DNAJC30

Summary: Mitochondrial inner-membrane localization is supported.

Reason: The current UniProt subcellular-location mapping explicitly maps SL-0168 to GO:0005743. Independent target localization and mitochondrial membrane enrichment support the biological placement. The highest-resolution immunogold experiment in PMID:30318146 used macaque brain, while the study also contains human tissue fractionation; these are not described as human immunogold data.

Summary: Retain the heterogeneous HuRI binary interactions as non-core binding evidence.

Reason: The 23 current partner records underlying this historical grouped assertion each have a positive validated two-hybrid record plus screening stages, with target and exact partner-product sequence/taxon hashes verified. The original study reports quadruplicate pairwise retesting and sequence confirmation. Membrane-protein identity alone does not establish an artifact, so the inherited artifact claim is withdrawn. The partners span transporters, enzymes and proteins with incompletely defined activities; a single enzyme- or receptor-binding replacement would misrepresent this aggregate. Individual partner classes and the short RNF170-5/SLC35H1-3 products are distinguished in the source guide. These assays establish binding capacity without demonstrating native mitochondrial complexes, a shared mechanism or DNAJC30 transport/catalytic activity.

Summary: Brain development is a supported contextual outcome.

Reason: The literal mouse donor P59041 has an IMP brain-development annotation from PMID:30318146, and current Ensembl confirms the named one-to-one ortholog. Mouse knockout produces neuronal and brain morphological phenotypes, which are compatible with the broad process but are contextual consequences of the mitochondrial role. Retain the inherited inference as non-core rather than claiming that neuronal enrichment alone is a developmental assay. Human Williams-Beuren samples carry a multigene deletion and do not isolate DNAJC30 as the cause of every observed phenotype.

Summary: DNAJC30 can regulate mitochondrial ATP synthesis in the tested context.

Reason: The literal mouse donor P59041 carries an IMP annotation to this exact regulatory process from PMID:30318146. Dnajc30 loss decreased ATP output from isolated mouse cortical mitochondria supplied with malate, pyruvate and ADP (Figure 4F and ATP-production Methods), alongside reduced neuronal respiration. This is positive support for regulation of mitochondrial ATP production; GO:1905706 does not require intrinsic ATP-synthase catalysis. Native human ATP-synthase association and subunit-binding evidence provide complementary molecular context, but the ATP-output assay does not isolate a direct effect on complex V from upstream respiratory-chain contributions. PMID:33465056 found no complex-V activity, abundance or turnover defect in its tested human systems. Retain the valid ortholog transfer and include the bounded regulatory role in the ATP-synthase core, without claiming that its physical association is the established cause of the output change, universal dimer stabilization or a single mechanism in all tissues.

Summary: Refine the supported mitochondrial localization to the inner membrane.

Reason: The original MitoCoP workbook identifies Q96LL9/DNAJC30 in Table S1A row 322 (protein group 9379), with subtractive Class 1, spatial Cluster 1 and importomics Class 1 assignments; carbonate/sonication analysis classifies it as integral. These measurements establish mitochondrial membrane association, not inner-versus-outer membrane topology by themselves. The more specific inner-membrane placement uses independent localization evidence and the existing GO:0005743 source contexts, preserving the scope of this HTP paper.

Proposed replacements: mitochondrial inner membrane

Summary: Refine the ATP-synthase association to binding the mitochondrial ATP synthase complex.

Reason: GO:0140260 specifies binding to the mitochondrial proton-transporting ATP synthase complex. PMID:30318146 reports native human-brain complex immunoprecipitation and human DNAJC30 bait interactions with ATP-synthase components. The MINT records independently preserve MT-ATP6 and ATP5MC2 two-hybrid pairs; tagged MT-ATP6 co-IP is a separate assay using an engineered codon-optimized, mitochondrially targeted construct. Complex association and subunit-binding evidence support the specific class without assigning ATPase activity or treating the complete complex as purified in the binary assay.

Proposed replacements: mitochondrial proton-transporting ATP synthase complex binding

Summary: Retain the inner-membrane localization with its actual specimen limits.

Reason: The gene-level localization is supported by the original multimodal study and current mitochondrial proteomics. The immunogold evidence in PMID:30318146 is macaque neocortex, not human brain; human tissue fractionation and target immunoprecipitation are separate experiments. Preserve the imported human IDA context while explicitly identifying the specimen scope rather than interpreting a mixed-species paper as a wrong-target citation.

Summary: Retain the mouse-grounded developmental inference as non-core.

Reason: The literal mouse donor P59041 has an IMP brain-development annotation from PMID:30318146, and current Ensembl confirms the named one-to-one ortholog. Mouse knockout produces neuronal and brain morphological phenotypes, which are compatible with the broad process but are contextual consequences of the mitochondrial role. Retain the inherited inference as non-core rather than claiming that neuronal enrichment alone is a developmental assay. Human Williams-Beuren samples carry a multigene deletion and do not isolate DNAJC30 as the cause of every observed phenotype.

Summary: Retain the ortholog-grounded regulation of mitochondrial ATP synthesis.

Reason: The literal mouse donor P59041 carries an IMP annotation to this exact regulatory process from PMID:30318146. Dnajc30 loss decreased ATP output from isolated mouse cortical mitochondria supplied with malate, pyruvate and ADP (Figure 4F and ATP-production Methods), alongside reduced neuronal respiration. This is positive support for regulation of mitochondrial ATP production; GO:1905706 does not require intrinsic ATP-synthase catalysis. Native human ATP-synthase association and subunit-binding evidence provide complementary molecular context, but the ATP-output assay does not isolate a direct effect on complex V from upstream respiratory-chain contributions. PMID:33465056 found no complex-V activity, abundance or turnover defect in its tested human systems. Retain the valid ortholog transfer and include the bounded regulatory role in the ATP-synthase core, without claiming that its physical association is the established cause of the output change, universal dimer stabilization or a single mechanism in all tissues.

Summary: Retain the inherited proposal for remodeling pre-existing complex I.

Reason: This is the previously merged authored proposal, not a current GOA assertion. GO:0034367 covers acquisition or loss of macromolecules from an existing complex. In PMID:33465056, transient complex-I association/co-migration accompanies selective defects in N-module subunit turnover while complex-I assembly remains intact; this supports an accessory contribution to exchange within an existing complex, beyond the necessity phenotype alone. DNAJC30 is not asserted to be a respiratory catalytic subunit or the substrate consumed in that exchange. Direct substrate extraction, CLPXP access and HSP70 activation remain mechanistic models rather than measured DNAJC30 activities. The comparator audit found no GO:0034367 on CLPX, CLPP or NDUFAF2, whose established proteolysis/assembly roles differ; that absence is not treated as evidence of a curation gap. No selected GO-CAM target was found, and this process is not an ancestor or descendant of the other process terms retained here. No additional NEW term is proposed.