HSPA1B (Heat shock 70 kDa protein 1B, also known as HSP72/HSP70-2) encodes a stress-inducible member of the HSP70 molecular chaperone family. The protein encoded by HSPA1B is >99% identical to HSPA1A (HSP70-1) and functions as an ATP-dependent foldase chaperone. It has the conserved tripartite HSP70 architecture: an N-terminal nucleotide-binding domain (NBD/ATPase, residues 2-386), a C-terminal substrate-binding domain (SBD) that engages client polypeptides via exposed hydrophobic segments, and a C-terminal tail mediating co-chaperone interactions (DOI:10.3390/biom13020272). HSPA1B plays a pivotal role in the protein quality control system, assisting in the correct folding of newly synthesized polypeptides, refolding of misfolded proteins, prevention of protein aggregation, and targeting of terminally misfolded proteins for proteasomal degradation. Its chaperone cycle is regulated by co-chaperones including J-domain proteins (HSP40s/DNAJs) that stimulate ATP hydrolysis and assist substrate recognition, nucleotide exchange factors (BAG1/2/3, HSPH1), and TPR domain co-chaperones (HOPX, STUB1/CHIP) (DOI:10.3390/biom13020272). Stress-induced expression can reach very high levels, reported up to approximately 15% of total cellular protein (DOI:10.3390/biom13020272). Beyond its intracellular roles, HSPA1B is also found on the plasma membrane and in extracellular vesicles (exosomes), where it can be actively secreted via non-classical pathways including secretory granules, ABC transporter-mediated endolysosomal translocation, and exosome/ectosome release (DOI:10.3389/fonc.2024.1388999). Membrane- associated HSPA1B binds negatively charged phospholipids (especially phosphatidylserine), oligomerizes upon membrane insertion, and exposes a defined extracellular epitope (TKD peptide, aa450-461) detectable by cmHSP70.1 antibody (DOI:10.3390/biom13040604). HSPA1B also participates in centrosome function during mitosis, regulation of apoptosis, and various signaling pathways including NF-kappaB and NOD2 signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: HSP70/HSPA1B localizes to the nucleus under stress conditions. IDA evidence from PMID:10205060 and PMID:17167422 confirms nuclear localization. UniProt notes HSPA1B translocates to the nucleus during heat shock, where it participates in mRNA decay regulation and erythropoiesis-related functions. Reactome entries describe HSP70 nuclear transport via Hikeshi (R-HSA-5252041) and nuclear roles in HSF1 regulation. Reason: Well-supported by phylogenetic inference and confirmed by multiple IDA annotations. HSPA1B is known to shuttle between cytoplasm and nucleus, particularly under stress conditions. Supporting Evidence: PMID:10205060 Induction of hsp70 by heat shock, down-regulation of the ubiquitin-proteasome network, or inactivation of ubiquitinating enzyme E1 all result in hsp70 sequestration of AUF1 in the perinucleus-nucleus |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: HSPA1B is predominantly cytoplasmic under basal conditions. UniProt lists cytoplasm as a primary subcellular location (ECO:0000269|PubMed:17289661). Multiple IDA annotations confirm cytoplasmic localization (PMID:10859165, PMID:24061851, PMID:9553041, PMID:24790089). Reason: Core localization for HSPA1B, well-supported by IBA and multiple IDA annotations. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference places HSPA1B at the plasma membrane. HSP70 family members have been reported at the cell surface in some contexts, including extracellular HSP70 signaling and membrane-associated chaperone pools. The rotavirus receptor citation is not used as HSPA1B-specific support because the local UniProt citation describes recombinant hsc70. Reason: Plasma membrane localization is not a core feature of HSPA1B function but is phylogenetically plausible and consistent with cell-surface HSP70-family observations. |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATP hydrolysis is the central enzymatic activity of HSP70 chaperones. HSPA1B has a conserved N-terminal nucleotide-binding/ATPase domain. The available HSPA1A/HSPA6-specific PMID:21231916 evidence should not be treated as direct HSPA1B evidence, but the IBA inference is consistent with conserved HSP70 family mechanism and Reactome HSP70 ATP-hydrolysis models. Reason: Core molecular function of HSPA1B. ATP hydrolysis drives the chaperone cycle and is essential for all HSP70 functions. Supporting Evidence: file:human/HSPA1B/HSPA1B-deep-research-falcon.md HSPA1B is a stress-inducible HSP70 paralog with conserved ATP-dependent chaperone architecture, while isoform-specific claims require caution. |
| GO:0031072 heat shock protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: HSPA1B interacts with numerous heat shock proteins including HSP40/DNAJ co-chaperones (DNAJC7, DNAJC8, DNAJC9, DNAJB1), HSP90, and HSP110/HSPH1. These interactions are essential for the chaperone cycle. IPI evidence from PMID:17182002, PMID:21231916, and PMID:23921388 confirms these interactions. Reason: Core function. HSP70 co-chaperone interactions are fundamental to the chaperone cycle and are well-supported by both phylogenetic and experimental evidence. |
| GO:0044183 protein folding chaperone | IBA GO_REF:0000033 | ACCEPT | Summary: HSPA1B is a bona fide ATP-dependent protein folding chaperone. This is the core molecular function annotation for this gene, supported by HSP70-family phylogenetic inference and conserved domain architecture. UniProt describes HSPA1B as a "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides." Reason: The defining molecular function of HSPA1B, well-supported by phylogenetic inference and conserved HSP70 chaperone architecture. Supporting Evidence: file:human/HSPA1B/HSPA1B-deep-research-falcon.md HSPA1B is a stress-inducible Hsp70 paralog with a core proteostasis role, while many HSP70/HSP72 studies do not distinguish it cleanly from HSPA1A. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosol is the primary subcellular compartment where HSPA1B exerts its chaperone function. Confirmed by IDA (GO_REF:0000052, PMID:21231916) and multiple Reactome TAS annotations describing cytosolic chaperone activities. Reason: Core localization for HSPA1B chaperone function in the cytosol. |
| GO:0042026 protein refolding | IBA GO_REF:0000033 | ACCEPT | Summary: Protein refolding is a core biological process inferred for HSPA1B from conserved HSP70-family chaperone architecture and IBA evidence. Local HSPA1A/HSPA6-specific assays should not be treated as direct HSPA1B evidence; HSPA1B-specific claims require caution. Reason: Core biological process. HSPA1B actively refolds heat-denatured substrates through its ATP-dependent chaperone cycle. Supporting Evidence: file:human/HSPA1B/HSPA1B-deep-research-falcon.md HSPA1B is a major stress-inducible HSP70 protein with central roles in proteostasis, but many HSP70/HSP72 studies do not distinguish it cleanly from HSPA1A. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: HSPA1B participates in targeting misfolded proteins for proteasomal degradation through its interaction with STUB1/CHIP E3 ubiquitin ligase. PMID:27708256 shows that deacetylated HSP70 binds STUB1, promoting ubiquitin-mediated protein degradation. PMID:12150907 demonstrates the CHIP-Hsp70-Parkin complex facilitating ubiquitination. Reason: Core function of the HSP70 chaperone system. HSP70 triages substrates between refolding and degradation pathways, with STUB1/CHIP mediating the degradation arm. |
| GO:0046718 symbiont entry into host cell | IEA GO_REF:0000108 | REMOVE | Summary: The source evidence for this rotavirus-entry inference is PMID:16537599, but the local UniProt citation describes recombinant hsc70 rather than HSPA1B. This is therefore a paralog/evidence mismatch for HSPA1B. Reason: The cited rotavirus receptor evidence does not establish HSPA1B-specific symbiont entry activity. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: IEA from UniProt keyword mapping. HSPA1B binds ATP/ADP through its N-terminal NBD, confirmed by crystal structures and IDA evidence for ATP binding (PMID:23921388). This is a broad parent term of ATP binding. Reason: Correct but very general. Subsumed by the more specific ATP binding annotation which is also present. Acceptable as an IEA broadening. |
| GO:0001618 virus receptor activity | IEA GO_REF:0000043 | REMOVE | Summary: IEA from UniProt keyword mapping for host cell receptor for virus entry. The cited PMID:16537599 evidence in the local UniProt record describes recombinant hsc70 rather than HSPA1B. Reason: Virus receptor activity is not supported by HSPA1B-specific evidence in the available local citation. |
| GO:0001664 G protein-coupled receptor binding | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: IEA from ARBA models. IDA evidence from PMID:12150907 documents HSP70 interaction with Pael-R (an orphan GPCR). UniProt also records an interaction with F2RL1 (a GPCR). However, this binding is in the context of chaperone substrate recognition, not classical GPCR signaling. Reason: While HSPA1B does bind GPCRs such as Pael-R, this is in the context of chaperone-substrate interaction, not GPCR-specific binding activity. The term implies a specific functional binding to GPCRs as signaling partners. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from combined automated annotation. ATP binding is a core function of HSPA1B confirmed by crystal structures of the NBD domain with ADP/ATP and IDA evidence (PMID:23921388). Reason: Core molecular function. ATP binding drives the chaperone cycle. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location mapping. Confirmed by multiple IDA annotations and IBA. Reason: Correct and redundant with IBA and IDA annotations for this localization. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location. UniProt records centrosome localization (ECO:0000269|PubMed:27137183). IDA evidence from PMID:27137183 confirms HSP70 accumulates at the mitotic centrosome during prometaphase to metaphase. Reason: Supported by experimental evidence. HSPA1B localizes to centrosomes during mitosis where it regulates centrosome integrity. |
| GO:0005814 centriole | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: IEA from ARBA models. The supporting experimental paper PMID:24061851 tested HSPA1A and HSPA6, not HSPA1B, so it does not provide direct HSPA1B-specific centriole-localization evidence. Reason: Centriole localization is plausible by paralog inference, but the cited experimental evidence is HSPA1A/HSPA6-specific. This should not be accepted as a supported HSPA1B localization without HSPA1B-specific data. |
| GO:0006402 mRNA catabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. Supported by IDA from PMID:10205060 which demonstrates that hsp70 participates in AU-rich element-mediated mRNA decay by sequestering AUF1 in the perinucleus-nucleus during heat shock. Reason: While experimentally supported, mRNA catabolism is a secondary consequence of HSP70 chaperone activity on AUF1, not a core function. |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IMP evidence from PMID:9553041 shows that HSP70 association with WT1 is required for WT1-mediated inhibition of cell proliferation. Reason: Experimentally supported but represents a secondary, context-dependent function dependent on interaction with specific partners like WT1. |
| GO:0016235 aggresome | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. IDA evidence from PMID:15885686 confirms aggresome localization. HSP70 chaperones are recruited to aggresomes as part of the protein quality control response. Reason: Confirmed by IDA evidence. Aggresome localization is consistent with HSP70 role in protein quality control. |
| GO:0016607 nuclear speck | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IDA evidence from PMID:9553041 confirms nuclear speck localization of HSP70. Reason: Experimentally confirmed but represents a specific subnuclear localization that is not central to HSPA1B core function. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from combined automated annotation. Redundant with IBA and IDA annotations for the same term. Core function of HSPA1B. Reason: Correct and consistent with IBA and IDA evidence for this core activity. |
| GO:0030308 negative regulation of cell growth | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IMP evidence from PMID:9553041 shows HSP70 is required for WT1-mediated growth inhibition. Reason: Context-dependent secondary function mediated through WT1 interaction. |
| GO:0031072 heat shock protein binding | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. Redundant with IBA and multiple IPI annotations for the same term. Well-supported by extensive co-chaperone interaction data. Reason: Correct and consistent with IBA and IPI evidence. |
| GO:0031397 negative regulation of protein ubiquitination | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IDA evidence from PMID:12150907 shows HSP70 participates in regulating ubiquitination of Pael-R in the CHIP-Parkin complex. HSP70 binding can shield substrates from ubiquitination. Reason: Experimentally supported but represents a context-dependent regulatory outcome of chaperone activity rather than a core function. |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. IPI evidence from PMID:12150907 and PMID:15603737 confirms binding to E3 ligases CHIP/STUB1, Parkin, and BAG5. This is a key part of the chaperone triage system. Reason: Core co-chaperone interaction. HSP70 binding to E3 ubiquitin ligases like STUB1/CHIP is integral to the protein quality control triage mechanism. |
| GO:0032757 positive regulation of interleukin-8 production | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IMP evidence from PMID:24790089 shows HSP70 involvement in NOD2-mediated NF-kappaB signaling, which leads to IL-8 production in response to bacterial cell wall fragments. Reason: Experimentally supported but a downstream consequence of HSP70 stabilization of NOD2, not a core chaperone function. |
| GO:0034599 cellular response to oxidative stress | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. TAS evidence from PMID:24252804 supports this annotation in the context of Parkinson disease pathogenesis. Reason: HSP70 is induced by and participates in oxidative stress response, but this is a general stress-responsive phenotype rather than a core function. |
| GO:0042026 protein refolding | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. Redundant with IBA and IDA annotations for the same term. Core function of HSPA1B. Reason: Correct and consistent with IBA and multiple IDA annotations. |
| GO:0042826 histone deacetylase binding | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. IPI evidence from PMID:16809764 confirms interaction with HDAC8, and UniProt documents interaction with HDAC4 (PMID:27708256). HDAC4 deacetylates HSP70 at Lys-77 to regulate chaperone function. Reason: Confirmed by experimental evidence. HDAC binding is functionally relevant to regulation of HSP70 chaperone activity. |
| GO:0044183 protein folding chaperone | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. Redundant with IBA and IDA for the same core molecular function. Reason: Core molecular function, confirmed by multiple evidence types. |
| GO:0045648 positive regulation of erythrocyte differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IMP evidence from PMID:17167422 shows Hsp70 protects GATA-1 from caspase-3-mediated cleavage during erythropoiesis. Reason: Experimentally supported but a tissue-specific downstream consequence of HSP70 anti-apoptotic activity rather than a core function. |
| GO:0046034 ATP metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: HSPA1B hydrolyzes ATP as part of its chaperone cycle, but ATP metabolic process is a broad biological-process term. The actual molecular activity is captured by ATP hydrolysis activity and ATP-dependent chaperone terms. Reason: This broad BP term is less informative than the molecular-function terms describing HSPA1B's ATPase-driven chaperone cycle. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. IDA evidence from PMID:10205060 and PMID:15603737 confirms perinuclear localization. Reason: Confirmed by IDA evidence. Perinuclear localization is observed particularly during stress conditions. |
| GO:0050821 protein stabilization | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. TAS evidence from PMID:24252804 supports this. PMID:24790089 directly demonstrates HSP70 stabilizes NOD2 by increasing its half-life. UniProt also describes HSP70 stabilization of ATF5 (PMID:22528486). Reason: Well-supported function. HSP70 chaperone activity inherently stabilizes client proteins, preventing misfolding and degradation. |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000117 | MODIFY | Summary: GO:0051082 (unfolded protein binding) is now formally obsolete (go-ontology#30962). This IEA annotation from ARBA machine learning models reflects the well-known ability of HSP70 chaperones to bind unfolded/misfolded proteins as substrates, but the term conflates substrate binding with the chaperone activity itself. HSPA1B is a bona fide ATP-dependent foldase chaperone that actively assists protein folding through iterative cycles of ATP hydrolysis, substrate binding, and release (PMID:21231916, PMID:24012426). The correct molecular function annotation is GO:0044183 (protein folding chaperone), which already has both IBA and IDA support for this gene product. UniProt describes HSPA1B as a "Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides" (UniProt:P0DMV9). Reason: GO:0051082 is now formally obsolete. HSPA1B does not merely bind unfolded proteins passively; it is an active ATP-dependent protein folding chaperone. The replacement term GO:0044183 (protein folding chaperone) accurately captures the molecular function and is already annotated to HSPA1B via IBA (GO_REF:0000033) and IDA (PMID:15603737) evidence. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:21231916 Overexpressed chaperones that suppressed polyQ aggregation were found not to be able to stimulate luciferase refolding. Inversely, chaperones that supported luciferase refolding were poor suppressors of polyQ aggregation. |
| GO:0055131 C3HC4-type RING finger domain binding | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. IPI evidence from PMID:25281747 confirms interaction with RNF207, a RING finger protein. HSP70 also interacts with CHIP/STUB1 which contains a U-box domain related to RING fingers. Reason: Confirmed by experimental evidence for binding to RING domain proteins. |
| GO:0070370 cellular heat acclimation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. HSPA1B is a stress-inducible HSP70 paralog, but PMID:21231916 directly reports HSPA1A protection from heat-induced cell death and warns that HSPA-family functional differences can be larger than expected. The evidence should not be treated as HSPA1B-specific proof of heat acclimation. Reason: HSPA1B likely participates in heat-stress proteostasis as an inducible HSP70, but the cited direct evidence is paralog-specific to HSPA1A/HSPA6. Keep this as non-core rather than accepting it as a demonstrated HSPA1B heat-acclimation function. |
| GO:0070434 positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IMP evidence from PMID:24790089 confirms that HSP70 binds and stabilizes NOD2, enhancing NOD2-mediated signaling in response to bacterial cell wall fragments. Reason: Experimentally supported but represents a specific downstream signaling consequence of HSP70 chaperone activity on NOD2, not a core function. |
| GO:0071383 cellular response to steroid hormone stimulus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. TAS evidence from Reactome R-HSA-3371497 documents HSP70 role in the HSP90 chaperone cycle for steroid hormone receptors. HSP70 participates in the maturation of steroid hormone receptor complexes. Reason: HSP70 participates in steroid hormone receptor maturation as part of the HSP70/HSP90 chaperone relay, but this is a general chaperone function rather than a specific steroid hormone response. |
| GO:0090063 positive regulation of microtubule nucleation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IMP evidence from PMID:27137183 confirms HSP70 is required for microtubule nucleation from the mitotic centrosome, interacting with NEDD1 and gamma-tubulin. Reason: Experimentally supported centrosome-related function during mitosis but not a core chaperone function. |
| GO:0090084 negative regulation of inclusion body assembly | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. IDA evidence from PMID:21231916 and PMID:15603737 confirms HSPA1B suppresses protein aggregation and inclusion body formation. Reason: Core chaperone function. Preventing protein aggregation and inclusion body formation is a direct consequence of HSP70 foldase activity. |
| GO:0140545 ATP-dependent protein disaggregase activity | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: IEA from ARBA models. PMID:23921388 describes METTL21A methylation and altered HSPA8/Hsc70 affinity for alpha-synuclein, not direct HSPA1B ATP-dependent disaggregase activity. The HSP70/HSP110/HSP40 system can participate in disaggregation, but this evidence is not HSPA1B-specific. Reason: This overextends family-level disaggregation biology and HSPA8-focused evidence to HSPA1B. HSPA1B's core role should be represented as ATP-dependent folding/refolding unless direct HSPA1B disaggregase evidence is available. |
| GO:1901673 regulation of mitotic spindle assembly | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IMP evidence from PMID:27137183 shows HSP70 is required for bipolar spindle assembly, and its inhibition disrupts spindle formation. Reason: Experimentally supported but represents a specific mitotic function rather than the core chaperone activity. |
| GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IMP evidence from PMID:24790089 supports HSP70 involvement in inflammatory signaling through NOD2 stabilization. Reason: Experimentally supported downstream effect of HSP70 chaperone activity on innate immune signaling components. |
| GO:1904813 ficolin-1-rich granule lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. TAS evidence from Reactome R-HSA-6800434 (exocytosis of ficolin-rich granule lumen proteins) supports this localization in neutrophils. Reason: Cell-type-specific localization in neutrophils, supported by Reactome but not a core localization for HSPA1B. |
| GO:1990904 ribonucleoprotein complex | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA models. IDA evidence from PMID:17289661 confirms HSPA1B is a component of IGF2BP1 (IMP1) mRNP granules containing untranslated mRNAs. UniProt notes this localization. Reason: Confirmed by mass spectrometry identification in mRNP granule complex. |
| GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA models. IMP evidence from PMID:17167422 shows Hsp70 protects GATA-1 from caspase-3 cleavage, preventing apoptosis during erythropoiesis. Reason: Experimentally supported anti-apoptotic function but represents a specific downstream effect of HSP70 chaperone activity. |
| GO:0005515 protein binding | IPI PMID:28298427 Systematic protein-protein interaction mapping for clinicall... | MARK AS OVER ANNOTATED | Summary: Protein binding from systematic GPCR-protein interaction mapping. HSPA1B binds many proteins as a chaperone; protein binding is uninformative. Reason: GO:0005515 protein binding is uninformative for a molecular chaperone that interacts with hundreds of substrates and co-chaperones. More specific binding terms are already annotated. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:24790089 The molecular chaperone HSP70 binds to and stabilizes NOD2, ... | KEEP AS NON CORE | Summary: PMID:24790089 demonstrates that HSP70 stabilizes NOD2, and an HSP70 inhibitor (KNK437) decreases NOD2-mediated NF-kappaB activation in response to bacterial cell wall stimulation. Reason: Experimentally well-supported but a downstream consequence of HSP70 stabilization of NOD2 rather than a core chaperone function. Supporting Evidence: PMID:24790089 an HSP70 inhibitor, KNK437, was capable of decreasing NOD2-mediated NF-kappaB activation in response to bacterial cell wall stimulation |
| GO:0070434 positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway | IMP PMID:24790089 The molecular chaperone HSP70 binds to and stabilizes NOD2, ... | KEEP AS NON CORE | Summary: PMID:24790089 shows induced HSP70 expression increases NOD2 response to bacterial cell wall fragments by stabilizing NOD2 protein. Reason: Experimentally well-supported. HSP70 enhances NOD2 signaling by increasing NOD2 stability, but this is a secondary consequence of chaperone activity. Supporting Evidence: PMID:24790089 Induced HSP70 expression in cells increased the response of NOD2 to bacterial cell wall fragments. |
| GO:0005814 centriole | IDA GO_REF:0000052 | ACCEPT | Summary: IDA from immunofluorescence curation. HSPA1B localizes to centrioles under stress conditions, consistent with its role in centrosome integrity during mitosis (PMID:24061851, PMID:27137183). Reason: Confirmed by immunofluorescence data and consistent with published literature on HSP70 centrosome function. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: IDA from immunofluorescence curation confirming cytosolic localization. Core localization for HSPA1B. Reason: Core localization confirmed by immunofluorescence. |
| GO:0071383 cellular response to steroid hormone stimulus | TAS Reactome:R-HSA-3371497 | KEEP AS NON CORE | Summary: TAS from Reactome describing HSP90 chaperone cycle for steroid hormone receptors, in which HSP70 participates by delivering client proteins to the HSP90 complex via HOP/STIP1. Reason: HSP70 participates in steroid hormone receptor maturation as part of the HSP70-HSP90 relay system, but this is a general chaperone function. |
| GO:0016887 ATP hydrolysis activity | TAS Reactome:R-HSA-3371422 | ACCEPT | Summary: TAS from Reactome entry R-HSA-3371422 describing ATP hydrolysis by HSP70. Core molecular function. Reason: Core molecular function, consistent with IBA and IDA annotations. |
| GO:0005515 protein binding | IPI PMID:33857403 DNAJC9 integrates heat shock molecular chaperones into the h... | MARK AS OVER ANNOTATED | Summary: PMID:33857403 demonstrates DNAJC9 interacts with HSP70 to integrate heat shock chaperones into the histone chaperone network. The specific interaction is with DNAJC9 via J domain. Reason: GO:0005515 protein binding is uninformative. The specific interaction with DNAJC9 is better captured by heat shock protein binding (GO:0031072). |
| GO:0140545 ATP-dependent protein disaggregase activity | IDA PMID:23921388 Identification and characterization of a novel human methylt... | REMOVE | Summary: PMID:23921388 characterizes METTL21A methylation and altered HSPA8/Hsc70 affinity for alpha-synuclein fibrils. It does not provide direct HSPA1B ATP-dependent protein disaggregase evidence. Reason: The cited IDA evidence is mismatched for HSPA1B and should not be accepted as HSPA1B-specific disaggregase activity. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | REMOVE | Summary: PMID:21231916 directly demonstrates J-protein-stimulated intrinsic ATPase activity for HSPA1A and HSPA6, but it does not provide direct HSPA1B-specific ATPase evidence. Reason: The cited IDA evidence is paralog-specific and should not be accepted as direct HSPA1B ATP hydrolysis activity. Supporting Evidence: PMID:21231916 HSPA6 has a functional substrate-binding domain and possesses intrinsic ATPase activity that is as high as that of the canonical HSPA1A when stimulated by J-proteins. |
| GO:0005634 nucleus | IDA PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | ACCEPT | Summary: PMID:17167422 shows Hsp70 localizes to the nucleus where it protects GATA-1 from caspase-3 cleavage during erythropoiesis. Reason: Nuclear localization confirmed by direct assay in the context of erythropoiesis studies. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | KEEP AS NON CORE | Summary: PMID:17167422 demonstrates Hsp70 prevents caspase-3-mediated cleavage of GATA-1, thereby inhibiting apoptosis during erythroid differentiation. Reason: Well-established anti-apoptotic function of HSP70 but represents a downstream consequence of chaperone activity rather than core function. |
| GO:0045648 positive regulation of erythrocyte differentiation | IMP PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | KEEP AS NON CORE | Summary: PMID:17167422 shows Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1, a key erythroid transcription factor. Reason: Experimentally supported tissue-specific function but not a core chaperone activity. |
| GO:0005515 protein binding | IPI PMID:27133716 A novel nuclear DnaJ protein, DNAJC8, can suppress the forma... | MARK AS OVER ANNOTATED | Summary: PMID:27133716 shows DNAJC8 interacts with HSP70. This is a specific co-chaperone interaction better captured by heat shock protein binding. Reason: GO:0005515 protein binding is uninformative. The DNAJC8 interaction is better captured by GO:0031072 (heat shock protein binding). |
| GO:0005515 protein binding | IPI PMID:23349634 A newly uncovered group of distantly related lysine methyltr... | MARK AS OVER ANNOTATED | Summary: PMID:23349634 identifies lysine methyltransferases that interact with molecular chaperones including HSP70. Protein binding is uninformative. Reason: GO:0005515 protein binding is uninformative for a chaperone. |
| GO:0032991 protein-containing complex | IDA PMID:23349634 A newly uncovered group of distantly related lysine methyltr... | ACCEPT | Summary: PMID:23349634 demonstrates HSP70 exists in complexes with lysine methyltransferases. HSP70 participates in many protein complexes as part of its chaperone function. Reason: HSP70 is found in multiple protein complexes as part of its chaperone and co-chaperone machinery. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | KEEP AS NON CORE | Summary: PMID:22658674 (Castello et al. 2012) is a large-scale mRNA interactome capture study identifying mRNA-binding proteins. HSPA1B was identified as an mRNA-binding protein. This is consistent with its role in mRNP granules (PMID:17289661). Reason: High-throughput data supports RNA binding. HSP70 association with mRNP granules is documented but RNA binding is not a core chaperone function. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | KEEP AS NON CORE | Summary: PMID:22681889 (Baltz et al. 2012) is another large-scale mRNA-bound proteome study confirming HSPA1B as an mRNA-associated protein. Reason: Consistent with other high-throughput data but RNA binding is not a core function of HSPA1B. |
| GO:0005515 protein binding | IPI PMID:15671022 Heat shock protein 70 inhibits alpha-synuclein fibril format... | MARK AS OVER ANNOTATED | Summary: PMID:15671022 shows HSP70 binds alpha-synuclein prefibrillar species, inhibiting fibril formation. This reflects chaperone substrate binding. Reason: GO:0005515 protein binding is uninformative. The alpha-synuclein interaction reflects chaperone substrate binding already captured by protein folding chaperone (GO:0044183). |
| GO:0005515 protein binding | IPI PMID:18975920 Interactions between Hsp70 and the hydrophobic core of alpha... | MARK AS OVER ANNOTATED | Summary: PMID:18975920 demonstrates Hsp70 interactions with alpha-synuclein hydrophobic core inhibit fibril assembly. Chaperone substrate binding. Reason: GO:0005515 protein binding is uninformative for a molecular chaperone. |
| GO:0005515 protein binding | IPI PMID:21081504 ChChd3, an inner mitochondrial membrane protein, is essentia... | MARK AS OVER ANNOTATED | Summary: PMID:21081504 identifies interaction between HSPA1B and ChChd3/CHCHD3, an inner mitochondrial membrane protein. UniProt confirms this interaction. Reason: GO:0005515 protein binding is uninformative for a molecular chaperone. |
| GO:0005515 protein binding | IPI PMID:9553041 Inhibition of cellular proliferation by the Wilms tumor supp... | MARK AS OVER ANNOTATED | Summary: PMID:9553041 shows HSP70 interaction with WT1 is required for WT1-mediated growth inhibition. Reason: GO:0005515 protein binding is uninformative for a molecular chaperone. |
| GO:0005634 nucleus | IDA PMID:10205060 Control of mRNA decay by heat shock-ubiquitin-proteasome pat... | ACCEPT | Summary: PMID:10205060 shows hsp70 sequesters AUF1 in the perinucleus-nucleus during heat shock, confirming nuclear localization. Reason: Direct experimental evidence for nuclear localization during stress. Supporting Evidence: PMID:10205060 Induction of hsp70 by heat shock, down-regulation of the ubiquitin-proteasome network, or inactivation of ubiquitinating enzyme E1 all result in hsp70 sequestration of AUF1 in the perinucleus-nucleus |
| GO:0005737 cytoplasm | IDA PMID:10859165 Chaperone hsp27 inhibits translation during heat shock by bi... | ACCEPT | Summary: PMID:10859165 documents cytoplasmic localization of HSP70 in the context of translation regulation during heat shock. Reason: Core localization confirmed by direct assay. |
| GO:0005737 cytoplasm | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | ACCEPT | Summary: TAS from proteomics study PMID:16130169 identifying HSPA1B among 162 proteins in human endothelial cells. Reason: Core localization. |
| GO:0005737 cytoplasm | IDA PMID:24061851 Stress-induced localization of HSPA6 (HSP70B') and HSPA1A (H... | REMOVE | Summary: PMID:24061851 documents cytoplasmic and centriolar localization of HSPA1A and HSPA6 under stress conditions, not HSPA1B. Reason: The cited IDA evidence does not support HSPA1B-specific cytoplasmic localization. |
| GO:0005737 cytoplasm | IDA PMID:9553041 Inhibition of cellular proliferation by the Wilms tumor supp... | ACCEPT | Summary: PMID:9553041 shows cytoplasmic localization of HSP70 in the context of WT1 interaction studies. Reason: Core localization confirmed by direct assay. |
| GO:0005739 mitochondrion | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | KEEP AS NON CORE | Summary: TAS from proteomics study. HSPA1B is primarily cytosolic but has been detected in mitochondrial fractions. UniProt lists mitochondrion as a TAS localization. HSP70 participates in mitochondrial protein import. Reason: Supported by proteomics data but mitochondrial localization is not a primary site for HSPA1B. Note that HSPA9/mortalin is the dedicated mitochondrial HSP70. |
| GO:0005783 endoplasmic reticulum | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | KEEP AS NON CORE | Summary: TAS from proteomics study. HSPA1B has been detected in ER fractions. HSP70 participates in ER stress response and ERAD. Note that HSPA5/BiP is the dedicated ER HSP70. Reason: Detected in ER fractions but HSPA1B is primarily cytosolic. HSPA5/BiP is the dedicated ER-resident HSP70. |
| GO:0006402 mRNA catabolic process | IDA PMID:10205060 Control of mRNA decay by heat shock-ubiquitin-proteasome pat... | KEEP AS NON CORE | Summary: PMID:10205060 directly demonstrates HSP70 role in AU-rich element-mediated mRNA decay through regulation of AUF1 localization and ubiquitination. Reason: Experimentally well-supported but a secondary function of HSP70 rather than its core chaperone activity. Supporting Evidence: PMID:10205060 Rapid decay involves AU-rich binding protein AUF1, which complexes with heat shock proteins hsc70-hsp70, translation initiation factor eIF4G, and poly(A) binding protein. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:9553041 Inhibition of cellular proliferation by the Wilms tumor supp... | KEEP AS NON CORE | Summary: PMID:9553041 shows HSP70 association with WT1 is required for WT1-mediated inhibition of cellular proliferation. Reason: Context-dependent secondary function mediated through WT1 interaction. |
| GO:0016235 aggresome | IDA PMID:15885686 TRIM37 defective in mulibrey nanism is a novel RING finger u... | ACCEPT | Summary: PMID:15885686 shows TRIM37 forms aggresomes that are chaperone-positive, indicating HSP70 recruitment to aggresomes. Consistent with HSP70 role in protein quality control at aggresomes. Reason: Direct evidence for aggresome localization, consistent with protein quality control function. |
| GO:0016607 nuclear speck | IDA PMID:9553041 Inhibition of cellular proliferation by the Wilms tumor supp... | KEEP AS NON CORE | Summary: PMID:9553041 shows HSP70 localization to nuclear speckles in the context of WT1 interaction studies. Reason: Experimentally confirmed but a specific subnuclear localization that is context-dependent. |
| GO:0030308 negative regulation of cell growth | IMP PMID:9553041 Inhibition of cellular proliferation by the Wilms tumor supp... | KEEP AS NON CORE | Summary: PMID:9553041 demonstrates HSP70 is required for WT1-mediated growth inhibition. Reason: Context-dependent secondary function mediated through WT1 interaction. |
| GO:0031982 vesicle | HDA PMID:19190083 Characterization of exosome-like vesicles released from huma... | KEEP AS NON CORE | Summary: PMID:19190083 characterizes exosome-like vesicles from human tracheobronchial ciliated epithelium, identifying HSPA1B. Reason: High-throughput proteomics data. Vesicle localization is a secondary feature, not core localization. |
| GO:0043066 negative regulation of apoptotic process | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | KEEP AS NON CORE | Summary: TAS from proteomics study describing HSPA1B in context of endothelial cell resistance to etoposide-induced apoptosis. Reason: Anti-apoptotic function is well-established for HSP70 but represents a downstream consequence of chaperone activity. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:10205060 Control of mRNA decay by heat shock-ubiquitin-proteasome pat... | ACCEPT | Summary: PMID:10205060 demonstrates that hsp70 sequesters AUF1 in the perinucleus-nucleus during heat shock, confirming perinuclear localization of HSP70 by direct assay. Reason: Confirmed by direct experimental evidence. Perinuclear localization is observed during stress conditions when HSP70 participates in mRNA decay regulation through AUF1 sequestration. Supporting Evidence: PMID:10205060 Induction of hsp70 by heat shock, down-regulation of the ubiquitin-proteasome network, or inactivation of ubiquitinating enzyme E1 all result in hsp70 sequestration of AUF1 in the perinucleus-nucleus |
| GO:0051082 unfolded protein binding | TAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | MODIFY | Summary: GO:0051082 (unfolded protein binding) is now formally obsolete (go-ontology#30962). This TAS annotation references PMID:16130169 (Bruneel et al. 2005), a proteomics study of human umbilical vein endothelial cells during etoposide-induced apoptosis. The study identified HSPA1B among 162 proteins and discusses functions related to "protein folding" in the context of endothelial cell biology. The paper does not specifically characterize HSPA1B unfolded protein binding activity but rather identifies it in the context of broader chaperone-related functions. HSPA1B is a well-established ATP-dependent foldase chaperone and the correct molecular function term is GO:0044183 (protein folding chaperone). Reason: GO:0051082 is now formally obsolete. The referenced paper (PMID:16130169) is a proteomics study that does not specifically demonstrate unfolded protein binding activity for HSPA1B but identifies it among proteins with chaperone-related functions. HSPA1B is an established protein folding chaperone whose primary molecular function is actively assisting protein folding through ATP-dependent cycles, not merely binding unfolded substrates. The replacement term GO:0044183 is already supported by direct experimental evidence (IDA, PMID:15603737) and phylogenetic inference (IBA, GO_REF:0000033). Proposed replacements: protein folding chaperone Supporting Evidence: PMID:16130169 The overall functional characterization of the 162 identified proteins from primary cultures of HUVECs confirms the metabolic capabilities of endothelium and illustrates various cellular functions more related to cell motility and angiogenesis, protein folding, anti-oxidant defenses, signal transduction, proteasome pathway and resistance to apoptosis. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: PMID:19199708 is a proteomic analysis of human parotid gland exosomes identifying HSPA1B among exosome proteins. HSP70 is a commonly identified exosomal protein, consistent with extracellular release as described in reviews of eHsp70 biology. Reason: High-throughput proteomics data. Exosomal localization of HSP70 is well-documented but represents a non-core secondary localization. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: PMID:20458337 identifies MHC class II-associated proteins in B-cell exosomes, including HSPA1B. Consistent with known exosomal release of HSP70 family members. Reason: High-throughput proteomics data. Exosomal localization is a secondary, non-core feature of HSPA1B. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: PMID:23533145 identifies HSPA1B in exosomes isolated from expressed prostatic secretions in urine. Consistent with known exosomal HSP70 release from various cell types. Reason: High-throughput proteomics data. Exosomal localization is non-core. |
| GO:1990904 ribonucleoprotein complex | IDA PMID:17289661 Molecular composition of IMP1 ribonucleoprotein granules. | ACCEPT | Summary: PMID:17289661 identifies HSPA1B as a component of IGF2BP1 (IMP1) mRNP granules containing untranslated mRNAs by mass spectrometry. UniProt confirms this localization (ECO:0000269|PubMed:17289661). Reason: Confirmed by mass spectrometry identification in mRNP granule complex. Consistent with known HSP70 association with RNA granules. |
| GO:0005515 protein binding | IPI PMID:24318877 Binding of human nucleotide exchange factors to heat shock p... | MARK AS OVER ANNOTATED | Summary: PMID:24318877 (Rauch and Gestwicki 2014) characterizes how binding of human nucleotide exchange factors (BAG1, BAG2, BAG3, HSPH1) to Hsp70 generates functionally distinct complexes. The protein binding annotation is uninformative for a chaperone with many specific co-chaperone interactions. Reason: GO:0005515 protein binding is uninformative for a molecular chaperone. The specific interactions with NEFs are better captured by heat shock protein binding (GO:0031072) already annotated. |
| GO:0005515 protein binding | IPI PMID:27137183 HSP70 regulates the function of mitotic centrosomes. | MARK AS OVER ANNOTATED | Summary: PMID:27137183 shows HSP70 interacts with NEDD1 and gamma-tubulin at the mitotic centrosome. Protein binding is uninformative for a chaperone that interacts with many client proteins. Reason: GO:0005515 protein binding is uninformative for a molecular chaperone. The specific NEDD1 interaction is in the context of centrosome function already captured by more specific annotations. |
| GO:0005515 protein binding | IPI PMID:27708256 ARD1-mediated Hsp70 acetylation balances stress-induced prot... | MARK AS OVER ANNOTATED | Summary: PMID:27708256 demonstrates specific interactions between Hsp70 and NAA10 (ARD1), HDAC4, HOPX, STUB1, HSP40, and HSP90 in the context of acetylation-regulated chaperone switching. Protein binding is uninformative for a chaperone with many well-characterized co-chaperone interactions. Reason: GO:0005515 protein binding is uninformative. The specific interactions with HDAC4, STUB1, HOPX etc. are better captured by more specific MF terms already annotated (e.g., histone deacetylase binding, ubiquitin protein ligase binding, heat shock protein binding). |
| GO:0005813 centrosome | IDA PMID:27137183 HSP70 regulates the function of mitotic centrosomes. | ACCEPT | Summary: PMID:27137183 directly demonstrates that HSP70 accumulates at the mitotic centrosome during prometaphase to metaphase by immunofluorescence. UniProt confirms this localization (ECO:0000269|PubMed:27137183). Reason: Confirmed by direct assay showing centrosome accumulation during mitosis. HSP70 is required for centrosome integrity and bipolar spindle assembly. Supporting Evidence: PMID:27137183 heat shock protein (HSP) 70 considerably accumulates at the mitotic centrosome during prometaphase to metaphase and is required for bipolar spindle assembly |
| GO:0042026 protein refolding | IMP PMID:27708256 ARD1-mediated Hsp70 acetylation balances stress-induced prot... | ACCEPT | Summary: PMID:27708256 demonstrates that acetylated Hsp70 binds HOPX to facilitate protein refolding during the early stress response. K77R mutation impairs refolding capacity. Core biological process. Reason: Protein refolding is a core function of HSPA1B, confirmed by direct demonstration that the acetylation state regulates the refolding vs degradation switch. Supporting Evidence: PMID:27708256 During the early stress response, Hsp70 is immediately acetylated by ARD1 at K77, and the acetylated Hsp70 binds to the co-chaperone Hop to allow protein refolding |
| GO:0090063 positive regulation of microtubule nucleation | IMP PMID:27137183 HSP70 regulates the function of mitotic centrosomes. | KEEP AS NON CORE | Summary: PMID:27137183 demonstrates that inhibition or depletion of HSP70 impaired microtubule nucleation and polymerization from the spindle pole. HSP70 associates with NEDD1 and gamma-tubulin, two PCM components essential for MT nucleation. Reason: Experimentally well-supported centrosome-related function during mitosis but not a core chaperone function. Supporting Evidence: PMID:27137183 Inhibition or depletion of HSP70 impaired the function of mitotic centrosome and disrupted MT nucleation and polymerization from the spindle pole |
| GO:1901673 regulation of mitotic spindle assembly | IMP PMID:27137183 HSP70 regulates the function of mitotic centrosomes. | KEEP AS NON CORE | Summary: PMID:27137183 shows HSP70 is required for bipolar spindle assembly. Its inhibition disrupts spindle formation and may result in formation of abnormal mitotic spindles. Reason: Experimentally supported but represents a specific mitotic function rather than the core chaperone activity. Supporting Evidence: PMID:27137183 HSP70 is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: TAS from Reactome R-HSA-6800434 (exocytosis of ficolin-rich granule lumen proteins) describing release of HSP70 into the extracellular space during neutrophil degranulation. HSP70 is known to be released extracellularly via exosomes and neutrophil granules. Reason: Extracellular localization is supported by Reactome and proteomics data but is a secondary, cell-type-specific feature. |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: TAS from Reactome R-HSA-6800434 describing HSP70 in ficolin-rich granule lumen of neutrophils. Cell-type-specific localization in neutrophils. Reason: Cell-type-specific localization in neutrophils, supported by Reactome but not a core localization for HSPA1B. |
| GO:0032757 positive regulation of interleukin-8 production | IMP PMID:24790089 The molecular chaperone HSP70 binds to and stabilizes NOD2, ... | KEEP AS NON CORE | Summary: PMID:24790089 shows induced HSP70 expression increases NOD2 response to bacterial cell wall fragments, which leads to NF-kappaB-dependent IL-8 production. HSP70 stabilizes NOD2 protein, enhancing its signaling capacity. Reason: Experimentally supported downstream consequence of HSP70 stabilization of NOD2, not a core chaperone function. Supporting Evidence: PMID:24790089 Induced HSP70 expression in cells increased the response of NOD2 to bacterial cell wall fragments |
| GO:0031396 regulation of protein ubiquitination | IDA PMID:16809764 Histone deacetylase 8 safeguards the human ever-shorter telo... | KEEP AS NON CORE | Summary: PMID:16809764 shows that phosphorylated HDAC8 recruits Hsp70 to a complex that inhibits CHIP E3 ligase-mediated degradation of hEST1B. HSP70 participates in regulating ubiquitination of client proteins through its interaction with CHIP/STUB1. Reason: Experimentally supported regulation of ubiquitination in the context of HDAC8-mediated hEST1B stabilization. This is a specific downstream consequence of HSP70 chaperone-E3 ligase interaction rather than core function. Supporting Evidence: PMID:16809764 Phosphorylated HDAC8 preferentially recruits Hsp70 to a complex that inhibits the CHIP (C-terminal heat shock protein interacting protein) E3 ligase-mediated degradation of hEST1B |
| GO:0042826 histone deacetylase binding | IPI PMID:16809764 Histone deacetylase 8 safeguards the human ever-shorter telo... | ACCEPT | Summary: PMID:16809764 confirms interaction between HSP70 and HDAC8. Phosphorylated HDAC8 recruits Hsp70 to a complex. UniProt also documents interaction with HDAC4 (PMID:27708256), which deacetylates Hsp70 at Lys-77 to regulate chaperone function. Reason: Confirmed by experimental evidence from multiple studies. HDAC binding is functionally relevant to regulation of HSP70 chaperone activity through acetylation/deacetylation of Lys-77. Supporting Evidence: PMID:16809764 Phosphorylated HDAC8 preferentially recruits Hsp70 to a complex that inhibits the CHIP (C-terminal heat shock protein interacting protein) E3 ligase-mediated degradation of hEST1B |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3371467 | ACCEPT | Summary: TAS from Reactome R-HSA-3371467 (SIRT1 deacetylates HSF1) describing HSP70 involvement in the nucleoplasm during HSF1-mediated heat shock response regulation. HSP70 shuttles to the nucleus during stress via Hikeshi-mediated import. Reason: Nucleoplasm localization is consistent with HSP70 nuclear functions during the heat shock response, particularly in HSF1 regulation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3371518 | ACCEPT | Summary: TAS from Reactome R-HSA-3371518 (SIRT1 binds to HSF1) describing nucleoplasmic localization of HSP70 in the context of HSF1 regulation. Redundant with other nucleoplasm TAS annotations. Reason: Consistent with established HSP70 nuclear localization during stress. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3371554 | ACCEPT | Summary: TAS from Reactome R-HSA-3371554 (HSF1 acetylation at Lys80) describing nucleoplasmic localization of HSP70 during the heat shock response attenuation phase. Reason: Consistent with established HSP70 nuclear localization during stress and its role in HSF1 regulation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5082356 | ACCEPT | Summary: TAS from Reactome R-HSA-5082356 (HSF1-mediated gene expression) describing nucleoplasmic localization of HSP70 during HSF1-dependent transactivation. HSP70 feeds back on HSF1 to attenuate the heat shock response. Reason: Consistent with nucleoplasmic localization during HSF1 regulation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5082369 | ACCEPT | Summary: TAS from Reactome R-HSA-5082369 (acetylated HSF1 dissociates from DNA) describing HSP70 nucleoplasmic role in HSF1 attenuation. Reason: Consistent with established nucleoplasmic localization of HSP70 during stress response regulation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5082384 | ACCEPT | Summary: TAS from Reactome R-HSA-5082384 (HSP70:DNAJB1 binds HSF1) describing HSP70 nucleoplasmic function in the attenuation phase of the heat shock response, where HSP70 with DNAJB1 binds to HSF1 to suppress transcription. Reason: Core nuclear function of HSP70 in regulating HSF1. This is a well-established feedback mechanism. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5251955 | ACCEPT | Summary: TAS from Reactome R-HSA-5251955 (HSP40s activate intrinsic ATPase activity of HSP70s in the nucleoplasm) describing nucleoplasmic HSP70 ATPase cycle driven by J-domain proteins. Reason: Consistent with HSP70 functioning in the nucleoplasm during stress. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5252041 | ACCEPT | Summary: TAS from Reactome R-HSA-5252041 (NPC transports Hikeshi:HSP70s:ATP from cytosol to nucleoplasm) describing Hikeshi-mediated nuclear import of HSP70 during heat shock. Reason: Consistent with the established Hikeshi-dependent HSP70 nuclear import mechanism under stress conditions. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3371422 | ACCEPT | Summary: TAS from Reactome R-HSA-3371422 (ATP hydrolysis by HSP70) describing cytosolic HSP70 ATPase activity. Core localization for HSPA1B. Reason: Core localization. Cytosol is the primary site of HSP70 chaperone activity, consistent with IBA and IDA annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3371503 | ACCEPT | Summary: TAS from Reactome R-HSA-3371503 (STIP1/HOP binds HSP90 and HSP70:HSP40:nascent protein) describing cytosolic HSP70 in the HSP70-HSP90 chaperone relay. Reason: Core localization. Cytosolic HSP70-HSP90 relay is a well-established chaperone pathway. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3371590 | ACCEPT | Summary: TAS from Reactome R-HSA-3371590 (HSP70 binds to HSP40:nascent protein) describing cytosolic HSP70 initial substrate engagement. Reason: Core localization. HSP70 engagement with HSP40-bound nascent proteins occurs in the cytosol. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5251942 | ACCEPT | Summary: TAS from Reactome R-HSA-5251942 (Hikeshi binds HSP70s:ATP) describing cytosolic HSP70:ATP binding to Hikeshi for nuclear import during heat stress. Reason: Core localization. HSP70 is cytosolic prior to Hikeshi-mediated nuclear transport. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5251959 | ACCEPT | Summary: TAS from Reactome R-HSA-5251959 (HSP40s activate intrinsic ATPase activity of HSP70s in the cytosol) describing cytosolic HSP70 ATPase cycle activation by J-domain proteins. Reason: Core localization. Cytosolic chaperone cycle activation is a central function of HSP70. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5252041 | ACCEPT | Summary: TAS from Reactome R-HSA-5252041 (NPC transports Hikeshi:HSP70s:ATP from cytosol to nucleoplasm) describing cytosolic origin of HSP70 prior to nuclear import. Reason: Core localization. HSP70 is cytosolic prior to nuclear import. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5252079 | ACCEPT | Summary: TAS from Reactome R-HSA-5252079 (HSP110s exchange ATP for ADP on HSP70s:ADP) describing cytosolic nucleotide exchange on HSP70 by HSP110 nucleotide exchange factors. Reason: Core localization. NEF-mediated nucleotide exchange occurs in the cytosol as part of the chaperone cycle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5618085 | ACCEPT | Summary: TAS from Reactome R-HSA-5618085 (FKBP4 binds HSP90:ATP:STIP1:HSP70: nascent protein) describing cytosolic HSP70 in the HSP90 chaperone cycle for steroid hormone receptors. Reason: Core localization. Cytosolic HSP70 participates in HSP90 chaperone relay for client protein maturation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5618098 | ACCEPT | Summary: TAS from Reactome R-HSA-5618098 (p23/PTGES3 binds HSP90:ATP:FKBP5: nascent protein) describing cytosolic localization of HSP70 during HSP90 chaperone cycle. Reason: Core localization in the cytosol during HSP90 chaperone cycle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5618105 | ACCEPT | Summary: TAS from Reactome R-HSA-5618105 (FKBP5 binds HSP90:ATP:STIP1:HSP70: nascent protein) describing cytosolic HSP70 in HSP90 chaperone cycle. Reason: Core localization in the cytosol. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5618107 | ACCEPT | Summary: TAS from Reactome R-HSA-5618107 (ATP binding to HSP90 triggers conformation change) describing cytosolic localization of HSP70 in the context of HSP90 chaperone machinery. Reason: Core localization in the cytosol. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5618110 | ACCEPT | Summary: TAS from Reactome R-HSA-5618110 (p23/PTGES3 binds HSP90:ATP:FKBP4: nascent protein) describing cytosolic localization of HSP70 during HSP90 chaperone cycle maturation steps. Reason: Core localization in the cytosol. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835411 | ACCEPT | Summary: TAS from Reactome R-HSA-9835411 (FA core complex:HSP70s binds PKR) describing cytosolic HSP70 involvement in PKR-mediated signaling. Reason: Core localization in the cytosol. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9857076 | ACCEPT | Summary: TAS from Reactome R-HSA-9857076 (oxidized DNAJA1 binds HSPA1A,B displacing HSF1) describing cytosolic HSP70 involved in redox-sensitive HSF1 regulation. Reason: Core localization in the cytosol. |
| GO:0005515 protein binding | IPI PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | MARK AS OVER ANNOTATED | Summary: PMID:22528486 identifies HSP70 as an ATF5-interacting protein. NPM1 displaces HSP70 from ATF5, leading to ATF5 degradation. The HSP70-ATF5 interaction reflects chaperone client stabilization. Protein binding is uninformative for a chaperone. Reason: GO:0005515 protein binding is uninformative for a molecular chaperone. The ATF5 interaction is a specific client stabilization function better captured by protein stabilization (GO:0050821) already annotated. Supporting Evidence: PMID:22528486 NPM1 interaction with ATF5 displaces HSP70, a known ATF5-interacting protein, from ATF5 protein complexes and antagonizes its role in stabilization of ATF5 protein |
| GO:0055131 C3HC4-type RING finger domain binding | IPI PMID:25281747 RING finger protein RNF207, a novel regulator of cardiac exc... | ACCEPT | Summary: PMID:25281747 demonstrates that coexpression of RNF207 and HSP70 increases HERG expression in a heat shock protein-dependent manner. RNF207 is a RING finger protein that interacts with HSP70 via its C-terminus. Reason: Confirmed by experimental evidence showing HSP70 interaction with the RING finger protein RNF207 to regulate HERG trafficking. Supporting Evidence: PMID:25281747 coexpression of RNF207 and HSP70 increased HERG expression compared with HSP70 alone. This effect was dependent on the C terminus of RNF207 |
| GO:0031072 heat shock protein binding | IPI PMID:17182002 HDJC9, a novel human type C DnaJ/HSP40 member interacts with... | ACCEPT | Summary: PMID:17182002 shows DNAJC9 (HDJC9), a novel type C DnaJ/HSP40 member, interacts with and cochaperones HSP70 through the J domain. DNAJC9 activates the ATPase activity of HSP70. Reason: Core co-chaperone interaction. J-domain protein (DNAJC9) binding to HSP70 is fundamental to the chaperone cycle. Supporting Evidence: PMID:17182002 HDJC9 can interact with HSP70s and activate the ATPase activity of HSP70s, both of which are dependent on the J domain |
| GO:0001664 G protein-coupled receptor binding | IDA PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | MARK AS OVER ANNOTATED | Summary: PMID:12150907 shows CHIP, Hsp70, Parkin, and unfolded Pael-R (an orphan GPCR) form a complex. Hsp70 binds Pael-R as a chaperone substrate, not as a GPCR signaling partner. Reason: While HSPA1B does bind the GPCR Pael-R, this is in the context of chaperone-substrate interaction for an unfolded receptor, not GPCR signaling. The term implies specific binding to GPCRs as signaling partners. Supporting Evidence: PMID:12150907 CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo |
| GO:0031397 negative regulation of protein ubiquitination | IDA PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | KEEP AS NON CORE | Summary: PMID:12150907 demonstrates that Hsp70 binding to Pael-R can shield the substrate from ubiquitination. CHIP promotes dissociation of Hsp70 from the complex, facilitating Parkin-mediated ubiquitination. HSP70 thus negatively regulates ubiquitination by sequestering substrates from E3 ligases. Reason: Experimentally supported but represents a context-dependent regulatory outcome of chaperone activity on substrate triage. Supporting Evidence: PMID:12150907 CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | ACCEPT | Summary: PMID:12150907 demonstrates that Hsp70 forms a complex with CHIP (an E3 ubiquitin ligase) and Parkin (an E3 ubiquitin ligase) in the context of Pael-R ubiquitination. HSP70 directly binds E3 ligases as part of its chaperone triage function. Reason: Core co-chaperone interaction. HSP70 binding to E3 ubiquitin ligases like CHIP/STUB1 and Parkin is integral to the protein quality control triage mechanism. Supporting Evidence: PMID:12150907 CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo |
| GO:0034599 cellular response to oxidative stress | TAS PMID:24252804 The role of oxidative stress in Parkinson's disease. | KEEP AS NON CORE | Summary: TAS from PMID:24252804 (a review of the role of oxidative stress in Parkinson disease pathogenesis) supporting HSP70 involvement in oxidative stress response. HSP70 is induced by and participates in oxidative stress response. Reason: HSP70 is induced by and participates in oxidative stress response, but this is a general stress-responsive phenotype rather than a core chaperone function. |
| GO:0050821 protein stabilization | TAS PMID:24252804 The role of oxidative stress in Parkinson's disease. | ACCEPT | Summary: TAS from PMID:24252804 supporting HSP70 protein stabilization function in the context of Parkinson disease. HSP70 chaperone activity inherently stabilizes client proteins. PMID:24790089 directly demonstrates HSP70 stabilizes NOD2 by increasing its half-life. Reason: Well-supported core function. HSP70 chaperone activity inherently stabilizes client proteins, preventing misfolding and degradation. |
| GO:0051082 unfolded protein binding | NAS PMID:12150907 CHIP is associated with Parkin, a gene responsible for famil... | MODIFY | Summary: GO:0051082 (unfolded protein binding) is now formally obsolete (go-ontology#30962). This NAS annotation references PMID:12150907 (Imai et al. 2002), which describes how CHIP, Hsp70, Parkin, and unfolded Pael receptor (Pael-R) form a complex involved in ER stress-related ubiquitination. The paper demonstrates that Hsp70 participates in a chaperone-E3 ligase complex facilitating ubiquitination of the unfolded substrate Pael-R, consistent with Hsp70 functioning as a protein folding chaperone that triages substrates between refolding and degradation pathways. HSPA1B is an ATP-dependent foldase chaperone and the correct replacement term is GO:0044183 (protein folding chaperone). Reason: GO:0051082 is now formally obsolete. The referenced paper (PMID:12150907) describes Hsp70 participating in a complex with CHIP and Parkin for ubiquitination of unfolded Pael-R, which reflects Hsp70 chaperone triage function rather than simple unfolded protein binding. HSPA1B is an active ATP-dependent protein folding chaperone whose substrate binding is coupled to its ATPase cycle. GO:0044183 (protein folding chaperone) correctly captures the molecular function. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:12150907 CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. |
| GO:0005814 centriole | IDA PMID:24061851 Stress-induced localization of HSPA6 (HSP70B') and HSPA1A (H... | REMOVE | Summary: PMID:24061851 documents stress-induced localization of HSPA1A and HSPA6 to centrioles in human neuronal cells, but it does not test HSPA1B. Reason: The cited IDA evidence is not HSPA1B-specific and should not be accepted for HSPA1B centriole localization. |
| GO:0005829 cytosol | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | ACCEPT | Summary: PMID:21231916 (Hageman et al. 2011) characterized HSP70 family members in the cytosol, demonstrating cytosolic chaperone activities including luciferase refolding and polyQ aggregation suppression. Reason: Core localization confirmed by direct assay. Cytosol is the primary site of HSP70 chaperone function. |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Summary: PMID:21423176 is a proteomic analysis of the myosin-II-responsive focal adhesion proteome that identified HSPA1B among focal adhesion proteins. Reason: High-throughput proteomics data. Focal adhesion localization is a secondary, context-dependent feature, not a core localization for HSP70. |
| GO:0031072 heat shock protein binding | IPI PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | UNDECIDED | Summary: PMID:21231916 demonstrates functional interactions between HSP70-family proteins and J-domain co-chaperones, but the local supporting excerpt specifically names HSPA6 and HSPA1A rather than HSPA1B. Reason: HSP70-HSP40 interactions are fundamental to the chaperone cycle, but the available local evidence does not resolve HSPA1B-specific IPI support for this source. Supporting Evidence: PMID:21231916 HSPA6 has a functional substrate-binding domain and possesses intrinsic ATPase activity that is as high as that of the canonical HSPA1A when stimulated by J-proteins |
| GO:0034605 cellular response to heat | IDA PMID:24061851 Stress-induced localization of HSPA6 (HSP70B') and HSPA1A (H... | REMOVE | Summary: PMID:24061851 demonstrates stress-induced localization changes of HSPA1A and HSPA6 to centrioles in human neuronal cells, but it does not test HSPA1B. Reason: The cited IDA evidence is not HSPA1B-specific and should not be accepted as direct cellular response to heat for HSPA1B. |
| GO:0042026 protein refolding | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | REMOVE | Summary: PMID:21231916 reports HSPA1A-associated luciferase refolding activity, but the available local evidence does not establish this as an HSPA1B-specific IDA result. Reason: The cited IDA evidence should not be accepted as direct HSPA1B protein refolding evidence. HSPA1B refolding/chaperone function is represented by better-supported chaperone annotations. Supporting Evidence: PMID:21231916 Overexpressed chaperones that suppressed polyQ aggregation were found not to be able to stimulate luciferase refolding. Inversely, chaperones that supported luciferase refolding were poor suppressors of polyQ aggregation |
| GO:0051082 unfolded protein binding | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | REMOVE | Summary: GO:0051082 (unfolded protein binding) is now formally obsolete (go-ontology#30962). This IDA annotation references PMID:21231916 (Hageman et al. 2011), a key study that systematically compared chaperone activities of mammalian HSP70 family members. The study demonstrated HSPA1A and HSPA6 activities but did not directly test HSPA1B for this annotation. While HSP70 proteins bind heat-denatured substrates, this binding is intrinsically coupled to the ATP-dependent chaperone folding cycle. The correct molecular function term is GO:0044183 (protein folding chaperone), which captures the active chaperone function rather than the passive substrate-binding aspect that GO:0051082 implies. Reason: GO:0051082 is now formally obsolete, and the cited PMID:21231916 evidence is not HSPA1B-specific. HSPA1B's chaperone function is already represented by GO:0044183 from better-supported annotations. Supporting Evidence: PMID:21231916 HSPA6 has a functional substrate-binding domain and possesses intrinsic ATPase activity that is as high as that of the canonical HSPA1A when stimulated by J-proteins. PMID:21231916 whereas overexpression of HSPA1A protected cells from heat-induced cell death, overexpression of HSPA6 did not |
| GO:0070370 cellular heat acclimation | IMP PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | REMOVE | Summary: PMID:21231916 reports HSPA1A protection from heat-induced cell death and HSPA6 lack of thermotolerance; it does not directly test HSPA1B for cellular heat acclimation. Reason: The cited IMP evidence is HSPA1A/HSPA6-specific and should not be accepted as a direct HSPA1B heat-acclimation annotation. Supporting Evidence: PMID:21231916 whereas overexpression of HSPA1A protected cells from heat-induced cell death, overexpression of HSPA6 did not |
| GO:0072562 blood microparticle | HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d... | KEEP AS NON CORE | Summary: PMID:22516433 is a proteomic analysis of microvesicles from plasma of healthy donors identifying HSPA1B among blood microparticle proteins. Consistent with known extracellular release of HSP70. Reason: High-throughput proteomics data. Blood microparticle localization is a secondary, non-core feature consistent with extracellular HSP70 release. |
| GO:0090084 negative regulation of inclusion body assembly | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | REMOVE | Summary: PMID:21231916 discusses HSPA-family effects on polyQ aggregation, but the local evidence does not establish this as an HSPA1B-specific IDA result. Reason: The cited IDA evidence should not be accepted as HSPA1B-specific negative regulation of inclusion body assembly. |
| GO:0005515 protein binding | IPI PMID:15603737 BAG5 inhibits parkin and enhances dopaminergic neuron degene... | MARK AS OVER ANNOTATED | Summary: PMID:15603737 shows BAG5 directly interacts with Hsp70 and inhibits Hsp70-mediated refolding of misfolded proteins. Protein binding is uninformative for a chaperone. Reason: GO:0005515 protein binding is uninformative for a molecular chaperone. The BAG5 interaction is a specific co-chaperone interaction better captured by heat shock protein binding (GO:0031072). Supporting Evidence: PMID:15603737 bcl-2-associated athanogene 5 (BAG5), a BAG family member, directly interacts with parkin and the chaperone Hsp70. Within this complex, BAG5 inhibits both parkin E3 ubiquitin ligase activity and Hsp70-mediated refolding of misfolded proteins |
| GO:0005524 ATP binding | IDA PMID:23921388 Identification and characterization of a novel human methylt... | ACCEPT | Summary: PMID:23921388 characterizes METTL21A methylation of HSP70, with the methylation reaction stimulated by ATP, demonstrating HSP70 ATP binding. Core molecular function confirmed by crystal structures of the NBD domain with ADP/ATP. Reason: Core molecular function. ATP binding drives the chaperone cycle and is essential for all HSP70 functions. Supporting Evidence: PMID:23921388 the reaction was stimulated by ATP |
| GO:0010628 positive regulation of gene expression | IMP PMID:25281747 RING finger protein RNF207, a novel regulator of cardiac exc... | REMOVE | Summary: PMID:25281747 reports increased total and membrane HERG/KCNH2 protein and current density with RNF207 and HSP70, consistent with chaperone-mediated trafficking or stabilization rather than regulation of gene expression. Reason: The evidence supports effects on HERG protein trafficking/localization and current density, not positive regulation of gene expression. Supporting Evidence: PMID:25281747 coexpression of RNF207 and HSP70 increased HERG expression compared with HSP70 alone |
| GO:0016234 inclusion body | IDA PMID:15603737 BAG5 inhibits parkin and enhances dopaminergic neuron degene... | ACCEPT | Summary: PMID:15603737 shows BAG5 enhances parkin sequestration within protein aggregates, with HSP70 localized to inclusion bodies as part of its protein quality control response. Reason: Confirmed by direct assay. HSP70 localizes to inclusion bodies as part of its role in protein aggregate management and quality control. Supporting Evidence: PMID:15603737 BAG5 enhances parkin sequestration within protein aggregates and mitigates parkin-dependent preservation of proteasome function |
| GO:0019899 enzyme binding | IPI PMID:23921388 Identification and characterization of a novel human methylt... | ACCEPT | Summary: PMID:23921388 demonstrates METTL21A (HSPA-KMT) is a highly specific methyltransferase that interacts with and methylates HSP70 family members. Enzyme binding is confirmed by the direct enzyme-substrate interaction. Reason: Confirmed by experimental evidence. METTL21A is a specific enzyme that binds and modifies HSP70 at Lys-561. Supporting Evidence: PMID:23921388 we identified the methyltransferase METTL21A as the enzyme responsible for trimethylation of a conserved lysine residue found in several human Hsp70 (HSPA) proteins |
| GO:0031072 heat shock protein binding | IPI PMID:23921388 Identification and characterization of a novel human methylt... | ACCEPT | Summary: PMID:23921388 demonstrates that METTL21A trimethylation alters the affinity of Hsp70 for alpha-synuclein fibrils, reflecting functionally relevant HSP-HSP interactions. The study also shows METTL21A interacts with HSP70 family members. Reason: Core co-chaperone interaction. HSP70 binding to other heat shock proteins and modifiers is fundamental to chaperone regulation. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:15603737 BAG5 inhibits parkin and enhances dopaminergic neuron degene... | ACCEPT | Summary: PMID:15603737 demonstrates that BAG5 directly interacts with both parkin (an E3 ubiquitin ligase) and Hsp70, forming a complex. HSP70 binding to E3 ligases is a core part of the chaperone triage system. Reason: Core co-chaperone interaction. HSP70 binding to E3 ubiquitin ligases like Parkin is integral to the protein quality control triage mechanism. Supporting Evidence: PMID:15603737 bcl-2-associated athanogene 5 (BAG5), a BAG family member, directly interacts with parkin and the chaperone Hsp70 |
| GO:0042026 protein refolding | IDA PMID:15603737 BAG5 inhibits parkin and enhances dopaminergic neuron degene... | ACCEPT | Summary: PMID:15603737 demonstrates Hsp70-mediated refolding of misfolded proteins, which is inhibited by BAG5. Core biological process for HSP70. Reason: Core biological process confirmed by direct assay. HSP70 refolds misfolded proteins through its ATP-dependent chaperone cycle. Supporting Evidence: PMID:15603737 BAG5 inhibits both parkin E3 ubiquitin ligase activity and Hsp70-mediated refolding of misfolded proteins |
| GO:0044183 protein folding chaperone | IDA PMID:15603737 BAG5 inhibits parkin and enhances dopaminergic neuron degene... | ACCEPT | Summary: PMID:15603737 demonstrates Hsp70 chaperone activity in the context of the BAG5-Parkin-Hsp70 complex. Hsp70 actively refolds misfolded proteins. This is the core molecular function annotation for HSPA1B. Reason: The defining molecular function of HSPA1B. HSP70 is an ATP-dependent protein folding chaperone confirmed by direct assay. Supporting Evidence: PMID:15603737 BAG5 inhibits both parkin E3 ubiquitin ligase activity and Hsp70-mediated refolding of misfolded proteins |
| GO:0046034 ATP metabolic process | IDA PMID:23921388 Identification and characterization of a novel human methylt... | REMOVE | Summary: PMID:23921388 describes METTL21A methylation assays and HSPA8/Hsc70 functional effects, not HSPA1B-specific ATP metabolic process. Reason: The cited IDA evidence does not support a broad HSPA1B ATP metabolic process annotation; ATP use is better captured by ATPase/chaperone molecular-function annotations. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:15603737 BAG5 inhibits parkin and enhances dopaminergic neuron degene... | ACCEPT | Summary: PMID:15603737 documents perinuclear localization of HSP70 in the context of dopaminergic neuron studies with BAG5 and Parkin. Consistent with perinuclear HSP70 localization during stress. Reason: Confirmed by direct assay. Perinuclear localization is observed particularly in the context of protein quality control near the nucleus. |
| GO:0090084 negative regulation of inclusion body assembly | IDA PMID:15603737 BAG5 inhibits parkin and enhances dopaminergic neuron degene... | ACCEPT | Summary: PMID:15603737 shows HSP70 suppresses protein aggregation and inclusion body formation, which is inhibited by BAG5. Core protein quality control function. Reason: Core chaperone function. Preventing protein aggregation and inclusion body formation is a direct consequence of HSP70 foldase activity. |
| GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand | IMP PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | KEEP AS NON CORE | Summary: PMID:17167422 shows Hsp70 protects GATA-1 from caspase-3 cleavage, preventing apoptosis during erythroid differentiation. This is a specific anti-apoptotic function mediated through chaperone protection of GATA-1. Reason: Experimentally supported anti-apoptotic function but represents a specific downstream effect of HSP70 chaperone-mediated protection of client proteins from caspase cleavage. |
| GO:0005102 signaling receptor binding | IPI PMID:24790089 The molecular chaperone HSP70 binds to and stabilizes NOD2, ... | KEEP AS NON CORE | Summary: PMID:24790089 demonstrates HSP70 binds NOD2, an intracellular pattern recognition receptor. This interaction stabilizes NOD2 and enhances its signaling capacity. Reason: Experimentally supported but reflects chaperone-client stabilization of NOD2 rather than specific signaling receptor binding activity. The interaction is in the context of HSP70 chaperone function. Supporting Evidence: PMID:24790089 We identified heat shock protein 70 (HSP70) as a protein interactor of both wild type and Crohn mutant NOD2 |
| GO:0005737 cytoplasm | IDA PMID:24790089 The molecular chaperone HSP70 binds to and stabilizes NOD2, ... | ACCEPT | Summary: PMID:24790089 documents cytoplasmic localization of HSP70 in the context of NOD2 interaction studies. Core localization for HSPA1B. Reason: Core localization confirmed by direct assay. |
| GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway | IMP PMID:24790089 The molecular chaperone HSP70 binds to and stabilizes NOD2, ... | KEEP AS NON CORE | Summary: PMID:24790089 shows HSP70 stabilizes NOD2, enhancing NOD2-mediated signaling which includes TNF-mediated pathway activation in response to bacterial cell wall fragments. Reason: Experimentally supported downstream effect of HSP70 chaperone activity on innate immune signaling components through NOD2 stabilization. Supporting Evidence: PMID:24790089 Induced HSP70 expression in cells increased the response of NOD2 to bacterial cell wall fragments |
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