DNAJC22 (DnaJ homolog subfamily C member 22) is a poorly characterized polytopic membrane protein of the HSP40/DnaJ family. It has an N-terminal TM2-type region, multiple predicted transmembrane helices, and a C-terminal J-domain, the hallmark module that engages and stimulates HSP70-family chaperones. It is a multi-pass membrane protein and is predicted to act as a co-chaperone. Its Drosophila ortholog Wurst is a transmembrane J-domain protein that recruits clathrin and Hsc70 to the apical membrane to drive clathrin-mediated endocytosis (e.g. airway liquid clearance), suggesting DNAJC22 may have a related membrane co-chaperone/endocytic role, but direct functional data for the human protein are lacking. DNAJC22 is tissue-enriched in liver.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016020 membrane | IBA GO_REF:0000033 | ACCEPT | Summary: DNAJC22 is a multi-pass membrane protein, consistent with its multiple predicted transmembrane helices and the membrane localization of its Drosophila ortholog Wurst. The generic 'membrane' term is the most that can be assigned. Reason: The protein is a multi-pass membrane protein by UniProt subcellular location, and the IBA from membrane-localized DnaJ family members (including the fly Wurst ortholog) is consistent with its predicted topology. Supporting Evidence: file:human/DNAJC22/DNAJC22-uniprot.txt SUBCELLULAR LOCATION: Membrane |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation of membrane localization from the UniProt subcellular location, redundant with and consistent with the IBA membrane annotation. Reason: Correct localization for this multi-pass membrane protein; agrees with the IBA membrane annotation and the predicted transmembrane topology. Supporting Evidence: file:human/DNAJC22/DNAJC22-uniprot.txt Multi-pass membrane protein |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: IPI interaction with MEOX2 (Q6FHY5) from a high-throughput interactome screen. The bare 'protein binding' term is uninformative and the partner does not illuminate DNAJC22's function. Reason: Bare protein binding from a single high-throughput screen with a partner (MEOX2, a homeobox transcription factor) unrelated to DNAJC22's predicted membrane co-chaperone role; uninformative and not core. Supporting Evidence: file:human/DNAJC22/DNAJC22-uniprot.txt Q8N4W6; Q6FHY5: MEOX2 |
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Download this section (compressed HTML)Q: Does human DNAJC22 functionally recapitulate the Drosophila Wurst role in clathrin-mediated endocytosis, recruiting HSC70/HSPA8 to membranes?
Q: At which membrane (plasma membrane, endosome, ER) does DNAJC22 reside, and does its J-domain stimulate a specific HSP70 paralog?
Experiment: Determine DNAJC22 subcellular membrane localization by immunofluorescence/organelle fractionation and test J-domain-dependent HSP70 (HSPA8) ATPase stimulation in vitro using wild-type versus HPD-motif-mutant protein.
Experiment: Affinity purification-mass spectrometry of tagged DNAJC22 in liver-derived cells to identify physiological partners (e.g. clathrin, HSC70) and test the Wurst-analogous endocytic hypothesis.
Experiment: CRISPR knockout of DNAJC22 in hepatocytes followed by endocytosis/membrane-trafficking assays to define its biological process.
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