DNAJB1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006457 protein folding	IBA GO_REF:0000033	ACCEPT	Summary: DNAJB1 is a class II J-domain co-chaperone that promotes protein folding through the HSP70 chaperone machinery. Rauch and Gestwicki (PMID:24318877) showed that combinations of J proteins including DnaJB1 with NEFs and HSP70 produce potent chaperone activities in luciferase refolding assays. Hageman et al. (PMID:21231916) showed that DNAJB1 supports luciferase refolding when paired with HSP70, classifying it as a foldase-type co-chaperone. The IBA annotation for protein folding is well supported by phylogenetic inference and experimental data. Reason: Protein folding is the core biological process of DNAJB1. As a class II J-domain co-chaperone, DNAJB1 delivers substrates to HSP70 and stimulates the ATPase-dependent folding cycle (PMID:24318877, PMID:21231916). This IBA annotation is consistent with extensive experimental evidence and phylogenetic conservation. Supporting Evidence: PMID:24318877 we combined the Hsp70-NEF pairs with cochaperones of the J protein family (DnaJA1, DnaJA2, DnaJB1, and DnaJB4) to generate 16 permutations. The activity of the combinations in ATPase and luciferase refolding assays were dependent on the identity and stoichiometry of both the J protein and NEF PMID:21231916 chaperones that supported luciferase refolding were poor suppressors of polyQ aggregation. file:human/DNAJB1/DNAJB1-deep-research-falcon.md DNAJB1 stimulates the ATPase activity of HSP70 and delivers substrates to the HSP70 chaperone machinery, promoting protein folding (foldase-type activity).
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: DNAJB1 is primarily a cytosolic protein. Hageman et al. (PMID:21231916) stated that most HSP70/HSPA and HSP40/DNAJ proteins are localized in the cytosol. UniProt confirms cytoplasmic localization. The IBA annotation for cytosol is well supported. Reason: Cytosol is the primary localization of DNAJB1 under normal conditions, consistent with its role as a cytosolic co-chaperone for HSP70. Phylogenetic inference and direct experimental evidence (immunofluorescence, PMID:21231916) support this. Supporting Evidence: PMID:21231916 Humans contain many HSP (heat-shock protein) 70/HSPA- and HSP40/DNAJ-encoding genes and most of the corresponding proteins are localized in the cytosol.
GO:0000122 negative regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: DNAJB1 negatively regulates HSF1-driven transcription during the attenuation phase of the heat shock response. Shi et al. (PMID:9499401) demonstrated that Hsp70 and the cochaperone Hdj1 (DNAJB1) interact directly with the transactivation domain of HSF1 and repress heat shock gene transcription. The IBA annotation is well supported. Reason: While experimentally validated (PMID:9499401), negative regulation of transcription is not a core molecular function of DNAJB1 but rather a downstream consequence of its co-chaperone activity in the HSP70 complex. DNAJB1 represses HSF1 transcription as part of the heat shock attenuation mechanism, which is a secondary regulatory role. The IBA annotation is phylogenetically sound. Supporting Evidence: PMID:9499401 the molecular chaperone Hsp70 and the cochaperone Hdj1 interact directly with the transactivation domain of HSF1 and repress heat shock gene transcription.
GO:0003714 transcription corepressor activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Shi et al. (PMID:9499401) showed that overexpression of Hdj1 (DNAJB1) represses the transcriptional activity of HSF1, including a transfected GAL4-HSF1 activation domain fusion protein. This demonstrates transcription corepressor activity. The IBA annotation is phylogenetically consistent. Reason: Transcription corepressor activity is a real but non-core function of DNAJB1. It acts as a corepressor specifically in the context of HSF1-mediated heat shock gene transcription, working together with HSP70 to repress the HSF1 transactivation domain (PMID:9499401). This is a secondary regulatory role dependent on its primary co-chaperone activity, not a general transcription corepressor function. Supporting Evidence: PMID:9499401 Overexpression of either chaperone represses the transcriptional activity of a transfected GAL4-HSF1 activation domain fusion protein and endogenous HSF1.
GO:0030544 Hsp70 protein binding	IBA GO_REF:0000033	ACCEPT	Summary: DNAJB1 is a J-domain co-chaperone that physically binds HSP70 family members through its J-domain. UniProt records interactions with HSP70/HSPA1A (PMID:14503850) and this is a defining feature of all J-domain proteins. The IBA annotation accurately reflects the core molecular function of DNAJB1. Reason: HSP70 binding via the J-domain is the core molecular function of DNAJB1 as a J-domain co-chaperone. This is the defining feature of the DnaJ family and is essential for DNAJB1's ability to stimulate HSP70 ATPase activity and deliver substrates. Phylogenetically well-conserved and experimentally validated.
GO:0051082 unfolded protein binding	IBA GO_REF:0000033	MODIFY	Summary: GO:0051082 (unfolded protein binding) is now formally obsolete (go-ontology#30962). DNAJB1 is a class II J-domain protein that functions as a foldase-type co-chaperone for HSP70, not as an independent holdase. Hageman et al. (PMID:21231916) showed that DNAJB1 promotes efficient luciferase refolding when paired with HSP70, placing it in the foldase category. UniProt describes DNAJB1 as stimulating ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B. The correct replacement term is GO:0044183 (protein folding chaperone), which accurately describes DNAJB1's role in binding to proteins to assist the protein folding process as part of the HSP70 chaperone machinery. Reason: GO:0051082 is now formally obsolete. The obsolescence notice (go-ontology#30962) specifies that annotations should be migrated to either holdase chaperone activity or GO:0044183 (protein folding chaperone, i.e. foldase). DNAJB1 is definitively a foldase-type co-chaperone, not a holdase. Hageman et al. (PMID:21231916) demonstrated that chaperones supporting luciferase refolding (foldase activity) were poor suppressors of polyQ aggregation (holdase activity), and vice versa. DNAJB1 promotes refolding when paired with HSP70, classifying it as a foldase. This IBA annotation by phylogenetic inference correctly identified the general chaperone activity of DNAJB1, but the term needs updating to GO:0044183 to reflect the foldase function and the obsolescence of GO:0051082. 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:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: DNAJB1 translocates from the cytoplasm to the nucleus upon heat shock. UniProt subcellular location annotation confirms nuclear localization under stress conditions, supported by Hattori et al. (PubMed:1586970). This IEA annotation from UniProtKB subcellular location vocabulary mapping is consistent with known biology. Reason: Nuclear localization of DNAJB1 upon heat shock is well-documented. UniProt states that DNAJB1 translocates rapidly from the cytoplasm to the nucleus upon heat shock. The IEA mapping from UniProt subcellular location is appropriate.
GO:0005730 nucleolus	IEA GO_REF:0000044	ACCEPT	Summary: DNAJB1 translocates to the nucleolus upon heat shock. UniProt subcellular location confirms nucleolar localization under stress, supported by Hattori et al. (PubMed:1586970). The IEA annotation is consistent with known stress-induced translocation behavior. Reason: Nucleolar localization of DNAJB1 upon heat shock is documented in UniProt based on Hattori et al. The IEA mapping from UniProt subcellular location vocabulary is appropriate. DNAJB1 translocates to the nucleolus under heat shock stress.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: DNAJB1 is primarily cytoplasmic under normal conditions. UniProt subcellular location lists cytoplasm as a primary location. This is broader than the cytosol annotation but acceptable as an IEA annotation. Reason: Cytoplasmic localization of DNAJB1 is well-established. While the cytosol annotation is more specific, cytoplasm is a valid broader term from the UniProt mapping. Both are correct.
GO:0006457 protein folding	IEA GO_REF:0000120	ACCEPT	Summary: Protein folding is a core process for DNAJB1 as a J-domain co-chaperone. This IEA annotation from combined automated methods is consistent with the IBA annotation and experimental evidence. Reason: Redundant with the IBA annotation for the same term, but the IEA is independently valid. Protein folding is a core function of DNAJB1 through its HSP70 co-chaperone activity.
GO:0006986 response to unfolded protein	IEA GO_REF:0000117	ACCEPT	Summary: DNAJB1 is a heat shock-inducible co-chaperone that participates in the cellular response to unfolded proteins. As a J-domain protein that delivers substrates to HSP70, it is involved in the response to unfolded protein. This IEA annotation from ARBA machine learning is reasonable. Reason: DNAJB1 is indeed involved in the response to unfolded protein as a heat shock-inducible J-domain co-chaperone. While the term is broad, it is appropriate for an IEA annotation. It is consistent with the TAS annotation for the same term (PMID:8975727).
GO:0051082 unfolded protein binding	IEA GO_REF:0000002	MODIFY	Summary: GO:0051082 (unfolded protein binding) is now formally obsolete (go-ontology#30962). This IEA annotation was inferred from the InterPro domain IPR008971 (HSP40/DnaJ peptide-binding domain) mapping to GO:0051082. While the DnaJ peptide-binding domain does indeed interact with substrates, the function of DNAJB1 is best described as protein folding chaperone activity (GO:0044183), as DNAJB1 acts as a foldase-type co-chaperone for HSP70. DNAJB1 does not independently hold unfolded proteins; it delivers substrates to HSP70 and stimulates the ATPase-dependent folding cycle. Reason: GO:0051082 is now formally obsolete (go-ontology#30962). This IEA annotation derives from the InterPro domain mapping (IPR008971, HSP40/DnaJ peptide-binding domain). The InterPro2GO mapping will need to be updated when GO:0051082 is obsoleted. For DNAJB1 specifically, the correct replacement is GO:0044183 (protein folding chaperone), since DNAJB1 is a foldase-type J-domain protein that promotes protein refolding in concert with HSP70 (PMID:21231916). 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:0051087 protein-folding chaperone binding	IEA GO_REF:0000117	ACCEPT	Summary: DNAJB1 binds HSP70 family members (protein-folding chaperones) through its J-domain. This IEA annotation from ARBA machine learning is consistent with the known interaction between DNAJB1 and HSP70 chaperones (PMID:9499401, PMID:24318877). Reason: DNAJB1 is a co-chaperone that physically binds protein-folding chaperones (HSP70 family members). This IEA annotation is appropriate and consistent with the more specific Hsp70 protein binding annotation.
GO:0005515 protein binding	IPI PMID:17024176 A novel HSF1-mediated death pathway that is suppressed by he...	REMOVE	Summary: Hayashida et al. (PMID:17024176) studied a novel HSF1-mediated death pathway suppressed by heat shock proteins. The paper reports that Hsps bound directly to the N-terminal pleckstrin-homology like domain of Tdag51 and suppressed death activity. DNAJB1 binding was detected in this context. Reason: Protein binding is uninformative as a GO annotation. The interaction described in PMID:17024176 between HSPs and Tdag51 is tangential to DNAJB1 core function. More specific terms such as Hsp70 protein binding or protein-folding chaperone binding already capture the meaningful interactions of DNAJB1. Supporting Evidence: PMID:17024176 Hsps bound directly to the N-terminal pleckstrin-homology like (PHL) domain of Tdag51, and suppressed death activity of the C-terminal proline/glutamine/histidine-rich domain.
GO:0005515 protein binding	IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi...	REMOVE	Summary: PMID:21044950 is a genome-wide YFP fluorescence complementation screen for telomere signaling regulators. This is a large-scale screen and the protein binding annotation is uninformative. Reason: Protein binding is uninformative. This large-scale screen result does not provide specific functional insight into DNAJB1's molecular function. More informative MF terms such as Hsp70 protein binding already exist.
GO:0005515 protein binding	IPI PMID:21163940 Interactome mapping suggests new mechanistic details underly...	REMOVE	Summary: PMID:21163940 is an interactome mapping study related to Alzheimer's disease. The protein binding annotation from this large-scale study is uninformative. Reason: Protein binding is uninformative. Large-scale interactome mapping does not provide specific functional insight for DNAJB1 curation.
GO:0005515 protein binding	IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc...	REMOVE	Summary: PMID:25036637 describes a quantitative chaperone interaction network. While relevant to understanding DNAJB1 as a chaperone, the protein binding annotation is uninformative. The interactions are better captured by Hsp70 protein binding and protein-folding chaperone binding terms. Reason: Protein binding is uninformative. The chaperone interaction network data is better captured by the more specific Hsp70 protein binding and protein-folding chaperone binding annotations already present.
GO:0005515 protein binding	IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis...	REMOVE	Summary: PMID:27173435 describes an organelle-specific protein landscape. The protein binding annotation is uninformative for DNAJB1 curation. Reason: Protein binding is uninformative. Large-scale proteomics does not provide specific functional insight for DNAJB1.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: PMID:28514442 describes architecture of the human interactome. The protein binding annotation from this large-scale interactome study is uninformative. Reason: Protein binding is uninformative. Large-scale interactome mapping does not provide specific functional insight for DNAJB1.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: PMID:32296183 is a reference map of the human binary protein interactome. The protein binding annotation is uninformative. Reason: Protein binding is uninformative. Large-scale interactome mapping does not provide specific functional insight for DNAJB1.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: PMID:32814053 is an interactome mapping study of neurodegenerative disease proteins. The protein binding annotation is uninformative. Reason: Protein binding is uninformative. Interactome mapping for neurodegenerative disease does not provide specific functional insight for DNAJB1.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: PMID:33961781 describes dual proteome-scale networks of the human interactome. The protein binding annotation is uninformative. Reason: Protein binding is uninformative. Large-scale interactome mapping does not provide specific functional insight for DNAJB1.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	REMOVE	Summary: PMID:35271311 (OpenCell) is an endogenous tagging study for cellular organization cartography. The protein binding annotation is uninformative. Reason: Protein binding is uninformative. Large-scale cellular organization studies do not provide specific functional insight for DNAJB1.
GO:0005515 protein binding	IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c...	REMOVE	Summary: PMID:36931259 describes a chaperone-like role for 14-3-3 proteins. The protein binding annotation is uninformative. Reason: Protein binding is uninformative. The interaction with 14-3-3 proteins may be interesting but the generic protein binding term does not capture any specific functional relationship.
GO:0014069 postsynaptic density	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This IEA annotation was transferred from an ortholog by Ensembl Compara. DNAJB1 is a ubiquitous co-chaperone without specific synaptic function. While chaperones may be present at the postsynaptic density for proteostasis, there is no evidence that postsynaptic density is a primary or functionally significant localization for DNAJB1. Reason: DNAJB1 is a ubiquitously expressed co-chaperone. Its presence at the postsynaptic density likely reflects general proteostasis rather than a specific synaptic function. This ortholog transfer may over-annotate a non-specific localization.
GO:0030900 forebrain development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This IEA annotation was transferred from an ortholog by Ensembl Compara. DNAJB1 is a ubiquitous co-chaperone, and there is no specific evidence linking it to forebrain development as a core function. Reason: DNAJB1 is ubiquitously expressed and functions as a general co-chaperone for HSP70. Forebrain development likely reflects pleiotropic developmental consequences of general protein folding activity rather than a specific role for DNAJB1 in forebrain development. This is likely an over-annotation from ortholog transfer.
GO:0043025 neuronal cell body	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This IEA annotation was transferred from an ortholog by Ensembl Compara. DNAJB1 is a ubiquitous cytosolic co-chaperone. Its presence in neuronal cell bodies reflects general cytoplasmic/cytosolic localization rather than specific neuronal enrichment. Reason: DNAJB1 is ubiquitously expressed. Neuronal cell body localization likely reflects general cytosolic presence rather than specific neuronal targeting. This is an over-annotation from ortholog transfer.
GO:0043197 dendritic spine	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This IEA annotation was transferred from an ortholog by Ensembl Compara. DNAJB1 is a ubiquitous co-chaperone without known specific dendritic spine function. Reason: DNAJB1 is a ubiquitous co-chaperone. Dendritic spine localization from ortholog transfer likely represents general proteostasis rather than specific synaptic function. This is an over-annotation.
GO:0044183 protein folding chaperone	IEA GO_REF:0000107	ACCEPT	Summary: DNAJB1 functions as a protein folding chaperone (foldase-type) as part of the HSP70 machinery. Hageman et al. (PMID:21231916) demonstrated that DNAJB1 supports luciferase refolding when paired with HSP70. This IEA annotation from Ensembl Compara ortholog transfer is accurate. Reason: Protein folding chaperone is the correct MF term for DNAJB1 as a foldase-type J-domain co-chaperone. This is consistent with the proposed replacement for the obsolete GO:0051082 annotations and accurately reflects DNAJB1 core function. 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:0061827 sperm head	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This IEA annotation was transferred from an ortholog by Ensembl Compara. While PMID:21630459 (HDA) independently identifies DNAJB1 in the sperm nucleus proteome, sperm head localization is likely a reflection of general chaperone presence rather than specific function. Reason: Sperm head localization is not a core annotation for DNAJB1 but is supported by independent proteomic evidence (PMID:21630459, HDA for nucleus). Chaperones are expected to be present in spermatozoa for proteostasis. Keep as non-core.
GO:0098794 postsynapse	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This IEA annotation was transferred from an ortholog by Ensembl Compara. DNAJB1 is a ubiquitous co-chaperone; postsynaptic localization is not specific to DNAJB1. Reason: DNAJB1 is ubiquitously expressed. Postsynapse localization from ortholog transfer likely represents general proteostasis presence rather than specific synaptic function. Over-annotation.
GO:0098978 glutamatergic synapse	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This IEA annotation was transferred from an ortholog by Ensembl Compara. DNAJB1 is a ubiquitous co-chaperone without known specific glutamatergic synapse function. Reason: DNAJB1 is ubiquitously expressed. Glutamatergic synapse localization from ortholog transfer likely represents general proteostasis rather than specific synaptic function. Over-annotation.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: DNAJB1 is detected in the nucleoplasm by HPA immunofluorescence (GO_REF:0000052). This is consistent with the known translocation of DNAJB1 to the nucleus upon heat shock (UniProt) and its role in HSF1 regulation in the nucleus (PMID:9499401). Reason: Nucleoplasm localization is consistent with DNAJB1's known nuclear translocation under stress and its role in repressing HSF1 transcriptional activity in the nucleus. HPA immunofluorescence data provides direct evidence.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: DNAJB1 is detected in the cytosol by HPA immunofluorescence (GO_REF:0000052). Consistent with its primary cytosolic localization and role as a cytosolic co-chaperone for HSP70. Reason: Cytosol is the primary localization of DNAJB1 under normal conditions. HPA immunofluorescence confirms this well-established localization.
GO:1900034 regulation of cellular response to heat	TAS Reactome:R-HSA-3371453	ACCEPT	Summary: Reactome R-HSA-3371453 models the regulation of HSF1-mediated heat shock response. DNAJB1 participates in this pathway by repressing HSF1 transcriptional activity together with HSP70 during the attenuation phase (PMID:9499401). Reason: DNAJB1 is a key regulator of the cellular response to heat. It participates in the attenuation of the HSF1-mediated heat shock response by binding HSF1 with HSP70 and repressing transcription (PMID:9499401, Reactome:R-HSA-5082384). This is a well- supported annotation.
GO:0001671 ATPase activator activity	IDA PMID:23921388 Identification and characterization of a novel human methylt...	UNDECIDED	Summary: Jakobsson et al. (PMID:23921388) characterized METTL21A methyltransferase and its effects on HSP70. The paper mentions that J-proteins stimulate intrinsic ATPase activity of HSP70s, but this paper primarily studies METTL21A rather than DNAJB1 directly. Reason: ATPase activator activity is a core molecular function of DNAJB1. As a J-domain co-chaperone, DNAJB1 stimulates the intrinsic ATPase activity of HSP70 family members. However, PMID:23921388 is a METTL21A/HSP70 methylation paper and the cached text does not provide DNAJB1-specific direct evidence for this annotation. Direct support is captured separately from PMID:24318877 and Reactome. Supporting Evidence: PMID:23921388 Hsp70 proteins constitute an evolutionarily conserved protein family of ATP-dependent molecular chaperones involved in a wide range of biological processes.
GO:1903334 positive regulation of protein folding	IDA PMID:23921388 Identification and characterization of a novel human methylt...	UNDECIDED	Summary: Jakobsson et al. (PMID:23921388) studied methylation effects on HSP70 chaperone function. DNAJB1 positively regulates protein folding through its HSP70 co-chaperone role, but this source does not directly establish that activity for DNAJB1. Reason: Positive regulation of protein folding is a sound DNAJB1 function, but PMID:23921388 is not usable as direct DNAJB1-specific evidence from the cached source. Keep the source-specific annotation undecided.
GO:0000122 negative regulation of transcription by RNA polymerase II	IDA PMID:9499401 Molecular chaperones as HSF1-specific transcriptional repres...	KEEP AS NON CORE	Summary: Shi et al. (PMID:9499401) directly demonstrated that Hdj1 (DNAJB1) interacts with the transactivation domain of HSF1 and represses heat shock gene transcription. Overexpression of DNAJB1 represses HSF1-driven transcription. Reason: Directly demonstrated by Shi et al. (PMID:9499401) using overexpression of Hdj1 repressing GAL4-HSF1 activation domain fusion and endogenous HSF1. While experimentally valid, this transcriptional repression is specific to the heat shock attenuation context and is a secondary consequence of co-chaperone activity, not a core function. Supporting Evidence: PMID:9499401 Overexpression of either chaperone represses the transcriptional activity of a transfected GAL4-HSF1 activation domain fusion protein and endogenous HSF1.
GO:0034605 cellular response to heat	IDA PMID:9499401 Molecular chaperones as HSF1-specific transcriptional repres...	ACCEPT	Summary: Shi et al. (PMID:9499401) demonstrated that DNAJB1 (Hdj1) participates in the cellular response to heat by interacting with HSF1 during the attenuation phase of the heat shock response. The heat shock response involves DNAJB1 acting with HSP70 to repress HSF1 transcriptional activity. Reason: DNAJB1 is heat shock-inducible and plays a direct role in the cellular response to heat by participating in the attenuation of HSF1-mediated transcription (PMID:9499401). This is well-supported by direct experimental evidence. Supporting Evidence: PMID:9499401 the molecular chaperone Hsp70 and the cochaperone Hdj1 interact directly with the transactivation domain of HSF1 and repress heat shock gene transcription.
GO:0140416 transcription regulator inhibitor activity	IDA PMID:9499401 Molecular chaperones as HSF1-specific transcriptional repres...	KEEP AS NON CORE	Summary: Shi et al. (PMID:9499401) showed that DNAJB1 (Hdj1) directly inhibits HSF1 transcriptional activity by binding to the HSF1 transactivation domain. This constitutes transcription regulator inhibitor activity. Reason: DNAJB1 inhibits HSF1 transcriptional activity during heat shock attenuation (PMID:9499401). While the annotation is accurate, this is not a core molecular function of DNAJB1 but rather a specialized regulatory activity in the HSF1 heat shock response pathway. Its primary role is as a co-chaperone for HSP70. Supporting Evidence: PMID:9499401 the molecular chaperone Hsp70 and the cochaperone Hdj1 interact directly with the transactivation domain of HSF1 and repress heat shock gene transcription.
GO:0001671 ATPase activator activity	TAS Reactome:R-HSA-5251955	ACCEPT	Summary: Reactome R-HSA-5251955 models HSP40s activating intrinsic ATPase activity of HSP70s in the nucleoplasm. DNAJB1 translocates to the nucleus under heat shock and activates HSP70 ATPase activity there. Reason: ATPase activator activity is a core molecular function of DNAJB1. The Reactome annotation for nucleoplasmic ATPase activation is consistent with DNAJB1's known nuclear translocation under heat shock and its ability to stimulate HSP70 ATPase.
GO:0001671 ATPase activator activity	TAS Reactome:R-HSA-5251959	ACCEPT	Summary: Reactome R-HSA-5251959 models HSP40s activating intrinsic ATPase activity of HSP70s in the cytosol. DNAJB1 is explicitly listed as one of the HSP40s that modulates intrinsic ATPase activity of HSP70s. Reason: ATPase activator activity in the cytosol is a core function of DNAJB1. The Reactome pathway explicitly lists DNAJB1 as an HSP40 that activates HSP70 ATPase activity.
GO:0045296 cadherin binding	HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	MARK AS OVER ANNOTATED	Summary: PMID:25468996 describes an E-cadherin interactome study using quantitative proteomics. DNAJB1 was identified in the cadherin interactome by high-throughput proteomics. This is likely a non-specific interaction due to DNAJB1's general chaperone activity. Reason: Cadherin binding is not a known or expected function of DNAJB1. As a general co-chaperone, DNAJB1 may associate with many cellular protein complexes for proteostasis without specific binding activity. The HDA evidence from a proteomics screen is not sufficient to establish specific cadherin binding as a function.
GO:0051087 protein-folding chaperone binding	IPI PMID:21231916 The diverse members of the mammalian HSP70 machine show dist...	ACCEPT	Summary: Hageman et al. (PMID:21231916) systematically assessed functional differences among HSP70/HSPA and HSP40/DNAJ family members. DNAJB1 was shown to interact with and modulate HSP70 chaperone activity, directly demonstrating protein-folding chaperone binding. Reason: DNAJB1 binds HSP70 chaperones through its J-domain, which is central to its function. PMID:21231916 provides direct evidence of functional DNAJB1-HSP70 interaction in luciferase refolding and polyQ aggregation assays. Supporting Evidence: PMID:21231916 Humans contain many HSP (heat-shock protein) 70/HSPA- and HSP40/DNAJ-encoding genes and most of the corresponding proteins are localized in the cytosol. To test for possible functional differences and/or substrate specificity, we assessed the effect of overexpression of each of these HSPs on refolding of heat-denatured luciferase and on the suppression of aggregation of a non-foldable polyQ (polyglutamine)-expanded Huntingtin fragment.
GO:0001671 ATPase activator activity	IDA PMID:24318877 Binding of human nucleotide exchange factors to heat shock p...	ACCEPT	Summary: Rauch and Gestwicki (PMID:24318877) combined Hsp70-NEF pairs with J proteins including DnaJB1 and measured ATPase and luciferase refolding activities. DNAJB1 was directly shown to stimulate HSP70 ATPase activity in these in vitro assays. Reason: ATPase activator activity is a core molecular function of DNAJB1. PMID:24318877 provides direct biochemical evidence of DNAJB1 stimulating HSP70 ATPase activity in vitro. Supporting Evidence: PMID:24318877 we combined the Hsp70-NEF pairs with cochaperones of the J protein family (DnaJA1, DnaJA2, DnaJB1, and DnaJB4) to generate 16 permutations. The activity of the combinations in ATPase and luciferase refolding assays were dependent on the identity and stoichiometry of both the J protein and NEF
GO:0003714 transcription corepressor activity	IDA PMID:9499401 Molecular chaperones as HSF1-specific transcriptional repres...	KEEP AS NON CORE	Summary: Shi et al. (PMID:9499401) demonstrated that Hdj1 (DNAJB1) represses HSF1 transcriptional activity. Overexpression of DNAJB1 represses both GAL4-HSF1 fusion and endogenous HSF1, functioning as a transcription corepressor in the heat shock response context. Reason: The IDA evidence from PMID:9499401 directly demonstrates corepressor activity on HSF1. This is a duplicate of the IBA annotation for the same term, both supported by the same mechanism. Keep as non-core since transcription corepression is secondary to the primary co-chaperone function. Supporting Evidence: PMID:9499401 Overexpression of either chaperone represses the transcriptional activity of a transfected GAL4-HSF1 activation domain fusion protein and endogenous HSF1.
GO:0005515 protein binding	IPI PMID:9499401 Molecular chaperones as HSF1-specific transcriptional repres...	REMOVE	Summary: Shi et al. (PMID:9499401) showed that Hdj1 (DNAJB1) interacts directly with the transactivation domain of HSF1. This interaction is real but better described by more specific terms (transcription regulator inhibitor activity, protein-folding chaperone binding). Reason: Protein binding is uninformative. The specific interaction with HSF1 described in PMID:9499401 is already captured by the transcription regulator inhibitor activity and transcription corepressor activity annotations. The generic protein binding term adds no additional information.
GO:0005515 protein binding	IPI PMID:27120771 Polyhydramnios, Transient Antenatal Bartter's Syndrome, and ...	REMOVE	Summary: PMID:27120771 concerns MAGED2 mutations and Bartter's syndrome. The paper mentions interaction with a cytoplasmic heat-shock protein but DNAJB1 is not the focus. This protein binding annotation is tangential to DNAJB1 function. Reason: Protein binding is uninformative. PMID:27120771 is primarily about MAGED2 and Bartter's syndrome. Any interaction with DNAJB1 described here is tangential and the generic protein binding term adds no useful information about DNAJB1 function.
GO:0005737 cytoplasm	IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	ACCEPT	Summary: PMID:25468996 is an E-cadherin interactome study. DNAJB1 being detected in the cytoplasm is consistent with its known primary cytoplasmic localization. However, the IDA evidence code from a proteomics study is appropriate. Reason: Cytoplasmic localization of DNAJB1 is well-established and consistent with UniProt subcellular location data. Acceptable as independent confirmation.
GO:0001671 ATPase activator activity	IDA PMID:20060297 Chaperone-assisted selective autophagy is essential for musc...	UNDECIDED	Summary: Arndt et al. (PMID:20060297) described chaperone-assisted selective autophagy (CASA) for muscle maintenance. The paper focuses on BAG-3 coordinating Hsc70 and HspB8 during degradation of damaged Z disk components. DNAJB1 ATPase activator activity may be referenced in the context of the HSP70 chaperone cycle but this paper primarily studies the BAG3/CASA pathway. Reason: ATPase activator activity is a core function of DNAJB1. While PMID:20060297 focuses on CASA, the cached text does not provide DNAJB1-specific ATPase activation evidence. Direct support is already represented by PMID:24318877 and Reactome, so this particular IDA annotation should not be accepted on the basis of a mismatched source. Supporting Evidence: PMID:20060297 Stv and its mammalian ortholog BAG-3 coordinate the activity of Hsc70 and the small heat shock protein HspB8 during disposal that is initiated by the chaperone-associated ubiquitin ligase CHIP and the autophagic ubiquitin adaptor p62.
GO:0030544 Hsp70 protein binding	IPI PMID:23921388 Identification and characterization of a novel human methylt...	UNDECIDED	Summary: Jakobsson et al. (PMID:23921388) studied METTL21A methyltransferase effects on HSP70. HSP70 binding is a core interaction for DNAJB1, but this source focuses on METTL21A and does not provide accessible DNAJB1-specific interaction evidence in the cached text. Reason: Hsp70 protein binding is a core molecular function of DNAJB1 as a J-domain co-chaperone. The J-domain of DNAJB1 directly binds HSP70 to stimulate ATPase activity, but PMID:23921388 is not the supporting source to establish that specific DNAJB1 interaction. Supporting Evidence: PMID:23921388 Hsp70 proteins constitute an evolutionarily conserved protein family of ATP-dependent molecular chaperones involved in a wide range of biological processes.
GO:0051117 ATPase binding	IPI PMID:23921388 Identification and characterization of a novel human methylt...	UNDECIDED	Summary: DNAJB1 binds to the ATPase domain of HSP70 through its J-domain. Jakobsson et al. ATPase binding is consistent with DNAJB1's mechanism of action, but PMID:23921388 provides METTL21A/HSP70 methylation context rather than direct DNAJB1 ATPase-domain binding evidence. Reason: ATPase binding accurately describes DNAJB1's interaction with the ATPase domain of HSP70 via its J-domain. The action is undecided for this source-specific IPI because the cached PMID:23921388 evidence does not establish the interaction.
GO:0005829 cytosol	TAS Reactome:R-HSA-5690250	ACCEPT	Summary: Reactome R-HSA-5690250 describes phosphorylation of DNAJB1 by MAPKAPK5 in the cytosol. Cytosolic localization of DNAJB1 is well-established and this Reactome annotation is consistent. Reason: Cytosol is the primary localization of DNAJB1. The Reactome pathway for MAPKAPK5 phosphorylation of DNAJB1 correctly places this event in the cytosol.
GO:0005515 protein binding	IPI PMID:23921388 Identification and characterization of a novel human methylt...	REMOVE	Summary: PMID:23921388 studies METTL21A methyltransferase and its effects on HSP70. The protein binding annotation is uninformative, and the cached source does not provide DNAJB1-specific interaction evidence. Reason: Protein binding is too generic for curation. PMID:23921388 is a METTL21A/HSP70 methylation paper rather than a source establishing a specific DNAJB1 interaction.
GO:0005829 cytosol	IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist...	ACCEPT	Summary: Hageman et al. (PMID:21231916) noted that most HSP70/HSPA and HSP40/DNAJ proteins are localized in the cytosol. This directly supports cytosolic localization of DNAJB1. Reason: Cytosolic localization is directly stated in PMID:21231916. This is consistent with other evidence for DNAJB1 as a primarily cytosolic co-chaperone. Supporting Evidence: PMID:21231916 Humans contain many HSP (heat-shock protein) 70/HSPA- and HSP40/DNAJ-encoding genes and most of the corresponding proteins are localized in the cytosol.
GO:0051082 unfolded protein binding	IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist...	MODIFY	Summary: GO:0051082 (unfolded protein binding) is now formally obsolete (go-ontology#30962). This IDA annotation from Hageman et al. (PMID:21231916) demonstrated that DNAJB1 interacts with unfolded/denatured substrates in the context of the HSP70 chaperone machinery. The study assessed effects of overexpression of HSP70/HSPA and HSP40/DNAJ family members on refolding of heat-denatured luciferase and suppression of polyQ aggregation. DNAJB1 promoted efficient luciferase refolding when paired with HSP70, classifying it as a foldase-type co-chaperone. Unlike DNAJB6 and DNAJB8, which have independent holdase/anti-aggregation activity, DNAJB1 primarily functions by delivering substrates to HSP70 and stimulating HSP70 ATPase activity for the protein folding cycle. UniProt confirms that DNAJB1 stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B in vitro (PMID:24318877). The appropriate replacement is GO:0044183 (protein folding chaperone), which accurately captures DNAJB1's role in binding proteins to assist folding as part of the HSP70 machine. Reason: GO:0051082 is now formally obsolete (go-ontology#30962), with the recommended replacement being GO:0044183 (protein folding chaperone) for foldase-type chaperones or holdase chaperone activity for holdases. Hageman et al. (PMID:21231916) is the key reference for this IDA annotation. The paper showed that DNAJB1 belongs to the foldase class of J-domain co-chaperones: it promotes luciferase refolding when combined with HSP70 but is a poor suppressor of polyQ aggregation. This functional classification is consistent with DNAJB1's known mechanism as a class II J-domain protein that stimulates HSP70 ATPase activity and delivers substrates to the HSP70 folding machinery. Additionally, DNAJB1 is a component of the Hsp70 disaggregation machinery, working with Hsp70 and HSPA4 to disassemble protein aggregates in an ATP-dependent process. The correct replacement term is GO:0044183 (protein folding chaperone), defined as binding to a protein or protein-containing complex to assist the protein folding process. 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. PMID:21231916 Humans contain many HSP (heat-shock protein) 70/HSPA- and HSP40/DNAJ-encoding genes and most of the corresponding proteins are localized in the cytosol. To test for possible functional differences and/or substrate specificity, we assessed the effect of overexpression of each of these HSPs on refolding of heat-denatured luciferase and on the suppression of aggregation of a non-foldable polyQ (polyglutamine)-expanded Huntingtin fragment.
GO:0090084 negative regulation of inclusion body assembly	IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist...	KEEP AS NON CORE	Summary: Hageman et al. (PMID:21231916) showed that DNAJB1 overexpression suppresses polyQ aggregation (inclusion body assembly), though it was a poor suppressor compared to holdase-type chaperones like DNAJB6 and DNAJB8. The paper states that chaperones that supported luciferase refolding were poor suppressors of polyQ aggregation, and DNAJB1 falls into the foldase category. Reason: DNAJB1 can negatively regulate inclusion body assembly but is not primarily an anti-aggregation chaperone. Hageman et al. (PMID:21231916) showed that foldase-type chaperones like DNAJB1 are poor suppressors of polyQ aggregation compared to holdases like DNAJB6/DNAJB8. The annotation is valid but represents a minor aspect of DNAJB1 function. Keep as non-core. 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:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	ACCEPT	Summary: PMID:21630459 is a proteomic characterization of the human sperm nucleus. DNAJB1 was identified in the sperm nuclear proteome by mass spectrometry. This is consistent with known nuclear localization of DNAJB1. Reason: Nuclear localization of DNAJB1 is well-established from UniProt (stress-induced translocation) and HPA immunofluorescence. Detection in the sperm nucleus proteome by mass spectrometry provides additional supporting evidence.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3371467	ACCEPT	Summary: Reactome R-HSA-3371467 models SIRT1 deacetylation of HSF1. DNAJB1 is included in this pathway as part of the HSF1 regulatory complex in the nucleoplasm. Reason: Nucleoplasm localization is consistent with DNAJB1's role in HSF1 regulation in the nucleus during heat shock attenuation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3371518	ACCEPT	Summary: Reactome R-HSA-3371518 models SIRT1 binding to HSF1. DNAJB1 participates in the nucleoplasmic HSF1 regulatory complex. Reason: Nucleoplasm localization during heat shock response regulation is consistent with DNAJB1's known stress-induced nuclear translocation and HSF1 binding activity.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3371554	ACCEPT	Summary: Reactome R-HSA-3371554 models HSF1 acetylation at Lys80. DNAJB1 participates in this HSF1 regulatory pathway in the nucleoplasm. Reason: DNAJB1 is part of the HSF1 regulatory complex in the nucleoplasm during heat shock attenuation. Consistent with known biology.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5082356	ACCEPT	Summary: Reactome R-HSA-5082356 models HSF1-mediated gene expression. DNAJB1 is placed in the nucleoplasm as part of the HSF1 attenuation mechanism. Reason: DNAJB1 localizes to the nucleoplasm during the heat shock response to participate in HSF1 regulation. Consistent with UniProt and PMID:9499401.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5082369	ACCEPT	Summary: Reactome R-HSA-5082369 models acetylated HSF1 dissociation from DNA. DNAJB1 is part of the HSF1 attenuation complex in the nucleoplasm. Reason: DNAJB1 nucleoplasm localization is consistent with its role in HSF1 regulation during heat shock attenuation.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5082384	ACCEPT	Summary: Reactome R-HSA-5082384 specifically models HSP70:DNAJB1 binding HSF1 in the nucleoplasm. Shi et al. (PMID:9499401) showed that Hsp70 and Hdj1 interact with the HSF1 activation domain and repress transcription. Reason: This Reactome entry directly models the DNAJB1-HSP70-HSF1 interaction in the nucleoplasm, which is a well-characterized mechanism of heat shock attenuation (PMID:9499401).
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5251955	ACCEPT	Summary: Reactome R-HSA-5251955 models HSP40s activating HSP70 ATPase activity in the nucleoplasm. DNAJB1 is explicitly listed as one of the HSP40s that stimulates HSP70 ATPase activity in this compartment. Reason: Nucleoplasm localization is consistent with DNAJB1's nuclear translocation under heat shock and its ATPase activator function in the nucleoplasm.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: PMID:19056867 is a large-scale proteomics study of urinary exosomes. Detection of DNAJB1 in exosomes by mass spectrometry may represent passive inclusion rather than specific exosomal targeting. Reason: Detection in extracellular exosomes by proteomics (PMID:19056867) is valid but represents a non-specific finding. Many cytosolic proteins are found in exosomes without specific functional significance. Keep as non-core.
GO:0005829 cytosol	TAS Reactome:R-HSA-5251959	ACCEPT	Summary: Reactome R-HSA-5251959 models HSP40s activating HSP70 ATPase activity in the cytosol. DNAJB1 is one of the HSP40s that activates HSP70 ATPase in the cytosol. Reason: Cytosol is the primary location of DNAJB1. The Reactome pathway correctly places DNAJB1 ATPase activator function in the cytosol.
GO:0005829 cytosol	TAS Reactome:R-HSA-5690245	ACCEPT	Summary: Reactome R-HSA-5690245 models the binding of phosphorylated MAPKAPK5 to DNAJB1 in the cytosol. Cytosolic localization is consistent with known DNAJB1 biology. Reason: Cytosol localization is consistent with DNAJB1 primary localization. The Reactome pathway for MAPKAPK5 binding to DNAJB1 correctly places this interaction in the cytosol.
GO:0006457 protein folding	IDA PMID:18620420 Role of the cochaperone Tpr2 in Hsp90 chaperoning.	UNDECIDED	Summary: Moffatt et al. (PMID:18620420) studied the role of the cochaperone Tpr2 in Hsp90 chaperoning. The paper mentions that Tpr2 replaced type I and II J proteins (including DNAJB1-type) in Hsp90-dependent chaperoning. The source is Tpr2-centered and does not provide direct DNAJB1 protein-folding evidence in the cached text. Reason: Protein folding is a core function of DNAJB1. PMID:18620420 provides evidence that J-protein-like functions participate in chaperone cycles, but this paper focuses on Tpr2 and does not establish a DNAJB1-specific IDA annotation. Keep this source-specific annotation undecided. Supporting Evidence: PMID:18620420 Tpr2 replaced type I and II J proteins in the Hsp90-dependent chaperoning of the PR and the protein kinase, Chk1.
GO:0006986 response to unfolded protein	TAS PMID:8975727 Genomic cloning of a human heat shock protein 40 (Hsp40) gen...	ACCEPT	Summary: Hata et al. (PMID:8975727) cloned the genomic DNA for human Hsp40 (DNAJB1) and characterized its gene structure. The 5-prime region contains typical heat shock elements, indicating stress-responsive expression consistent with response to unfolded protein. Reason: DNAJB1 (Hsp40) is a heat shock protein with heat shock elements in its promoter (PMID:8975727), indicating stress-responsive induction. As a co-chaperone for HSP70 that assists in folding unfolded proteins, response to unfolded protein is an appropriate biological process annotation. Supporting Evidence: PMID:8975727 The 5' region of the gene is highly GC rich, and there are multiple basal elements for transcription factors including typical heat shock elements.

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