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.