DNAJC5B (cysteine-string protein isoform beta, CSP-beta) is a testis-specific paralog of the synaptic co-chaperone CSPalpha/DNAJC5. Like other cysteine string proteins it has an N-terminal J domain that engages the constitutive HSP70 chaperone HSC70/HSPA8 and a downstream cysteine-string region that can be palmitoylated. CSP-beta interacts with the HSC70-SGTA chaperone complex and is membrane-anchored, associating with the trans-Golgi network; unlike CSPalpha its membrane association does not require palmitoylation. Its physiological role is presumed to be HSP70 co-chaperone activity in a secretory/membrane-trafficking context of the testis, but it is otherwise poorly characterized.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic cytoplasm annotation. CSP-beta is a membrane-anchored co-chaperone with a cytoplasmic-facing pool. Reason: Generic cytoplasm localization; consistent with a J-domain co-chaperone but less informative than its membrane/TGN association. Supporting Evidence: file:human/DNAJC5B/DNAJC5B-uniprot.txt Interacts with the chaperone complex consisting of HSC70 |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Membrane localization from UniProt subcellular-location mapping, experimentally supported by detection as a lipid-anchored, TGN-associated protein. Reason: CSP-beta is experimentally documented as a membrane (lipid-anchor) protein that may associate with the trans-Golgi network; membrane is its core compartment. Supporting Evidence: file:human/DNAJC5B/DNAJC5B-uniprot.txt SUBCELLULAR LOCATION: Membrane |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Proteome-scale yeast two-hybrid map capturing a CSP-beta-TFCP2 interaction. The bare protein binding term is uninformative and the partner (the transcription factor TFCP2/CP2) does not define a chaperone function. Reason: Records a single high-throughput interaction; bare protein binding is uninformative and is not elevated to core. Supporting Evidence: file:human/DNAJC5B/DNAJC5B-uniprot.txt Q9UF47; Q12800: TFCP2; NbExp=3 |
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Download this section (compressed HTML)Q: What is the testis-specific physiological function of CSP-beta, and does it chaperone a secretory or membrane-trafficking client analogous to CSPalpha's SNAP-25?
Q: Does CSP-beta stimulate HSC70 ATPase activity via its J domain, and how does its palmitoylation-independent membrane targeting differ mechanistically from CSPalpha?
Experiment: Reconstituted HSC70 ATPase assays with purified CSP-beta (wild-type and J-domain HPD mutant) to confirm co-chaperone activity.
Experiment: Affinity purification-mass spectrometry of tagged CSP-beta from a testis-derived or beta-cell line to identify its client/interaction network and any secretory-pathway partners.
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