DNAJC16

UniProt ID: Q9Y2G8
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

DNAJC16 (ERdj8, "ER-resident protein ERdj8") is a large, single-pass type IV endoplasmic reticulum membrane protein of the DnaJ/HSP40 subfamily C. It has an N-terminal cleaved signal peptide, a cytoplasmically oriented N-terminal J domain and an adjacent thioredoxin (TRX) domain in its large cytoplasmic region, followed by a C-terminal transmembrane anchor. ERdj8 localizes to a meshwork-like ER subdomain together with phosphatidylinositol synthase and autophagy-related (Atg) proteins, and functions in autophagosome biogenesis where it regulates the size of forming autophagosomes, enabling engulfment of large targets; both its J domain and TRX domain are required for this activity. It is otherwise poorly characterized, and its direct molecular activity (presumed J-domain co-chaperone and/or redox function) has not been biochemically defined. An alternative splice isoform lacks the J and thioredoxin domains.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005789 endoplasmic reticulum membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Automated SubCell localization to the ER membrane, redundant with the direct experimental (IDA) ER membrane localization from the same characterizing study.
Reason: ERdj8 is a single-pass ER membrane protein; ER membrane is its core site of action and is supported by direct imaging.
Supporting Evidence:
PMID:32492081
ERdj8 localizes to a meshwork-like ER subdomain along with phosphatidylinositol synthase (PIS) and autophagy-related (Atg) proteins.
GO:0005789 endoplasmic reticulum membrane
IDA
PMID:32492081
ERdj8 governs the size of autophagosomes during the formatio... 		ACCEPT
Summary: Direct (IDA) evidence localizing ERdj8 to a meshwork-like ER membrane subdomain, co-distributing with phosphatidylinositol synthase and Atg proteins.
Reason: Direct experimental localization to the ER membrane; the core cellular component for this single-pass ER membrane protein.
Supporting Evidence:
PMID:32492081
ERdj8 localizes to a meshwork-like ER subdomain along with phosphatidylinositol synthase (PIS) and autophagy-related (Atg) proteins.
GO:0016243 regulation of autophagosome size
IMP
PMID:32492081
ERdj8 governs the size of autophagosomes during the formatio... 		ACCEPT
Summary: IMP evidence that ERdj8 regulates autophagosome size during formation; overexpression enlarges autophagosomes (dependent on the J and TRX domains) and ablation impairs engulfment of larger targets. This is the central, experimentally established biological role of ERdj8.
Reason: Directly supported by gain- and loss-of-function experiments (and conserved in C. elegans dnj-8); the core biological process for this gene.
Supporting Evidence:
PMID:32492081
ERdj8 overexpression extended the size of the autophagosome through its DnaJ and TRX domains. ERdj8 ablation resulted in a defect in engulfing larger targets.

Core Functions

ER membrane DnaJ/HSP40 protein that regulates the size of forming autophagosomes, enabling autophagic engulfment of large targets; activity requires both its J domain and its thioredoxin domain.

Directly Involved In:
regulation of autophagosome size
Cellular Locations:
endoplasmic reticulum membrane
Supporting Evidence:
  • PMID:32492081
    ERdj8 overexpression extended the size of the autophagosome through its DnaJ and TRX domains. ERdj8 ablation resulted in a defect in engulfing larger targets.

References

GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
PMID:32492081
ERdj8 governs the size of autophagosomes during the formation process.
  • ERdj8 is a novel ER membrane protein that localizes to a meshwork-like ER subdomain with PIS and Atg proteins; it governs autophagosome size during formation, with overexpression enlarging autophagosomes (requiring the J and TRX domains) and ablation impairing engulfment of larger targets; the role is conserved in the C. elegans orthologue dnj-8.
file:human/DNAJC16/DNAJC16-uniprot.txt
UniProt entry Q9Y2G8 (DJC16_HUMAN), DnaJ homolog subfamily C member 16 / ERdj8
  • Single-pass type IV ER membrane protein with an N-terminal J domain and a thioredoxin domain; regulates the size of autophagosomes during formation; J-domain (His-57) and thioredoxin (Cys-171/Cys-174) residues are required for the autophagosome-enlargement activity.

Suggested Questions for Experts

Q: What is the direct molecular activity of ERdj8 - does its J domain recruit and stimulate an ER-luminal/cytosolic HSP70 (e.g. BiP/HSPA5), and is its thioredoxin domain redox-active?

Q: How does ERdj8 mechanistically couple the ER subdomain (with phosphatidylinositol synthase) to the control of autophagosome membrane size?

Suggested Experiments

Experiment: Reconstitute and assay ERdj8 J-domain-stimulated HSP70 ATPase activity and test the redox activity of its thioredoxin domain in vitro, using the H57Q and C171A/C174A mutants as controls, to define the molecular function underlying autophagosome-size regulation.

Experiment: Proximity labeling (BioID/APEX) from ERdj8 at the ER-phagophore subdomain to identify its HSP70 partner(s) and Atg/lipid-synthesis machinery it engages during autophagosome formation.

📚 Additional Documentation

Notes

(DNAJC16-notes.md)

DNAJC16 (ERdj8 / ERDJ8) research notes

Identity

  • UniProt Q9Y2G8, HGNC:29157, 782 aa precursor. DnaJ/HSP40 subfamily C member 16.
  • AltName: ER-resident protein ERdj8 (Endoplasmic reticulum DNA J domain-containing protein 8).
  • Architecture: N-terminal signal peptide (1-25), N-terminal J domain (29-93, cytoplasmic side),
    a thioredoxin (TRX) domain (119-247), single C-terminal TM helix (536-556; type IV membrane
    anchor); large cytoplasmic region 26-535. N-glycosylated. Two isoforms (isoform 2 lacks 1-312, so
    it lacks the J and TRX domains). [file:human/DNAJC16/DNAJC16-uniprot.txt]
  • Pharos "Tdark"; PAN-GO 0 annotations; poorly characterized.

Core function: ER membrane J-protein regulating autophagosome size

  • Single functional study: PMID:32492081 (Yamamoto 2020, J Cell Biol): "ERdj8 governs the size of
    autophagosomes during the formation process." "ERdj8 localizes to a meshwork-like ER subdomain
    along with phosphatidylinositol synthase (PIS) and autophagy-related (Atg) proteins. ERdj8
    overexpression extended the size of the autophagosome through its DnaJ and TRX domains. ERdj8
    ablation resulted in a defect in engulfing larger targets." C. elegans orthologue dnj-8.
    PMID:32492081
  • Mutagenesis: H57Q (J-domain HPD), C171A/C174A (TRX active-site cysteines) abolish the
    autophagosome-enlargement phenotype on overexpression — implicates both domains. [file:human/DNAJC16/DNAJC16-uniprot.txt]
  • UniProt FUNCTION: "Plays an important role in regulating the size of autophagosomes during the
    formation process." [file:human/DNAJC16/DNAJC16-uniprot.txt]

Localization

  • ER membrane (IDA, PMID:32492081); single-pass type IV membrane protein. Also IEA SubCell.
    [file:human/DNAJC16/DNAJC16-uniprot.txt]

GOA annotations (all 3 from PMID:32492081 / SubCell)

  • GO:0005789 ER membrane IEA (SubCell) + IDA (PMID:32492081): ACCEPT, core localization.
  • GO:0016243 regulation of autophagosome size IMP (PMID:32492081): ACCEPT, core BP.

Curation

  • Core function: ER membrane J-domain protein required for regulating autophagosome size; the
    precise molecular function (J-domain co-chaperone activity recruiting an ER Hsp70 such as
    BiP/HSPA5, and a redox/TRX activity) is not directly established — the readout is autophagosome
    size. No GOA MF term exists. Core captured via the BP GO:0016243 + ER membrane location. Do not
    over-claim a specific MF. The gene is otherwise poorly characterized.

Pn Notes

(DNAJC16-pn-notes.md)

DNAJC16 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9Y2G8
  • 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: DNAJC16 (ERdj8, "ER-resident protein ERdj8") is a large, single-pass type IV endoplasmic reticulum membrane protein of the DnaJ/HSP40 subfamily C. It has an N-terminal cleaved signal peptide, a cytoplasmically oriented N-terminal J domain and an adjacent thioredoxin (TRX) domain in its large cytoplasmic region, followed by a C-terminal transmembrane anchor. ERdj8 localizes to a meshwork-like ER subdomain together with phosphatidylinositol synthase and autophagy-related (Atg) proteins, and functions in autophagosome biogenesis where it regulates the size of forming autophagosomes, enabling engulfment of large targets; both its J domain and TRX domain are required for this activity. It is otherwise poorly characterized, and its direct molecular activity (presumed J-domain co-chaperone and/or redox function) has not been biochemically defined. An alternative splice isoform lacks the J and thioredoxin domains.
  • Existing/core annotation action counts: ACCEPT: 3

PN Consistency Summary

  • Consistency: Partial mismatch. Deep-research notes and review agree the gene is poorly characterized (Pharos Tdark, PAN-GO 0): the ONLY experimental function is ER-membrane localization (GO:0005789) and regulation of autophagosome size (GO:0016243, IMP, PMID:32492081). Crucially the review states the "direct molecular activity (presumed J-domain co-chaperone... ) has not been biochemically defined" — so the PN assertion of Hsp70 binding is an inference, not established. The PN node nonetheless tags it as a confident new-to-GOA propagation, which over-states the evidence.
  • PN story / NEW pressure: PN proposes ADD of GO:0030544 Hsp70 protein binding as new_to_goa. GO:0030544 is verified real (OLS), but for DNAJC16 there is no experimental HSP70-binding/co-chaperone data; the J domain is required for autophagosome enlargement but no HSP70 partner has been identified (the review's own suggested experiment is to test this). This is over-reach at the gene level: the projection rests purely on family/domain membership.
  • Evidence alignment: Single shared paper PMID:32492081 (Yamamoto 2020). PN node carries no DNAJC16-specific reference; the projection is purely taxonomic. No evidence divergence, but no positive evidence for the Hsp70-binding claim either.
  • Verdict: Over-reaches for this gene — Hsp70 binding is domain-inferred only, no HSP70 partner shown; flag as family-level inference, not new_to_goa. Recommended edits: [MAP] downgrade DNAJC16's GO:0030544 projection from new_to_goa confident annotation to family/ISS-level inference (no experimental HSP70 binding); note the established function (autophagosome-size regulation) lies outside this HSP70-cochaperone node.

Full Consistency Review

  • UniProt: Q9Y2G8 (ERdj8) · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
  • PN placement: Cytonuclear proteostasis | Chaperone | HSP70 system | J-domain containing HSP70 cochaperone (branch CY) ; PN-node mapping: type=mapped, scope=ok_for_propagation_to_go, GO:0030544 Hsp70 protein binding (goa_status=new_to_goa)
  • Consistency: Partial mismatch. Deep-research notes and review agree the gene is poorly characterized (Pharos Tdark, PAN-GO 0): the ONLY experimental function is ER-membrane localization (GO:0005789) and regulation of autophagosome size (GO:0016243, IMP, PMID:32492081). Crucially the review states the "direct molecular activity (presumed J-domain co-chaperone... ) has not been biochemically defined" — so the PN assertion of Hsp70 binding is an inference, not established. The PN node nonetheless tags it as a confident new-to-GOA propagation, which over-states the evidence.
  • PN story / NEW pressure: PN proposes ADD of GO:0030544 Hsp70 protein binding as new_to_goa. GO:0030544 is verified real (OLS), but for DNAJC16 there is no experimental HSP70-binding/co-chaperone data; the J domain is required for autophagosome enlargement but no HSP70 partner has been identified (the review's own suggested experiment is to test this). This is over-reach at the gene level: the projection rests purely on family/domain membership.
  • Mapping strategy: The node-level mapping (J-domain cochaperones bind Hsp70) is defensible as a family heuristic, but for DNAJC16 specifically the new_to_goa propagation should be down-weighted to an inference (ISS/family-level) rather than asserted as a confident annotation, since the molecular function is explicitly undefined. PN-projected term is broader than the review's actual core (autophagosome-size regulation), which the node does not capture at all.
  • Evidence alignment: Single shared paper PMID:32492081 (Yamamoto 2020). PN node carries no DNAJC16-specific reference; the projection is purely taxonomic. No evidence divergence, but no positive evidence for the Hsp70-binding claim either.
  • Verdict: Over-reaches for this gene — Hsp70 binding is domain-inferred only, no HSP70 partner shown; flag as family-level inference, not new_to_goa. Recommended edits: [MAP] downgrade DNAJC16's GO:0030544 projection from new_to_goa confident annotation to family/ISS-level inference (no experimental HSP70 binding); note the established function (autophagosome-size regulation) lies outside this HSP70-cochaperone node.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/DNAJC16/DNAJC16-ai-review.yaml
  • PN workbook rows: 1

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

  • UniProt: Q9Y2G8
  • In branches: CY
  • PN-node mapping records (path + ancestors):
    • [type] Cytonuclear 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] Cytonuclear proteostasis|Chaperone|HSP70 system
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a specific GO class. The member genes span multiple activities, complexes, or contexts, so propagation from this node would overstate the shared biology; use narrower child or gene-level curations.
    • [class] Cytonuclear proteostasis|Chaperone
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a specific GO class. The member genes span multiple activities, complexes, or contexts, so propagation from this node would overstate the shared biology; use narrower child or gene-level curations.
    • [branch] Cytonuclear 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=new_to_goa | from=Cytonuclear 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: Q9Y2G8
gene_symbol: DNAJC16
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DNAJC16 (ERdj8, "ER-resident protein ERdj8") is a large, single-pass type IV endoplasmic reticulum membrane protein of the DnaJ/HSP40 subfamily C. It has an N-terminal cleaved signal peptide, a cytoplasmically oriented N-terminal J domain and an adjacent thioredoxin (TRX) domain in its large cytoplasmic region, followed by a C-terminal transmembrane anchor. ERdj8 localizes to a meshwork-like ER subdomain together with phosphatidylinositol synthase and autophagy-related (Atg) proteins, and functions in autophagosome biogenesis where it regulates the size of forming autophagosomes, enabling engulfment of large targets; both its J domain and TRX domain are required for this activity. It is otherwise poorly characterized, and its direct molecular activity (presumed J-domain co-chaperone and/or redox function) has not been biochemically defined. An alternative splice isoform lacks the J and thioredoxin domains.
alternative_products:
- name: '1'
  id: Q9Y2G8-1
- name: '2'
  id: Q9Y2G8-2
  sequence_note: VSP_018583
existing_annotations:
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated SubCell localization to the ER membrane, redundant with the direct experimental (IDA) ER membrane localization from the same characterizing study.
    action: ACCEPT
    reason: ERdj8 is a single-pass ER membrane protein; ER membrane is its core site of action and is supported by direct imaging.
    supported_by:
    - reference_id: PMID:32492081
      supporting_text: ERdj8 localizes to a meshwork-like ER subdomain along with phosphatidylinositol synthase (PIS) and autophagy-related (Atg) proteins.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:32492081
  qualifier: located_in
  review:
    summary: Direct (IDA) evidence localizing ERdj8 to a meshwork-like ER membrane subdomain, co-distributing with phosphatidylinositol synthase and Atg proteins.
    action: ACCEPT
    reason: Direct experimental localization to the ER membrane; the core cellular component for this single-pass ER membrane protein.
    supported_by:
    - reference_id: PMID:32492081
      supporting_text: ERdj8 localizes to a meshwork-like ER subdomain along with phosphatidylinositol synthase (PIS) and autophagy-related (Atg) proteins.
- term:
    id: GO:0016243
    label: regulation of autophagosome size
  evidence_type: IMP
  original_reference_id: PMID:32492081
  qualifier: involved_in
  review:
    summary: IMP evidence that ERdj8 regulates autophagosome size during formation; overexpression enlarges autophagosomes (dependent on the J and TRX domains) and ablation impairs engulfment of larger targets. This is the central, experimentally established biological role of ERdj8.
    action: ACCEPT
    reason: Directly supported by gain- and loss-of-function experiments (and conserved in C. elegans dnj-8); the core biological process for this gene.
    supported_by:
    - reference_id: PMID:32492081
      supporting_text: ERdj8 overexpression extended the size of the autophagosome through its DnaJ and TRX domains. ERdj8 ablation resulted in a defect in engulfing larger targets.
references:
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: PMID:32492081
  title: ERdj8 governs the size of autophagosomes during the formation process.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publication title matches the YAML title; Results establish ERdj8 as an ER-membrane DnaJ protein that 'governs the size of autophagosomes', with overexpression enlarging autophagosomes via its DnaJ and TRX domains and ablation impairing engulfment of larger targets. Sole experimental reference establishing the core function (regulation of autophagosome size, GO:0016243) and ER-membrane localization (cited in core_functions.supported_by)."
  findings:
  - statement: ERdj8 is a novel ER membrane protein that localizes to a meshwork-like ER subdomain with PIS and Atg proteins; it governs autophagosome size during formation, with overexpression enlarging autophagosomes (requiring the J and TRX domains) and ablation impairing engulfment of larger targets; the role is conserved in the C. elegans orthologue dnj-8.
    reference_section_type: RESULTS
- id: file:human/DNAJC16/DNAJC16-uniprot.txt
  title: UniProt entry Q9Y2G8 (DJC16_HUMAN), DnaJ homolog subfamily C member 16 / ERdj8
  findings:
  - statement: Single-pass type IV ER membrane protein with an N-terminal J domain and a thioredoxin domain; regulates the size of autophagosomes during formation; J-domain (His-57) and thioredoxin (Cys-171/Cys-174) residues are required for the autophagosome-enlargement activity.
    reference_section_type: OTHER
core_functions:
- description: ER membrane DnaJ/HSP40 protein that regulates the size of forming autophagosomes, enabling autophagic engulfment of large targets; activity requires both its J domain and its thioredoxin domain.
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:32492081
    supporting_text: ERdj8 overexpression extended the size of the autophagosome through its DnaJ and TRX domains. ERdj8 ablation resulted in a defect in engulfing larger targets.
  directly_involved_in:
  - id: GO:0016243
    label: regulation of autophagosome size
proposed_new_terms: []
suggested_questions:
- question: What is the direct molecular activity of ERdj8 - does its J domain recruit and stimulate an ER-luminal/cytosolic HSP70 (e.g. BiP/HSPA5), and is its thioredoxin domain redox-active?
- question: How does ERdj8 mechanistically couple the ER subdomain (with phosphatidylinositol synthase) to the control of autophagosome membrane size?
suggested_experiments:
- description: Reconstitute and assay ERdj8 J-domain-stimulated HSP70 ATPase activity and test the redox activity of its thioredoxin domain in vitro, using the H57Q and C171A/C174A mutants as controls, to define the molecular function underlying autophagosome-size regulation.
- description: Proximity labeling (BioID/APEX) from ERdj8 at the ER-phagophore subdomain to identify its HSP70 partner(s) and Atg/lipid-synthesis machinery it engages during autophagosome formation.