DNAJB5 (Hsc40, "heat shock protein cognate 40") is a cytosolic HSP40/J-domain co-chaperone of the DNAJB subfamily and a paralog of DNAJB1 and DNAJB4. Through its N-terminal J domain it is predicted to bind and stimulate the HSP70 chaperone (HSPA1A/HSPA1B/HSPA8), acting as a co-chaperone that delivers client proteins to HSP70 for folding. It is expressed constitutively and further induced by stress, is enriched in skeletal muscle and tongue, and produces several alternatively spliced isoforms. Compared with its better-studied paralogs it remains poorly characterized, with most molecular data derived from family-level inference and high-throughput interaction studies.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006457 protein folding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) annotation that DNAJB5 participates in protein folding as a J-protein co-chaperone. DNAJB5 assists the HSP70 folding machine rather than autonomously catalyzing folding. Reason: Protein folding is a downstream process outcome of DNAJB5's co-chaperone role; the direct molecular activity is HSP70 binding/stimulation, so folding is non-core. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0006457 protein folding biological_process ECO:0000318 IBA GO_REF:0000033 |
| GO:0051087 protein-folding chaperone binding | IBA GO_REF:0000033 | ACCEPT | Summary: DNAJB5 binds the HSP70 chaperone, the defining molecular interaction of a J-protein co-chaperone. Supported phylogenetically and by IPI evidence against HSP70 isoforms. Reason: HSP70 binding is the core co-chaperone molecular function of DNAJB5 and is corroborated by experimental IPI annotations to HSPA1A/HSPA1B. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0051087 protein-folding chaperone binding molecular_function ECO:0000353 IPI PMID:21231916 UniProtKB:P0DMV8 |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: DNAJB5 is a cytosolic J-protein; cytosolic site of action is supported phylogenetically and by direct IDA evidence (PubMed:21231916). Reason: The cytosol is the compartment in which DNAJB5 acts as an HSP70 co-chaperone, consistent with the IDA cytosol annotation. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0005829 cytosol cellular_component ECO:0000314 IDA PMID:21231916 |
| GO:0006457 protein folding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based electronic annotation of protein folding, redundant with the IBA protein folding call. Reason: Same downstream-process rationale as the IBA protein folding annotation; DNAJB5 assists rather than autonomously catalyzes folding. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0006457 protein folding biological_process ECO:0000256 IEA GO_REF:0000002 InterPro:IPR008971 |
| GO:0006986 response to unfolded protein | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Rule-based electronic annotation that DNAJB5 participates in the response to unfolded protein, consistent with its stress-inducible expression and chaperone role. Reason: Consistent with DNAJB5's stress induction and client-handling role; a genuine process annotation but downstream of its molecular co-chaperone function. Supporting Evidence: file:human/DNAJB5/DNAJB5-uniprot.txt Expressed under normal conditions, its expression can further be increased after various stress treatments. |
| GO:0051087 protein-folding chaperone binding | IEA GO_REF:0000117 | ACCEPT | Summary: Rule-based electronic annotation of chaperone (HSP70) binding, redundant with the IBA and IPI protein-folding chaperone binding annotations. Reason: Correct molecular function; DNAJB5 binds HSP70, supported by stronger IPI/IBA evidence. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0051087 protein-folding chaperone binding molecular_function ECO:0000256 IEA GO_REF:0000117 |
| GO:0005515 protein binding | IPI PMID:18457437 Identification of intracellular proteins associated with the... | KEEP AS NON CORE | Summary: High-throughput interaction capturing DNAJB5 with the Epstein-Barr virus nuclear antigen EBNA-LP (Q8AZK7). Bare protein binding is uninformative and this cross-species viral interaction does not define DNAJB5's core function. Reason: Records a real (viral) interaction but bare protein binding is uninformative per curation guidelines; not part of the core chaperone function. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18457437 UniProtKB:Q8AZK7 |
| GO:0005515 protein binding | IPI PMID:21078624 Comparison of an expanded ataxia interactome with patient me... | KEEP AS NON CORE | Summary: Expanded ataxia interactome screen capturing DNAJB5 with the calcium channel subunit CACNA1A (O00555). Bare protein binding is uninformative. Reason: Records a real high-throughput interaction but bare protein binding is uninformative; the CACNA1A partner does not define DNAJB5's core chaperone function. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21078624 UniProtKB:O00555 |
| GO:0005515 protein binding | IPI PMID:22810586 Interpreting cancer genomes using systematic host network pe... | KEEP AS NON CORE | Summary: Cancer host-network perturbation interactome again capturing the DNAJB5-EBNA-LP (Q8AZK7) interaction. Bare protein binding is uninformative. Reason: Records a real high-throughput interaction but bare protein binding is uninformative and not part of the core function. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:22810586 UniProtKB:Q8AZK7 |
| GO:0005515 protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | KEEP AS NON CORE | Summary: Human skeletal-muscle interactome capturing DNAJB5 with titin (TTN, Q8WZ42). Bare protein binding is uninformative, though a titin interaction together with DNAJB5's skeletal-muscle enrichment is suggestive of a sarcomeric role analogous to its paralogs. Reason: Records a real high-throughput interaction; bare protein binding is uninformative as a core MF, and a muscle/sarcomere role for DNAJB5 is not yet functionally demonstrated. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23414517 UniProtKB:Q8WZ42 |
| GO:0005634 nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl ortholog-based electronic annotation of nuclear localization, transferred from the mouse ortholog. DNAJB5's experimentally supported localization is cytosolic; a nuclear pool is not independently demonstrated for the human protein. Reason: Orthology-projected nuclear localization without direct human evidence; DNAJB5 is characterized as a cytosolic co-chaperone, so a nuclear pool is at best secondary/non-core. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0005634 nucleus cellular_component ECO:0000265 IEA GO_REF:0000107 |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl ortholog-based electronic annotation of cytosolic localization, consistent with the IDA and IBA cytosol annotations. Reason: Correct compartment for this cytosolic co-chaperone; agrees with stronger IDA/IBA cytosol evidence. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0005829 cytosol cellular_component ECO:0000265 IEA GO_REF:0000107 |
| GO:0051087 protein-folding chaperone binding | IPI PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | ACCEPT | Summary: Functional study of the mammalian HSP70/DNAJ machine; DNAJB5 binds HSP70 isoforms (HSPA1A/HSPA1B) as a co-chaperone. This is the most direct molecular evidence for DNAJB5's function. Reason: Binding to HSP70 chaperones is the core molecular interaction of DNAJB5 as a J-protein co-chaperone. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0051087 protein-folding chaperone binding molecular_function ECO:0000353 IPI PMID:21231916 UniProtKB:P0DMV8 |
| GO:0005829 cytosol | IDA PMID:21231916 The diverse members of the mammalian HSP70 machine show dist... | ACCEPT | Summary: Direct evidence places DNAJB5 in the cytosol, consistent with its co-chaperone role and all other localization data. Reason: IDA cytosol localization corroborates the established cytosolic site of action. Supporting Evidence: file:human/DNAJB5/DNAJB5-goa.tsv GO:0005829 cytosol cellular_component ECO:0000314 IDA PMID:21231916 |
| GO:0006986 response to unfolded protein | IEP PMID:10570961 Hsc40, a new member of the hsp40 family, exhibits similar ex... | KEEP AS NON CORE | Summary: The original Hsc40 cloning/characterization paper reports expression behavior (constitutive plus stress-inducible) supporting involvement in the response to unfolded protein, inferred from expression patterns (IEP). Reason: Expression-based (IEP) evidence for stress involvement; consistent with DNAJB5's chaperone role but a downstream process annotation rather than its molecular function. Supporting Evidence: file:human/DNAJB5/DNAJB5-uniprot.txt Expressed under normal conditions, its expression can further be increased after various stress treatments. |
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Download this section (compressed HTML)Q: Does DNAJB5 stimulate HSP70 ATPase activity and refold/disaggregate clients autonomously, or is it functionally redundant with DNAJB1/DNAJB4 in the cytosol?
Q: Given its skeletal-muscle enrichment and titin interaction, does DNAJB5 have a sarcomeric/Z-disc proteostasis role analogous to DNAJB4 and DNAJB6?
Experiment: In vitro reconstitution measuring DNAJB5-dependent stimulation of HSP70 ATPase and luciferase refolding/disaggregation, benchmarked against DNAJB1 and DNAJB4.
Experiment: Affinity purification-mass spectrometry of tagged DNAJB5 in muscle cells to define its physiological client/interaction network and test the titin/sarcomere association.
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