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.
| 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}. |
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Download this section (compressed HTML)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?
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.
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