DNAJB2 (HSJ1) is a neuronally enriched J-domain co-chaperone that couples Hsp70-family ATPase regulation to handling of aggregation-prone proteins. Its J domain binds Hsp70/Hsc70 and stimulates ATP hydrolysis, while two ubiquitin-interacting motifs recognize ubiquitinated clients and coordinate their processing with the chaperone and proteasome systems. Client outcomes include aggregation suppression, functional recovery or degradation and depend on the substrate and experimental context. The long HSJ1b product is prenylated and associated with the cytoplasmic face of the endoplasmic reticulum; the shorter HSJ1a product occupies cytosolic and nuclear pools. Pathogenic DNAJB2 variants cause inherited peripheral neuropathy and related neuromuscular phenotypes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001671 ATPase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: J-domain activation of Hsp70 ATP hydrolysis is a central DNAJB2 activity. Reason: The literal PTHR45168 target path descends from PTN002376289, whose IBD uses human P25686 experimental evidence. Target self-inclusion is expected. PMID:7957263 demonstrates stimulation of Hsc70 by both HSJ1 isoforms; purified human HSP70 assays and J-domain constructs in PMID:22219199 corroborate the activity. This is activation of a partner ATPase, not intrinsic ATP hydrolysis by DNAJB2. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002376289 Literal ancestor of target PTN002554731 in the recovered PTHR45168 tree; four current IBDs retain P25686 target evidence. UniProtKB:P25686 Experimental target evidence is a valid descendant source, not circular. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: The soluble HSJ1a product has a cytosolic pool. Reason: The target lies below the literal cytosol IBD at PTN002376289. Human expressed-construct localization in PMID:21231916 and PMID:28031292 supports the cytosolic pool. This does not relocate the prenylated HSJ1b product from the ER membrane. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002376289 Literal ancestor of target PTN002554731 in the recovered PTHR45168 tree; four current IBDs retain P25686 target evidence. UniProtKB:P25686 Experimental target evidence is a valid descendant source, not circular. |
| GO:0030544 Hsp70 protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: DNAJB2 directly binds Hsp70-family chaperones. Reason: The current IBD at PTN002376289 is grounded in target P25686 and lies on its actual lineage. Purified pull-down, NMR and ATPase experiments in PMID:22219199 establish the J-domain interaction with human HSP70. The historical HSJ1a construct ends at residue 274 and is not silently equated with the current 277-residue natural product. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002376289 Literal ancestor of target PTN002554731 in the recovered PTHR45168 tree; four current IBDs retain P25686 target evidence. UniProtKB:P25686 Experimental target evidence is a valid descendant source, not circular. Supporting Evidence: |
| GO:0042026 protein refolding | IBA GO_REF:0000033 | ACCEPT | Summary: DNAJB2 can support client-specific recovery of protein function. Reason: The target inherits the literal protein-refolding IBD at PTN002376289; the target-derived source is not circular. PMID:21231916 found no improvement of heat-denatured luciferase refolding by DNAJB2a, so it is not positive support for that reporter. Independent PMID:20889486 demonstrates J-domain-dependent rescue of mutant Parkin mitochondrial recruitment and mitophagy-related function, supporting client-specific folding recovery. This is a cellular functional-rescue interpretation, not purified refolding kinetics or a universal client effect. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002376289 Literal ancestor of target PTN002554731 in the recovered PTHR45168 tree; four current IBDs retain P25686 target evidence. UniProtKB:P25686 Experimental target evidence is a valid descendant source, not circular. |
| GO:0051082 unfolded protein binding | IBA GO_REF:0000033 | MODIFY | Summary: Replace obsolete unfolded-protein binding with supported holdase-mediated client handling. Reason: The historical PAINT assertion is retained verbatim as source metadata. GO:0051082 is obsolete; its previous automatic replacement by a folding activity overstated the assigned assays. GO:0140309 requires aggregation prevention plus delivery, not just binding. The source-specific client-binding/antiaggregation contribution is integrated with independent PMID:15936278, whose primary abstract explicitly reports HSJ1 client binding, aggregation prevention and proteasome sorting. For PMID:21231916, luciferase refolding was negative; for PMID:24023695, reduced SOD1 aggregation is not a measurement of restored SOD1 enzyme activity. The replacement describes a supported gene-level client-handling mechanism without claiming every source measured delivery. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN002376289 Historical0051082 assertion preserved; this obsolete IBD is absent from the current download, while the literal target lineage remains resolved. UniProtKB:P25686 Experimental target evidence is a valid descendant source, not circular. Proposed replacements: unfolded protein holdase activity |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: HSJ1a occupies a nuclear as well as cytosolic pool. Reason: The UniProt SL-0191 mapping agrees with the explicitly labeled DNAJB2a experimental-localization panel in PMID:21231916 and human SK-N-SH imaging in PMID:28031292. The experimental panel is distinct from the paper’s prediction column; no quantitative nuclear partition or universal isoform localization is inferred. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO_REF:0000044 Official UniProt subcellular-location mapping corroborated by product-aware target localization. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: Resolve broad cytoplasm into the supported cytosolic and ER-membrane pools. Reason: The combined SL-0086/ARBA mapping is biologically sound. Current ARBA00026971 condition set 928 matches the official DNAJB2 FunFam. HSJ1a is cytosolic, whereas the prenylated HSJ1b product associates with the cytoplasmic face of the ER. Both specific locations are already represented by other source assertions; the refinement adds no new source evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: ARBA:ARBA00026971 Actual rule conditions matched to target FunFam and applicable taxonomic lineage. Proposed replacements: cytosol endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The long HSJ1b product is associated with the ER membrane. Reason: The SL-0097 mapping is supported by the PMID:12754272 primary abstract, which describes geranylgeranylation-dependent targeting to the cytosolic face of the ER, and by independent PMID:28031292 imaging. The original PMID:12754272 full Methods were inaccessible; exact mutant and quantitative fractionation details are not inferred beyond the inspected abstract. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO_REF:0000044 Official UniProt subcellular-location mapping corroborated by product-aware target localization. |
| GO:0030544 Hsp70 protein binding | IEA GO_REF:0000002 | ACCEPT | Summary: The DNJB2/6-like signature correctly maps DNAJB2 to Hsp70 binding. Reason: Current InterPro2GO contains the literal IPR043183→GO:0030544 mapping; the official target record has that signature. Target-specific purified HSP70/J-domain experiments independently support the inference, rather than relying on a family label alone. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR043183 Official target signature and literal current0030544 mapping inspected; obsolete0051082 historical source retained. Supporting Evidence: |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000002 | MODIFY | Summary: Replace obsolete unfolded-protein binding with supported holdase-mediated client handling. Reason: The historical InterPro assertion is retained verbatim as source metadata. GO:0051082 is obsolete; its previous automatic replacement by a folding activity overstated the assigned assays. GO:0140309 requires aggregation prevention plus delivery, not just binding. The source-specific client-binding/antiaggregation contribution is integrated with independent PMID:15936278, whose primary abstract explicitly reports HSJ1 client binding, aggregation prevention and proteasome sorting. For PMID:21231916, luciferase refolding was negative; for PMID:24023695, reduced SOD1 aggregation is not a measurement of restored SOD1 enzyme activity. The replacement describes a supported gene-level client-handling mechanism without claiming every source measured delivery. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: InterPro:IPR043183 Official target signature and literal current0030544 mapping inspected; obsolete0051082 historical source retained. Proposed replacements: unfolded protein holdase activity |
| GO:0051087 protein-folding chaperone binding | IEA GO_REF:0000117 | MODIFY | Summary: Refine general folding-chaperone binding to Hsp70 binding. Reason: The historical ARBA00088077 branch 7 matches DNAJB2 FunFam 1.10.287.110:FF:000021 and Homo. Its broad chaperone-binding output is supported, and the experimentally characterized partner class is Hsp70. This refinement does not claim that DNAJB2 itself catalyzes ATP-dependent folding. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: ARBA:ARBA00088077 Actual rule conditions matched to target FunFam and applicable taxonomic lineage. Proposed replacements: Hsp70 protein binding |
| GO:0090084 negative regulation of inclusion body assembly | IEA GO_REF:0000117 | ACCEPT | Summary: DNAJB2 suppresses inclusion formation in tested misfolded-client systems. Reason: The current ARBA00087599 branch 1 matches the DNAJB2 FunFam and Haplorrhini lineage. Target-specific HDQ74, luciferase and mutant-SOD1 experiments corroborate antiaggregation. The effect is client- and product-dependent: HSJ1b can instead enhance rhodopsin inclusions under the overexpression conditions in PMID:12754272. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00087599 Actual rule conditions matched to target FunFam and applicable taxonomic lineage. |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | KEEP AS NON CORE | Summary: Retain the positive DNAJB2–MLF1 LUMIER association. Reason: The literal human P58340–P25686 record EBI-9364639/IM-22301-375 identifies Renilla-tagged MLF1 and FLAG-tagged DNAJB2 in HEK293T cells; both participant sequence/taxon hashes match the official canonical records. LUMIER measures capture from cell lysate, not a purified binary interface. MLF1’s proposed transcription-factor role is not sufficiently resolved here to refine this association to DNA-binding transcription-factor binding, and the pair does not by itself define a core client-triage mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the positive DNAJB2–MLF1 BioPlex association. Reason: The literal human P58340–P25686 record EBI-54862867/IM-29278-19149 is an HCT116 anti-tag co-immunoprecipitation with tagged MLF1 bait and DNAJB2 prey, represented by spoke expansion. Both participant sequence/taxon hashes match the official canonical records. This is a positive co-complex association, not proof of direct contact or a specific physiological transcriptional mechanism. No justified more-specific partner-binding activity is established. Supporting Evidence: |
| GO:0031965 nuclear membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas supports nuclear-membrane localization. Reason: The actual ENSG00000135924 record reports enhanced-reliability ICC/IF nuclear-membrane localization in A-431, U-251MG and U2OS, including an siRNA validation record. This resolves the former access-based uncertainty. The antibody record does not establish which natural splice product supplies the signal; no independent image quantification is claimed. |
| GO:0120283 protein serine/threonine kinase binding | IPI PMID:28031292 Protein kinase CK2 modulates HSJ1 function through phosphory... | KEEP AS NON CORE | Summary: CK2 binding is a supported regulatory interaction. Reason: PMID:28031292 establishes HSJ1 interaction with and phosphorylation by CK2, with UIM2 phosphorylation changing ubiquitinated-client association. DNAJB2 is the kinase substrate, not a kinase. Retain the specific binding activity as regulatory context rather than creating an additional core mechanism for every modifying partner. Supporting Evidence: |
| GO:0140318 protein transporter activity | TAS PMID:28031292 Protein kinase CK2 modulates HSJ1 function through phosphory... | MODIFY | Summary: Specify client transport as unfolded-protein holdase activity. Reason: The general protein-transporter assertion is consistent with client delivery, but the relevant cargo is aggregation-prone protein handled by HSJ1. Independent PMID:15936278 explicitly describes aggregation prevention and proteasome sorting, supplying the delivery criterion of GO:0140309. PMID:28031292 chiefly tests phosphorylation-dependent recognition and client levels; it is not relabeled as a direct transport assay. Proposed replacements: unfolded protein holdase activity |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | TAS PMID:28031292 Protein kinase CK2 modulates HSJ1 function through phosphory... | ACCEPT | Summary: DNAJB2 promotes proteasomal disposal of selected clients. Reason: The TAS claim is supported by independent target experiments: the J domain promotes HSP70-dependent Atx3 degradation in PMID:21625540, and mutant-SOD1 turnover and ubiquitylation change in PMID:24023695. The direction is conditional: isolated UIM-dependent preservation can retard Atx3 degradation. Accept the demonstrated positive process without asserting that every bound client is degraded faster or that DNAJB2 is a protease. |
| GO:0043130 ubiquitin binding | IDA PMID:28031292 Protein kinase CK2 modulates HSJ1 function through phosphory... | ACCEPT | Summary: UIM-dependent ubiquitin binding is a core recognition mechanism. Reason: PMID:28031292 compares phosphosite and UIM-disrupting mutants for ubiquitinated-client association. Independent purified UIM/diubiquitin ITC and NMR in PMID:21625540 support direct ubiquitin-chain recognition. The readout is ubiquitin binding, not ubiquitin transfer or hydrolase activity. |
| GO:0070050 neuron cellular homeostasis | TAS PMID:28031292 Protein kinase CK2 modulates HSJ1 function through phosphory... | KEEP AS NON CORE | Summary: Neuronal homeostasis is a supported physiological consequence. Reason: DNAJB2 is neuronally enriched and its client-handling activity can protect neuronal systems, but this broad process summarizes downstream physiology rather than an additional molecular mechanism. The source PMID:28031292 provides biochemical regulation of recognition; detailed neuronal protection is independently supported by the human-HSJ1a transgenic mutant-SOD1 study. |
| GO:0140036 ubiquitin-modified protein reader activity | IDA PMID:28031292 Protein kinase CK2 modulates HSJ1 function through phosphory... | ACCEPT | Summary: DNAJB2 recognizes ubiquitinated clients and coordinates their handling. Reason: The UIM-mutant and phosphorylation comparisons in PMID:28031292 demonstrate modification-dependent recognition. Purified ubiquitin binding plus the J-domain/HSP70–CHIP–client experiments in PMID:21625540, and the sorting result in PMID:15936278, supply the adaptor component of GO:0140036. This is more than ubiquitin binding alone, while client fate remains context-dependent. |
| GO:0005515 protein binding | IPI PMID:21625540 Co-chaperone HSJ1a dually regulates the proteasomal degradat... | KEEP AS NON CORE | Summary: Retain DNAJB2a self-association with unresolved attribution to the original source. Reason: The historical GOA WITH/FROM is P25686-2. The inspected full original PMID:21625540 establishes HSJ1a interactions with HSP70 and Atx3, but the corresponding self-association experiment was not resolved in that paper or the current IntAct/MINT queries. Independent DOI:10.1093/hmg/ddad058 explicitly reports polydisperse oligomers of both wild-type and extension-mutant DNAJB2a in its verified primary abstract. Retain the gene-level positive association without claiming a homodimer stoichiometry, validating the unresolved source pair, or substituting an unrelated partner. |
| GO:0008285 negative regulation of cell population proliferation | IGI PMID:9553041 Inhibition of cellular proliferation by the Wilms tumor supp... | MARK AS OVER ANNOTATED | Summary: The engineered J-domain–WT1 result does not establish a native DNAJB2 cell population proliferation function. Reason: PMID:9553041 genuinely tests a human HSJ1 78-residue J domain fused to WT1; it is not a wrong-gene citation. The fusion recruits Hsp70 and restores colony suppression/G1 arrest in a WT1 DNA-binding-dependent context, whereas an HPD mutation disrupts the effect. This establishes a functional chaperone-recruiting module in an engineered transcription-factor construct. Assigning the resulting growth-control process to native full-length DNAJB2 exceeds that demonstrated scope. Supporting Evidence: |
| GO:0030308 negative regulation of cell growth | IGI PMID:9553041 Inhibition of cellular proliferation by the Wilms tumor supp... | MARK AS OVER ANNOTATED | Summary: The engineered J-domain–WT1 result does not establish a native DNAJB2 cell growth function. Reason: PMID:9553041 genuinely tests a human HSJ1 78-residue J domain fused to WT1; it is not a wrong-gene citation. The fusion recruits Hsp70 and restores colony suppression/G1 arrest in a WT1 DNA-binding-dependent context, whereas an HPD mutation disrupts the effect. This establishes a functional chaperone-recruiting module in an engineered transcription-factor construct. Assigning the resulting growth-control process to native full-length DNAJB2 exceeds that demonstrated scope. Supporting Evidence: |
| GO:0051087 protein-folding chaperone binding | IPI PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | MODIFY | Summary: Refine the chaperone association to the demonstrated Hsp70 partner class. Reason: The original PMID:21231916 includes tagged/cross-linked HSPA–DNAJ association experiments. These support the Hsp70 partner class, independently confirmed by purified PMID:22219199 assays; they do not establish a fixed native complex or direct contact in every cellular sample. DNAJB2a’s negative luciferase-refolding result does not negate binding. Proposed replacements: Hsp70 protein binding |
| GO:0006457 protein folding | IMP PMID:24023695 Molecular chaperone mediated late-stage neuroprotection in t... | MODIFY | Summary: Refine the gene-level folding claim to supported client-specific protein refolding. Reason: The current GO hierarchy places protein refolding (GO:0042026) under protein folding. PMID:24023695 demonstrates mutant-SOD1 association, reduced aggregation and altered ubiquitination/turnover, without measuring restoration of SOD1 catalytic activity. Independent PMID:20889486 demonstrates J-domain-dependent recovery of mutant Parkin mitochondrial recruitment and mitophagy-related function, supporting the more specific gene-level refolding interpretation already represented elsewhere in this review. The refinement uses that independent functional evidence; it does not relabel the SOD1 antiaggregation assay as a refolding assay or imply recovery of every client. Proposed replacements: protein refolding |
| GO:0031396 regulation of protein ubiquitination | IMP PMID:24023695 Molecular chaperone mediated late-stage neuroprotection in t... | ACCEPT | Summary: DNAJB2 can regulate client ubiquitination. Reason: PMID:24023695 measures enhanced mutant-SOD1 ubiquitylation with HSJ1a, including J-domain/UIM perturbations. This supports regulation of ubiquitin addition in that client-handling setting. DNAJB2 does not become an E3 ligase, and pre-existing-chain binding alone would not support this process. Supporting Evidence: |
| GO:0051082 unfolded protein binding | IDA PMID:24023695 Molecular chaperone mediated late-stage neuroprotection in t... | MODIFY | Summary: Replace obsolete unfolded-protein binding with supported holdase-mediated client handling. Reason: The mutant-SOD1 binding and antiaggregation experiments in PMID:24023695 is retained verbatim as source metadata. GO:0051082 is obsolete; its previous automatic replacement by a folding activity overstated the assigned assays. GO:0140309 requires aggregation prevention plus delivery, not just binding. The source-specific client-binding/antiaggregation contribution is integrated with independent PMID:15936278, whose primary abstract explicitly reports HSJ1 client binding, aggregation prevention and proteasome sorting. For PMID:21231916, luciferase refolding was negative; for PMID:24023695, reduced SOD1 aggregation is not a measurement of restored SOD1 enzyme activity. The replacement describes a supported gene-level client-handling mechanism without claiming every source measured delivery. Proposed replacements: unfolded protein holdase activity |
| GO:0001671 ATPase activator activity | IDA PMID:7957263 Regulation of 70-kDa heat-shock-protein ATPase activity and ... | ACCEPT | Summary: Both HSJ1 products stimulate Hsc70 ATPase activity. Reason: The verified primary abstract of PMID:7957263 reports more than fivefold stimulation and increased hydrolysis of bound ATP without enhanced ADP release. The full original Methods remained inaccessible, so the animal origin of the brain Hsc70 and exact construct details are not inferred. Independent purified human HSP70/J-domain assays in PMID:22219199 corroborate the gene-level activity. |
| GO:0032091 negative regulation of protein binding | IDA PMID:7957263 Regulation of 70-kDa heat-shock-protein ATPase activity and ... | KEEP AS NON CORE | Summary: HSJ1 changes substrate binding within the Hsc70 cycle. Reason: PMID:7957263 describes reduced Hsc70 binding to carboxymethylated alpha-lactalbumin under the tested conditions. Retain this assay-dependent regulatory effect; it does not imply global suppression of protein interactions or a second evolved inhibitory mechanism independent of ATPase-cycle regulation. Supporting Evidence: |
| GO:0032781 positive regulation of ATP-dependent activity | IDA PMID:7957263 Regulation of 70-kDa heat-shock-protein ATPase activity and ... | ACCEPT | Summary: HSJ1 positively regulates Hsc70’s ATP-dependent chaperone cycle. Reason: The measured increase in partner ATP hydrolysis supports this process. It is partner regulation, not autonomous ATPase activity or an increase in nucleotide-exchange rate; ADP release was unchanged in the primary abstract. Supporting Evidence: |
| GO:1903332 regulation of protein folding | IDA PMID:7957263 Regulation of 70-kDa heat-shock-protein ATPase activity and ... | ACCEPT | Summary: DNAJB2 regulates folding through Hsp70-cycle and client handling. Reason: PMID:7957263 reports regulation of Hsc70 ATP hydrolysis and substrate binding; independent PMID:20889486 connects DNAJB2/Hsp70 cooperation with recovery of mutant Parkin function. This supports regulation of folding as a biological role, with client-dependent outcomes and the negative luciferase-refolding result in PMID:21231916 retained. Regulation of protein folding is not an is_a/part_of ancestor of positive regulation of ATP-dependent activity: one describes the controlled biological outcome and the other the measured partner activity. Their relationship through the chaperone mechanism does not make either biological claim false or merely a generic duplicate. |
| GO:0001671 ATPase activator activity | IDA PMID:22219199 The C-terminal helices of heat shock protein 70 are essentia... | ACCEPT | Summary: The DNAJB2 J domain directly stimulates human HSP70 ATPase activity. Reason: PMID:22219199 uses purified human HSP70 and engineered HSJ1a J-domain constructs in a phosphate-release assay. Pull-down and NMR address binding separately. The partner’s C-terminal helices are required for stimulation in the tested constructs; that does not make DNAJB2 an ATPase or demonstrate a direct J-domain interaction with those helices. Supporting Evidence: |
| GO:0030544 Hsp70 protein binding | IPI PMID:22219199 The C-terminal helices of heat shock protein 70 are essentia... | ACCEPT | Summary: Direct Hsp70 binding is supported by purified-domain experiments. Reason: PMID:22219199 combines GST-controlled pull-down, NMR and construct comparisons. The historical HSJ1a full construct is 1–274 and the isolated J domains are shorter; retain this distinction from the current 277-aa natural HSJ1a product. The evidence supports the gene-level Hsp70-binding mechanism. Supporting Evidence: |
| GO:0032781 positive regulation of ATP-dependent activity | IDA PMID:22219199 The C-terminal helices of heat shock protein 70 are essentia... | ACCEPT | Summary: DNAJB2 stimulates a partner ATP-dependent activity. Reason: The purified human HSP70 assay in PMID:22219199 measures increased ATP hydrolysis in the presence of the HSJ1a J domain. It supports positive regulation of ATP-dependent activity while leaving catalysis on HSP70. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | ACCEPT | Summary: Expressed DNAJB2a has a nuclear pool. Reason: The actual DNAJB2a-labeled experimental panel in Figure 2C of the separately recovered PMID:21231916 manuscript supports nucleus localization together with cytoplasmic signal. It is not merely the neighboring prediction column. The protected normal cache remains abstract-only, and no quantitative partition or all-product localization is inferred. Supporting Evidence: |
| GO:0005829 cytosol | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | ACCEPT | Summary: Expressed DNAJB2a has a cytosolic pool. Reason: The target-labeled experimental localization panel in PMID:21231916 and independent human SK-N-SH imaging in PMID:28031292 support the soluble cytoplasmic product. This does not transfer the same localization to prenylated HSJ1b. |
| GO:0042026 protein refolding | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | ACCEPT | Summary: Retain client-specific refolding while correcting the assigned reporter interpretation. Reason: The recovered full original PMID:21231916 explicitly finds that DNAJB2a suppresses aggregation but does not improve heat-denatured luciferase refolding. The previous positive-luciferase rationale is withdrawn. At gene level, independent PMID:20889486 supports J-domain-dependent restoration of mutant Parkin recruitment and mitophagy-related function. ACCEPT reflects that integrated, client-specific evidence, not a positive refolding result from PMID:21231916 or purified refolding kinetics. |
| GO:0051082 unfolded protein binding | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | MODIFY | Summary: Replace obsolete unfolded-protein binding with supported holdase-mediated client handling. Reason: The DNAJB2a antiaggregation experiments in PMID:21231916 is retained verbatim as source metadata. GO:0051082 is obsolete; its previous automatic replacement by a folding activity overstated the assigned assays. GO:0140309 requires aggregation prevention plus delivery, not just binding. The source-specific client-binding/antiaggregation contribution is integrated with independent PMID:15936278, whose primary abstract explicitly reports HSJ1 client binding, aggregation prevention and proteasome sorting. For PMID:21231916, luciferase refolding was negative; for PMID:24023695, reduced SOD1 aggregation is not a measurement of restored SOD1 enzyme activity. The replacement describes a supported gene-level client-handling mechanism without claiming every source measured delivery. Proposed replacements: unfolded protein holdase activity |
| GO:0090084 negative regulation of inclusion body assembly | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | ACCEPT | Summary: DNAJB2a suppresses inclusion formation in the tested reporter systems. Reason: PMID:21231916 reports suppression of HDQ74 and heat-induced luciferase aggregation by the expressed DNAJB2a construct. This is a valid antiaggregation result even though luciferase refolding is negative. It is not a universal claim for all clients or both splice products. Supporting Evidence: |
| GO:0006986 response to unfolded protein | TAS PMID:1599432 Human homologues of the bacterial heat-shock protein DnaJ ar... | KEEP AS NON CORE | Summary: Retain the broad unfolded-client response as physiological context. Reason: The scanned original PMID:1599432 establishes human HSJ1 cloning, expression and sequence relationships, while discussing possible chaperone functions prospectively. It is not a direct unfolded-client response assay. Nevertheless, later target experiments demonstrate action on misfolded Parkin, SOD1 and aggregation reporters. Constitutive expression does not refute this broad response term, which does not require transcriptional induction. Retain it as non-core context with the source limitation explicit. |
| GO:0001671 ATPase activator activity | IDA PMID:28031292 Protein kinase CK2 modulates HSJ1 function through phosphory... | ACCEPT | Summary: The newly imported ATPase-activator assertion matches the established activity. Reason: PMID:28031292 chiefly examines CK2/UIM regulation; no new DNAJB2 ATPase experiment was identified in the inspected Methods. The gene-level activity is independently direct in PMID:7957263 and PMID:22219199, so incomplete recovery of this source’s supporting chain is not grounds to reject a clearly established function. This is an ordinary current GOA addition, not a proposed NEW annotation. |
| GO:0005634 nucleus | EXP PMID:12754272 The chaperone environment at the cytoplasmic face of the end... | ACCEPT | Summary: The newly imported nuclear localization is independently corroborated. Reason: The original PMID:12754272 full text was inaccessible; its abstract does not itself resolve nuclear localization. The curated EXP assertion is retained because actual target-specific localization in PMID:21231916 and PMID:28031292 supports a nuclear HSJ1a pool. Do not claim that the inaccessible source’s exact nuclear experiment was verified. |
| GO:0005737 cytoplasm | EXP PMID:12754272 The chaperone environment at the cytoplasmic face of the end... | MODIFY | Summary: Resolve the broad current cytoplasmic annotation by product-associated location. Reason: The PMID:12754272 primary abstract directly supports prenylation-dependent HSJ1b targeting to the cytosolic face of the ER. Independent PMID:21231916 and PMID:28031292 support cytosolic HSJ1a. Use both established specific locations rather than imply all cytoplasmic products are soluble; no new biological coverage is manufactured. Proposed replacements: cytosol endoplasmic reticulum membrane |
| GO:0005737 cytoplasm | EXP PMID:21625540 Co-chaperone HSJ1a dually regulates the proteasomal degradat... | MODIFY | Summary: Refine HSJ1a’s broad cytoplasmic annotation to cytosol. Reason: The PMID:21625540 cellular client experiments concern HSJ1a; independently verified PMID:21231916/ PMID:28031292 localization supports its soluble cytoplasmic pool. The refinement does not infer cytosol from lysis alone or relocate the distinct membrane-associated HSJ1b product. Proposed replacements: cytosol |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:12754272 The chaperone environment at the cytoplasmic face of the end... | ACCEPT | Summary: The current ER-membrane assertion matches the HSJ1b localization mechanism. Reason: The PMID:12754272 primary abstract explicitly links geranylgeranylation-dependent targeting to the cytosolic face of the ER with altered rhodopsin handling. Independent PMID:28031292 imaging corroborates the ER-associated product. Exact full-text methods from PMID:12754272 are not claimed to have been inspected. |
Loading supporting content…
Download this section (compressed HTML)Q: Which client features determine whether DNAJB2 promotes functional recovery, protects ubiquitinated intermediates or accelerates degradation?
Q: Which DNAJB2 splice product contributes to the HPA nuclear-membrane signal, and how does this pool relate to established HSJ1a and HSJ1b localization?
Q: What experiment underlies the PMID:21625540 self-product WITH/FROM assertion, and how does it relate to independently reported DNAJB2a oligomers?
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)