DNAJC17

UniProt ID: Q9NVM6
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

DNAJC17 is a poorly characterized, predominantly nuclear protein of the DnaJ/HSP40 subfamily C that combines an N-terminal J domain with a C-terminal RNA recognition motif (RRM), separated by a disordered acidic/basic region. The domain architecture marks it as a putative HSP70 co-chaperone with RNA-binding capacity. Convergent evidence (phylogenetic inference from the yeast ortholog Cwc23, an RRM domain with a solved RNA-binding-domain structure, nuclear-speckle localization, and interaction with the U5 snRNP component EFTUD2) implicates DNAJC17 in spliceosome function, most likely spliceosomal complex disassembly. By orthology it has also been suggested to negatively affect PAX8-induced thyroglobulin transcription. It is phosphorylated at Ser-112 and methylated at Lys-264, and its mouse ortholog is essential for viability. Its precise molecular and cellular function in human cells has not been directly established.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000390 spliceosomal complex disassembly
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Phylogenetic (IBA) annotation transferred from yeast orthologs (Cwc23; PomBase SPCC10H11.02, SGD S000003096), J-domain proteins that act with the Prp43 helicase in spliceosome disassembly. Consistent with DNAJC17's RRM, nuclear-speckle localization and interaction with the spliceosomal component EFTUD2, though not directly demonstrated in human.
Reason: Convergent orthology, domain and interactome evidence supports a spliceosome-disassembly role, but there is no direct human experimental demonstration; retained as a plausible non-core process pending direct validation.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-goa.tsv
GO:0000390 spliceosomal complex disassembly biological_process ECO:0000318 IBA GO_REF:0000033
GO:0005681 spliceosomal complex
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic (IBA) annotation placing DNAJC17 in the spliceosomal complex, transferred from yeast orthologs. Supported by its interaction with the core U5 snRNP component EFTUD2 and nuclear-speckle localization.
Reason: Orthology plus a documented interaction with the spliceosomal GTPase EFTUD2 supports association with the spliceosomal complex; a reasonable cellular-component annotation.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-goa.tsv
GO:0005681 spliceosomal complex cellular_component ECO:0000318 IBA GO_REF:0000033
GO:0003676 nucleic acid binding
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: InterPro2GO electronic annotation of nucleic acid binding based on the RRM domain. A generic parent of the more specific RNA binding term, supported by the same RRM evidence.
Reason: Correct but generic; RNA binding (the specific child term) is the informative molecular function for this RRM-containing protein.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-uniprot.txt
DOMAIN 178..249
GO:0003723 RNA binding
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro2GO electronic annotation of RNA binding based on the C-terminal RRM domain, whose structure has been solved by NMR (PDB:2D9O). A plausible, specific molecular function for this J-domain/RRM protein.
Reason: DNAJC17 has a bona fide RRM (RNA recognition motif) with a solved RNA-binding-domain structure; RNA binding is a well-justified molecular function.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-uniprot.txt
DOMAIN 178..249
GO:0005634 nucleus
IEA
GO_REF:0000044 		ACCEPT
Summary: Automated SubCell nuclear localization, consistent with the ISS annotation and the reported predominantly nuclear distribution (nuclear speckles).
Reason: DNAJC17 is predominantly nuclear; nuclear localization is well supported and is its principal site of action.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:D3ZSC8}. Nucleus
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: Automated SubCell cytoplasmic localization, consistent with the ISS annotation; DNAJC17 is predominantly nuclear but also present in the cytoplasm.
Reason: A genuine secondary localization (the protein is predominantly nuclear); retained as non-core relative to its nuclear site of action.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:D3ZSC8}. Nucleus
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		KEEP AS NON CORE
Summary: HuRI binary-interactome (Y2H) screen capturing a DNAJC17-MEOX2 (Q6FHY5) interaction. The bare protein binding term is uninformative and the homeobox-TF partner is not clearly related to DNAJC17's inferred spliceosome/RNA function.
Reason: Records a real high-throughput interaction but GO:0005515 is uninformative and the partner does not inform DNAJC17's core function; not elevated to core.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:Q6FHY5
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce... 		KEEP AS NON CORE
Summary: OpenCell endogenous-tagging interactome capturing a DNAJC17-EFTUD2 (Q15029) interaction. EFTUD2 is a core U5 snRNP/spliceosome component, so this interaction corroborates DNAJC17's spliceosome association, although the bare protein binding term itself is uninformative.
Reason: A real and functionally suggestive interaction (with the spliceosomal component EFTUD2), but GO:0005515 is uninformative; the functional meaning is captured by the spliceosomal-complex annotation.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311 UniProtKB:Q15029
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func... 		KEEP AS NON CORE
Summary: Multimodal cell-maps interactome capturing the same DNAJC17-EFTUD2 (Q15029) interaction. The bare protein binding term is uninformative but the partner reinforces spliceosome association.
Reason: Corroborates the EFTUD2 (spliceosome) interaction; GO:0005515 itself is uninformative and not core, with the functional consequence captured by the spliceosomal-complex annotation.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:Q15029
GO:0005634 nucleus
ISS
GO_REF:0000024 		ACCEPT
Summary: Sequence-similarity (ISS, from rat ortholog D3ZSC8) annotation of nuclear localization, consistent with the reported predominantly nuclear distribution.
Reason: Corroborates the nuclear localization (the protein is predominantly nuclear); a core cellular component.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-uniprot.txt
Note=Predominantly nuclear.
GO:0005737 cytoplasm
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Sequence-similarity (ISS, from rat ortholog D3ZSC8) annotation of cytoplasmic localization, redundant with the IEA cytoplasm annotation.
Reason: A genuine secondary localization; retained as non-core relative to the predominantly nuclear site of action.
Supporting Evidence:
file:human/DNAJC17/DNAJC17-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:D3ZSC8}.

Core Functions

Putative HSP70 co-chaperone and RNA-binding protein (J domain plus RRM) that associates with the spliceosome, most likely functioning in spliceosomal complex disassembly by analogy to its yeast ortholog Cwc23; localizes predominantly to the nucleus.

Molecular Function:
RNA binding
Cellular Locations:
nucleus
In Complex:
spliceosomal complex
Supporting Evidence:
  • file:human/DNAJC17/DNAJC17-goa.tsv
    GO:0005681 spliceosomal complex cellular_component ECO:0000318 IBA GO_REF:0000033
  • file:human/DNAJC17/DNAJC17-uniprot.txt
    Note=Predominantly nuclear.

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
PMID:32296183
A reference map of the human binary protein interactome.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
file:human/DNAJC17/DNAJC17-uniprot.txt
UniProt entry Q9NVM6 (DJC17_HUMAN), DnaJ homolog subfamily C member 17
  • Predominantly nuclear J-domain protein with a C-terminal RRM (RNA recognition motif); may negatively affect PAX8-induced thyroglobulin transcription (by similarity); phosphorylated at Ser-112 and methylated at Lys-264.

Suggested Questions for Experts

Q: Does human DNAJC17 function in spliceosome disassembly (as the ortholog of yeast Cwc23), and does its J domain recruit/stimulate an HSP70 to remodel the spliceosome together with DHX15/Prp43?

Q: What RNA targets does the DNAJC17 RRM bind, and is the nuclear-speckle localization dependent on RNA binding or on the EFTUD2/spliceosome interaction?

Suggested Experiments

Experiment: CLIP-seq or in vitro RNA-binding assays with recombinant DNAJC17 RRM to identify its RNA targets, paired with co-immunoprecipitation to map its spliceosomal interaction network.

Experiment: Test DNAJC17 function in spliceosome disassembly using in vitro splicing extracts (depletion/add-back) and J-domain HPD-motif mutants to determine whether its co-chaperone activity is required, given the essentiality of the mouse ortholog.

📚 Additional Documentation

Notes

(DNAJC17-notes.md)

DNAJC17 research notes

Identity

  • UniProt Q9NVM6, HGNC:25556, 304 aa. DnaJ/HSP40 subfamily C member 17. Poorly characterized
    (Pharos Tbio).
  • Architecture: N-terminal J domain (11-76), central disordered acidic/basic region (79-145),
    C-terminal RRM (RNA recognition motif, 178-249; NMR structure PDB:2D9O). [file:human/DNAJC17/DNAJC17-uniprot.txt]
  • So it is a J-domain + RRM protein: a putative HSP70 co-chaperone with RNA-binding capacity.
  • Predominantly nuclear (also cytoplasmic). Phosphorylated at Ser-112 (many MS studies);
    methylated at Lys-264. Associated with nuclear speckles (CD-CODE 804901D1). [file:human/DNAJC17/DNAJC17-uniprot.txt]

Inferred functions

  • Spliceosome / spliceosomal complex disassembly (IBA, GO_REF:0000033): inferred from orthologs
    PomBase:SPCC10H11.02 and SGD:S000003096 (yeast Cwc23), a J-domain protein that functions with the
    Prp43 helicase in spliceosome disassembly. RRM + nuclear-speckle localization + EFTUD2 interaction
    are consistent. [file:human/DNAJC17/DNAJC17-goa.tsv]
  • RNA binding (IEA from InterPro RRM, IPR000504) and nucleic acid binding (IEA, IPR035979): supported
    by the RRM domain and the RIKEN NMR structure of the RNA-binding domain. [file:human/DNAJC17/DNAJC17-uniprot.txt]
  • UniProt FUNCTION (by similarity to mouse Q91WT4): "May negatively affect PAX8-induced
    thyroglobulin/TG transcription." Speculative/orthology-based; the gene is also reported essential
    in mouse (lethal knockout). [file:human/DNAJC17/DNAJC17-uniprot.txt]
  • GO:0000122 negative regulation of transcription by RNA pol II (IEA Ensembl) - in UniProt DR but not
    in seeded ai-review/goa list; reflects the PAX8/TG inference.

Interactions (IPI GO:0005515)

  • Q15029 = EFTUD2 (SNRP116/U5-116K), a core U5 snRNP/spliceosome GTPase. PMID:35271311 (OpenCell),
    PMID:40205054 (cell maps). Corroborates spliceosome association.
  • Q6FHY5 = MEOX2 (homeobox TF). PMID:32296183 (HuRI Y2H). Less clearly relevant.

Localization

  • Nucleus (IEA SubCell + ISS from rat D3ZSC8), cytoplasm (IEA + ISS), predominantly nuclear.
    [file:human/DNAJC17/DNAJC17-uniprot.txt]

Curation

  • Core function uncertain. Best-supported convergent picture: a nuclear J-domain/RRM protein
    associated with the spliceosome (likely human ortholog of yeast Cwc23 acting in spliceosome
    disassembly). RNA binding (RRM) is a genuine inferred MF. Keep spliceosome BP/CC as
    KEEP_AS_NON_CORE / ACCEPT given convergent (IBA + EFTUD2 IPI) but not direct human experimental
    evidence; flag the PAX8/TG transcription inference as orthology-only.
  • Use UNDECIDED only where truly unable to assess. Here we can reason from orthology + domain +
    interactome, so avoid UNDECIDED; use ACCEPT/KEEP_AS_NON_CORE for the convergent spliceosome/RNA
    picture and KEEP_AS_NON_CORE for the protein-binding HT terms.

Pn Notes

(DNAJC17-pn-notes.md)

DNAJC17 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9NVM6
  • 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: DNAJC17 is a poorly characterized, predominantly nuclear protein of the DnaJ/HSP40 subfamily C that combines an N-terminal J domain with a C-terminal RNA recognition motif (RRM), separated by a disordered acidic/basic region. The domain architecture marks it as a putative HSP70 co-chaperone with RNA-binding capacity. Convergent evidence (phylogenetic inference from the yeast ortholog Cwc23, an RRM domain with a solved RNA-binding-domain structure, nuclear-speckle localization, and interaction with the U5 snRNP component EFTUD2) implicates DNAJC17 in spliceosome function, most likely spliceosomal complex disassembly. By orthology it has also been suggested to negatively affect PAX8-induced thyroglobulin transcription. It is phosphorylated at Ser-112 and methylated at Lys-264, and its mouse ortholog is essential for viability. Its precise molecular and cellular function in human cells has not been directly established.
  • Existing/core annotation action counts: ACCEPT: 4; KEEP_AS_NON_CORE: 7

PN Consistency Summary

  • Consistency: Mismatch in emphasis. Deep-research notes and review converge on a nuclear J-domain+RRM protein whose best-supported (convergent IBA + EFTUD2 IPI + nuclear-speckle) function is spliceosome association / spliceosomal complex disassembly (yeast Cwc23 ortholog) plus RNA binding. The PN node frames it solely as an HSP70 co-chaperone. The HSP70-binding role is plausible from the J domain but is NOT demonstrated and NOT the review's core; the review never asserts Hsp70 binding. So PN and review diverge on what the gene principally does.
  • PN story / NEW pressure: PN proposes GO:0030544 (verified real). There is no existing Hsp70-binding annotation and no direct evidence one exists for DNAJC17; the "more_specific_than_existing_goa" tag is questionable (no existing parent MF in GOA to be more specific than — existing MF terms are RNA binding/nucleic acid binding, a different axis). Family-level inference only; over-reaches as a confident projection.
  • Evidence alignment: Divergent. Review cites EFTUD2 interactome papers (PMID:35271311 OpenCell, PMID:40205054 cell maps) and the IBA spliceosome-disassembly inference; PN node carries no DNAJC17-specific reference, only the family heuristic. No shared functional paper supports Hsp70 binding.
  • Verdict: Plausible family inference but over-reaches as confident projection; gene's real function (spliceosome/RNA) sits outside the HSP70-cochaperone node. Recommended edits: [MAP] mark DNAJC17's GO:0030544 as family/domain-level inference (no experimental HSP70 binding); correct the "more_specific_than_existing_goa" tag (existing GOA MF is RNA binding, not an HSP70 parent).

Full Consistency Review

  • UniProt: Q9NVM6 · 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=more_specific_than_existing_goa)
  • Consistency: Mismatch in emphasis. Deep-research notes and review converge on a nuclear J-domain+RRM protein whose best-supported (convergent IBA + EFTUD2 IPI + nuclear-speckle) function is spliceosome association / spliceosomal complex disassembly (yeast Cwc23 ortholog) plus RNA binding. The PN node frames it solely as an HSP70 co-chaperone. The HSP70-binding role is plausible from the J domain but is NOT demonstrated and NOT the review's core; the review never asserts Hsp70 binding. So PN and review diverge on what the gene principally does.
  • PN story / NEW pressure: PN proposes GO:0030544 (verified real). There is no existing Hsp70-binding annotation and no direct evidence one exists for DNAJC17; the "more_specific_than_existing_goa" tag is questionable (no existing parent MF in GOA to be more specific than — existing MF terms are RNA binding/nucleic acid binding, a different axis). Family-level inference only; over-reaches as a confident projection.
  • Mapping strategy: Node heuristic is fine generically, but for DNAJC17 the projection is purely domain-based and the gene's real placement is in the spliceosome (Translation/RNA branch), not captured here. PN-projected Hsp70 binding is orthogonal to (not broader/narrower than) the review's RNA-binding/spliceosome core. Treat as family inference.
  • Evidence alignment: Divergent. Review cites EFTUD2 interactome papers (PMID:35271311 OpenCell, PMID:40205054 cell maps) and the IBA spliceosome-disassembly inference; PN node carries no DNAJC17-specific reference, only the family heuristic. No shared functional paper supports Hsp70 binding.
  • Verdict: Plausible family inference but over-reaches as confident projection; gene's real function (spliceosome/RNA) sits outside the HSP70-cochaperone node. Recommended edits: [MAP] mark DNAJC17's GO:0030544 as family/domain-level inference (no experimental HSP70 binding); correct the "more_specific_than_existing_goa" tag (existing GOA MF is RNA binding, not an HSP70 parent).

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/DNAJC17/DNAJC17-ai-review.yaml
  • PN workbook rows: 1

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

  • UniProt: Q9NVM6
  • 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: Q9NVM6
gene_symbol: DNAJC17
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DNAJC17 is a poorly characterized, predominantly nuclear protein of the DnaJ/HSP40
  subfamily C that combines an N-terminal J domain with a C-terminal RNA recognition motif (RRM),
  separated by a disordered acidic/basic region. The domain architecture marks it as a putative
  HSP70 co-chaperone with RNA-binding capacity. Convergent evidence (phylogenetic inference from the
  yeast ortholog Cwc23, an RRM domain with a solved RNA-binding-domain structure, nuclear-speckle
  localization, and interaction with the U5 snRNP component EFTUD2) implicates DNAJC17 in spliceosome
  function, most likely spliceosomal complex disassembly. By orthology it has also been suggested to
  negatively affect PAX8-induced thyroglobulin transcription. It is phosphorylated at Ser-112 and
  methylated at Lys-264, and its mouse ortholog is essential for viability. Its precise molecular and
  cellular function in human cells has not been directly established.
existing_annotations:
- term:
    id: GO:0000390
    label: spliceosomal complex disassembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) annotation transferred from yeast orthologs (Cwc23; PomBase
      SPCC10H11.02, SGD S000003096), J-domain proteins that act with the Prp43 helicase in
      spliceosome disassembly. Consistent with DNAJC17's RRM, nuclear-speckle localization and
      interaction with the spliceosomal component EFTUD2, though not directly demonstrated in human.
    action: KEEP_AS_NON_CORE
    reason: Convergent orthology, domain and interactome evidence supports a spliceosome-disassembly
      role, but there is no direct human experimental demonstration; retained as a plausible
      non-core process pending direct validation.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-goa.tsv
      supporting_text: GO:0000390 spliceosomal complex disassembly biological_process ECO:0000318 IBA GO_REF:0000033
- term:
    id: GO:0005681
    label: spliceosomal complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: Phylogenetic (IBA) annotation placing DNAJC17 in the spliceosomal complex, transferred
      from yeast orthologs. Supported by its interaction with the core U5 snRNP component EFTUD2 and
      nuclear-speckle localization.
    action: ACCEPT
    reason: Orthology plus a documented interaction with the spliceosomal GTPase EFTUD2 supports
      association with the spliceosomal complex; a reasonable cellular-component annotation.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-goa.tsv
      supporting_text: GO:0005681 spliceosomal complex cellular_component ECO:0000318 IBA GO_REF:0000033
- term:
    id: GO:0003676
    label: nucleic acid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO electronic annotation of nucleic acid binding based on the RRM domain. A
      generic parent of the more specific RNA binding term, supported by the same RRM evidence.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; RNA binding (the specific child term) is the informative molecular
      function for this RRM-containing protein.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-uniprot.txt
      supporting_text: DOMAIN          178..249
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO electronic annotation of RNA binding based on the C-terminal RRM domain,
      whose structure has been solved by NMR (PDB:2D9O). A plausible, specific molecular function for
      this J-domain/RRM protein.
    action: ACCEPT
    reason: DNAJC17 has a bona fide RRM (RNA recognition motif) with a solved RNA-binding-domain
      structure; RNA binding is a well-justified molecular function.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-uniprot.txt
      supporting_text: DOMAIN          178..249
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated SubCell nuclear localization, consistent with the ISS annotation and the
      reported predominantly nuclear distribution (nuclear speckles).
    action: ACCEPT
    reason: DNAJC17 is predominantly nuclear; nuclear localization is well supported and is its
      principal site of action.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:D3ZSC8}. Nucleus'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated SubCell cytoplasmic localization, consistent with the ISS annotation;
      DNAJC17 is predominantly nuclear but also present in the cytoplasm.
    action: KEEP_AS_NON_CORE
    reason: A genuine secondary localization (the protein is predominantly nuclear); retained as
      non-core relative to its nuclear site of action.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:D3ZSC8}. Nucleus'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: HuRI binary-interactome (Y2H) screen capturing a DNAJC17-MEOX2 (Q6FHY5) interaction. The
      bare protein binding term is uninformative and the homeobox-TF partner is not clearly related
      to DNAJC17's inferred spliceosome/RNA function.
    action: KEEP_AS_NON_CORE
    reason: Records a real high-throughput interaction but GO:0005515 is uninformative and the
      partner does not inform DNAJC17's core function; not elevated to core.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:Q6FHY5
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: OpenCell endogenous-tagging interactome capturing a DNAJC17-EFTUD2 (Q15029) interaction.
      EFTUD2 is a core U5 snRNP/spliceosome component, so this interaction corroborates DNAJC17's
      spliceosome association, although the bare protein binding term itself is uninformative.
    action: KEEP_AS_NON_CORE
    reason: A real and functionally suggestive interaction (with the spliceosomal component EFTUD2),
      but GO:0005515 is uninformative; the functional meaning is captured by the spliceosomal-complex
      annotation.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311 UniProtKB:Q15029
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-maps interactome capturing the same DNAJC17-EFTUD2 (Q15029) interaction.
      The bare protein binding term is uninformative but the partner reinforces spliceosome
      association.
    action: KEEP_AS_NON_CORE
    reason: Corroborates the EFTUD2 (spliceosome) interaction; GO:0005515 itself is uninformative and
      not core, with the functional consequence captured by the spliceosomal-complex annotation.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:Q15029
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity (ISS, from rat ortholog D3ZSC8) annotation of nuclear localization,
      consistent with the reported predominantly nuclear distribution.
    action: ACCEPT
    reason: Corroborates the nuclear localization (the protein is predominantly nuclear); a core
      cellular component.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-uniprot.txt
      supporting_text: Note=Predominantly nuclear.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity (ISS, from rat ortholog D3ZSC8) annotation of cytoplasmic
      localization, redundant with the IEA cytoplasm annotation.
    action: KEEP_AS_NON_CORE
    reason: A genuine secondary localization; retained as non-core relative to the predominantly
      nuclear site of action.
    supported_by:
    - reference_id: file:human/DNAJC17/DNAJC17-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:D3ZSC8}.'
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  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: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "Cached title matches the YAML title; this is a high-throughput endogenous-tagging cell-map study (not a DNAJC17-focused paper). It contributes only an IPI protein-binding annotation (to EFTUD2/Q15029, a spliceosome component), which is corroborating but background; it does not directly establish the core RNA-binding/spliceosome function."
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "Cached title matches the YAML title; large-scale multimodal cell-mapping study, not DNAJC17-specific. Supplies only an IPI protein-binding annotation (to EFTUD2/Q15029); background/corroborating relevance, does not establish the core function."
  findings: []
- id: file:human/DNAJC17/DNAJC17-uniprot.txt
  title: UniProt entry Q9NVM6 (DJC17_HUMAN), DnaJ homolog subfamily C member 17
  findings:
  - statement: Predominantly nuclear J-domain protein with a C-terminal RRM (RNA recognition motif);
      may negatively affect PAX8-induced thyroglobulin transcription (by similarity); phosphorylated
      at Ser-112 and methylated at Lys-264.
    reference_section_type: OTHER
core_functions:
- description: Putative HSP70 co-chaperone and RNA-binding protein (J domain plus RRM) that
    associates with the spliceosome, most likely functioning in spliceosomal complex disassembly by
    analogy to its yeast ortholog Cwc23; localizes predominantly to the nucleus.
  molecular_function:
    id: GO:0003723
    label: RNA binding
  locations:
  - id: GO:0005634
    label: nucleus
  in_complex:
    id: GO:0005681
    label: spliceosomal complex
  supported_by:
  - reference_id: file:human/DNAJC17/DNAJC17-goa.tsv
    supporting_text: GO:0005681 spliceosomal complex cellular_component ECO:0000318 IBA GO_REF:0000033
  - reference_id: file:human/DNAJC17/DNAJC17-uniprot.txt
    supporting_text: Note=Predominantly nuclear.
proposed_new_terms: []
suggested_questions:
- question: Does human DNAJC17 function in spliceosome disassembly (as the ortholog of yeast Cwc23),
    and does its J domain recruit/stimulate an HSP70 to remodel the spliceosome together with DHX15/Prp43?
- question: What RNA targets does the DNAJC17 RRM bind, and is the nuclear-speckle localization
    dependent on RNA binding or on the EFTUD2/spliceosome interaction?
suggested_experiments:
- description: CLIP-seq or in vitro RNA-binding assays with recombinant DNAJC17 RRM to identify its
    RNA targets, paired with co-immunoprecipitation to map its spliceosomal interaction network.
- description: Test DNAJC17 function in spliceosome disassembly using in vitro splicing extracts
    (depletion/add-back) and J-domain HPD-motif mutants to determine whether its co-chaperone
    activity is required, given the essentiality of the mouse ortholog.