id: Q9UBS4
gene_symbol: DNAJB11
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DNAJB11 (ERdj3, also HEDJ/ERj3p/ABBP-2) is a soluble, glycosylated, ER-lumenal HSP40/J-domain co-chaperone and the principal J-protein partner of the ER HSP70 chaperone BiP (HSPA5). Through its N-terminal J domain it binds and stimulates the ATPase activity of BiP, and through a cysteine-rich substrate-binding domain it binds unfolded and misfolded peptides directly; it recruits BiP to substrates and then dissociates as BiP engages, promoting proper folding, maturation, trafficking and ERAD-targeted degradation of secretory and membrane proteins. It is a stress (UPR)-inducible component of a large ER chaperone complex (with HSPA5, HSP90B1, HYOU1, PDIA proteins, SDF2L1, UGGT1 and others) and is required for the maturation and trafficking of polycystin-1 (PKD1). Monoallelic loss-of-function variants in DNAJB11 cause an atypical autosomal-dominant polycystic kidney disease (PKD6).
existing_annotations:
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: DNAJB11/ERdj3 is an ER-resident J-protein; the ER (lumen) is its site of action. Strongly supported by experimental data and phylogeny.
    action: ACCEPT
    reason: The ER lumen is the established compartment in which ERdj3 acts as a BiP co-chaperone; the IBA call agrees with multiple experimental annotations.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen'
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: ERdj3 participates in maturation of secretory/membrane proteins as a BiP co-chaperone; corroborated by IMP evidence for PKD1/polycystin-1 maturation.
    action: ACCEPT
    reason: Protein maturation is a well-supported biological-process role of ERdj3, with direct genetic evidence (PKD1 maturation/trafficking) in addition to phylogeny.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: It is necessary for maturation and correct
- term:
    id: GO:0051787
    label: misfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: ERdj3 binds unfolded/misfolded substrate proteins directly via its cysteine-rich domain. Supported by IDA and phylogeny; a core molecular function (substrate/holdase binding).
    action: ACCEPT
    reason: Direct binding to misfolded/unfolded substrates is a defining ERdj3 molecular activity, supported experimentally (PubMed:28597544 IDA; substrate-binding mutagenesis).
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: Binds directly to both unfolded
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated ER-lumen localization derived from the UniProt subcellular-location annotation; this is the precise and experimentally established compartment for ERdj3.
    action: ACCEPT
    reason: ER lumen is the correct, experimentally supported localization; the IEA call agrees with TAS/IDA evidence.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen'
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro-based electronic annotation of protein folding. ERdj3 assists BiP-mediated folding rather than autonomously catalyzing it.
    action: KEEP_AS_NON_CORE
    reason: Protein folding is a downstream process outcome of ERdj3's BiP co-chaperone activity; the direct molecular roles are BiP ATPase stimulation and substrate binding.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: required for proper
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18923428
  qualifier: enables
  review:
    summary: Mechanistic study of the ERdj3-BiP interaction; the WITH partner is BiP/HSPA5 (P11021). Bare protein binding is uninformative, but this records the functionally central BiP interaction.
    action: KEEP_AS_NON_CORE
    reason: Records the core ERdj3-BiP interaction, but the bare protein binding term is uninformative per curation guidelines; the informative MF (BiP binding/ATPase stimulation) is captured by other terms.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18923428 UniProtKB:P11021
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20335166
  qualifier: enables
  review:
    summary: Interaction data including BiP/HSPA5 (P11021) and the Salmonella effector SlrP (Q8ZQQ2, xeno). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real interactions (the meaningful one being BiP), but bare protein binding is uninformative; the xeno SlrP interaction is not part of the core function.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20335166 UniProtKB:P11021
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21900206
  qualifier: enables
  review:
    summary: Directed interaction network capturing ERdj3 with SIMC1 (Q8NDZ2). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction but bare protein binding is uninformative and the partner does not define ERdj3's core BiP co-chaperone function.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21900206 UniProtKB:Q8NDZ2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24189400
  qualifier: enables
  review:
    summary: Mutated-EGFR interactome study capturing ERdj3-BiP/HSPA5 (P11021). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the core ERdj3-BiP interaction, but bare protein binding is uninformative as a core MF.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:24189400 UniProtKB:P11021
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Human interactome community study capturing ERdj3 with BiP/HSPA5 (P11021) and SIMC1 (Q8NDZ2). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real interactions (including BiP) but bare protein binding is uninformative as a core MF.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28514442 UniProtKB:P11021
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Binary interactome map capturing ERdj3 with histatin-3 (HTN3, P15516). Bare protein binding is uninformative; HTN3 is a salivary peptide and likely an incidental substrate-like interaction.
    action: KEEP_AS_NON_CORE
    reason: Records a real high-throughput interaction but bare protein binding is uninformative and the partner does not define ERdj3's core function.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:P15516
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-purification interactome capturing ERdj3 with BiP/HSPA5 (P11021) and SIMC1 (Q8NDZ2). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real interactions (including the core BiP partner) but bare protein binding is uninformative as a core MF.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:P11021
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Ensembl ortholog-projected molecular function. There is no direct evidence that the ER-lumenal ERdj3 acts as a signaling receptor ligand; this conflicts with its established BiP co-chaperone function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Orthology-projected term unsupported for human ERdj3 and inconsistent with its ER-lumenal chaperone role; likely an over-annotation.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005102 signaling receptor binding molecular_function ECO:0000265 IEA GO_REF:0000107
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl ortholog-projected extracellular localization. ERdj3 is an ER-lumenal resident; although a minor secreted pool has been described for ERdj3, this orthology transfer conflicts with the predominant, functionally relevant ER-lumen localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: Orthology-projected extracellular localization is not the functionally relevant compartment for ERdj3 and conflicts with its established ER-lumen residence.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005576 extracellular region cellular_component ECO:0000265 IEA GO_REF:0000107
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl ortholog-projected nuclear localization. UniProt explicitly cautions that a reported nuclear/cytosolic localization arose from an N-terminal GFP tag disrupting signal-peptide-driven ER targeting and is not the in vivo localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: Nuclear localization is an artifact of tag-disrupted ER targeting per UniProt CAUTION; ERdj3 is an ER-lumenal protein, so this is an over-annotation.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: reported a cytosolic, as well as nuclear
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl ortholog-projected cytoplasmic localization, also attributable to the tag-disrupted-targeting artifact described by UniProt. ERdj3 is ER-lumenal.
    action: MARK_AS_OVER_ANNOTATED
    reason: Cytoplasmic localization conflicts with signal-peptide-driven ER-lumen targeting and reflects an over-annotation/artifact, not the in vivo localization.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: reported a cytosolic, as well as nuclear
- term:
    id: GO:0034663
    label: endoplasmic reticulum chaperone complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: ERdj3 is a component of a large ER chaperone complex (with HSPA5, HSP90B1, HYOU1, PDIA proteins, SDF2L1, UGGT1, etc.). The orthology-projected term agrees with experimentally documented complex membership.
    action: ACCEPT
    reason: ERdj3's membership in the ER chaperone complex is experimentally established (UniProt SUBUNIT; PubMed:12475965), so this localization is correct.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: Part of a large chaperone multiprotein complex
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Orthology-projected general chaperone molecular function. ERdj3 is a J-protein co-chaperone that binds substrates and assists BiP; the term is broadly consistent though less specific than its BiP co-chaperone/substrate-binding activities.
    action: KEEP_AS_NON_CORE
    reason: A correct but general chaperone term; the more informative core functions (BiP ATPase stimulation, misfolded protein binding) are captured by specific terms.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: ER-associated Hsp40 co-chaperone
- term:
    id: GO:0140309
    label: unfolded protein holdase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Orthology-projected holdase activity. ERdj3 binds unfolded substrates ATP-independently and holds them prior to BiP engagement, consistent with holdase activity.
    action: ACCEPT
    reason: ERdj3's documented ATP-independent binding of denatured substrates supports an unfolded-protein holdase activity.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: Binds to denatured substrates in an ATP-independent manner
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct (HPA immunofluorescence) evidence for ER localization, consistent with ERdj3's ER-lumenal residence.
    action: ACCEPT
    reason: IDA ER localization corroborates the established ER-lumen site of action.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005783 endoplasmic reticulum cellular_component ECO:0000314 IDA GO_REF:0000052
- term:
    id: GO:0051787
    label: misfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:28597544
  qualifier: enables
  review:
    summary: Direct evidence that ERdj3 binds misfolded proteins, part of the BiP chaperone cycle preventing protein aggregation. A core molecular function.
    action: ACCEPT
    reason: Direct experimental evidence for misfolded-protein binding underpins ERdj3's substrate-recognition role.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: Binds directly to both unfolded
- term:
    id: GO:0101031
    label: protein folding chaperone complex
  evidence_type: IPI
  original_reference_id: PMID:28597544
  qualifier: part_of
  review:
    summary: ERdj3 is part of a chaperone complex with SDF2/SDF2L1 (Q99470/Q9HCN8) in the BiP chaperone cycle. Consistent with its membership in the ER chaperone machinery.
    action: ACCEPT
    reason: Experimentally supported membership in a BiP-cycle chaperone complex, consistent with the ER chaperone complex annotation.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0101031 protein folding chaperone complex cellular_component ECO:0000353 IPI PMID:28597544
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: IMP
  original_reference_id: PMID:29706351
  qualifier: involved_in
  review:
    summary: DNAJB11-null cells and patient tissue show maturation and trafficking defects of polycystin-1 (PC1/PKD1) and other secretory proteins, demonstrating ERdj3's role in protein maturation. This is the disease-relevant core process.
    action: ACCEPT
    reason: Direct genetic/mutant-phenotype (IMP) evidence that ERdj3 is required for maturation/trafficking of client proteins (PKD1), underlying PKD6 pathogenesis.
    supported_by:
    - reference_id: PMID:29706351
      supporting_text: maturation and trafficking defects involving the ADPKD protein
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:20335166
  qualifier: located_in
  review:
    summary: Direct evidence for ER localization, consistent with ERdj3's ER-lumenal residence.
    action: ACCEPT
    reason: IDA ER localization corroborates the established ER site of action.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-goa.tsv
      supporting_text: GO:0005783 endoplasmic reticulum cellular_component ECO:0000314 IDA PMID:20335166
- term:
    id: GO:0032781
    label: positive regulation of ATP-dependent activity
  evidence_type: IDA
  original_reference_id: PMID:20335166
  qualifier: involved_in
  review:
    summary: Direct evidence that ERdj3 positively regulates an ATP-dependent activity, reflecting stimulation of BiP/HSPA5 ATPase activity by the J domain. This is a core molecular activity of ERdj3.
    action: ACCEPT
    reason: ERdj3's J domain stimulates BiP ATPase activity (UniProt FUNCTION; PubMed:18923428), and this IDA captures that activation; central to its co-chaperone role.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: Stimulates HSPA5 ATPase activity
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput membrane-proteome (NK cell) detection. ERdj3 is a soluble ER-lumenal protein; UniProt notes ER-membrane association only with a C-terminally tagged construct. This generic membrane localization is non-core.
    action: KEEP_AS_NON_CORE
    reason: ERdj3 is soluble in the ER lumen; the generic membrane assignment from a proteomics screen is peripheral and not its functional compartment.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: Associated with the ER membrane in a C-terminally epitope-tagged construct
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1791075
  qualifier: located_in
  review:
    summary: Reactome-curated ER-lumen localization, consistent with the precise, experimentally established compartment.
    action: ACCEPT
    reason: ER lumen is the correct, well-supported localization for ERdj3.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen'
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: TAS
  original_reference_id: PMID:16130169
  qualifier: located_in
  review:
    summary: Author-stated ER localization, consistent with ERdj3's ER residence.
    action: ACCEPT
    reason: TAS ER localization agrees with the established ER-lumen site of action.
    supported_by:
    - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen'
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- 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: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: PMID:16130169
  title: Proteomics of human umbilical vein endothelial cells applied to etoposide-induced apoptosis.
  findings: []
- id: PMID:18923428
  title: Regulated release of ERdj3 from unfolded proteins by BiP.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches; Results show ERdj3 binds unfolded substrates and stimulates BiP ATPase, supporting DNAJB11's core ER co-chaperone/Hsp70-recruitment function.
  findings:
  - statement: ERdj3 binds unfolded substrates and recruits BiP; BiP releases ERdj3 from substrate only in the presence of ATP and requires ERdj3 stimulation of BiP's ATPase activity.
    reference_section_type: RESULTS
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:20335166
  title: The Salmonella type III secretion effector, salmonella leucine-rich repeat protein (SlrP), targets the human chaperone ERdj3.
  findings:
  - statement: ERdj3 localizes to the ER and positively regulates an ATP-dependent activity (stimulation of BiP ATPase); the Salmonella effector SlrP targets ERdj3.
    reference_section_type: RESULTS
- id: PMID:21900206
  title: A directed protein interaction network for investigating intracellular signal transduction.
  findings: []
- id: PMID:24189400
  title: Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:28597544
  title: Endoplasmic reticulum proteins SDF2 and SDF2L1 act as components of the BiP chaperone cycle to prevent protein aggregation.
  findings:
  - statement: ERdj3 binds misfolded proteins and is part of a BiP chaperone-cycle complex (with SDF2/SDF2L1) that prevents protein aggregation in the ER.
    reference_section_type: RESULTS
- id: PMID:29706351
  title: Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches PubMed; body confirms DNAJB11 is
      a BiP co-factor whose monoallelic loss-of-function causes atypical ADPKD with
      PC1/PKD1 maturation and trafficking defects, supporting the gene's in-vivo ER
      co-chaperone function.
  findings:
  - statement: DNAJB11 is a co-factor of BiP, and DNAJB11-null cells/patient tissue show maturation and trafficking defects of the ADPKD protein PC1 (PKD1) and other secretory proteins.
    reference_section_type: RESULTS
  - statement: Monoallelic loss-of-function DNAJB11 variants cause an atypical autosomal-dominant polycystic kidney disease that is a phenotypic hybrid of ADPKD and ADTKD.
    reference_section_type: RESULTS
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: Reactome:R-HSA-1791075
  title: Reactome pathway annotation (ER lumen localization of DNAJB11/ERdj3)
  findings: []
core_functions:
- description: ER-lumenal J-domain co-chaperone of BiP (HSPA5) that stimulates BiP's ATPase activity via its J domain, coupling substrate delivery to BiP's ATP-dependent folding cycle.
  molecular_function:
    id: GO:0001671
    label: ATPase activator activity
  locations:
  - id: GO:0005788
    label: endoplasmic reticulum lumen
  supported_by:
  - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
    supporting_text: Stimulates HSPA5 ATPase activity
  - reference_id: PMID:18923428
    supporting_text: the ability to stimulate BiP's ATPase
- description: Binds unfolded and misfolded substrate proteins directly (ATP-independent holdase via its cysteine-rich domain), recruiting BiP to nascent and ERAD substrates to promote folding, maturation, trafficking and degradation in the ER.
  molecular_function:
    id: GO:0051787
    label: misfolded protein binding
  locations:
  - id: GO:0005788
    label: endoplasmic reticulum lumen
  supported_by:
  - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
    supporting_text: Binds directly to both unfolded
  - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
    supporting_text: Binds to denatured substrates in an ATP-independent manner
- description: Required for the maturation and correct trafficking of secretory/membrane clients including polycystin-1 (PKD1); loss causes ADPKD (PKD6).
  molecular_function:
    id: GO:0001671
    label: ATPase activator activity
  locations:
  - id: GO:0005788
    label: endoplasmic reticulum lumen
  supported_by:
  - reference_id: file:human/DNAJB11/DNAJB11-uniprot.txt
    supporting_text: It is necessary for maturation and correct
  - reference_id: PMID:29706351
    supporting_text: maturation and trafficking defects involving the ADPKD protein
  directly_involved_in:
  - id: GO:0051604
    label: protein maturation
proposed_new_terms: []
suggested_questions:
- question: Which secretory/membrane clients besides PKD1 and UMOD depend on ERdj3 for ER maturation, and how does the cysteine-rich substrate-binding domain define client specificity?
- question: How do PKD6-causing DNAJB11 variants mechanistically impair BiP co-chaperone activity (substrate binding vs. BiP ATPase stimulation), and does haploinsufficiency versus dominant-negative action explain the phenotype?
suggested_experiments:
- description: Reconstituted assays measuring ERdj3-stimulated BiP ATPase activity and substrate holdase binding for wild-type versus PKD6 variants (P54R, L77P, truncation).
- description: Proximity-labeling or client-capture proteomics in DNAJB11-null versus wild-type cells to define the ERdj3-dependent secretory clientome and quantify PC1/UMOD maturation.