ELAC2

Summary: Human ELAC2 binds RNA directly in a tRNA-bound structure; the original capture-screen measurement remains unverified.

Reason: PMID:39516281 directly places human ELAC2 residues against the mitochondrial tRNA T loop, acceptor-arm backbone and 5′ phosphate in a reconstituted RNase Z complex (Results Par22–25, Fig. 3). These ELAC2–RNA contacts establish RNA binding independently of the capture screens; the conclusion is not inferred only from the need for a nuclease to encounter its substrate. The recombinant preparation is an added serine plus canonical residues 31–826, with TRMT10C/SDR5C1 in the structural complex, and does not establish equivalent binding by all four natural splice products. Retain the broad gene-level term as a corroborating non-core annotation because the established catalytic activity is represented in the core. The ELAC2-specific supplementary result in PMID:22658674 was not recovered from the accessible original overview. Defer to the curated positive HDA assertion while leaving its original measurement unverified; this independent structural evidence does not authenticate that mRNA-capture result or establish an mRNA-regulatory function.

Summary: Human ELAC2 binds RNA directly in a tRNA-bound structure; the original capture-screen measurement remains unverified.

Reason: PMID:39516281 directly places human ELAC2 residues against the mitochondrial tRNA T loop, acceptor-arm backbone and 5′ phosphate in a reconstituted RNase Z complex (Results Par22–25, Fig. 3). These ELAC2–RNA contacts establish RNA binding independently of the capture screens; the conclusion is not inferred only from the need for a nuclease to encounter its substrate. The recombinant preparation is an added serine plus canonical residues 31–826, with TRMT10C/SDR5C1 in the structural complex, and does not establish equivalent binding by all four natural splice products. Retain the broad gene-level term as a corroborating non-core annotation because the established catalytic activity is represented in the core. The operative full Methods and ELAC2-specific supplementary result in PMID:22681889 were not recovered. Defer to the curated positive HDA assertion while leaving its original measurement unverified; this independent structural evidence does not authenticate that mRNA-capture result or establish an mRNA-regulatory function.

Summary: The modeled reaction is specifically precursor tRNA 3′-trailer cleavage.

Reason: Reactome R-HSA-9708812 resolves through catalyst 9708817 and physical entity 9708824 to human Q9BQ52. Its substrate is pre-tRNA, and its described cleavage makes the mature 3′ end plus a trailer fragment. The source and direct recombinant human evidence support GO:0042781, the specific child of RNA endonuclease activity. PMID:19933153 independently supports precursor/trailer processing after ELAC2 RNAi; its RNA fractionation is not treated as ELAC2 protein-localization evidence.

Proposed replacements: 3'-tRNA processing endoribonuclease activity

Summary: Direct recombinant human ELAC2 cleavage supports the specific tRNA 3′-processing endonuclease activity.

Reason: PMID:12711671 maps cleavage of a human pre-tRNA after the discriminator nucleotide using recombinant human ELAC2 and preparation controls. GO:0004549 is biologically correct but broad; GO:0042781 names the measured removal of the precursor 3′ trailer. The human preparation, pig purification and yeast ortholog tests remain distinct. Engineered halves are not natural splice isoforms.

Proposed replacements: 3'-tRNA processing endoribonuclease activity

Summary: Human long ELAC2 directly cleaves precursor tRNA at the 3′ maturation site.

Reason: PMID:15317868 compares full human long ELAC2, engineered halves and other enzymes on defined substrates. Specific precursor-trailer cleavage is better represented by GO:0042781 than generic tRNA phosphodiester hydrolysis. Guide-dependent artificial target-RNA assays are separate and do not establish physiological general mRNA decay.

Proposed replacements: 3'-tRNA processing endoribonuclease activity

Summary: The human long-enzyme substrate study supports the established tRNA 3′-processing reaction.

Reason: The authenticated PMID:16361254 abstract explicitly studies human long tRNase Z cleavage of mitochondrial tRNA substrates. Full construct and kinetic details were not recovered, so they are not asserted. The specific reaction is independently demonstrated in accessible human originals PMID:12711671 and PMID:15317868; those data justify refining the broad activity to GO:0042781 without rejecting the curated experimental assertion.

Proposed replacements: 3'-tRNA processing endoribonuclease activity

Summary: The cited mutagenesis study addresses the established human long tRNase Z processing activity.

Reason: The PMID:18809514 abstract explicitly includes human long-enzyme variants and pre-tRNA cleavage under different divalent-ion conditions, alongside distinct bacterial enzymes. Full experimental details remain inaccessible. Direct human precursor-trailer cleavage in PMID:12711671 and PMID:15317868 independently supports the more informative GO:0042781; no bacterial residue or construct result is assigned to human ELAC2.

Proposed replacements: 3'-tRNA processing endoribonuclease activity

Summary: ELAC2 has the specific precursor tRNA 3′-cleaving activity; the cited paper principally examines targeting.

Reason: PMID:21559454 studies translation-start context and localization of C-terminal EGFP constructs, rather than directly measuring a new nuclease reaction. The broad activity is nevertheless established by the direct human experiments in PMID:12711671 and PMID:15317868. Refine it to GO:0042781 using that explicit independent support; preserve the original source and evidence code, and do not map the initiation constructs onto splice products 2–4.

Proposed replacements: 3'-tRNA processing endoribonuclease activity

Summary: Human-cell processing evidence is consistent with the directly established tRNA 3′ endonuclease reaction.

Reason: PMID:21593607 shows a mitochondrial 3′ processing defect after ELAC2 depletion. Direct human recombinant catalysis in PMID:12711671 and PMID:15317868 establishes the specific GO:0042781 reaction. Refine the broad nuclease term while retaining the distinction between cellular perturbation and purified-enzyme assays.

Proposed replacements: 3'-tRNA processing endoribonuclease activity

Summary: Human ELAC2 has a nuclear pool.

Reason: PMID:21593607 includes endogenous human antibody localization, corroborated by the native-start-context targeting experiments in PMID:21559454. These support the existing nuclear location without assigning it to an individual splice isoform.

Summary: The electronic nucleus mapping agrees with direct human localization.

Reason: The literal SL-0191 mapping emits GO:0005634 and the target UniProt location cites PMID:21593607. Endogenous human antibody localization in that study and native-start-context targeting in PMID:21559454 support a nuclear pool. This source is retained at its broad nuclear precision; separate HPA nucleoplasmic evidence does not redefine the original experiment.

Summary: HPA immunofluorescence metadata support nucleoplasmic ELAC2.

Reason: The official HPA019535 record identifies nucleoplasm in A-431, U-251MG and U2OS and reports enhanced siRNA validation in U2OS. Its antigen matches canonical ELAC2 residues 357–464. The official annotations and validation metadata were inspected, not the image pixels. This supports the curated location without distinguishing individual splice products or excluding other compartments.

Summary: The nuclear processing model and independent HPA evidence support nucleoplasmic ELAC2.

Reason: Reactome R-HSA-5696815 explicitly links catalyst 5696814 to Q9BQ52 entity 5696766 in nucleoplasm. The compartment is attached to ELAC2 itself. Independent HPA localization corroborates that precision, while the original human antibody work supports the broader nucleus. The database coordinate 17–826 is protein-processing metadata, not proof of the nuclear experimental construct.

Summary: ELAC2 is experimentally included in the human mitochondrial proteome.

Reason: PMID:34800366 Table S1 sheet A row 341 identifies the Q9BQ52-centered ELAC2 group as subtractive Class 1, spatial Cluster 1 and importomics Class 1; sheet B row 309 supplies its gene-level MitoCoP entry. This is positive experimental localization evidence. Multiple product accessions occur in the group, so the measurement does not distinguish the four splice products.

Summary: The PAINT mitochondrial assertion is inherited from an experimentally grounded ancestral node.

Reason: The exact canonical 826-aa sequence occupies PTN002488759 beneath PTN000284963. The literal GO:0005739 IBD on line 47155 matches the imported donor set, and the full saved target path has no NOT/IRD loss record. All selected donors have current exact-term experimental records. Human target evidence is legitimate descendant grounding, not circularity. Direct human localization and mitochondrial processing corroborate an active mitochondrial pool; preserve the imported is_active_in qualifier even though many donor records use located_in. This does not assign every splice product to mitochondria.

Summary: Human ELAC2 has a mitochondrial pool.

Reason: The endogenous localization result in PMID:21593607 agrees with native-context and optimized-start construct experiments in PMID:21559454 and the independent proteomic evidence in PMID:34800366. Preserve the source assertion without extending it to every splice product.

Summary: The electronic mitochondrial location is correctly mapped and experimentally corroborated.

Reason: SL-0173 maps directly to GO:0005739, and the target location carries PMID:21593607 provenance. The endogenous human localization, targeting constructs and independent MitoCoP result support mitochondria. This broad vocabulary mapping alone does not resolve matrix topology or splice-specific targeting.

Summary: The mitochondrial location is biologically supported.

Reason: Retain this NAS assertion alongside the independent direct localization and proteomic support. Repeated location terms with different evidence codes are legitimate source records.

Summary: The matrix location is consistent with ELAC2’s mitochondrial RNA-processing machinery.

Reason: PMID:21857155 establishes mitochondrial colocalization of an optimized-start EYFP construct and a mitochondrial tRNA-processing phenotype; its imaging alone does not resolve the matrix. Retain the curated matrix assignment in light of ELAC2 nucleoid association in PMID:24703694: the current ontology explicitly places the mitochondrial nucleoid within the matrix. The human mitochondrial processing system in PMID:39516281 is concordant. This does not reinterpret fluorescent colocalization as a direct matrix-topology assay.

Summary: The H-strand processing model explicitly places ELAC2 in the mitochondrial matrix.

Reason: The H-strand event resolves through catalyst 6786864 to Q9BQ52 entity 6786837 in the matrix. The modeled ELAC2 role is tRNA 3′ cleavage. The nucleoid association in PMID:24703694 and the current nucleoid part_of matrix relation support retaining the curated matrix location; original mitochondrial fluorescence alone does not resolve it. The shared 17–826 database coordinate does not identify the experimental insert or the four splice products.

Summary: The L-strand processing model explicitly places ELAC2 in the mitochondrial matrix.

Reason: The L-strand event resolves through catalyst 6786864 to Q9BQ52 entity 6786837 in the matrix. The modeled ELAC2 role is tRNA 3′ cleavage. The nucleoid association in PMID:24703694 and the current nucleoid part_of matrix relation support retaining the curated matrix location; original mitochondrial fluorescence alone does not resolve it. The shared 17–826 database coordinate does not identify the experimental insert or the four splice products.

Summary: The cytosolic model is genuine, but the underlying ELAC2 protein-localization evidence remains unresolved.

Reason: Reactome R-HSA-9708812 contains a literal cytosolic Q9BQ52 entity, so this is not a missing-target error. The inspected PMID:19933153 experiment fractionates precursor and product RNA; it does not directly fractionate or image ELAC2 protein. Its protein-localization statement cites an earlier study whose operative original was not recovered here. Later native-context targeting experiments do not exclude every context-specific cytosolic pool. Preserve the assertion with UNDECIDED rather than treating this access and inference boundary as proof of absence.

Summary: The supported tRNA-processing role is specifically 3′-end maturation.

Reason: IPR027794 matches canonical residues 61–120 and literally maps to tRNA processing. This is a valid domain association, not a direct assay of that segment. The family description and independently read human catalytic studies identify precursor 3′-trailer removal, so GO:0042780 is a more informative process term. Nuclear and mitochondrial contexts both exist; do not limit this domain-level source to mitochondria alone.

Proposed replacements: tRNA 3'-end processing

Summary: The target-resolved source supports precursor 3′ processing rather than tRNA decay.

Reason: R-HSA-9708296 currently describes tRNA-derived small RNA biogenesis. Its ELAC2 child R-HSA-9708812 consumes pre-tRNA and releases a downstream trailer, whereas GO:0016078 describes tRNA breakdown. PMID:19933153 shows reduced trailer tRF-1001 and increased precursor after ELAC2 RNAi; it does not demonstrate destruction of mature tRNA. This is a lateral correction of the modeled process, not an ontology descendant refinement: replace the decay assignment with GO:0042780 for the actual maturation step. Other ANG/DICER pathway reactions cannot supply ELAC2 with their distinct substrate or chemistry, and no additional small-RNA regulatory process is proposed.

Proposed replacements: tRNA 3'-end processing

Summary: ELAC2 associates with mitochondrial nucleoids during early RNA processing.

Reason: The authenticated PMID:24703694 abstract explicitly identifies ELAC2 among nucleoid-associated RNA-processing enzymes, supporting the curated location. Operative original Methods were not recovered, so no precise construct or cellular assay is invented. Association does not make ELAC2 a DNA-replication, transcription or ribosome-assembly factor.

Summary: The nucleoid mappings agree with positive target and ortholog evidence.

Reason: ARBA00086796 condition set 0 matches the target FunFam 3.60.15.10:FF:000014 and Eukaryota lineage and emits GO:0042645; SL-0269 maps to the same location. Mouse Q80Y81 has a current MGI IDA record for PMID:24703694, distinct from its human-based UniProt location inference. ENSMUSP00000098610.3 maps to mouse Q80Y81-2, 824 aa; it is not evidence about a corresponding human splice product. The human source abstract explicitly reports ELAC2 nucleoid association. Retain the location without inventing unrecovered original assay details or treating the broad rule premise as an experimental measurement.

Summary: The human reconstitution directly demonstrates mitochondrial tRNA 3′-end processing.

Reason: The independently read PMID:39516281 original shows recombinant human ELAC2 cleaving mitochondrial tRNA trailers, with acceleration by TRMT10C/SDR5C1. GO:1990180 adds the compartment specificity directly tested in this source. This does not deny nuclear processing elsewhere. The assayed ELAC2 is engineered residues 31–826 with a tag remnant, not all four natural splice products.

Proposed replacements: mitochondrial tRNA 3'-end processing

Summary: ELAC2 catalyzes precursor tRNA 3′-end maturation.

Reason: R-HSA-5696815 explicitly assigns Q9BQ52 the pre-tRNA 3′ cleavage reaction. Human recombinant assays establish the same enzymatic mechanism, and nuclear localization supports the modeled setting. Preserve the process at this general compartment-independent scope; the coordinate 17–826 in the database is not a nuclear construct measurement.

Summary: The PAINT catalytic assertion matches ELAC2’s directly demonstrated 3′ processing chemistry.

Reason: The GO:0042781 IBD at PTN000284963, line 37796, lies on the exact canonical target path, has the literal imported donor set and no recorded target-path loss. Each donor has current exact-term experimental grounding. The nuclear fission-yeast donor Q10155 supports the shared catalytic reaction, not mitochondrial localization. Direct human ELAC2 precursor-cleavage assays independently corroborate the specific activity. No equivalence of splice products 2–4 is inferred.

Summary: The InterPro and EC mappings identify the experimentally established 3′-tRNA processing endonuclease.

Reason: IPR047151 matches canonical residues 57–792 and maps to GO:0042781; the official EC2GO mapping for EC:3.1.26.11 independently emits the same term. Human biochemical and structural evidence supports that function. The InterPro description contains a separate citation defect: PUB00102035 points literally to PMID:2159360, an unrelated cerebral-blood-flow paper. Preserve that defect in the evidence notes without inventing a replacement identifier or rejecting the independently grounded catalytic mapping.

Summary: The H-strand source specifically assigns mitochondrial tRNA 3′ processing to ELAC2.

Reason: The H-strand Reactome event has an explicit Q9BQ52 catalyst for 3′ cleavage within mitochondrial tRNA processing. GO:1990180 is the current specific child of GO:0090646 and GO:0042780 and names the step performed by ELAC2. Other event components perform 5′ cleavage or other RNA-processing chemistry; their roles are not transferred to ELAC2. Human cell processing and direct human reconstitution independently support this refinement.

Proposed replacements: mitochondrial tRNA 3'-end processing

Summary: The L-strand source specifically assigns mitochondrial tRNA 3′ processing to ELAC2.

Reason: The L-strand Reactome event has an explicit Q9BQ52 catalyst for 3′ cleavage within mitochondrial tRNA processing. GO:1990180 is the current specific child of GO:0090646 and GO:0042780 and names the step performed by ELAC2. Other event components perform 5′ cleavage or other RNA-processing chemistry; their roles are not transferred to ELAC2. Human cell processing and direct human reconstitution independently support this refinement.

Proposed replacements: mitochondrial tRNA 3'-end processing

Summary: ELAC2 is the catalytic component of a reconstituted human mitochondrial endoribonuclease complex.

Reason: PMID:39516281 supports ELAC2 association with TRMT10C/SDR5C1 and RNA, structurally and biochemically. The platform enhances cleavage, while ELAC2 also acts without it. Endoribonuclease-complex membership is justified without asserting obligatory partner dependence, fixed cellular stoichiometry or equivalent activities of every splice product.

Summary: The inherited mitochondrial 3′-processing assertion is phylogenetically and experimentally supported.

Reason: The GO:1990180 IBD on line 42928 at PTN000284963 is ancestral to the exact canonical human sequence, with the literal four-donor set and no target-path loss record. Current exact-term experimental records ground all selected donors, including human PMID:21593607 and PMID:21857155. Human self-evidence legitimately helps place the IBD. Target biochemical reconstitution and cellular rescue corroborate the mechanism without assigning RNase P’s 5′ reaction or equivalent activity to every splice product.

Summary: ELAC2 performs mitochondrial tRNA 3′ maturation.

Reason: The cellular processing evidence in PMID:21593607 agrees with direct catalytic and human complementation experiments. This term describes ELAC2’s own cleavage step.

Summary: ELAC2 participates directly in mitochondrial tRNA 3′-end processing.

Reason: PMID:21857155 provides RNAi, junction and RNA-sequencing evidence. Its global ELAC2 3′-read ratio p=0.0581 is not silently treated as below 0.05. Direct catalysis and patient-cell rescue independently establish the processing mechanism; downstream translation or respiratory phenotypes are not separate direct functions.