summary: Generic protein binding annotation from PMID:20618441. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22085931
  review:
    summary: Generic protein binding annotation from PMID:22085931. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22365833
  review:
    summary: Generic protein binding annotation from PMID:22365833. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22645275
  review:
    summary: Generic protein binding annotation from PMID:22645275. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22990239
  review:
    summary: Generic protein binding annotation from PMID:22990239. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23414517
  review:
    summary: Generic protein binding annotation from PMID:23414517. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23455607
  review:
    summary: Generic protein binding annotation from PMID:23455607. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23523103
  review:
    summary: Generic protein binding annotation from PMID:23523103. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24136289
  review:
    summary: Generic protein binding annotation from PMID:24136289. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24189400
  review:
    summary: Generic protein binding annotation from PMID:24189400. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24510904
  review:
    summary: Generic protein binding annotation from PMID:24510904. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24658140
  review:
    summary: Generic protein binding annotation from PMID:24658140. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24947832
  review:
    summary: Generic protein binding annotation from PMID:24947832. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: Generic protein binding annotation from PMID:25416956. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25502805
  review:
    summary: Generic protein binding annotation from PMID:25502805. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25609649
  review:
    summary: Generic protein binding annotation from PMID:25609649. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  review:
    summary: Generic protein binding annotation from PMID:25910212. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25959826
  review:
    summary: Generic protein binding annotation from PMID:25959826. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  review:
    summary: Generic protein binding annotation from PMID:26871637. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27107014
  review:
    summary: Generic protein binding annotation from PMID:27107014. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  review:
    summary: Generic protein binding annotation from PMID:28514442. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29519959
  review:
    summary: Generic protein binding annotation from PMID:29519959. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29568061
  review:
    summary: Generic protein binding annotation from PMID:29568061. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29764935
  review:
    summary: Generic protein binding annotation from PMID:29764935. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30021884
  review:
    summary: Generic protein binding annotation from PMID:30021884. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30827827
  review:
    summary: Generic protein binding annotation from PMID:30827827. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31273097
  review:
    summary: Generic protein binding annotation from PMID:31273097. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31980649
  review:
    summary: Generic protein binding annotation from PMID:31980649. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: Generic protein binding annotation from PMID:32296183. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: Generic protein binding annotation from PMID:32814053. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: Generic protein binding annotation from PMID:33961781. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: Generic protein binding annotation from PMID:35271311. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  review:
    summary: Generic protein binding annotation from PMID:40205054. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0071383
    label: cellular response to steroid hormone stimulus
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3371497
  review:
    summary: HSPA8 participates in the HSP90 chaperone cycle for steroid hormone receptors (Reactome). This is a non-core
      chaperoning role.
    action: KEEP_AS_NON_CORE
    reason: Well-documented role of HSP70/HSP90 machinery in steroid hormone receptor maturation but not a core defining function
      of HSPA8.
- term:
    id: GO:0061024
    label: membrane organization
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-199991
  review:
    summary: HSPA8 is involved in membrane organization through its role in clathrin-mediated vesicle trafficking and uncoating
      (Reactome:R-HSA-199991).
    action: KEEP_AS_NON_CORE
    reason: A broad process annotation capturing the consequence of HSPA8's clathrin uncoating activity.
- term:
    id: GO:0000398
    label: mRNA splicing, via spliceosome
  evidence_type: NAS
  original_reference_id: PMID:23742842
  review:
    summary: HSPA8 participates in mRNA splicing as a component of the PRP19-CDC5L complex (PMID:20176811, PMID:23742842).
    action: ACCEPT
    reason: Supported by HSPA8's established membership in the spliceosomal PRP19-CDC5L complex.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:17289661
  review:
    summary: HSPA8 identified in cytoplasmic IMP1 mRNP granules by mass spectrometry (PMID:17289661).
    action: ACCEPT
    reason: Direct experimental confirmation of cytoplasmic localization.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:40281343
  review:
    summary: HSPA8 functions as a protein-macromolecule adaptor, connecting substrate proteins to the degradation/autophagy
      machinery (PMID:40281343). In CMA, it bridges KFERQ-motif substrates to LAMP2A.
    action: ACCEPT
    reason: Adaptor activity accurately describes HSPA8's role in CMA where it recognizes substrates and delivers them to
      LAMP2A, and in ERAD where it connects substrates to the ubiquitin-proteasome system.
- term:
    id: GO:0061684
    label: chaperone-mediated autophagy
  evidence_type: IDA
  original_reference_id: PMID:40281343
  review:
    summary: CMA function of HSPA8 confirmed by IDA in the context of ferroptosis regulation (PMID:40281343).
    action: ACCEPT
    reason: Further experimental confirmation of HSPA8's core CMA function.
- term:
    id: GO:0160020
    label: positive regulation of ferroptosis
  evidence_type: IDA
  original_reference_id: PMID:40281343
  review:
    summary: HSPA8 promotes ferroptosis through CMA-mediated degradation of GPX4 in the context of PSAT1 regulation (PMID:40281343).
      This is a downstream consequence of CMA activity.
    action: KEEP_AS_NON_CORE
    reason: Ferroptosis regulation is a specific downstream outcome of HSPA8's CMA activity, not a core function.
- term:
    id: GO:0061684
    label: chaperone-mediated autophagy
  evidence_type: TAS
  original_reference_id: PMID:25719862
  review:
    summary: CMA is a core function of HSPA8, which recognizes KFERQ-motif substrates and delivers them to LAMP2A. PMID:25719862
      demonstrates P140 peptide modulates CMA through HSPA8.
    action: ACCEPT
    reason: CMA is one of the most well-established and defining functions of HSPA8/HSC70.
- term:
    id: GO:0101031
    label: protein folding chaperone complex
  evidence_type: IDA
  original_reference_id: PMID:25719862
  review:
    summary: HSPA8 forms part of protein folding chaperone complexes, including with HSP90, co-chaperones, and client proteins
      (PMID:25719862).
    action: ACCEPT
    reason: Core localization reflecting HSPA8's function in multi-chaperone complexes.
- term:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  evidence_type: TAS
  original_reference_id: PMID:25719862
  review:
    summary: HSPA8 is an ATP-dependent protein folding chaperone, the most specific and accurate MF term for its primary molecular
      function.
    action: ACCEPT
    reason: GO:0140662 is the ideal MF term for HSPA8, capturing both its ATP-dependent mechanism and chaperone function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:39225180
  review:
    summary: Generic protein binding annotation from PMID:39225180. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IDA
  original_reference_id: PMID:17785435
  review:
    summary: Extracellular HSPA8 acts as a ligand for EWI-2/CD316 on dendritic cells, enhancing CCL21-dependent cell migration
      (PMID:17785435).
    action: KEEP_AS_NON_CORE
    reason: A non-core extracellular signaling function of HSPA8 in the immune system.
    supported_by:
    - reference_id: PMID:17785435
      supporting_text: The ligation of EWI-2 enhanced the CCL21/SLC-dependent migration of activated mature dendritic cells
        but attenuated their antigen-specific stimulatory capacities
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:17785435
  review:
    summary: Extracellular HSPA8 acts as a ligand for the EWI-2/CD316 receptor on dendritic cells (PMID:17785435).
    action: KEEP_AS_NON_CORE
    reason: A non-core extracellular function; receptor ligand activity is atypical for a cytosolic chaperone but documented
      for the extracellular pool of HSPA8.
    supported_by:
    - reference_id: PMID:17785435
      supporting_text: human heat shock protein A8 (HSPA8), a member of the hsp70 family, was identified as the ligand for
        EWI-2
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3371422
  review:
    summary: ATP hydrolysis is the core enzymatic activity of HSPA8, driving the chaperone cycle. Reactome pathway confirms
      this.
    action: ACCEPT
    reason: Core enzymatic function of HSPA8, well-established.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8868658
  review:
    summary: ATP hydrolysis is the core enzymatic activity of HSPA8, driving the chaperone cycle. Reactome pathway confirms
      this.
    action: ACCEPT
    reason: Core enzymatic function of HSPA8, well-established.
- term:
    id: GO:0072318
    label: clathrin coat disassembly
  evidence_type: IDA
  original_reference_id: PMID:8524399
  review:
    summary: Seminal paper demonstrating HSPA8/HSC70 mediates clathrin coat disassembly together with auxilin. Auxilin recruits
      HSC70 to clathrin lattices and the J-domain stimulates ATP-dependent disassembly (PMID:8524399).
    action: ACCEPT
    reason: Direct experimental demonstration of HSPA8's core role in clathrin uncoating.
    supported_by:
    - reference_id: PMID:8524399
      supporting_text: Clathrin-coated vesicles transport selected integral membrane proteins from the cell surface and the
        trans-Golgi network to the endosomal system
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32671205
  review:
    summary: Generic protein binding annotation from PMID:32671205. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26775844
  review:
    summary: Generic protein binding annotation from PMID:26775844. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IDA
  original_reference_id: PMID:11559757
  review:
    summary: HSPA8 localizes to the lysosomal membrane as part of the CMA translocation complex (PMID:11559757).
    action: ACCEPT
    reason: Direct experimental evidence for lysosomal membrane localization in CMA.
    supported_by:
    - reference_id: PMID:11559757
      supporting_text: A molecular chaperone complex at the lysosomal membrane is required for protein translocation.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:11559757
  review:
    summary: HSPA8 functions as a protein-macromolecule adaptor, connecting substrate proteins to the degradation/autophagy
      machinery (PMID:11559757). In CMA, it bridges KFERQ-motif substrates to LAMP2A.
    action: ACCEPT
    reason: Adaptor activity accurately describes HSPA8's role in CMA where it recognizes substrates and delivers them to
      LAMP2A, and in ERAD where it connects substrates to the ubiquitin-proteasome system.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:2799391
  review:
    summary: HSPA8 functions as a protein-macromolecule adaptor, connecting substrate proteins to the degradation/autophagy
      machinery (PMID:2799391). In CMA, it bridges KFERQ-motif substrates to LAMP2A.
    action: ACCEPT
    reason: Adaptor activity accurately describes HSPA8's role in CMA where it recognizes substrates and delivers them to
      LAMP2A, and in ERAD where it connects substrates to the ubiquitin-proteasome system.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:36586411
  review:
    summary: HSPA8 functions as a protein-macromolecule adaptor, connecting substrate proteins to the degradation/autophagy
      machinery (PMID:36586411). In CMA, it bridges KFERQ-motif substrates to LAMP2A.
    action: ACCEPT
    reason: Adaptor activity accurately describes HSPA8's role in CMA where it recognizes substrates and delivers them to
      LAMP2A, and in ERAD where it connects substrates to the ubiquitin-proteasome system.
- term:
    id: GO:0061740
    label: protein targeting to lysosome involved in chaperone-mediated autophagy
  evidence_type: IDA
  original_reference_id: PMID:11559757
  review:
    summary: HSPA8 targets proteins to lysosomes for CMA-mediated degradation by recognizing KFERQ motifs and delivering substrates
      to LAMP2A (PMID:11559757).
    action: ACCEPT
    reason: Core CMA function of HSPA8 demonstrated by direct assay.
- term:
    id: GO:0061740
    label: protein targeting to lysosome involved in chaperone-mediated autophagy
  evidence_type: IDA
  original_reference_id: PMID:36586411
  review:
    summary: HSPA8 targets palmitoylated NLRP3 to lysosomes for CMA-mediated degradation, limiting inflammasome activation
      (PMID:36586411).
    action: ACCEPT
    reason: Further demonstration of HSPA8's CMA substrate-targeting function.
- term:
    id: GO:1900226
    label: negative regulation of NLRP3 inflammasome complex assembly
  evidence_type: IDA
  original_reference_id: PMID:36586411
  review:
    summary: HSPA8 negatively regulates NLRP3 inflammasome assembly by targeting palmitoylated NLRP3 for CMA-mediated degradation
      (PMID:36586411).
    action: KEEP_AS_NON_CORE
    reason: A specific downstream consequence of HSPA8's CMA activity on a particular substrate (NLRP3), not a core function.
- term:
    id: GO:0061635
    label: regulation of protein complex stability
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: HSPA8 regulates protein complex stability, inferred from sequence similarity. Consistent with its roles in complex
      assembly/disassembly.
    action: ACCEPT
    reason: ISS annotation consistent with known functions of HSPA8 in protein complex remodeling.
- term:
    id: GO:1904589
    label: regulation of protein import
  evidence_type: TAS
  original_reference_id: PMID:20176123
  review:
    summary: HSPA8 regulates protein import including delivery of preproteins to Tom70 at the mitochondrial import receptor
      (PMID:12526792) and CMA substrate import at lysosomes.
    action: KEEP_AS_NON_CORE
    reason: Reflects HSPA8's role in protein targeting to mitochondria and lysosomes, but is a broad annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35044787
  review:
    summary: Generic protein binding annotation from PMID:35044787. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33857403
  review:
    summary: Generic protein binding annotation from PMID:33857403. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0140545
    label: ATP-dependent protein disaggregase activity
  evidence_type: IDA
  original_reference_id: PMID:23921388
  review:
    summary: HSPA8 has ATP-dependent disaggregase activity, working with HSPH1/HSP110 to solubilize protein aggregates (PMID:23921388).
      Methylation at K561 modulates this activity.
    action: ACCEPT
    reason: Core chaperone function demonstrated by direct assay. The disaggregase complex (HSPA8+HSPH1+DNAJ) is a mammalian
      equivalent of the yeast Hsp104 disaggregase.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18320024
  review:
    summary: Generic protein binding annotation from PMID:18320024. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23801752
  review:
    summary: Generic protein binding annotation from PMID:23801752. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29601588
  review:
    summary: Generic protein binding annotation from PMID:29601588. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25760597
  review:
    summary: Generic protein binding annotation from PMID:25760597. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: HDA
  original_reference_id: PMID:25468996
  review:
    summary: Cadherin binding from high-throughput data (PMID:25468996). HSPA8 is an abundant protein that co-purifies with
      many complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Likely non-specific; HSPA8's abundance leads to co-purification in many proteomic datasets.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IPI
  original_reference_id: PMID:16207813
  review:
    summary: HSPA8 adaptor function demonstrated through interaction data (PMID:16207813). HSPA8 bridges substrates to the
      CHIP E3 ligase for ubiquitination.
    action: ACCEPT
    reason: HSPA8 functions as an adaptor connecting client proteins to the ubiquitin-proteasome degradation machinery.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:16207813
  review:
    summary: HSPA8 binds ubiquitin protein ligases including CHIP/STUB1 and Parkin (PMID:16207813), linking chaperone activity
      to ubiquitin-dependent degradation.
    action: ACCEPT
    reason: Core functional interaction between HSPA8 and E3 ligases in protein quality control.
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IPI
  original_reference_id: PMID:16207813
  review:
    summary: HSPA8 binds other folding chaperones including BAG2, which inhibits the CHIP-HSPA8 complex (PMID:16207813).
    action: ACCEPT
    reason: Core interaction of HSPA8 with co-chaperones.
- term:
    id: GO:0101031
    label: protein folding chaperone complex
  evidence_type: IPI
  original_reference_id: PMID:16207813
  review:
    summary: HSPA8 forms protein folding chaperone complexes with BAG2 and CHIP/STUB1, demonstrated by interaction data (PMID:16207813).
    action: ACCEPT
    reason: Core complex formation for HSPA8's chaperone-ubiquitin triage function. BAG-2 acts as an inhibitor of the chaperone-associated
      ubiquitin ligase CHIP.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24122553
  review:
    summary: Generic protein binding annotation from PMID:24122553. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21148293
  review:
    summary: Generic protein binding annotation from PMID:21148293. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21150129
  review:
    summary: Generic protein binding annotation from PMID:21150129. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27916661
  review:
    summary: Generic protein binding annotation from PMID:27916661. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27103069
  review:
    summary: Generic protein binding annotation from PMID:27103069. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24318877
  review:
    summary: Generic protein binding annotation from PMID:24318877. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27708256
  review:
    summary: Generic protein binding annotation from PMID:27708256. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15708368
  review:
    summary: Generic protein binding annotation from PMID:15708368. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9499401
  review:
    summary: Generic protein binding annotation from PMID:9499401. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23431407
  review:
    summary: Generic protein binding annotation from PMID:23431407. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0061740
    label: protein targeting to lysosome involved in chaperone-mediated autophagy
  evidence_type: IMP
  original_reference_id: PMID:26212789
  review:
    summary: HSPA8's role in CMA-mediated lysosomal targeting demonstrated by mutant phenotype analysis (PMID:26212789).
    action: ACCEPT
    reason: Mutant phenotype evidence supporting HSPA8's CMA function in targeting BBC3/PUMA for degradation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8932221
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798748
  review:
    summary: HSPA8 is found in the extracellular region, including secretory granule contents and ficolin-1-rich granules
      released by neutrophils.
    action: KEEP_AS_NON_CORE
    reason: Extracellular localization of HSPA8 is documented but represents a non-core localization.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800434
  review:
    summary: HSPA8 is found in the extracellular region, including secretory granule contents and ficolin-1-rich granules
      released by neutrophils.
    action: KEEP_AS_NON_CORE
    reason: Extracellular localization of HSPA8 is documented but represents a non-core localization.
- term:
    id: GO:0034774
    label: secretory granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798748
  review:
    summary: HSPA8 is found in secretory granule lumen (Reactome). This reflects its presence as a protein released during
      degranulation.
    action: KEEP_AS_NON_CORE
    reason: Not a core localization for HSPA8's primary chaperone functions.
- term:
    id: GO:1904813
    label: ficolin-1-rich granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800434
  review:
    summary: HSPA8 is found in ficolin-1-rich granule lumen (Reactome), reflecting its presence in neutrophil granules.
    action: KEEP_AS_NON_CORE
    reason: Specialized localization not central to HSPA8's primary functions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24787902
  review:
    summary: Generic protein binding annotation from PMID:24787902. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0009267
    label: cellular response to starvation
  evidence_type: TAS
  original_reference_id: PMID:20176123
  review:
    summary: CMA is upregulated during starvation, and HSPA8 is the key chaperone recognizing CMA substrates. This indirectly
      involves HSPA8 in the starvation response.
    action: KEEP_AS_NON_CORE
    reason: HSPA8 participates in starvation response through CMA, which is upregulated under nutrient deprivation (PMID:20176123).
- term:
    id: GO:0061684
    label: chaperone-mediated autophagy
  evidence_type: TAS
  original_reference_id: PMID:20176123
  review:
    summary: CMA is a core function of HSPA8 per the review by Cuervo and Dice (PMID:20176123).
    action: ACCEPT
    reason: Authoritative review confirming HSPA8's essential role in CMA.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Lysosomal membrane localization inferred from orthologs, consistent with IDA evidence (PMID:11559757).
    action: ACCEPT
    reason: Consistent with direct experimental evidence for HSPA8 at lysosomal membrane.
- term:
    id: GO:0061684
    label: chaperone-mediated autophagy
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: CMA involvement inferred from orthologs, consistent with extensive direct evidence for HSPA8 in CMA.
    action: ACCEPT
    reason: Consistent with HSPA8's well-established role in CMA.
- term:
    id: GO:1904764
    label: chaperone-mediated autophagy translocation complex disassembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: HSPA8 participates in disassembly of the CMA translocation complex at the lysosomal membrane, inferred from orthologs.
    action: ACCEPT
    reason: Consistent with known role of lumenal HSPA8 in CMA complex dynamics.
- term:
    id: GO:0061740
    label: protein targeting to lysosome involved in chaperone-mediated autophagy
  evidence_type: TAS
  original_reference_id: PMID:2799391
  review:
    summary: The seminal paper by Chiang et al. 1989 (PMID:2799391) first identified the 70 kDa heat shock protein's role
      in lysosomal degradation, establishing HSPA8's function in CMA.
    action: ACCEPT
    reason: Foundational discovery of HSPA8's role in CMA-mediated lysosomal targeting.
- term:
    id: GO:0043254
    label: regulation of protein-containing complex assembly
  evidence_type: TAS
  original_reference_id: PMID:20176123
  review:
    summary: HSPA8 regulates assembly/disassembly of protein complexes including the CMA translocation complex and clathrin
      lattices (PMID:20176123).
    action: ACCEPT
    reason: Core function related to HSPA8's role in complex remodeling.
- term:
    id: GO:0098575
    label: lumenal side of lysosomal membrane
  evidence_type: TAS
  original_reference_id: PMID:20176123
  review:
    summary: HSPA8 is found on the lumenal side of the lysosomal membrane where it assists in CMA translocation complex disassembly
      and substrate unfolding (PMID:20176123).
    action: ACCEPT
    reason: Documented localization of HSPA8 at lysosomal lumen, essential for CMA.
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: IMP
  original_reference_id: PMID:26212789
  review:
    summary: HSPA8 regulates protein stability through CMA, as demonstrated by its role in BBC3/PUMA degradation preventing
      apoptosis (PMID:26212789).
    action: ACCEPT
    reason: Experimental evidence via mutant phenotype for HSPA8's role in protein stability regulation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26212789
  review:
    summary: Generic protein binding annotation from PMID:26212789. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25719862
  review:
    summary: Generic protein binding annotation from PMID:25719862. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IDA
  original_reference_id: PMID:25719862
  review:
    summary: Direct assay evidence for HSPA8's protein refolding activity (PMID:25719862). HSPA8 assists refolding of heat-denatured
      substrates.
    action: ACCEPT
    reason: Core chaperone function of HSPA8 demonstrated experimentally.
- term:
    id: GO:0043202
    label: lysosomal lumen
  evidence_type: TAS
  original_reference_id: PMID:25719862
  review:
    summary: HSPA8 is present in the lysosomal lumen where it participates in CMA substrate unfolding and translocation complex
      disassembly (PMID:25719862).
    action: ACCEPT
    reason: Supported by HSPA8's established role in the lumenal side of CMA.
- term:
    id: GO:0031072
    label: heat shock protein binding
  evidence_type: IPI
  original_reference_id: PMID:17182002
  review:
    summary: HSPA8 binds heat shock proteins including DNAJ family members (PMID:17182002), which are essential co-chaperones.
    action: ACCEPT
    reason: Core functional interactions with co-chaperones.
- term:
    id: GO:0046034
    label: ATP metabolic process
  evidence_type: IDA
  original_reference_id: PMID:23921388
  review:
    summary: HSPA8 is involved in ATP metabolism through its ATPase activity, confirmed by direct assay (PMID:23921388).
    action: ACCEPT
    reason: Core metabolic consequence of HSPA8's ATPase activity.
- term:
    id: GO:0055131
    label: C3HC4-type RING finger domain binding
  evidence_type: IPI
  original_reference_id: PMID:25281747
  review:
    summary: HSPA8 binds C3HC4-type RING finger domain of RNF207, a cardiac excitation regulator (PMID:25281747).
    action: ACCEPT
    reason: Demonstrates HSPA8's interaction with RING-type E3 ligases beyond CHIP.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14532270
  review:
    summary: Generic protein binding annotation from PMID:14532270. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0001664
    label: G protein-coupled receptor binding
  evidence_type: IPI
  original_reference_id: PMID:12150907
  review:
    summary: HSPA8 binds CXCR4 as part of LPS receptor cluster and interacts with CHIP/Parkin (PMID:12150907).
    action: KEEP_AS_NON_CORE
    reason: Non-core interaction; HSPA8 is a chaperone, not primarily a GPCR-binding protein.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:12150907
  review:
    summary: HSPA8 binds ubiquitin protein ligases including CHIP/STUB1 and Parkin (PMID:12150907), linking chaperone activity
      to ubiquitin-dependent degradation.
    action: ACCEPT
    reason: Core functional interaction between HSPA8 and E3 ligases in protein quality control.
- term:
    id: GO:0005925
    label: focal adhesion
  evidence_type: HDA
  original_reference_id: PMID:21423176
  review:
    summary: Focal adhesion localization from high-throughput proteomics (PMID:21423176). Likely reflects HSPA8's cytoplasmic
      abundance.
    action: MARK_AS_OVER_ANNOTATED
    reason: HDA from mass spectrometry; HSPA8 is not known to have specific focal adhesion functions.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  review:
    summary: HSPA8 detected in extracellular exosomes by high-throughput proteomics (PMID:23533145). HSPA8 is consistently
      found in exosome preparations across multiple studies.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization. HSPA8 is one of the most frequently identified exosomal proteins.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: IDA
  original_reference_id: PMID:21235781
  review:
    summary: HSPA8 identified in extracellular exosomes by direct assay (PMID:21235781). HSPA8 is one of the most commonly
      found proteins in exosome proteomics.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization. HSPA8 is abundantly found in exosomes but this reflects its high cellular abundance.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: IDA
  original_reference_id: PMID:19028452
  review:
    summary: HSPA8 identified in extracellular exosomes by direct assay (PMID:19028452). HSPA8 is one of the most commonly
      found proteins in exosome proteomics.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization. HSPA8 is abundantly found in exosomes but this reflects its high cellular abundance.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  review:
    summary: HSPA8 associates with membranes including lysosomal, plasma, and ER membranes, consistent with its chaperone
      roles in these compartments.
    action: ACCEPT
    reason: Broad but accurate annotation for a chaperone with multiple membrane-associated functions.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: HDA
  original_reference_id: PMID:16502470
  review:
    summary: HSPA8 detected in extracellular space (colostrum) by proteomics (PMID:16502470). Consistent with extracellular
      localization.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization supported by multiple proteomic studies.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15936278
  review:
    summary: Generic protein binding annotation from PMID:15936278. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:23921388
  review:
    summary: ATP binding by HSPA8 confirmed by direct assay (PMID:23921388).
    action: ACCEPT
    reason: Core biochemical property of HSPA8.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:23921388
  review:
    summary: HSPA8 binds enzymes including METTL21A methyltransferase that modulates HSPA8 function (PMID:23921388).
    action: ACCEPT
    reason: Functional interaction with the enzyme that methylates HSPA8 at K561.
- term:
    id: GO:0031072
    label: heat shock protein binding
  evidence_type: IPI
  original_reference_id: PMID:23921388
  review:
    summary: HSPA8 binds heat shock proteins including DNAJ family members (PMID:23921388), which are essential co-chaperones.
    action: ACCEPT
    reason: Core functional interactions with co-chaperones.
- term:
    id: GO:1902904
    label: negative regulation of supramolecular fiber organization
  evidence_type: IDA
  original_reference_id: PMID:23921388
  review:
    summary: HSPA8 negatively regulates supramolecular fiber organization, preventing aggregation of alpha-synuclein fibrils
      (PMID:23921388).
    action: KEEP_AS_NON_CORE
    reason: Specific consequence of HSPA8's disaggregase activity on amyloid fibrils.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:21231916
  review:
    summary: Cytosolic localization of HSPA8 confirmed by direct assay (PMID:21231916).
    action: ACCEPT
    reason: Core localization supported by multiple lines of evidence.
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IDA
  original_reference_id: PMID:21231916
  review:
    summary: Direct assay evidence for HSPA8's protein refolding activity (PMID:21231916). HSPA8 assists refolding of heat-denatured
      substrates.
    action: ACCEPT
    reason: Core chaperone function of HSPA8 demonstrated experimentally.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:21231916
  review:
    summary: GO:0051082 (unfolded protein binding) is being obsoleted. HSPA8 functions as a protein folding chaperone, binding
      unfolded/misfolded substrates via its SBD to assist their correct folding through ATP-driven conformational cycles.
    action: MODIFY
    reason: GO:0051082 is being obsoleted as part of the unfolded protein binding obsoletion project. The correct replacement
      for HSPA8 is GO:0044183 (protein folding chaperone) since HSPA8/HSC70 binds client polypeptides to assist their folding,
      not merely to bind unfolded proteins. More specifically, GO:0140662 (ATP-dependent protein folding chaperone) is the
      most appropriate term.
    proposed_replacement_terms:
    - id: GO:0044183
      label: protein folding chaperone
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  review:
    summary: RNA binding detected by high-throughput methods (PMID:22658674). Consistent with HSPA8's role in mRNP granules
      and spliceosome.
    action: KEEP_AS_NON_CORE
    reason: Non-core function; HSPA8 associates with RNA-containing complexes but is not primarily an RNA-binding protein.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  review:
    summary: RNA binding detected by high-throughput methods (PMID:22681889). Consistent with HSPA8's role in mRNP granules
      and spliceosome.
    action: KEEP_AS_NON_CORE
    reason: Non-core function; HSPA8 associates with RNA-containing complexes but is not primarily an RNA-binding protein.
- term:
    id: GO:0072562
    label: blood microparticle
  evidence_type: HDA
  original_reference_id: PMID:22516433
  review:
    summary: HSPA8 detected in blood microparticles by proteomics (PMID:22516433).
    action: KEEP_AS_NON_CORE
    reason: Non-core localization reflecting HSPA8's presence in extracellular particles.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3371467
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3371518
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3371554
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5082356
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5082369
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5082384
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9770131
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9770141
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9770145
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9770236
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9770847
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9772351
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9794542
  review:
    summary: HSPA8 is found in the nucleoplasm as part of the PRP19-CDC5L spliceosomal complex and HSF1 regulatory complexes.
    action: ACCEPT
    reason: Nucleoplasm localization is consistent with HSPA8's roles in splicing and HSF1 regulation.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19199708
  review:
    summary: HSPA8 detected in extracellular exosomes by high-throughput proteomics (PMID:19199708). HSPA8 is consistently
      found in exosome preparations across multiple studies.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization. HSPA8 is one of the most frequently identified exosomal proteins.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  review:
    summary: HSPA8 detected in extracellular exosomes by high-throughput proteomics (PMID:19056867). HSPA8 is consistently
      found in exosome preparations across multiple studies.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization. HSPA8 is one of the most frequently identified exosomal proteins.
- term:
    id: GO:0023026
    label: MHC class II protein complex binding
  evidence_type: HDA
  original_reference_id: PMID:20458337
  review:
    summary: HSPA8 associates with MHC class II complexes in B-cell exosomes (PMID:20458337). May relate to antigen chaperoning.
    action: KEEP_AS_NON_CORE
    reason: Non-core interaction potentially relevant to antigen presentation via exosomes.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  review:
    summary: HSPA8 detected in extracellular exosomes by high-throughput proteomics (PMID:20458337). HSPA8 is consistently
      found in exosome preparations across multiple studies.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization. HSPA8 is one of the most frequently identified exosomal proteins.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-888589
  review:
    summary: Plasma membrane localization of HSPA8, supported by its role in clathrin-coated vesicle dynamics at the plasma
      membrane.
    action: ACCEPT
    reason: Consistent with HSPA8's role in clathrin coat disassembly at the plasma membrane.
- term:
    id: GO:0061202
    label: clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-888589
  review:
    summary: HSPA8 is found at clathrin-sculpted GABA transport vesicle membranes (Reactome), reflecting its general role
      in clathrin-coated vesicle dynamics.
    action: KEEP_AS_NON_CORE
    reason: Specific vesicle type annotation from Reactome; reflects general clathrin uncoating function applied to neuronal
      vesicles.
- term:
    id: GO:0061202
    label: clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917744
  review:
    summary: HSPA8 is found at clathrin-sculpted GABA transport vesicle membranes (Reactome), reflecting its general role
      in clathrin-coated vesicle dynamics.
    action: KEEP_AS_NON_CORE
    reason: Specific vesicle type annotation from Reactome; reflects general clathrin uncoating function applied to neuronal
      vesicles.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3371422
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3371503
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3371590
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-421836
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-432688
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-450551
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-450580
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5618085
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5618098
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5618105
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5618107
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5618110
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6797269
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8868658
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8868660
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9835411
  review:
    summary: Cytosol localization confirmed by multiple Reactome pathways. HSPA8 is primarily cytosolic.
    action: ACCEPT
    reason: Core localization of HSPA8, consistent with IBA and IDA evidence.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:21362503
  review:
    summary: HSPA8 detected in extracellular exosomes by high-throughput proteomics (PMID:21362503). HSPA8 is consistently
      found in exosome preparations across multiple studies.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization. HSPA8 is one of the most frequently identified exosomal proteins.
- term:
    id: GO:0000974
    label: Prp19 complex
  evidence_type: IDA
  original_reference_id: PMID:20176811
  review:
    summary: HSPA8 is a component of the PRP19-CDC5L complex, demonstrated by mass spectrometry and biochemical characterization
      (PMID:20176811).
    action: ACCEPT
    reason: Direct experimental evidence for HSPA8 membership in this spliceosomal complex.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:20176811
  review:
    summary: Nuclear localization of HSPA8 demonstrated in the context of the PRP19-CDC5L complex (PMID:20176811).
    action: ACCEPT
    reason: Confirmed by direct assay in the spliceosome study.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10954706
  review:
    summary: Generic protein binding annotation from PMID:10954706. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10722728
  review:
    summary: Generic protein binding annotation from PMID:10722728. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:10722728
  review:
    summary: HSPA8 suppresses Smad-mediated transcription by sequestering MSG1/CITED1 (PMID:10722728). This is a non-core
      regulatory consequence of HSPA8's protein binding activity.
    action: KEEP_AS_NON_CORE
    reason: Transcriptional regulation is not a core function of HSPA8 but reflects its ability to modulate transcription
      factor activity through client binding.
    supported_by:
    - reference_id: PMID:10722728
      supporting_text: Hsc70 heat-shock cognate protein also forms complex with MSG1 in vivo, suppressing both binding of
        MSG1 to p300/CBP and enhancement of Smad-mediated transcription by MSG1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9305631
  review:
    summary: Generic protein binding annotation from PMID:9305631. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:1990904
    label: ribonucleoprotein complex
  evidence_type: IDA
  original_reference_id: PMID:17289661
  review:
    summary: HSPA8 is found in ribonucleoprotein complexes including IMP1 mRNP granules (PMID:17289661).
    action: ACCEPT
    reason: Direct experimental identification by mass spectrometry in mRNP granules.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16531398
  review:
    summary: Generic protein binding annotation from PMID:16531398. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14557246
  review:
    summary: Generic protein binding annotation from PMID:14557246. HSP70 chaperones bind many client proteins and co-chaperones;
      this annotation is uninformative without specifying the nature of the interaction.
    action: REMOVE
    reason: GO:0005515 (protein binding) is uninformative for a molecular chaperone that by definition interacts with many
      substrate proteins and co-chaperones. More specific MF terms such as GO:0044183 (protein folding chaperone), GO:0051087
      (protein-folding chaperone binding), GO:0031072 (heat shock protein binding), or GO:0030674 (protein-macromolecule adaptor
      activity) are preferable depending on the specific interaction.
- term:
    id: GO:0006986
    label: response to unfolded protein
  evidence_type: NAS
  original_reference_id: PMID:11093761
  review:
    summary: HSPA8 responds to unfolded proteins as a constitutive molecular chaperone. PMID:11093761 characterizes HSC54,
      a variant of HSPA8.
    action: ACCEPT
    reason: Core function of HSPA8 as a chaperone that recognizes and responds to unfolded proteins.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: NAS
  original_reference_id: PMID:8530083
  review:
    summary: ATP hydrolysis activity of HSPA8, referenced from PMID:8530083 describing HSP73 gene localization and function.
    action: ACCEPT
    reason: Core enzymatic activity of HSPA8.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: NAS
  original_reference_id: PMID:8530083
  review:
    summary: Protein folding is a core biological process of HSPA8, which assists nascent and misfolded proteins to achieve
      their native conformations.
    action: ACCEPT
    reason: Central biological process function of HSPA8 as a molecular chaperone.
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  title: The endoplasmic reticulum-associated Hsp40 DNAJB12 and Hsc70 cooperate to facilitate RMA1 E3-dependent degradation
    of nascent CFTRDeltaF508.
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- id: PMID:21150129
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    lysine methylation.
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    in vitro.
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  title: Quantitative interaction proteomics of neurodegenerative disease proteins.
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  title: Salivary protein histatin 3 regulates cell proliferation by enhancing p27(Kip1) and heat shock cognate protein 70
    ubiquitination.
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  title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
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    death.
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  title: A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins.
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  title: Architecture of the human interactome defines protein communities and disease networks.
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  title: P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) substrate that enhances neuronal toxicity.
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- id: PMID:29568061
  title: An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.
  findings: []
- id: PMID:29601588
  title: ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms.
  findings: []
- id: PMID:29764935
  title: The disorderly conduct of Hsc70 and its interaction with the Alzheimer's-related Tau protein.
  findings: []
- id: PMID:30021884
  title: Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.
  findings: []
- id: PMID:30827827
  title: A Legionella pneumophila Kinase Phosphorylates the Hsp70 Chaperone Family to Inhibit Eukaryotic Protein Synthesis.
  findings: []
- id: PMID:31273097
  title: The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling.
  findings: []
- id: PMID:31980649
  title: Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
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- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
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- id: PMID:32671205
  title: A micropeptide encoded by lncRNA MIR155HG suppresses autoimmune inflammation via modulating antigen presentation.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation
    in Affected Brains.
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- id: PMID:33857403
  title: DNAJC9 integrates heat shock molecular chaperones into the histone chaperone network.
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- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35044787
  title: Loss-of-function mutations in the co-chaperone protein BAG5 cause dilated cardiomyopathy requiring heart transplantation.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:36586411
  title: Palmitoylation prevents sustained inflammation by limiting NLRP3 inflammasome activation through chaperone-mediated
    autophagy.
  findings: []
- id: PMID:39225180
  title: ABHD8 antagonizes inflammation by facilitating chaperone-mediated autophagy-mediated degradation of NLRP3.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:40281343
  title: PSAT1 impairs ferroptosis and reduces immunotherapy efficacy via GPX4 hydroxylation.
  findings: []
- id: PMID:8524399
  title: Role of auxilin in uncoating clathrin-coated vesicles.
  findings: []
- id: PMID:8530083
  title: Localization of the gene encoding the human heat shock cognate protein, HSP73, to chromosome 11.
  findings: []
- id: PMID:9305631
  title: BAG-1 modulates the chaperone activity of Hsp70/Hsc70.
  findings: []
- id: PMID:9499401
  title: Molecular chaperones as HSF1-specific transcriptional repressors.
  findings: []
- id: Reactome:R-HSA-199991
  title: Membrane Trafficking
  findings: []
- id: Reactome:R-HSA-3371422
  title: ATP hydrolysis by HSP70
  findings: []
- id: Reactome:R-HSA-3371467
  title: SIRT1 deacetylates HSF1
  findings: []
- id: Reactome:R-HSA-3371497
  title: HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
  findings: []
- id: Reactome:R-HSA-3371503
  title: STIP1(HOP) binds HSP90 and HSP70:HSP40:nascent protein
  findings: []
- id: Reactome:R-HSA-3371518
  title: SIRT1 binds to HSF1
  findings: []
- id: Reactome:R-HSA-3371554
  title: HSF1 acetylation at Lys80
  findings: []
- id: Reactome:R-HSA-3371590
  title: HSP70 binds to HSP40:nascent protein
  findings: []
- id: Reactome:R-HSA-421836
  title: trans-Golgi Network Derived Vesicle Uncoating
  findings: []
- id: Reactome:R-HSA-432688
  title: trans-Golgi Network Derived Lysosomal Vesicle Uncoating
  findings: []
- id: Reactome:R-HSA-450551
  title: AUF1 binds translation and heat shock proteins
  findings: []
- id: Reactome:R-HSA-450580
  title: AUF1 (hnRNP D0) is ubiquitinylated
  findings: []
- id: Reactome:R-HSA-5082356
  title: HSF1-mediated gene expression
  findings: []
- id: Reactome:R-HSA-5082369
  title: Acetylated HSF1 dissociates from DNA
  findings: []
- id: Reactome:R-HSA-5082384
  title: HSP70:DNAJB1 binds HSF1
  findings: []
- id: Reactome:R-HSA-5618085
  title: FKBP4 binds HSP90:ATP:STIP1:HSP70:nascent protein
  findings: []
- id: Reactome:R-HSA-5618098
  title: p23 (PTGES3) binds HSP90:ATP:FKBP5:nascent protein
  findings: []
- id: Reactome:R-HSA-5618105
  title: FKBP5 binds HSP90:ATP:STIP1:HSP70:nascent protein
  findings: []
- id: Reactome:R-HSA-5618107
  title: ATP binding to HSP90 triggers conformation change
  findings: []
- id: Reactome:R-HSA-5618110
  title: p23 (PTGES3) binds HSP90:ATP:FKBP4:nascent protein
  findings: []
- id: Reactome:R-HSA-6797269
  title: Expression of HSPA8, ALOX15
  findings: []
- id: Reactome:R-HSA-6798748
  title: Exocytosis of secretory granule lumen proteins
  findings: []
- id: Reactome:R-HSA-6800434
  title: Exocytosis of ficolin-rich granule lumen proteins
  findings: []
- id: Reactome:R-HSA-8868658
  title: HSPA8-mediated ATP hydrolysis promotes vesicle uncoating
  findings: []
- id: Reactome:R-HSA-8868660
  title: Auxilin recruits HSPA8:ATP to the clathrin-coated vesicle
  findings: []
- id: Reactome:R-HSA-888589
  title: Release of GABA at the synapse
  findings: []
- id: Reactome:R-HSA-8932221
  title: METTL21A transfers 3xCH3 from 3xAdoMet to HSPA8
  findings: []
- id: Reactome:R-HSA-917744
  title: GABA loaded synaptic vesicle Docking and Priming
  findings: []
- id: Reactome:R-HSA-9770131
  title: Formation of the Spliceosomal B* complex
  findings: []
- id: Reactome:R-HSA-9770141
  title: Formation of the Spliceosomal C* complex
  findings: []
- id: Reactome:R-HSA-9770145
  title: Formation of the Spliceosomal Bact complex
  findings: []
- id: Reactome:R-HSA-9770236
  title: Formation of the Spliceosomal P complex and exon ligation
  findings: []
- id: Reactome:R-HSA-9770847
  title: Spliceosomal P complex dissociates yielding the intron-containing complex (ILS) and the spliced mRNP (new)
  findings: []
- id: Reactome:R-HSA-9772351
  title: Disassembly of the Intron Lariat Spliceosome (new)
  findings: []
- id: Reactome:R-HSA-9794542
  title: Formation of the Spliceosomal C complex containing intron lariat
  findings: []
- id: Reactome:R-HSA-9835411
  title: FA core complex:HSP70s binds PKR
  findings: []
core_functions:
- molecular_function:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  description: HSPA8/HSC70 is a constitutive ATP-dependent molecular chaperone that binds unfolded/misfolded
    client polypeptides through its substrate-binding domain (SBD) and assists their folding through
    iterative cycles of ATP binding, hydrolysis, and ADP release in the nucleotide-binding domain (NBD).
    This is the primary molecular function of HSPA8.
  directly_involved_in:
  - id: GO:0006457
    label: protein folding
  - id: GO:0042026
    label: protein refolding
  locations:
  - id: GO:0005829
    label: cytosol
- molecular_function:
    id: GO:0016887
    label: ATP hydrolysis activity
  description: ATP hydrolysis (EC 3.6.4.10) is the core enzymatic activity driving HSPA8's chaperone cycle.
    J-domain co-chaperones (DNAJ family) stimulate this ATPase activity over 1000-fold, coupling
    substrate recognition to high-affinity client binding.
  locations:
  - id: GO:0005829
    label: cytosol
- molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  description: HSPA8 is the essential substrate-recognition chaperone in CMA, recognizing KFERQ-like
    pentapeptide motifs on cytosolic proteins and delivering them to LAMP2A at the lysosomal membrane
    for translocation and degradation. This adaptor activity bridges CMA substrates to the lysosomal
    translocation machinery.
  directly_involved_in:
  - id: GO:0061684
    label: chaperone-mediated autophagy
  - id: GO:0061740
    label: protein targeting to lysosome involved in chaperone-mediated autophagy
  locations:
  - id: GO:0005765
    label: lysosomal membrane
- molecular_function:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  description: HSPA8 mediates ATP-dependent disassembly of clathrin lattices on coated vesicles, working
    with auxilin (DNAJC6) or GAK as J-domain co-chaperones. The chaperone function is applied to
    clathrin triskelions as substrates.
  directly_involved_in:
  - id: GO:0072318
    label: clathrin coat disassembly
  locations:
  - id: GO:0005829
    label: cytosol
- molecular_function:
    id: GO:0140545
    label: ATP-dependent protein disaggregase activity
  description: HSPA8 collaborates with HSP110/HSPH1 and DNAJ co-chaperones to form a mammalian disaggregase
    complex that solubilizes protein aggregates including amyloid fibrils. This represents a core
    proteostasis function.
  locations:
  - id: GO:0005829
    label: cytosol

Gene Description

Existing Annotations Review

Core Functions

ATP hydrolysis (EC 3.6.4.10) is the core enzymatic activity driving HSPA8's chaperone cycle. J-domain co-chaperones (DNAJ family) stimulate this ATPase activity over 1000-fold, coupling substrate recognition to high-affinity client binding.

HSPA8 mediates ATP-dependent disassembly of clathrin lattices on coated vesicles, working with auxilin (DNAJC6) or GAK as J-domain co-chaperones. The chaperone function is applied to clathrin triskelions as substrates.

HSPA8 collaborates with HSP110/HSPH1 and DNAJ co-chaperones to form a mammalian disaggregase complex that solubilizes protein aggregates including amyloid fibrils. This represents a core proteostasis function.

References

📚 Additional Documentation

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Question

Gene Research for Functional Annotation

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Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Citations

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