DNAJC19 is a small mitochondrial inner-membrane J-domain co-chaperone. It stimulates the ATPase activity of mitochondrial HSP70/Mortalin and forms a regulatory heterodimer with PAM16/Magmas, which attenuates that stimulation. Its association with the TIM23 translocon and conserved PAM machinery links this activity to protein import into the mitochondrial matrix. DNAJC19 also associates with prohibitin-containing membrane assemblies and contributes to regulation of cardiolipin remodeling. Biallelic loss-of-function variants cause dilated cardiomyopathy with ataxia syndrome. An annotated shorter splice product lacks the N-terminal membrane anchor; its localization and functional relationship to the full-length product remain unresolved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001405 PAM complex, Tim23 associated import motor | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved PAM import-motor membership is supported in the human translocon. Reason: The PAINT node and target descent are verified. Human mitochondrial DNAJC19 associates with PAM16/Magmas and with the Tim17-containing translocon in PMID:20053669 Figures 5 and 8. Together with the conserved import machinery, this supports the PAM membership assertion without making DNAJC19 the ATP-hydrolyzing motor itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000298641 SUPPORTS TRANSFER The protected PAINT IBD assigns this term to PTN000298641 (taxon 2759, dated 2017-02-28); the actual family tree places human Q96DA6 below that node. The SGD descendants are experimental grounding for a phylogenetic judgment, not a donor-count test. |
| GO:0001671 ATPase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: DNAJC19 directly activates mitochondrial HSP70 ATP hydrolysis. Reason: PMID:20053669 Figure 9B and the purified-protein Methods directly test human DNAJC19 and human Mortalin under single-turnover conditions; PAM16/Magmas attenuates the stimulation. This independently supports the inherited PAINT assertion. PMID:19564938 supplies human heterodimer biophysics, but its ATPase experiment uses yeast Pam18 and yeast mtHsp70. The current term is appropriate; its topoisomerase-II-specific child is inapplicable. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000298641 SUPPORTS TRANSFER The protected PAINT IBD assigns this term to PTN000298641 (taxon 2759, dated 2017-02-28); the actual family tree places human Q96DA6 below that node. The SGD descendants are experimental grounding for a phylogenetic judgment, not a donor-count test. |
| GO:0030150 protein import into mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: The conserved co-chaperone participates in import into the mitochondrial matrix. Reason: DNAJC19 contributes the ATPase-activating co-chaperone activity of the import motor, rather than serving as imported cargo. Verified PAINT inheritance, human Mortalin stimulation and human translocon association support the process. Import-kinetics and precursor-accumulation experiments in PMID:20053669 are on Magmas mutants in yeast; they are not described as human DNAJC19 loss-of-function assays. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000298641 SUPPORTS TRANSFER The protected PAINT IBD assigns this term to PTN000298641 (taxon 2759, dated 2017-02-28); the actual family tree places human Q96DA6 below that node. The SGD descendants are experimental grounding for a phylogenetic judgment, not a donor-count test. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The historical electronic inner-membrane assertion remains biologically correct. Reason: Human mitochondrial translocon association and the canonical membrane-anchor annotation support inner-membrane localization, so this biological assertion remains accepted. The historical GO_REF:0000120 source retains its original fields and is retired only because genuine current GOA supplies the same term and evidence under GO_REF:0000044. That current source is reviewed separately; the source-reference transition does not reject the localization. |
| GO:0098800 inner mitochondrial membrane protein complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the independently supported inner-membrane complex context. Reason: The traced mouse donor Q9CQV7 carries experimental GO:0098800 from PMID:24856930, which identifies a DNAJC19/prohibitin-associated membrane assembly. Its abstract reports PHB2 interaction and lipid-remodeling effects. The original full Methods could not be recovered, so a particular stable prohibitin stoichiometry is not asserted. This broad complex claim can represent a distinct pool from PAM; replacing it with PAM solely because another DNAJC19 complex is known would exchange the source claim. The positive curated transfer is retained without adding a separate molecular mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9CQV7 SUPPORTS TRANSFER The current donor has IDA GO:0098800 from PMID:24856930. Its experimental complex claim and the positive primary abstract support transfer; full original access remains limited. |
| GO:0099617 matrix side of mitochondrial inner membrane | IEA GO_REF:0000107 | ACCEPT | Summary: The membrane-associated co-chaperone acts on the matrix side. Reason: The current mouse donor Q9CQV7 carries an IDA matrix-side annotation from PMID:24856930. The human official record transfers this orientation, and the canonical N-terminal anchor plus C-terminal J domain and engagement of matrix Mortalin are compatible with it. Retain the curator-backed topology without pretending that the inaccessible donor Methods or the human co-IP directly measured both membrane faces. The natural shorter product lacks the anchor and is not assigned this localization independently. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9CQV7 SUPPORTS TRANSFER The current donor carries IDA GO:0099617 from PMID:24856930. This provides experimental grounding; human topology is a conserved inference, not a newly claimed protease-protection measurement. Supporting Evidence: GO_REF:0000107 file:human/DNAJC19/DNAJC19-uniprot.txt |
| GO:1900208 regulation of cardiolipin metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain positive cardiolipin-remodeling regulation as a distinct biological context. Reason: The current mouse donor has IMP GO:1900208 from PMID:24856930. The primary abstract reports altered cardiolipin acylation and acyl-chain composition after loss of PHB/DNAJC19 complexes, supporting regulation rather than merely an undifferentiated interaction. Human annotation by similarity does not mean that all underlying biology is only a prediction. Retain this positive contextual role, with full-original species/construct details unresolved here; do not assign lipid-transfer catalysis, a defined substrate-folding reaction, or an independently established second human core from the abstract. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9CQV7 SUPPORTS TRANSFER The donor has direct IMP GO:1900208 from PMID:24856930. The current term is regulation of cardiolipin metabolic process, without a negative-regulation qualifier. |
| GO:0005743 mitochondrial inner membrane | NAS PMID:10339406 Genetic and structural characterization of the human mitocho... | ACCEPT | Summary: The inner mitochondrial membrane is a supported target compartment. Reason: The original NAS citation describes human TIM17/TIM23/TIM44 organization in its accessible abstract; target-specific experiments in its unavailable main text are not invented. Independent human DNAJC19 translocon co-IP in PMID:20053669 and the official membrane annotation support the same compartment, so the existing statement is retained rather than rejected from incomplete source access. |
| GO:0005744 TIM23 mitochondrial import inner membrane translocase complex | NAS PMID:10339406 Genetic and structural characterization of the human mitocho... | ACCEPT | Summary: DNAJC19 is associated with the human TIM23 import translocon. Reason: PMID:20053669 Figure 8B uses digitonin-solubilized HEK293T mitochondria and anti-Tim17 pull-down, recovering DNAJC19 with Tim23, Tim44 and Magmas. This provides direct target grounding for the existing NAS complex assertion, whose original 1999 citation gives translocon context. The assay does not establish a fixed stoichiometry or show that the DNAJC19 J domain forms the transport pore. Supporting Evidence: PMID:20053669 other translocon components such as hTim44, hTim23, DnaJC19 |
| GO:0006886 intracellular protein transport | NAS PMID:10339406 Genetic and structural characterization of the human mitocho... | MODIFY | Summary: Refine intracellular transport to the import process performed by the co-chaperone. Reason: GO:0030150 names the mitochondrial matrix import process in which DNAJC19 supplies ATPase-activating co-chaperone activity. The checked is_a path leads through protein transmembrane import into an intracellular organelle and intracellular protein transmembrane transport to the original term. Human Mortalin stimulation and translocon association plus conserved PAINT support this refinement; the older NAS paper is not claimed to have performed a DNAJC19-specific transport assay. Proposed replacements: protein import into mitochondrial matrix |
| GO:0030150 protein import into mitochondrial matrix | NAS PMID:16055927 Mutation of DNAJC19, a human homologue of yeast inner mitoch... | ACCEPT | Summary: Retain the supported matrix-import role while distinguishing disease genetics from mechanism. Reason: The recovered PMID:16055927 original shows human variant segregation and exon-4-skipping RT-PCR, and proposes an import defect from homology and predicted topology. It does not directly measure import kinetics. Later human Mortalin stimulation/translocon association and the verified conserved PAM annotation independently support the existing NAS process; the disease phenotype alone is not being used as participation evidence. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MODIFY | Summary: Refine organelle localization to the supported inner membrane. Reason: The original MitoCoP Supplementary Table S1 identifies DNAJC19 as protein group 9092: subtractive Class 1, spatial Cluster 1 and importomics Class 1. The group includes Q96DA6 and Q96DA6-2, so it does not distinguish the natural isoforms. The source remains an organelle-level assertion; independent official membrane annotation and human translocon association in PMID:20053669 support refinement to mitochondrial inner membrane. The supplementary integral-membrane percentage is unavailable, and no membrane-face measurement is claimed. Proposed replacements: mitochondrial inner membrane |
| GO:0098800 inner mitochondrial membrane protein complex | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the independently supported inner-membrane complex context. Reason: The traced mouse donor Q9CQV7 carries experimental GO:0098800 from PMID:24856930, which identifies a DNAJC19/prohibitin-associated membrane assembly. Its abstract reports PHB2 interaction and lipid-remodeling effects. The original full Methods could not be recovered, so a particular stable prohibitin stoichiometry is not asserted. This broad complex claim can represent a distinct pool from PAM; replacing it with PAM solely because another DNAJC19 complex is known would exchange the source claim. The positive curated transfer is retained without adding a separate molecular mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9CQV7 SUPPORTS TRANSFER The current donor has IDA GO:0098800 from PMID:24856930. Its experimental complex claim and the positive primary abstract support transfer; full original access remains limited. |
| GO:0099617 matrix side of mitochondrial inner membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The membrane-associated co-chaperone acts on the matrix side. Reason: The current mouse donor Q9CQV7 carries an IDA matrix-side annotation from PMID:24856930. The human official record transfers this orientation, and the canonical N-terminal anchor plus C-terminal J domain and engagement of matrix Mortalin are compatible with it. Retain the curator-backed topology without pretending that the inaccessible donor Methods or the human co-IP directly measured both membrane faces. The natural shorter product lacks the anchor and is not assigned this localization independently. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9CQV7 SUPPORTS TRANSFER The current donor carries IDA GO:0099617 from PMID:24856930. This provides experimental grounding; human topology is a conserved inference, not a newly claimed protease-protection measurement. Supporting Evidence: GO_REF:0000024 file:human/DNAJC19/DNAJC19-uniprot.txt |
| GO:1900208 regulation of cardiolipin metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain positive cardiolipin-remodeling regulation as a distinct biological context. Reason: The current mouse donor has IMP GO:1900208 from PMID:24856930. The primary abstract reports altered cardiolipin acylation and acyl-chain composition after loss of PHB/DNAJC19 complexes, supporting regulation rather than merely an undifferentiated interaction. Human annotation by similarity does not mean that all underlying biology is only a prediction. Retain this positive contextual role, with full-original species/construct details unresolved here; do not assign lipid-transfer catalysis, a defined substrate-folding reaction, or an independently established second human core from the abstract. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9CQV7 SUPPORTS TRANSFER The donor has direct IMP GO:1900208 from PMID:24856930. The current term is regulation of cardiolipin metabolic process, without a negative-regulation qualifier. |
| GO:0005515 protein binding | IPI PMID:19564938 The mitochondrial protein translocation motor: structural co... | KEEP AS NON CORE | Summary: Retain the verified DNAJC19–PAM16 regulatory association. Reason: Purified soluble human DNAJC19 and PAM16/Magmas form a heterodimer, supported by recombinant purification and cross-linking in Results 2.1–2.2. The literal partner is Q9Y3D7 (official PAM16; also TIMM16/Magmas), traced from the genuine source. This pair is distinct from DNAJC19 activation of Mortalin/HSPA9, so the ATPase-activator term is not substituted for it. PAM16 inhibits co-chaperone stimulation and is not established here as an unfolded-substrate-binding chaperone or an ATPase. No more informative partner-class molecular function is asserted. The explicit ClinGen project instruction retains this positive generic binding as non-core. |
| GO:0005515 protein binding | IPI PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | KEEP AS NON CORE | Summary: Retain the verified DNAJC19–PAM16 regulatory association. Reason: Human reciprocal mitochondrial co-IP and purified-domain GST pull-down establish association of DNAJC19 with PAM16/Magmas in Figures 5 and 7. The literal partner is Q9Y3D7 (official PAM16; also TIMM16/Magmas), traced from the genuine source. This pair is distinct from DNAJC19 activation of Mortalin/HSPA9, so the ATPase-activator term is not substituted for it. PAM16 inhibits co-chaperone stimulation and is not established here as an unfolded-substrate-binding chaperone or an ATPase. No more informative partner-class molecular function is asserted. The explicit ClinGen project instruction retains this positive generic binding as non-core. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | ACCEPT | Summary: Human mitochondrial translocon association supports inner-membrane localization. Reason: PMID:20053669 recovers DNAJC19 in mitochondrial extracts and in anti-Tim17 pull-down of the digitonin-solubilized human translocon. Together with the canonical membrane-anchor annotation, this supports the existing inner-membrane assignment. The paper does not directly resolve the full topology of natural isoform 2, and its Magmas localization assays are not relabeled as DNAJC19-only topology experiments. |
| GO:0032991 protein-containing complex | IDA PMID:19564938 The mitochondrial protein translocation motor: structural co... | MODIFY | Summary: Specify the native PAM context of the demonstrated co-chaperone subcomplex. Reason: PMID:19564938 directly reconstitutes the human DNAJC19–PAM16 soluble heterodimer and tests its biophysical stability. The native import-associated interpretation is independently grounded by human translocon co-IP and Mortalin activation in PMID:20053669. Refine the generic complex term to PAM membership at the gene level; this does not claim that the purified 2009 binary preparation contained the entire motor or that the engineered fragment is a natural isoform. Proposed replacements: PAM complex, Tim23 associated import motor Supporting Evidence: PMID:19564938 one homologous human hetero-dimer and two heterologous human/yeast hetero-dimers |
| GO:0032991 protein-containing complex | IDA PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | MODIFY | Summary: Specify PAM membership within the human import translocon. Reason: The source demonstrates the DNAJC19–PAM16 subcomplex in human mitochondrial lysates and its association with the Tim17/Tim23/Tim44-containing machinery. Combined with direct human Mortalin stimulation, this supports the specific PAM motor-complex membership over undifferentiated protein-containing complex. The current typed path confirms that PAM is a protein-containing complex; no additional duplicate annotation is proposed. Proposed replacements: PAM complex, Tim23 associated import motor Supporting Evidence: |
| GO:0005739 mitochondrion | IDA PMID:12592411 Characterization of the human heart mitochondrial proteome. | MODIFY | Summary: Refine the historical heart-proteome localization to inner mitochondrial membrane. Reason: The recovered PMID:12592411 Supplementary Table 2 lists GI 16307227 as an unknown protein. NCBI resolves that identifier to human AAH09702.1/DNAJC19, whose 116-residue sequence exactly matches current Q96DA6-1. The original supplementary protocol describes purified mitochondrial complexes and mass-spectrometric identification. This preserves the positive organelle detection; independent human translocon evidence and the official location supply the inner-membrane refinement, not an unperformed membrane-face assay in the proteome study. Proposed replacements: mitochondrial inner membrane |
| GO:0016020 membrane | NAS PMID:16055927 Mutation of DNAJC19, a human homologue of yeast inner mitoch... | MODIFY | Summary: Specify mitochondrial inner membrane rather than membrane generally. Reason: The recovered disease paper predicts an N-terminal membrane helix and cites mitochondrial proteome detection; it does not experimentally map human membrane topology. Later human translocon association and the official localization support mitochondrial inner membrane as the informative target-level replacement. The disease-associated 47-residue predicted truncation and the annotated 91-residue product are kept distinct. Proposed replacements: mitochondrial inner membrane |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The current location mapping supports mitochondrial inner membrane. Reason: The genuine current GOA maps UniProt subcellular location SL-0168 to GO:0005743 under GO_REF:0000044. This preserves the biological assertion of the separately retained historical 0120 row. Official human localization and translocon association support the term; the change is a source-reference transition, not a newly discovered function or an authored NEW annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0168 SUPPORTS TRANSFER The current official location and exact QuickGO source mapping agree on mitochondrial inner membrane. Historical GO_REF:0000120 provenance remains archived and its row is retired without scientific rejection. |
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Download this section (compressed HTML)Q: Does the natural 91-residue Q96DA6-2 product enter mitochondria or act in another compartment, and does it retain PAM16 binding or Mortalin activation in cells?
Experiment: Reconstitute the human import motor in vitro with purified DNAJC19, PAM16, mtHSP70 and GRPEL to measure DNAJC19-dependent ATPase stimulation and precursor translocation, including disease-variant proteins.
Experiment: Conditional DNAJC19 depletion in cardiomyocytes followed by mitochondrial import assays and cardiolipin profiling to dissect import-motor versus cardiolipin-remodeling contributions to the DCMA phenotype.
Experiment: Cryo-EM of the human TIM23-PAM holo-translocase to define how the DNAJC19 J-domain engages mtHSP70 at the matrix exit of the channel.
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