DNAJC21 is a J-domain protein involved in large (60S) ribosomal subunit biogenesis through nucleolar RNA association and cytoplasmic cooperation with the Hsp70 chaperone HSPA8 and assembly factors PA2G4 and ZNF622. It associates with precursor 45S rRNA and supports PA2G4 recycling during subunit maturation. Its N-terminal J domain contains the conserved HPD motif, and the protein contains two C2H2 zinc fingers. DNAJC21 occupies nucleolar and cytosolic pools and redistributes toward the nucleus when ribosomal RNA synthesis is inhibited. Alternative transcripts encode three predicted protein isoforms that differ between the zinc fingers. Biallelic pathogenic variants cause a cancer-prone bone marrow failure syndrome associated with defective ribosome biogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MODIFY | Summary: Conserved cytoplasmic localization can be specified as a supported cytosolic pool. Reason: The original assertion correctly places DNAJC21 in the cytoplasm. HPA independently identifies a cytosolic pool in A-431, U-251MG and U2OS cells with supported reliability, and the human assembly-factor study corroborates cytoplasmic localization. Refine the target-level location to cytosol (GO:0005829), a part of cytoplasm that includes protein complexes. This does not claim the original broad assay resolved cytosol, exclude the nucleolar pool, or erase actinomycin-D-induced redistribution toward the nucleus. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001940778 SUPPORTS TRANSFER The actual PTHR44029 tree places human Q5F1R6 below PTN001940778. The positive cytoplasm IBD is dated 2026-05-30 at taxon 2759, with PomBase:SPAC6B12.08, SGD:S000005171 and target Q5F1R6 evidence. Target self-inclusion is legitimate experimental grounding, not circularity; the target-specific refinement does not challenge node placement. Proposed replacements: cytosol |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: RNA binding is the evidence-backed refinement of domain-based nucleic-acid binding. Reason: InterPro IPR003604 maps a Matrin/U1-C-like C2H2 domain at target residues 311–345 to nucleic-acid and zinc binding. The domain alone does not choose DNA versus RNA or locate a contact site. Independent human UV RNA capture (PMID:22658674, original Table S1 row 674) supports RNA contact, and PMID:27346687 supports native association with precursor 45S rRNA. Replace the broad term with GO:0003723 RNA binding; do not infer DNA binding, purified rRNA recognition, or RNase catalysis. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR003604 SUPPORTS TRANSFER The official domain mapping and target match are present. RNA specificity comes from independent target experiments, not from assuming all C2H2 fingers bind the same ligand. Proposed replacements: RNA binding Supporting Evidence: file:human/DNAJC21/DNAJC21-bioinformatics/source-extracts.json |
| GO:0005634 nucleus | IEA GO_REF:0000044 | MODIFY | Summary: Nucleolar localization refines the mapped nuclear compartment. Reason: The original nuclear localization is positive. PMID:27346687 additionally identifies predominant nucleolar localization by nucleophosmin colocalization in human cells, independently corroborated by HPA. Refine the target-level assertion to nucleolus (GO:0005730), which is part of the nucleus. This is nonexclusive: nuclear fractionation and actinomycin-D-induced redistribution retain their original broader scope, and no absence from other nuclear regions is asserted. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER The nucleus vocabulary mapping is correct; human nucleophosmin colocalization supports the nonexclusive target-specific nucleolar refinement. Proposed replacements: nucleolus Supporting Evidence: file:human/DNAJC21/DNAJC21-uniprot.txt primarily to the nucleolus |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | ACCEPT | Summary: DNAJC21 has an established nucleolar pool. Reason: The UniProt nucleolus mapping agrees with human nucleophosmin colocalization in PMID:27346687 and the independent HPA nucleoli call. Native nuclear RNA co-IP supports association with precursor 45S rRNA in this biological context; it does not establish purified direct contact. Other cellular pools are retained. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0188 SUPPORTS TRANSFER Official nucleolus mapping is corroborated by target experiments. Supporting Evidence: |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: Cytosol refines the supported cytoplasmic pool. Reason: The original assertion correctly places DNAJC21 in the cytoplasm. HPA independently identifies a cytosolic pool in A-431, U-251MG and U2OS cells with supported reliability, and the human assembly-factor study corroborates cytoplasmic localization. Refine the target-level location to cytosol (GO:0005829), a part of cytoplasm that includes protein complexes. This does not claim the original broad assay resolved cytosol, exclude the nucleolar pool, or erase actinomycin-D-induced redistribution toward the nucleus. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER The cytoplasm mapping is sound; independent target HPA localization supplies the more specific cytosolic scope. Proposed replacements: cytosol Supporting Evidence: |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: C2H2-domain zinc binding is a defensible structural annotation. Reason: The actual IPR003604 target match (311–345) overlaps the first official C2H2 zinc finger, and the official sequence contains the corresponding zinc-finger architecture. Retain the electronic zinc-binding inference as structural context. No direct target metal-stoichiometry assay or independently demonstrated zinc-dependent catalytic activity is claimed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR003604 SUPPORTS TRANSFER The Matrin/U1-C-like C2H2 domain-to-zinc-binding mapping and target match are verified; this is domain-supported structural inference. Supporting Evidence: file:human/DNAJC21/DNAJC21-uniprot.txt ZN_FING 314..338 file:human/DNAJC21/DNAJC21-bioinformatics/source-extracts.json |
| GO:0005515 protein binding | IPI PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neu... | KEEP AS NON CORE | Summary: DNAJC21 prey sequences interact with huntingtin N-terminal baits in the original Y2H screen. Reason: The genuine Table S2 lists DNAJA5/Entrez 134218 with 23 HTT positives; Table S3 rows 5351–5373 identify LOC134218/NM_194283.1 against HTT 1–450 constructs annotated with both 23Q and 55Q. Six curated IntAct records corroborate the human pair. Screening, sequencing and naive-cell retesting support the interaction, but the data do not resolve physiological full-length complex formation or a specific chaperone/cytoskeletal activity for this pair. Retain the positive generic assertion under the explicit project binding instruction. No claim of a DNAJC21-specific mouse-brain co-IP is made. Supporting Evidence: PMID:17500595 reintroduced with Htt-fragment bait into naive Y2H assay cells file:human/DNAJC21/DNAJC21-bioinformatics/source-extracts.json |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | KEEP AS NON CORE | Summary: Human MTERF1–DNAJC21 fragment association is supported by mRNA display. Reason: The original Table S5 rows 146–147 identify MTERF–DNAJA5 IR_751 (440–469; class 2) and IR_752 (363–395; class 1); Table S4 lists the underlying sequence tags. Pair-specific pulldown, reciprocal pulldown and real-time-PCR verification cells are blank. IntAct records EBI-2690135/2690148 corroborate display-based association and sufficient-binding-region annotations; parent-protein identifiers do not establish a full-length tested prey. The method can recover direct and indirect interactions. MTERF1 is a DNA-binding transcription termination factor, but this evidence does not establish specific recognition of that functional class or a native physiological complex. Preserve the positive generic assertion as non-core, without using compartment differences to call it false. Supporting Evidence: PMID:20195357 the method detects both direct and indirect interactions file:human/DNAJC21/DNAJC21-bioinformatics/source-extracts.json |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | ACCEPT | Summary: HPA directly supports nucleolar localization. Reason: The current HPA source reports nucleoli and cytosol as main locations, with supported reliability, in A-431, U-251MG and U2OS cells. This nucleolar call agrees with independent nucleophosmin colocalization in PMID:27346687. The HPA data record was read; no new interpretation of image pixels or isoform-specific antibody discrimination is claimed. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA directly supports cytosolic localization. Reason: The current HPA record identifies a cytosolic pool in A-431, U-251MG and U2OS cells with supported reliability. This is compatible with cytoplasmic assembly-factor interactions and PA2G4 recycling in PMID:27346687. The concurrent nucleolar pool is retained; no exclusive localization or isoform specificity is inferred. |
| GO:0005634 nucleus | EXP PMID:27346687 DNAJC21 Mutations Link a Cancer-Prone Bone Marrow Failure Sy... | MODIFY | Summary: The human nuclear assay has an independently resolved nucleolar component. Reason: The original nuclear localization is positive. PMID:27346687 additionally identifies predominant nucleolar localization by nucleophosmin colocalization in human cells, independently corroborated by HPA. Refine the target-level assertion to nucleolus (GO:0005730), which is part of the nucleus. This is nonexclusive: nuclear fractionation and actinomycin-D-induced redistribution retain their original broader scope, and no absence from other nuclear regions is asserted. Proposed replacements: nucleolus Supporting Evidence: |
| GO:0005737 cytoplasm | EXP PMID:27346687 DNAJC21 Mutations Link a Cancer-Prone Bone Marrow Failure Sy... | MODIFY | Summary: The human cytoplasmic assay is refined using independent cytosolic evidence. Reason: The original assertion correctly places DNAJC21 in the cytoplasm. HPA independently identifies a cytosolic pool in A-431, U-251MG and U2OS cells with supported reliability, and the human assembly-factor study corroborates cytoplasmic localization. Refine the target-level location to cytosol (GO:0005829), a part of cytoplasm that includes protein complexes. This does not claim the original broad assay resolved cytosol, exclude the nucleolar pool, or erase actinomycin-D-induced redistribution toward the nucleus. Proposed replacements: cytosol Supporting Evidence: |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | ACCEPT | Summary: DNAJC21 is recovered by UV-dependent mRNA-interactome capture in human cells. Reason: The genuine original Table S1 Excel row 674 identifies ENSG00000168724/DNAJC21 as an mRNA-interactome protein: detected in crosslinked samples, not controls, with IC-adjusted p 0.00647067467032329 (the separate DESeq-adjusted p is 0.713048068629827). The extended Methods use covalent UV crosslinking, LiCl/LiDS lysis and oligo(dT) capture, supporting RNA contact rather than ordinary native protein co-IP. The historical RefSeq identifiers are NP_001012339 and NP_919259; the experiment does not distinguish all three current products or identify a particular RNA sequence. PMID:27346687 independently supports native precursor-rRNA association. Supporting Evidence: PMID:22658674 covalent UV crosslinking of RBPs to RNA file:human/DNAJC21/DNAJC21-bioinformatics/source-extracts.json |
| GO:0005840 ribosome | NAS PMID:16952052 The diversity of the DnaJ/Hsp40 family, the crucial partners... | UNDECIDED | Summary: A mature-ribosome location remains unresolved for this assembly factor. Reason: The correctly identified family review PMID:16952052 names DnaJC21 in its abstract, but the target-specific full text was not recovered. Independent human experiments in PMID:27346687 establish native 45S precursor-rRNA association and interactions with maturation factors. Its gradient immunoblots measure PA2G4 and RPL7, not DNAJC21; those experiments therefore do not themselves localize DNAJC21 in mature ribosomes or free mature subunits. GO:0005840 includes ribosomal subunits, so the assembly-factor role does not contradict the annotation. Preserve UNDECIDED for this biological location ambiguity and the inaccessible original target-specific passage, without asserting nonassociation or an absent assay. |
| GO:0006457 protein folding | NAS PMID:16952052 The diversity of the DnaJ/Hsp40 family, the crucial partners... | KEEP AS NON CORE | Summary: The broad folding assertion is retained as contextual co-chaperone participation in multisubunit assembly. Reason: GO:0006457 includes assistance with assembly of multisubunit complexes into correct structure. Independent human evidence in PMID:27346687 supports DNAJC21 as a co-chaperone/assembly factor: nuclease-resistant HSPA8/PA2G4/ZNF622 association, selective P32A loss of HSPA8 association, altered PA2G4 retention and traffic after DNAJC21 loss, and restoration of traffic by wild-type DNAJC21. Together with the existing curated assertion, this supports retaining the broad folding term as non-core assembly context. HSPA8 binding alone would not establish protein folding, and no defined folding substrate, purified refolding reaction, direct human ATPase stimulation or reconstituted PA2G4 release was measured. The more informative structured core process is large-subunit biogenesis. The target-specific full text of the original NAS reference PMID:16952052 remains inaccessible; that access limit is not treated as overriding the independent positive assembly evidence. |
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Download this section (compressed HTML)Q: Does purified human DNAJC21 stimulate HSPA8 ATPase turnover, and is this required for PA2G4 release from assembling ribosomal subunits?
Q: Do the 45-residue and 13-residue insertions in the alternative DNAJC21 products alter RNA association, localization or assembly-factor interactions?
Q: What target-specific ribosome-localization evidence underlies the historical NAS assertion from PMID:16952052?
Experiment: Reconstitute human DNAJC21–HSPA8 with wild-type and P32A proteins, measuring ATP turnover and PA2G4 release separately with matched controls. Distinguish binding from ATPase activation.
Experiment: Compare the three sequence-verified natural products in matched-expression rescue and RNA-contact assays, separating UV-dependent contact from native co-immunoprecipitation.
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