id: Q8N4W6
gene_symbol: DNAJC22
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/DNAJC22/DNAJC22-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Membrane'
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation of membrane localization from the UniProt subcellular location, redundant with and consistent with the IBA membrane annotation.
    action: ACCEPT
    reason: Correct localization for this multi-pass membrane protein; agrees with the IBA membrane annotation and the predicted transmembrane topology.
    supported_by:
    - reference_id: file:human/DNAJC22/DNAJC22-uniprot.txt
      supporting_text: Multi-pass membrane protein
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/DNAJC22/DNAJC22-uniprot.txt
      supporting_text: 'Q8N4W6; Q6FHY5: MEOX2'
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "Cached publication title matches the YAML title; this is a systematic binary-interactome (Y2H) map, not a DNAJC22-focused study. It supplies only an interaction-level (protein binding) data point and does not establish DNAJC22's molecular function or biological process, which remain inferred from sequence/the Drosophila Wurst ortholog. The sole literature reference for this poorly characterized gene, and only background relevance."
  findings: []
- id: file:human/DNAJC22/DNAJC22-uniprot.txt
  title: UniProt entry Q8N4W6 (DJC22_HUMAN), DnaJ homolog subfamily C member 22
  findings:
  - statement: Predicted co-chaperone; multi-pass membrane protein with a C-terminal J-domain; member of the DnaJ/HSP40 family; orthologous to Drosophila Wurst.
    reference_section_type: OTHER
core_functions:
- description: Predicted membrane-anchored HSP40/J-domain co-chaperone that, via its C-terminal J-domain, would engage and stimulate HSP70-family chaperones at cellular membranes (by analogy to the Drosophila ortholog Wurst, which recruits Hsc70 and clathrin for endocytosis). Direct experimental evidence for the human protein is lacking.
  molecular_function:
    id: GO:0031072
    label: heat shock protein binding
  locations:
  - id: GO:0016020
    label: membrane
  supported_by:
  - reference_id: file:human/DNAJC22/DNAJC22-uniprot.txt
    supporting_text: May function as a co-chaperone.
  - reference_id: file:human/DNAJC22/DNAJC22-uniprot.txt
    supporting_text: DOMAIN          277..341
proposed_new_terms: []
suggested_questions:
- question: Does human DNAJC22 functionally recapitulate the Drosophila Wurst role in clathrin-mediated endocytosis, recruiting HSC70/HSPA8 to membranes?
- question: At which membrane (plasma membrane, endosome, ER) does DNAJC22 reside, and does its J-domain stimulate a specific HSP70 paralog?
suggested_experiments:
- description: 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.
- description: 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.
- description: CRISPR knockout of DNAJC22 in hepatocytes followed by endocytosis/membrane-trafficking assays to define its biological process.