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.
| 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. Supporting Evidence: file:human/HSPA8/HSPA8-deep-research-falcon.md HSPA8 encodes constitutive Hsc70, a central Hsp70 chaperone that uses ATP-dependent cycles to bind and release client polypeptides and maintain proteostasis. |
| 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 | MARK AS OVER ANNOTATED | Summary: This IEA annotation may reflect reported HSPA8 interactions with GPCR-context clients or receptor complexes, but the cited CXCR4/LPS source is not available in the local publication cache. The separately reviewed PMID:12150907 Pael-R/GPR37 annotation provides a better-supported GPCR-client context. Reason: GPCR binding is not a core HSPA8 function. The accessible Pael-R/GPR37 evidence supports a chaperone-client quality-control interaction rather than a general GPCR-binding role, so this IEA term overstates the biological meaning of the 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 | MARK AS OVER ANNOTATED | Summary: HSPA8 hydrolyzes ATP as part of its chaperone cycle, but ATP metabolism as a broad biological process overstates HSPA8 as an ATP-metabolism gene. The relevant activity is already captured by ATP hydrolysis activity and ATP-dependent chaperone molecular-function annotations. Reason: This broad BP parent is less informative than the molecular-function terms that describe HSPA8's ATPase-driven chaperone cycle. |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000117 | MODIFY | Summary: GO:0051082 (unfolded protein binding) is now formally obsolete. 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 now formally obsolete 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 HSP90Ξ± and HSP90Ξ² 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... | MARK AS OVER ANNOTATED | Summary: HSPA8 hydrolyzes ATP as part of its chaperone cycle, but GO:0046034 is a broad ATP metabolic process term. The direct molecular activity is already represented by ATP hydrolysis activity and ATP-dependent chaperone terms. Reason: HSPA8 should not be treated as a core ATP-metabolism gene simply because its chaperone cycle consumes ATP. |
| 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... | MARK AS OVER ANNOTATED | Summary: PMID:12150907 describes Hsp70 in a complex with CHIP, Parkin, and the unfolded Pael receptor/Pael-R (GPR37), supporting a GPCR-client interaction in a ubiquitin-dependent quality-control context. The paper does not support the CXCR4/LPS receptor-cluster wording previously used here. Reason: This is a specific chaperone/client quality-control interaction involving unfolded Pael-R/GPR37 and Parkin/CHIP, not evidence that GPCR binding is a biologically meaningful HSPA8 molecular function. Supporting Evidence: PMID:12150907 CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. |
| 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 now formally obsolete. 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 now formally obsolete 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. |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)