DNAJC9 (also called HDJC9 or DnaJ protein SB73) is a type C DnaJ/Hsp40 (DNAJC) co-chaperone with an N-terminal J domain and a C-terminal histone-binding domain. It has a dual role as a histone H3-H4 chaperone and an HSP70 heat-shock co-chaperone. As a histone chaperone it forms a co-chaperone complex with MCM2 and histone H3-H4 heterodimers, binds H3 variants (H3.1, H3.2, H3.3) and H4, and integrates HSP70-mediated ATP-driven protein folding into the histone supply chain during replication- and transcription-coupled nucleosome assembly, helping to resolve aberrant histone-folding intermediates and assemble histones into nucleosomes. Its J domain recruits and stimulates the ATPase activity of HSP70-type chaperones (HSPA1A, HSPA1B, HSPA8). DNAJC9 is predominantly nuclear under normal conditions and translocates to the cytoplasm and plasma membrane after heat shock via a non-classical, lipid-dependent pathway; its expression is induced by heat shock, LPS, PMA and TNF.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred nuclear localization, consistent with the experimentally established predominantly nuclear localization where DNAJC9 acts as a histone chaperone. Reason: Nucleus is the principal site of DNAJC9's core histone-chaperone function and is supported by direct experimental evidence (PMID:17182002, PMID:33857403). Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17182002}. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically inferred cytoplasmic localization. For DNAJC9, cytoplasmic localization arises mainly upon heat-shock translocation; the predominant resting compartment is the nucleus. Reason: Cytoplasmic localization reflects stress-induced relocalization rather than the predominant nuclear site of the core histone-chaperone function. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt Translocates to the cytoplasm and membrane after heat shock. |
| GO:0031072 heat shock protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: DNAJC9 binds HSP70-family chaperones (HSPA1A, HSPA1B, HSPA8) via its J domain, a core molecular function shared across the DNAJC9 orthologous group. Reason: Direct binding of HSP70 chaperones via the J domain is experimentally documented and is core to DNAJC9's co-chaperone activity. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt Interacts (via J domain) with HSPA1A, HSPA1B and HSPA8 |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Automated subcellular-location transfer of nuclear localization, the predominant compartment of DNAJC9. Reason: Nucleus is the experimentally supported principal compartment of DNAJC9's histone-chaperone function. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17182002}. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Automated transfer of cytoplasmic localization, which for DNAJC9 reflects heat-shock-induced translocation rather than the resting nuclear pool. Reason: Cytoplasmic localization is a stress-induced, non-core context for this predominantly nuclear histone chaperone. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt Translocates to the cytoplasm and membrane after heat shock. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Automated transfer of plasma membrane localization, which for DNAJC9 reflects a heat-shock-induced, non-classical lipid-dependent translocation. Reason: Plasma membrane localization is a specialized stress-induced context, peripheral to the core nuclear histone-chaperone function. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt it is transported into cytoplasm and plasma membrane upon heat shock stress through a non-classical and lipid-dependent pathway |
| GO:0005515 protein binding | IPI PMID:19410544 Centromere-specific assembly of CENP-a nucleosomes is mediat... | KEEP AS NON CORE | Summary: High-throughput interaction (IntAct WITH histone H3, P68431). The bare protein binding term records a real interaction but is uninformative; it reflects histone binding. Reason: Bare protein binding is uninformative; the informative function (histone binding) is captured by the dedicated histone binding annotation. Supporting Evidence: file:human/DNAJC9/DNAJC9-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19410544 UniProtKB:P68431 |
| GO:0005515 protein binding | IPI PMID:25281560 Proximity biotinylation and affinity purification are comple... | KEEP AS NON CORE | Summary: High-throughput interaction (IntAct WITH histone H3, P68431). Bare protein binding term reflecting histone binding. Reason: Bare protein binding is uninformative; the informative histone-binding function is captured separately. Supporting Evidence: file:human/DNAJC9/DNAJC9-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25281560 UniProtKB:P68431 |
| GO:0005515 protein binding | IPI PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive... | KEEP AS NON CORE | Summary: High-throughput interaction (IntAct WITH histone H3, P68431). Bare protein binding term reflecting histone binding. Reason: Bare protein binding is uninformative; the informative histone-binding function is captured separately. Supporting Evidence: file:human/DNAJC9/DNAJC9-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:29568061 UniProtKB:P68431 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: High-throughput interactions (IntAct WITH histone H3 P68431, H3-5 Q6NXT2, and MORN4 Q8NDC4). Bare protein binding term; the histone interactions reflect histone binding. Reason: Bare protein binding is uninformative; the histone interactions are captured by the dedicated histone binding annotation, and the MORN4 hit is an isolated high-throughput partner. Supporting Evidence: file:human/DNAJC9/DNAJC9-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:P68431 |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence showing nucleoplasmic localization, consistent with the predominantly nuclear histone-chaperone function. Reason: Nucleoplasm is a precise cellular-component annotation matching DNAJC9's principal nuclear site of action. Supporting Evidence: file:human/DNAJC9/DNAJC9-goa.tsv GO:0005654 nucleoplasm cellular_component ECO:0000314 IDA GO_REF:0000052 |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence showing cytosolic localization, consistent with the cytoplasmic pool of DNAJC9 (enhanced after heat shock). Reason: Cytosolic localization is a genuine but secondary compartment relative to the predominant nuclear site of action. Supporting Evidence: file:human/DNAJC9/DNAJC9-goa.tsv GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052 |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence showing plasma membrane localization, consistent with the heat-shock-induced translocation of DNAJC9. Reason: Plasma membrane localization is a stress-induced, non-core context for this predominantly nuclear histone chaperone. Supporting Evidence: file:human/DNAJC9/DNAJC9-goa.tsv GO:0005886 plasma membrane cellular_component ECO:0000314 IDA GO_REF:0000052 |
| GO:0005515 protein binding | IPI PMID:33857403 DNAJC9 integrates heat shock molecular chaperones into the h... | MODIFY | Summary: Structure-guided proteomics (Hammond et al.) capturing direct DNAJC9 interactions with histones H3.1/H3.2/H3.3 and H4, MCM2 and HSP70 (HSPA8). The bare term is uninformative; the central interaction is direct histone binding. Reason: Bare protein binding is uninformative. The biologically informative interaction demonstrated here is direct binding of histone H3-H4 substrates, best captured by histone binding (GO:0042393). Proposed replacements: histone binding Supporting Evidence: PMID:33857403 this dual histone and heat shock co-chaperone binds histone substrates |
| GO:0006334 nucleosome assembly | IDA PMID:33857403 DNAJC9 integrates heat shock molecular chaperones into the h... | ACCEPT | Summary: DNAJC9 functions in the histone supply chain during replication- and transcription-coupled nucleosome assembly and can assemble histones onto DNA in vitro, supporting this process annotation. Reason: Direct experimental evidence places DNAJC9 in nucleosome assembly as part of its histone-chaperone function. Supporting Evidence: PMID:33857403 during replication- and transcription-coupled nucleosome assembly |
| GO:0042393 histone binding | IDA PMID:33857403 DNAJC9 integrates heat shock molecular chaperones into the h... | ACCEPT | Summary: DNAJC9 binds histone H3-H4 substrates directly (structurally defined in complex with MCM2 and H3.3-H4). This is a core molecular function. Reason: Direct, structurally defined binding of histone H3-H4 substrates is a core molecular function of DNAJC9 as a histone chaperone. Supporting Evidence: PMID:33857403 this dual histone and heat shock co-chaperone binds histone substrates |
| GO:0051087 protein-folding chaperone binding | IDA PMID:33857403 DNAJC9 integrates heat shock molecular chaperones into the h... | ACCEPT | Summary: DNAJC9 binds chaperone partners (MCM2 and HSP70-type enzymes) within the histone co-chaperone complex, consistent with chaperone-binding function. Reason: DNAJC9 directly binds the histone chaperone MCM2 and recruits HSP70 enzymes, supporting protein-folding chaperone binding. Supporting Evidence: PMID:33857403 DNAJC9 recruits HSP70-type enzymes via its J domain to fold histone H3-H4 substrates |
| GO:0101031 protein folding chaperone complex | IDA PMID:33857403 DNAJC9 integrates heat shock molecular chaperones into the h... | ACCEPT | Summary: DNAJC9 is part of a co-chaperone complex with MCM2 and histone H3-H4, a bona fide protein-folding chaperone complex defined structurally. Reason: DNAJC9 is a structurally characterized component of an MCM2-histone co-chaperone complex, supporting this complex annotation. Supporting Evidence: PMID:33857403 in a histone H3-H4 co-chaperone complex with MCM2 |
| GO:0005576 extracellular region | IDA PMID:17182002 HDJC9, a novel human type C DnaJ/HSP40 member interacts with... | KEEP AS NON CORE | Summary: Detection at the cell surface/extracellular context following heat-shock-induced translocation. Peripheral to DNAJC9's nuclear histone-chaperone role. Reason: Extracellular/cell-surface localization arises from a stress-induced non-classical translocation and is not part of the core function. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt it is transported into cytoplasm and plasma membrane upon heat shock stress through a non-classical and lipid-dependent pathway |
| GO:0005634 nucleus | IDA PMID:17182002 HDJC9, a novel human type C DnaJ/HSP40 member interacts with... | ACCEPT | Summary: Direct experimental evidence that DNAJC9 is mainly localized in cell nuclei under normal conditions. Reason: Nucleus is the experimentally established predominant compartment of DNAJC9. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt HDJC9 is mainly localized in cell nuclei under normal culture conditions |
| GO:0005737 cytoplasm | IDA PMID:17182002 HDJC9, a novel human type C DnaJ/HSP40 member interacts with... | KEEP AS NON CORE | Summary: Direct evidence for cytoplasmic localization, observed mainly after heat-shock translocation from the nucleus. Reason: Cytoplasmic localization is a stress-induced relocalization, secondary to the predominant nuclear site of action. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt Translocates to the cytoplasm and membrane after heat shock. |
| GO:0005886 plasma membrane | IDA PMID:17182002 HDJC9, a novel human type C DnaJ/HSP40 member interacts with... | KEEP AS NON CORE | Summary: Direct evidence for plasma membrane localization following heat-shock-induced non-classical translocation. Reason: Plasma membrane localization is a specialized stress-induced context, peripheral to the core nuclear histone-chaperone function. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt it is transported into cytoplasm and plasma membrane upon heat shock stress through a non-classical and lipid-dependent pathway |
| GO:0031072 heat shock protein binding | IPI PMID:17182002 HDJC9, a novel human type C DnaJ/HSP40 member interacts with... | ACCEPT | Summary: DNAJC9 directly interacts with HSP70-family proteins (HSPA1A, HSPA1B, HSPA8, HSPA1L) through its J domain, a core molecular function. Reason: Direct J-domain-dependent binding of HSP70 chaperones is experimentally documented and central to DNAJC9's co-chaperone activity. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt HDJC9 can interact with HSP70s and activate the ATPase activity of HSP70s, both of which are dependent on the J domain |
| GO:0032781 positive regulation of ATP-dependent activity | IDA PMID:17182002 HDJC9, a novel human type C DnaJ/HSP40 member interacts with... | ACCEPT | Summary: DNAJC9's J domain activates the ATPase activity of HSP70, the defining activity of J-domain co-chaperones. This is the core molecular activity, captured here as a process-level term. Reason: J-domain-dependent stimulation of HSP70 ATPase activity is directly demonstrated and is central to DNAJC9's function. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt HDJC9 can interact with HSP70s and activate the ATPase activity of HSP70s, both of which are dependent on the J domain |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | ACCEPT | Summary: High-throughput proteomics detection of nuclear localization, consistent with the predominant nuclear localization of DNAJC9. Reason: Nuclear localization is corroborated by direct experimental evidence and is the core compartment of DNAJC9. Supporting Evidence: file:human/DNAJC9/DNAJC9-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17182002}. |
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Download this section (compressed HTML)Q: How is the choice between DNAJC9's nuclear histone-chaperone role and its cytoplasmic/membrane heat-shock-stress role regulated, and is the J-domain ATPase stimulation of HSP70 used in both contexts?
Q: Does DNAJC9 act as a general quality-control "clean-up" factor that resolves aberrant histone-folding intermediates across multiple histone chaperone handover steps?
Experiment: Reconstitute the DNAJC9-MCM2-H3-H4 complex with HSP70 and measure J-domain-dependent HSP70 ATPase stimulation and refolding of destabilized histone H3-H4, comparing wild-type with the HPD (J-domain) and histone-binding-region mutants.
Experiment: Acute degron depletion of DNAJC9 followed by genome-wide nucleosome occupancy and nascent-chromatin proteomics to define its requirement in replication- and transcription-coupled nucleosome assembly.
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