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.