DNAJB5

UniProt ID: O75953
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

DNAJB5 (Hsc40, "heat shock protein cognate 40") is a cytosolic HSP40/J-domain co-chaperone of the DNAJB subfamily and a paralog of DNAJB1 and DNAJB4. Through its N-terminal J domain it is predicted to bind and stimulate the HSP70 chaperone (HSPA1A/HSPA1B/HSPA8), acting as a co-chaperone that delivers client proteins to HSP70 for folding. It is expressed constitutively and further induced by stress, is enriched in skeletal muscle and tongue, and produces several alternatively spliced isoforms. Compared with its better-studied paralogs it remains poorly characterized, with most molecular data derived from family-level inference and high-throughput interaction studies.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0006457 protein folding
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Phylogenetic (IBA) annotation that DNAJB5 participates in protein folding as a J-protein co-chaperone. DNAJB5 assists the HSP70 folding machine rather than autonomously catalyzing folding.
Reason: Protein folding is a downstream process outcome of DNAJB5's co-chaperone role; the direct molecular activity is HSP70 binding/stimulation, so folding is non-core.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0006457 protein folding biological_process ECO:0000318 IBA GO_REF:0000033
GO:0051087 protein-folding chaperone binding
IBA
GO_REF:0000033 		ACCEPT
Summary: DNAJB5 binds the HSP70 chaperone, the defining molecular interaction of a J-protein co-chaperone. Supported phylogenetically and by IPI evidence against HSP70 isoforms.
Reason: HSP70 binding is the core co-chaperone molecular function of DNAJB5 and is corroborated by experimental IPI annotations to HSPA1A/HSPA1B.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0051087 protein-folding chaperone binding molecular_function ECO:0000353 IPI PMID:21231916 UniProtKB:P0DMV8
GO:0005829 cytosol
IBA
GO_REF:0000033 		ACCEPT
Summary: DNAJB5 is a cytosolic J-protein; cytosolic site of action is supported phylogenetically and by direct IDA evidence (PubMed:21231916).
Reason: The cytosol is the compartment in which DNAJB5 acts as an HSP70 co-chaperone, consistent with the IDA cytosol annotation.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000314 IDA PMID:21231916
GO:0006457 protein folding
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: InterPro-based electronic annotation of protein folding, redundant with the IBA protein folding call.
Reason: Same downstream-process rationale as the IBA protein folding annotation; DNAJB5 assists rather than autonomously catalyzes folding.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0006457 protein folding biological_process ECO:0000256 IEA GO_REF:0000002 InterPro:IPR008971
GO:0006986 response to unfolded protein
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Rule-based electronic annotation that DNAJB5 participates in the response to unfolded protein, consistent with its stress-inducible expression and chaperone role.
Reason: Consistent with DNAJB5's stress induction and client-handling role; a genuine process annotation but downstream of its molecular co-chaperone function.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-uniprot.txt
Expressed under normal conditions, its expression can further be increased after various stress treatments.
GO:0051087 protein-folding chaperone binding
IEA
GO_REF:0000117 		ACCEPT
Summary: Rule-based electronic annotation of chaperone (HSP70) binding, redundant with the IBA and IPI protein-folding chaperone binding annotations.
Reason: Correct molecular function; DNAJB5 binds HSP70, supported by stronger IPI/IBA evidence.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0051087 protein-folding chaperone binding molecular_function ECO:0000256 IEA GO_REF:0000117
GO:0005515 protein binding
IPI
PMID:18457437
Identification of intracellular proteins associated with the... 		KEEP AS NON CORE
Summary: High-throughput interaction capturing DNAJB5 with the Epstein-Barr virus nuclear antigen EBNA-LP (Q8AZK7). Bare protein binding is uninformative and this cross-species viral interaction does not define DNAJB5's core function.
Reason: Records a real (viral) interaction but bare protein binding is uninformative per curation guidelines; not part of the core chaperone function.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18457437 UniProtKB:Q8AZK7
GO:0005515 protein binding
IPI
PMID:21078624
Comparison of an expanded ataxia interactome with patient me... 		KEEP AS NON CORE
Summary: Expanded ataxia interactome screen capturing DNAJB5 with the calcium channel subunit CACNA1A (O00555). Bare protein binding is uninformative.
Reason: Records a real high-throughput interaction but bare protein binding is uninformative; the CACNA1A partner does not define DNAJB5's core chaperone function.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21078624 UniProtKB:O00555
GO:0005515 protein binding
IPI
PMID:22810586
Interpreting cancer genomes using systematic host network pe... 		KEEP AS NON CORE
Summary: Cancer host-network perturbation interactome again capturing the DNAJB5-EBNA-LP (Q8AZK7) interaction. Bare protein binding is uninformative.
Reason: Records a real high-throughput interaction but bare protein binding is uninformative and not part of the core function.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:22810586 UniProtKB:Q8AZK7
GO:0005515 protein binding
IPI
PMID:23414517
A human skeletal muscle interactome centered on proteins inv... 		KEEP AS NON CORE
Summary: Human skeletal-muscle interactome capturing DNAJB5 with titin (TTN, Q8WZ42). Bare protein binding is uninformative, though a titin interaction together with DNAJB5's skeletal-muscle enrichment is suggestive of a sarcomeric role analogous to its paralogs.
Reason: Records a real high-throughput interaction; bare protein binding is uninformative as a core MF, and a muscle/sarcomere role for DNAJB5 is not yet functionally demonstrated.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23414517 UniProtKB:Q8WZ42
GO:0005634 nucleus
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Ensembl ortholog-based electronic annotation of nuclear localization, transferred from the mouse ortholog. DNAJB5's experimentally supported localization is cytosolic; a nuclear pool is not independently demonstrated for the human protein.
Reason: Orthology-projected nuclear localization without direct human evidence; DNAJB5 is characterized as a cytosolic co-chaperone, so a nuclear pool is at best secondary/non-core.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0005634 nucleus cellular_component ECO:0000265 IEA GO_REF:0000107
GO:0005829 cytosol
IEA
GO_REF:0000107 		ACCEPT
Summary: Ensembl ortholog-based electronic annotation of cytosolic localization, consistent with the IDA and IBA cytosol annotations.
Reason: Correct compartment for this cytosolic co-chaperone; agrees with stronger IDA/IBA cytosol evidence.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000265 IEA GO_REF:0000107
GO:0051087 protein-folding chaperone binding
IPI
PMID:21231916
The diverse members of the mammalian HSP70 machine show dist... 		ACCEPT
Summary: Functional study of the mammalian HSP70/DNAJ machine; DNAJB5 binds HSP70 isoforms (HSPA1A/HSPA1B) as a co-chaperone. This is the most direct molecular evidence for DNAJB5's function.
Reason: Binding to HSP70 chaperones is the core molecular interaction of DNAJB5 as a J-protein co-chaperone.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0051087 protein-folding chaperone binding molecular_function ECO:0000353 IPI PMID:21231916 UniProtKB:P0DMV8
GO:0005829 cytosol
IDA
PMID:21231916
The diverse members of the mammalian HSP70 machine show dist... 		ACCEPT
Summary: Direct evidence places DNAJB5 in the cytosol, consistent with its co-chaperone role and all other localization data.
Reason: IDA cytosol localization corroborates the established cytosolic site of action.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000314 IDA PMID:21231916
GO:0006986 response to unfolded protein
IEP
PMID:10570961
Hsc40, a new member of the hsp40 family, exhibits similar ex... 		KEEP AS NON CORE
Summary: The original Hsc40 cloning/characterization paper reports expression behavior (constitutive plus stress-inducible) supporting involvement in the response to unfolded protein, inferred from expression patterns (IEP).
Reason: Expression-based (IEP) evidence for stress involvement; consistent with DNAJB5's chaperone role but a downstream process annotation rather than its molecular function.
Supporting Evidence:
file:human/DNAJB5/DNAJB5-uniprot.txt
Expressed under normal conditions, its expression can further be increased after various stress treatments.

Core Functions

J-domain co-chaperone that binds the HSP70 chaperone (HSPA1A/HSPA1B/HSPA8) and, by analogy to its DNAJB paralogs, delivers client proteins to HSP70 to promote their folding; acts in the cytosol and is stress-inducible.

Molecular Function:
protein-folding chaperone binding
Cellular Locations:
cytosol
Supporting Evidence:
  • file:human/DNAJB5/DNAJB5-goa.tsv
    GO:0051087 protein-folding chaperone binding molecular_function ECO:0000353 IPI PMID:21231916 UniProtKB:P0DMV8
  • file:human/DNAJB5/DNAJB5-goa.tsv
    GO:0005829 cytosol cellular_component ECO:0000314 IDA PMID:21231916

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
PMID:10570961
Hsc40, a new member of the hsp40 family, exhibits similar expression profile to that of hsc70 in mammalian cells.
  • DNAJB5/Hsc40 is a member of the HSP40 family that is constitutively expressed (similar to HSC70) and further induced by stress.
PMID:18457437
Identification of intracellular proteins associated with the EBV-encoded nuclear antigen 5 using an efficient TAP procedure and FT-ICR mass spectrometry.
PMID:21078624
Comparison of an expanded ataxia interactome with patient medical records reveals a relationship between macular degeneration and ataxia.
PMID:22810586
Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.
PMID:23414517
A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome.
  • DNAJB5 was captured interacting with titin (TTN) in a skeletal-muscle interactome, consistent with its skeletal-muscle enrichment.
PMID:21231916
The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities.
  • DNAJB5 is a cytosolic DNAJ/HSP40 co-chaperone that binds HSP70 isoforms.

Suggested Questions for Experts

Q: Does DNAJB5 stimulate HSP70 ATPase activity and refold/disaggregate clients autonomously, or is it functionally redundant with DNAJB1/DNAJB4 in the cytosol?

Q: Given its skeletal-muscle enrichment and titin interaction, does DNAJB5 have a sarcomeric/Z-disc proteostasis role analogous to DNAJB4 and DNAJB6?

Suggested Experiments

Experiment: In vitro reconstitution measuring DNAJB5-dependent stimulation of HSP70 ATPase and luciferase refolding/disaggregation, benchmarked against DNAJB1 and DNAJB4.

Experiment: Affinity purification-mass spectrometry of tagged DNAJB5 in muscle cells to define its physiological client/interaction network and test the titin/sarcomere association.

📚 Additional Documentation

Notes

(DNAJB5-notes.md)

DNAJB5 (Hsc40 / HSC40) research notes

UniProt: O75953. 348 aa. DnaJ homolog subfamily B member 5; "heat shock protein cognate 40".
J-domain residues 4-68. Paralog of DNAJB1/DNAJB4. Poorly characterized.

What is established

  • Class B cytosolic J-protein (HSP40). No UniProt FUNCTION line — function inferred from family.
  • HSP70 co-chaperone binding: GOA GO:0051087 IPI to HSPA1A/HSPA1B (P0DMV8/P0DMV9, P17066) from
    PMID:21231916 (Hageman et al., mammalian HSP70 machine study). This is the most direct MF evidence.
  • Cytosol: IDA GO:0005829 PMID:21231916; IBA cytosol.
  • Stress-inducible: [UniProt INDUCTION "Expressed under normal conditions, its expression can further
    be increased after various stress treatments."] Cloning paper PMID:10570961 (Hsc40) — IEP response
    to unfolded protein. Tissue enhanced in skeletal muscle/tongue (HPA).

Protein-binding IPIs (all high-throughput, uninformative)

  • PMID:18457437 EBNA-LP (Q8AZK7) — Epstein-Barr viral nuclear antigen interactome (xeno).
  • PMID:21078624 CACNA1A (O00555) — expanded ataxia interactome.
  • PMID:22810586 EBNA-LP again — cancer/host network perturbation.
  • PMID:23414517 TTN/titin (Q8WZ42) — human skeletal muscle interactome.
    None inform core chaperone function; KEEP_AS_NON_CORE (records real interactions).
    Note titin interaction + skeletal-muscle enrichment is suggestive of a muscle role akin to DNAJB4/DNAJB6
    but not functionally demonstrated.

Likely over-annotation

  • GO:0000122 negative regulation of transcription by Pol II — IEA:Ensembl (DR line only; not in GOA TSV
    as a reviewable row beyond Ensembl). Same family-transfer artifact as DNAJB4. (Not present as separate
    stub row; the GOA TSV does not include a 0000122 row for DNAJB5, so no annotation to review.)

MF/BP assignment

  • Core MF: GO:0051087 protein-folding chaperone binding (binds HSP70). Also GO:0051082 unfolded protein
    binding (IBA, DR line) is plausible holdase/client-binding.
  • GO:0006457 protein folding: KEEP_AS_NON_CORE (downstream, co-chaperone not foldase).
  • No experimental ATPase-stimulation data for DNAJB5 itself, so do NOT assert GO:0001671 as core.

Pn Notes

(DNAJB5-pn-notes.md)

DNAJB5 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: O75953
  • 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: DNAJB5 (Hsc40, "heat shock protein cognate 40") is a cytosolic HSP40/J-domain co-chaperone of the DNAJB subfamily and a paralog of DNAJB1 and DNAJB4. Through its N-terminal J domain it is predicted to bind and stimulate the HSP70 chaperone (HSPA1A/HSPA1B/HSPA8), acting as a co-chaperone that delivers client proteins to HSP70 for folding. It is expressed constitutively and further induced by stress, is enriched in skeletal muscle and tongue, and produces several alternatively spliced isoforms. Compared with its better-studied paralogs it remains poorly characterized, with most molecular data derived from family-level inference and high-throughput interaction studies.
  • Existing/core annotation action counts: ACCEPT: 6; KEEP_AS_NON_CORE: 9

PN Consistency Summary

  • Consistency: Consistent but note the weaker evidence base. Notes/YAML stress DNAJB5 is poorly characterized: it is a cytosolic class-B J-protein whose HSP70 binding rests on GOA GO:0051087 IPI (PMID:21231916) and family inference, with NO direct ATPase-stimulation data. The review correctly does NOT assert GO:0001671 as core (unlike DNAJB4). PN "J-domain HSP70 cochaperone" type is consistent with the available (family/IPI-level) evidence.
  • PN story / NEW pressure: PN asserts HSP70 interaction — captured by GO:0051087 (IPI PMID:21231916 + IBA/IEA, ACCEPT/core). PN-projected GO:0030544 (verified real) is a child of GO:0051087, so it is a more-specific refinement, defensible from the same IPI-to-HSP70 evidence. No NEW-term pressure. A possible muscle/titin role (PMID:23414517) is flagged in notes but explicitly not functionally demonstrated — correctly left as non-core. Verdict: already captured.
  • Evidence alignment: Shared anchor PMID:21231916 (HSP70 machine). Review adds HT-interactome PMIDs (titin, CACNA1A, EBNA-LP) absent from PN; PN adds nothing the review lacks.
  • Verdict: CONSISTENT — GO:0030544 defensible as narrower than the gene's GO:0051087; correct that no ATPase/holdase MF is asserted for this poorly-characterized member.

Full Consistency Review

  • UniProt: O75953 (Hsc40) · 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 (parents no_mapping)
  • Consistency: Consistent but note the weaker evidence base. Notes/YAML stress DNAJB5 is poorly characterized: it is a cytosolic class-B J-protein whose HSP70 binding rests on GOA GO:0051087 IPI (PMID:21231916) and family inference, with NO direct ATPase-stimulation data. The review correctly does NOT assert GO:0001671 as core (unlike DNAJB4). PN "J-domain HSP70 cochaperone" type is consistent with the available (family/IPI-level) evidence.
  • PN story / NEW pressure: PN asserts HSP70 interaction — captured by GO:0051087 (IPI PMID:21231916 + IBA/IEA, ACCEPT/core). PN-projected GO:0030544 (verified real) is a child of GO:0051087, so it is a more-specific refinement, defensible from the same IPI-to-HSP70 evidence. No NEW-term pressure. A possible muscle/titin role (PMID:23414517) is flagged in notes but explicitly not functionally demonstrated — correctly left as non-core. Verdict: already captured.
  • Mapping strategy: Mapping to GO:0030544 is appropriate; scope ok_for_propagation given the IPI HSP70 anchor. Because DNAJB5 lacks its own holdase/ATPase data, the type-level (rather than over-broad "unfolded protein binding") mapping is the right altitude — does not over-reach.
  • Evidence alignment: Shared anchor PMID:21231916 (HSP70 machine). Review adds HT-interactome PMIDs (titin, CACNA1A, EBNA-LP) absent from PN; PN adds nothing the review lacks.
  • Verdict: CONSISTENT — GO:0030544 defensible as narrower than the gene's GO:0051087; correct that no ATPase/holdase MF is asserted for this poorly-characterized member.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/DNAJB5/DNAJB5-ai-review.yaml
  • PN workbook rows: 1

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

  • UniProt: O75953
  • 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=more_specific_than_existing_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: O75953
gene_symbol: DNAJB5
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DNAJB5 (Hsc40, "heat shock protein cognate 40") is a cytosolic HSP40/J-domain co-chaperone of the DNAJB subfamily and a paralog of DNAJB1 and DNAJB4. Through its N-terminal J domain it is predicted to bind and stimulate the HSP70 chaperone (HSPA1A/HSPA1B/HSPA8), acting as a co-chaperone that delivers client proteins to HSP70 for folding. It is expressed constitutively and further induced by stress, is enriched in skeletal muscle and tongue, and produces several alternatively spliced isoforms. Compared with its better-studied paralogs it remains poorly characterized, with most molecular data derived from family-level inference and high-throughput interaction studies.
alternative_products:
- name: '1'
  id: O75953-3
- name: '2'
  id: O75953-4
  sequence_note: VSP_046223
- name: '3'
  id: O75953-5
  sequence_note: VSP_047250
existing_annotations:
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) annotation that DNAJB5 participates in protein folding as a J-protein co-chaperone. DNAJB5 assists the HSP70 folding machine rather than autonomously catalyzing folding.
    action: KEEP_AS_NON_CORE
    reason: Protein folding is a downstream process outcome of DNAJB5's co-chaperone role; the direct molecular activity is HSP70 binding/stimulation, so folding is non-core.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0006457 protein folding biological_process ECO:0000318 IBA GO_REF:0000033
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: DNAJB5 binds the HSP70 chaperone, the defining molecular interaction of a J-protein co-chaperone. Supported phylogenetically and by IPI evidence against HSP70 isoforms.
    action: ACCEPT
    reason: HSP70 binding is the core co-chaperone molecular function of DNAJB5 and is corroborated by experimental IPI annotations to HSPA1A/HSPA1B.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0051087 protein-folding chaperone binding molecular_function ECO:0000353 IPI PMID:21231916 UniProtKB:P0DMV8
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: DNAJB5 is a cytosolic J-protein; cytosolic site of action is supported phylogenetically and by direct IDA evidence (PubMed:21231916).
    action: ACCEPT
    reason: The cytosol is the compartment in which DNAJB5 acts as an HSP70 co-chaperone, consistent with the IDA cytosol annotation.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000314 IDA PMID:21231916
- 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, redundant with the IBA protein folding call.
    action: KEEP_AS_NON_CORE
    reason: Same downstream-process rationale as the IBA protein folding annotation; DNAJB5 assists rather than autonomously catalyzes folding.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0006457 protein folding biological_process ECO:0000256 IEA GO_REF:0000002 InterPro:IPR008971
- term:
    id: GO:0006986
    label: response to unfolded protein
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Rule-based electronic annotation that DNAJB5 participates in the response to unfolded protein, consistent with its stress-inducible expression and chaperone role.
    action: KEEP_AS_NON_CORE
    reason: Consistent with DNAJB5's stress induction and client-handling role; a genuine process annotation but downstream of its molecular co-chaperone function.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-uniprot.txt
      supporting_text: Expressed under normal conditions, its expression can further be increased after various stress treatments.
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: Rule-based electronic annotation of chaperone (HSP70) binding, redundant with the IBA and IPI protein-folding chaperone binding annotations.
    action: ACCEPT
    reason: Correct molecular function; DNAJB5 binds HSP70, supported by stronger IPI/IBA evidence.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0051087 protein-folding chaperone binding molecular_function ECO:0000256 IEA GO_REF:0000117
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18457437
  qualifier: enables
  review:
    summary: High-throughput interaction capturing DNAJB5 with the Epstein-Barr virus nuclear antigen EBNA-LP (Q8AZK7). Bare protein binding is uninformative and this cross-species viral interaction does not define DNAJB5's core function.
    action: KEEP_AS_NON_CORE
    reason: Records a real (viral) interaction but bare protein binding is uninformative per curation guidelines; not part of the core chaperone function.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18457437 UniProtKB:Q8AZK7
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21078624
  qualifier: enables
  review:
    summary: Expanded ataxia interactome screen capturing DNAJB5 with the calcium channel subunit CACNA1A (O00555). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real high-throughput interaction but bare protein binding is uninformative; the CACNA1A partner does not define DNAJB5's core chaperone function.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21078624 UniProtKB:O00555
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22810586
  qualifier: enables
  review:
    summary: Cancer host-network perturbation interactome again capturing the DNAJB5-EBNA-LP (Q8AZK7) interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real high-throughput interaction but bare protein binding is uninformative and not part of the core function.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:22810586 UniProtKB:Q8AZK7
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23414517
  qualifier: enables
  review:
    summary: Human skeletal-muscle interactome capturing DNAJB5 with titin (TTN, Q8WZ42). Bare protein binding is uninformative, though a titin interaction together with DNAJB5's skeletal-muscle enrichment is suggestive of a sarcomeric role analogous to its paralogs.
    action: KEEP_AS_NON_CORE
    reason: Records a real high-throughput interaction; bare protein binding is uninformative as a core MF, and a muscle/sarcomere role for DNAJB5 is not yet functionally demonstrated.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23414517 UniProtKB:Q8WZ42
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl ortholog-based electronic annotation of nuclear localization, transferred from the mouse ortholog. DNAJB5's experimentally supported localization is cytosolic; a nuclear pool is not independently demonstrated for the human protein.
    action: KEEP_AS_NON_CORE
    reason: Orthology-projected nuclear localization without direct human evidence; DNAJB5 is characterized as a cytosolic co-chaperone, so a nuclear pool is at best secondary/non-core.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0005634 nucleus cellular_component ECO:0000265 IEA GO_REF:0000107
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl ortholog-based electronic annotation of cytosolic localization, consistent with the IDA and IBA cytosol annotations.
    action: ACCEPT
    reason: Correct compartment for this cytosolic co-chaperone; agrees with stronger IDA/IBA cytosol evidence.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000265 IEA GO_REF:0000107
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IPI
  original_reference_id: PMID:21231916
  qualifier: enables
  review:
    summary: Functional study of the mammalian HSP70/DNAJ machine; DNAJB5 binds HSP70 isoforms (HSPA1A/HSPA1B) as a co-chaperone. This is the most direct molecular evidence for DNAJB5's function.
    action: ACCEPT
    reason: Binding to HSP70 chaperones is the core molecular interaction of DNAJB5 as a J-protein co-chaperone.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0051087 protein-folding chaperone binding molecular_function ECO:0000353 IPI PMID:21231916 UniProtKB:P0DMV8
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:21231916
  qualifier: located_in
  review:
    summary: Direct evidence places DNAJB5 in the cytosol, consistent with its co-chaperone role and all other localization data.
    action: ACCEPT
    reason: IDA cytosol localization corroborates the established cytosolic site of action.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000314 IDA PMID:21231916
- term:
    id: GO:0006986
    label: response to unfolded protein
  evidence_type: IEP
  original_reference_id: PMID:10570961
  qualifier: involved_in
  review:
    summary: The original Hsc40 cloning/characterization paper reports expression behavior (constitutive plus stress-inducible) supporting involvement in the response to unfolded protein, inferred from expression patterns (IEP).
    action: KEEP_AS_NON_CORE
    reason: Expression-based (IEP) evidence for stress involvement; consistent with DNAJB5's chaperone role but a downstream process annotation rather than its molecular function.
    supported_by:
    - reference_id: file:human/DNAJB5/DNAJB5-uniprot.txt
      supporting_text: Expressed under normal conditions, its expression can further be increased after various stress treatments.
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:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:10570961
  title: Hsc40, a new member of the hsp40 family, exhibits similar expression profile to that of hsc70 in mammalian cells.
  reference_review:
    relevance: MEDIUM
    correctness: UNVERIFIED
    review_notes: Original characterization of DNAJB5/Hsc40 (title plausibly supports HSP40-family membership and stress-inducible expression; GOA cites it for GO:0006986 response to unfolded protein, IEP), but the publication is not cached so the supporting text could not be confirmed against a checkable source.
  findings:
  - statement: DNAJB5/Hsc40 is a member of the HSP40 family that is constitutively expressed (similar to HSC70) and further induced by stress.
    reference_section_type: RESULTS
- id: PMID:18457437
  title: Identification of intracellular proteins associated with the EBV-encoded nuclear antigen 5 using an efficient TAP procedure and FT-ICR mass spectrometry.
  findings: []
- id: PMID:21078624
  title: Comparison of an expanded ataxia interactome with patient medical records reveals a relationship between macular degeneration and ataxia.
  findings: []
- id: PMID:22810586
  title: Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.
  findings: []
- id: PMID:23414517
  title: 'A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome.'
  findings:
  - statement: DNAJB5 was captured interacting with titin (TTN) in a skeletal-muscle interactome, consistent with its skeletal-muscle enrichment.
    reference_section_type: RESULTS
- id: PMID:21231916
  title: The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Anchored to GOA evidence - this PMID is cited for DNAJB5's GO:0051087 (protein-folding chaperone binding, IPI) and GO:0005829 (cytosol, IDA) - establishing DNAJB5's core cytosolic HSP70 co-chaperone function. Cached text is the family-wide HSP70-machine study; gene-specific detail confirmed via the GOA annotation rather than the cached abstract.
  findings:
  - statement: DNAJB5 is a cytosolic DNAJ/HSP40 co-chaperone that binds HSP70 isoforms.
    reference_section_type: RESULTS
core_functions:
- description: J-domain co-chaperone that binds the HSP70 chaperone (HSPA1A/HSPA1B/HSPA8) and, by analogy to its DNAJB paralogs, delivers client proteins to HSP70 to promote their folding; acts in the cytosol and is stress-inducible.
  molecular_function:
    id: GO:0051087
    label: protein-folding chaperone binding
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
    supporting_text: GO:0051087 protein-folding chaperone binding molecular_function ECO:0000353 IPI PMID:21231916 UniProtKB:P0DMV8
  - reference_id: file:human/DNAJB5/DNAJB5-goa.tsv
    supporting_text: GO:0005829 cytosol cellular_component ECO:0000314 IDA PMID:21231916
proposed_new_terms: []
suggested_questions:
- question: Does DNAJB5 stimulate HSP70 ATPase activity and refold/disaggregate clients autonomously, or is it functionally redundant with DNAJB1/DNAJB4 in the cytosol?
- question: Given its skeletal-muscle enrichment and titin interaction, does DNAJB5 have a sarcomeric/Z-disc proteostasis role analogous to DNAJB4 and DNAJB6?
suggested_experiments:
- description: In vitro reconstitution measuring DNAJB5-dependent stimulation of HSP70 ATPase and luciferase refolding/disaggregation, benchmarked against DNAJB1 and DNAJB4.
- description: Affinity purification-mass spectrometry of tagged DNAJB5 in muscle cells to define its physiological client/interaction network and test the titin/sarcomere association.