DNAJC25 (DnaJ homolog subfamily C member 25) is a poorly characterized multi-pass membrane protein of the HSP40/DnaJ co-chaperone family. It has an N-terminal signal-anchor/transmembrane segment followed by a J-domain bearing the canonical HPD tripeptide, plus additional predicted transmembrane helices. The J-domain is the module by which DnaJ proteins recruit and stimulate HSP70-family ATPases. By phylogenetic inference within its protein family, DNAJC25 is predicted to act at the endoplasmic reticulum membrane as a co-chaperone that assists HSP70-dependent protein folding/quality control, although no direct experimental functional data exist for the human protein. It is tissue-enriched in liver.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference places DNAJC25 at the ER membrane, consistent with its multi-pass membrane topology and membership in a family of membrane J-proteins. UniProt records only the generic 'membrane' localization for the human protein, so the specific ER-membrane assignment rests on orthology. Reason: The ER-membrane localization is an IBA inference; the human protein is experimentally documented only as a multi-pass membrane protein without a confirmed compartment. Plausible but not directly supported, so retained as non-core. Supporting Evidence: file:human/DNAJC25/DNAJC25-uniprot.txt SUBCELLULAR LOCATION: Membrane |
| GO:0006457 protein folding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: As a J-domain protein, DNAJC25 is inferred to participate in HSP70-assisted protein folding. J-proteins are co-chaperones that assist HSP70 rather than autonomously folding clients. The falcon deep-research synthesis reaches the same conclusion as a family-level (not gene-specific) inference. Reason: Protein folding is a generic downstream process of the HSP70 system that a J-domain co-chaperone assists; it is inferred from the J-domain and family membership and is non-core relative to the (uncharacterized) specific molecular co-chaperone function. The falcon report explicitly notes this is an inference from family membership ("Specific client proteins for DNAJC25 have not been experimentally identified") and is itself ungrounded synthesis, so it adds no independent experimental weight, only corroborating the family-level framing. Supporting Evidence: file:human/DNAJC25/DNAJC25-uniprot.txt DOMAIN 49..124 file:human/DNAJC25/DNAJC25-deep-research-falcon.md J-domain proteins stimulate HSP70 ATPase activity to facilitate protein folding and quality control. DNAJC25 does not have intrinsic enzymatic activity but would modulate HSP70 function. |
| GO:0006457 protein folding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO electronic annotation of protein folding, derived from the DnaJ-domain signature. Duplicates the IBA protein-folding annotation. Reason: Domain-based IEA for the generic protein-folding process; same rationale as the IBA annotation, a downstream HSP70-assisted process rather than the gene's specific molecular function. Supporting Evidence: file:human/DNAJC25/DNAJC25-uniprot.txt DOMAIN 49..124 |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Membrane localization from the UniProt subcellular location, the only experimentally grounded localization (a multi-pass membrane protein). Consistent with the more specific ER-membrane IBA inference. Reason: DNAJC25 is documented as a multi-pass membrane protein; the generic membrane localization is correct, though the specific membrane compartment remains to be established. Supporting Evidence: file:human/DNAJC25/DNAJC25-uniprot.txt Multi-pass membrane protein |
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Download this section (compressed HTML)Q: At which membrane (ER, plasma membrane, other) does DNAJC25 actually reside, and does its J-domain stimulate a specific HSP70 paralog (e.g. BiP/HSPA5 for an ER protein)?
Q: What is the physiological client repertoire and biological process of DNAJC25, given its liver-enriched expression?
Experiment: Determine DNAJC25 subcellular localization by immunofluorescence/organelle fractionation and membrane topology mapping to confirm or refute the predicted ER-membrane assignment.
Experiment: Test J-domain-dependent stimulation of candidate HSP70 ATPases (BiP/HSPA5, HSPA8) in vitro using wild-type versus HPD-motif (QPD) mutant DNAJC25.
Experiment: Affinity purification-mass spectrometry of tagged DNAJC25 in liver-derived cells to identify HSP70 partners and physiological clients, and CRISPR knockout to define its biological process.
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