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.