DNAJC28 (C21orf55/C21orf78) is a poorly characterized member of the DnaJ/HSP40 (J-domain) co-chaperone family encoded on chromosome 21. It contains a canonical J domain together with a predicted coiled-coil region, and its N-terminus resembles a mitochondrial-targeting presequence, suggesting it may act as a mitochondrial J-domain co-chaperone. By analogy to other J-domain proteins it is presumed to assist HSP70-type chaperones in protein folding, but no substrate, partner chaperone, or cellular process has been experimentally established. It is expressed in brain, testis, uterus, spleen and liver (tissue-enhanced in testis) and is phosphorylated at Thr-347.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001659 temperature homeostasis | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Phylogenetic (IBA) transfer of "temperature homeostasis" from a broad PANTHER family node. There is no experimental evidence that DNAJC28 participates in temperature homeostasis, and this protein is otherwise essentially uncharacterized. Reason: The biological process is inferred only by phylogenetic grouping with distantly related family members; no direct or organism-specific evidence supports a role for DNAJC28 in temperature homeostasis. Supporting Evidence: file:human/DNAJC28/DNAJC28-uniprot.txt May have a role in protein folding or as a chaperone. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | KEEP AS NON CORE | Summary: A single AgBase-curated interaction (with PYCARD/ASC, Q9ULZ3) reported in a study focused on PML and the ASC inflammasome. The bare protein binding term is uninformative and the interaction does not establish a chaperone function for DNAJC28. Reason: Records a real but isolated interaction; bare protein binding is uninformative per curation guidelines and there is no specific molecular function that this single high-throughput hit justifies. Supporting Evidence: file:human/DNAJC28/DNAJC28-goa.tsv UniProtKB:Q9ULZ3 |
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Download this section (compressed HTML)Q: Is DNAJC28 a genuine mitochondrial J-domain co-chaperone, and which HSP70-type partner (e.g. mortalin/HSPA9) does it stimulate?
Q: Does DNAJC28 have any client proteins or a defined cellular process, or is it functionally redundant/vestigial?
Experiment: Subcellular fractionation and fluorescence microscopy of tagged DNAJC28 to test the predicted mitochondrial localization and import dependence on the N-terminal presequence.
Experiment: In vitro HSP70 ATPase-stimulation assay with recombinant DNAJC28 (and HPD-motif mutant) to test whether the J domain is a functional co-chaperone.
Experiment: Affinity purification-mass spectrometry of DNAJC28 to identify its chaperone partners and candidate clients beyond the single reported ASC interaction.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: DNAJC28's direct HSP70 co-chaperone activity, obligate HSP70 partner, and client substrates have not been experimentally established.
OPEN BIOLOGYCURATION MF_DARK
What is known: The J-domain is structurally competent, with an intact conserved HPD motif and an HSP70-interaction surface consistent with co-chaperone function. This supports inferred protein-folding chaperone binding, but it does not identify the partner HSP70, demonstrate ATPase stimulation, or reveal client proteins.
Significance: DNAJC28's current molecular function is domain-inferred. Closing this gap would determine whether the protein is an active HSP70 co-chaperone and which chaperone system it belongs to.
What would resolve it: Test recombinant DNAJC28 in HSP70 ATPase-stimulation and binding assays against candidate HSP70s, including HSPA9/mortalin if mitochondrial targeting is confirmed, and identify candidate clients by interaction proteomics.
Provenance (the field's own admissions):
Gap: DNAJC28's compartment of action is unresolved.
OPEN BIOLOGYCURATION CC_DARK
What is known: Sequence features suggest a mitochondrial-targeting presequence, while project-level proteostasis placement has treated it as an ER/HSP70-system J-domain protein. Neither mitochondrial nor ER localization has been experimentally demonstrated for DNAJC28.
Significance: The compartment determines which HSP70 partner and client pathway are plausible. A mitochondrial DNAJC28 would imply a different chaperone system than an ER proteostasis assignment.
What would resolve it: Fluorescent-protein localization, organelle fractionation, protease-protection/import assays, and N-terminal presequence deletion or mutation experiments.
Provenance (the field's own admissions):
Gap: No DNAJC28-specific cellular process or physiological role has been established.
OPEN BIOLOGY BP_DARK
What is known: The current GOA process annotation to temperature homeostasis is marked as over-annotated, and the single ASC/PYCARD protein-binding record is non-core. Expression and phosphorylation are recorded, but they do not define a process.
Significance: Without a cellular-process anchor, DNAJC28 remains an uncharacterized J-domain protein with a plausible molecular activity but no demonstrated biological role.
What would resolve it: Loss-of-function and rescue experiments in cells or organisms, prioritized after compartment and HSP70-partner identification, with readouts chosen for the confirmed organelle and client pathway.
Provenance (the field's own admissions):
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