DNAJC22

UniProt ID: Q8N4W6
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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 Review

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

Core Functions

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:
heat shock protein binding
Cellular Locations:
membrane
Supporting Evidence:
  • file:human/DNAJC22/DNAJC22-uniprot.txt
    May function as a co-chaperone.
  • file:human/DNAJC22/DNAJC22-uniprot.txt
    DOMAIN 277..341

References

GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
PMID:32296183
A reference map of the human binary protein interactome.
file:human/DNAJC22/DNAJC22-uniprot.txt
UniProt entry Q8N4W6 (DJC22_HUMAN), DnaJ homolog subfamily C member 22
  • Predicted co-chaperone; multi-pass membrane protein with a C-terminal J-domain; member of the DnaJ/HSP40 family; orthologous to Drosophila Wurst.

Suggested Questions for Experts

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?

Suggested Experiments

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.

📚 Additional Documentation

Notes

(DNAJC22-notes.md)

DNAJC22 (Q8N4W6) research notes

Poorly characterized polytopic membrane protein of the HSP40/DnaJ co-chaperone
family; liver-enriched.

Architecture

  • N-terminal TM2-type region, multiple predicted transmembrane helices, and a
    C-terminal J-domain (the module that engages and stimulates HSP70 chaperones).
    [UniProt Q8N4W6]

Functional inference

  • 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. tracheal/airway liquid clearance), suggesting a related membrane
    co-chaperone/endocytic role for DNAJC22. Direct functional data for the human
    protein are lacking.

Curation calls

  • Core MF: predicted membrane-anchored HSP40 co-chaperone (GO:0031072 heat shock
    protein binding), family/domain-level inference only.
  • Bare protein binding to MEOX2 (high-throughput) marked over-annotated.

Pn Notes

(DNAJC22-pn-notes.md)

DNAJC22 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q8N4W6
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07b
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • 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/core annotation action counts: ACCEPT: 2; KEEP_AS_NON_CORE: 1

PN Consistency Summary

  • Consistency: Consistent at the inference level. Notes and review agree DNAJC22 is a poorly characterized polytopic membrane J-domain protein (liver-enriched) with NO direct human functional data; the co-chaperone role is inferred from the C-terminal J domain and the Drosophila ortholog Wurst (recruits Hsc70/clathrin for endocytosis). The PN node and review both treat it as a predicted HSP70 co-chaperone — no contradiction, but both rest on family/orthology inference, not experiment.
  • PN story / NEW pressure: PN proposes GO:0030544 Hsp70 protein binding (verified real, OLS). The review's core MF is the parent GO:0031072 heat shock protein binding (also inference-only). GO:0030544 is a verified more-specific child of GO:0031072, so the projection is internally defensible and consistent in direction with the review — but it remains a domain/orthology inference (candidate, no experimental HSP70-binding data). Existing GOA has only membrane (IBA/IEA) and bare protein binding (MEOX2 Y2H), so an HSP70-binding term would be new — but should be ISS/family-level, not a confident annotation.
  • Evidence alignment: Minimal and aligned. Only literature reference is PMID:32296183 (HuRI Y2H, MEOX2 — relevance LOW, supplies the uninformative protein-binding term). Both review and PN lean on UniProt/Wurst orthology; no functional paper supports the Hsp70-binding claim directly.
  • Verdict: Consistent family-level inference; GO:0030544 is a defensible more-specific candidate but unverified experimentally — flag as ISS/family inference rather than confident new annotation. Recommended edits: [MAP] retain GO:0030544 for DNAJC22 but mark as family/domain-level inference (no experimental HSP70 binding; Wurst-orthology basis only).

Full Consistency Review

  • UniProt: Q8N4W6 · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
  • PN placement: ER proteostasis | Chaperone | HSP70 system | J-domain containing HSP70 cochaperone (branch ER) ; PN-node mapping: type=mapped, scope=ok_for_propagation_to_go, GO:0030544 Hsp70 protein binding (goa_status=more_specific_than_existing_goa)
  • Consistency: Consistent at the inference level. Notes and review agree DNAJC22 is a poorly characterized polytopic membrane J-domain protein (liver-enriched) with NO direct human functional data; the co-chaperone role is inferred from the C-terminal J domain and the Drosophila ortholog Wurst (recruits Hsc70/clathrin for endocytosis). The PN node and review both treat it as a predicted HSP70 co-chaperone — no contradiction, but both rest on family/orthology inference, not experiment.
  • PN story / NEW pressure: PN proposes GO:0030544 Hsp70 protein binding (verified real, OLS). The review's core MF is the parent GO:0031072 heat shock protein binding (also inference-only). GO:0030544 is a verified more-specific child of GO:0031072, so the projection is internally defensible and consistent in direction with the review — but it remains a domain/orthology inference (candidate, no experimental HSP70-binding data). Existing GOA has only membrane (IBA/IEA) and bare protein binding (MEOX2 Y2H), so an HSP70-binding term would be new — but should be ISS/family-level, not a confident annotation.
  • Mapping strategy: Node heuristic applies cleanly here (genuine J domain). PN-projected GO:0030544 is appropriately specific (more specific than the review's GO:0031072) and the "more_specific_than_existing_goa" direction is at least internally consistent. Keep as inference-level propagation given the absence of any functional data; do not elevate to a confident new annotation.
  • Evidence alignment: Minimal and aligned. Only literature reference is PMID:32296183 (HuRI Y2H, MEOX2 — relevance LOW, supplies the uninformative protein-binding term). Both review and PN lean on UniProt/Wurst orthology; no functional paper supports the Hsp70-binding claim directly.
  • Verdict: Consistent family-level inference; GO:0030544 is a defensible more-specific candidate but unverified experimentally — flag as ISS/family inference rather than confident new annotation. Recommended edits: [MAP] retain GO:0030544 for DNAJC22 but mark as family/domain-level inference (no experimental HSP70 binding; Wurst-orthology basis only).

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/DNAJC22/DNAJC22-ai-review.yaml
  • PN workbook rows: 1

PN row 1: ER proteostasis | Chaperone | HSP70 system | J-domain containing HSP70 cochaperone

  • UniProt: Q8N4W6
  • In branches: ER
  • PN-node mapping records (path + ancestors):
    • [type] ER proteostasis|Chaperone|HSP70 system|J-domain containing HSP70 cochaperone
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0030544 Hsp70 protein binding]
      rationale: In the PN hierarchy, this type denotes J-domain cochaperones assigned to the HSP70 system. Their shared mechanistic role is direct interaction with HSP70-family chaperones, making Hsp70 protein binding the most defensible GO target in the current cache.
    • [group] ER proteostasis|Chaperone|HSP70 system
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
    • [class] ER proteostasis|Chaperone
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
    • [branch] ER proteostasis
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

Projected GO annotations (1)

  • GO:0030544 Hsp70 protein binding | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=ER proteostasis|Chaperone|HSP70 system|J-domain containing HSP70 cochaperone

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
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.