ELP2

Summary: ELP2 contributes to RNA polymerase II association in the historical human Elongator preparation.

Reason: PMID11714725 reports binding of purified human Elongator to calf-thymus RNA polymerase II and association with early elongation complexes; PMID11818576 independently reports purified-complex polymerase binding. The imported contributes_to qualifier limits this assertion to ELP2 in the complex, without establishing an isolated ELP2 contact. PMID27847465 identifies tRNA modification as the predominant role and discusses secondary transcription phenotypes. That reinterpretation does not contradict the observed biochemical association, so retain this specific interaction as non-core without making direct transcription regulation the core function.

Summary: ELP2 is a structural component of the Elongator machinery for wobble-uridine modification.

Reason: The current IPR037289 family explicitly maps to GO:0002098 and matches human Q6IA86 across residues5–823. This is an ELP2-specific family inference, not a generic WD40-domain transfer. Human complex purification and the ELP2 N-terminal deletion/co-IP experiments establish its physical contribution to Elongator assembly; the reviewed literature assigns wobble-uridine modification to that conserved complex. Accept involvement without attributing the chemical reaction to ELP2 independently of catalytic ELP3.

Summary: ELP2 participates in tRNA wobble-uridine modification as an Elongator subunit.

Reason: The cited article is a review: its complex-organization and substrate-specificity sections place ELP2 in the structural ELP1–3 unit and synthesize the tRNA U34-modification evidence. It is not a new human ELP2 catalytic assay, consistent with the imported NAS code. Independently inspected human complex and assembly experiments support the subunit role. The process annotation describes participation by the assembled machinery and does not imply that all seven natural products have separately demonstrated activity.

Summary: Refine the supported additional nuclear location to nucleoplasm.

Reason: PMID11714725 identified ELP2 in the human complex but localized ELP1 and ELP3, not ELP2 directly. Independent anti-ELP2 staining in PMID11818576 supports a nuclear pool. Target-specific HPA evidence resolves additional nucleoplasmic localization, supporting refinement to GO:0005654. As for the cytoplasm-to-cytosol refinements, this combines sources; it does not claim that the historical assay or mapping resolved the more specific compartment. Nucleoplasm is an additional location, not an exclusive location or evidence for ELP2 transcriptional catalysis.

Proposed replacements: nucleoplasm

Summary: Refine the supported additional nuclear location to nucleoplasm.

Reason: PMID11818576 directly examined ELP2 by immunofluorescence and found predominantly cytoplasmic staining with a smaller nuclear population (Methods, Immunofluorescence; Results, Cellular Localization; Fig. 3). Independent target-specific HPA evidence resolves additional nucleoplasmic localization, supporting refinement to GO:0005654. As for the cytoplasm-to-cytosol refinements, this combines sources; it does not claim that the historical assay or mapping resolved the more specific compartment. Nucleoplasm is an additional location, not an exclusive location or evidence for ELP2 transcriptional catalysis.

Proposed replacements: nucleoplasm

Summary: Refine the supported additional nuclear location to nucleoplasm.

Reason: SL-0191 maps literally to GO:0005634 and records a nuclear pool. Independent anti-ELP2 staining in PMID11818576 and target-specific HPA nucleoplasmic observations support refinement to GO:0005654. The vocabulary mapping is not an independent experiment. As for the cytoplasm-to-cytosol refinements, this combines sources; it does not claim that the historical assay or mapping resolved the more specific compartment. Nucleoplasm is an additional location, not an exclusive location or evidence for ELP2 transcriptional catalysis.

Proposed replacements: nucleoplasm

Summary: HPA supports additional nucleoplasmic localization of ELP2.

Reason: The target-specific HPA XML classifies nucleoplasm as an additional location and cytosol as the main location with supported reliability. Both antibody assay records include nucleoplasmic observations in specified human cell lines. Retain this direct localization context as non-core; no PML-body identity, exclusive compartment, or isoform-specific localization is inferred.

Summary: Refine the supported cytoplasmic location to cytosol.

Reason: PMID11818576 provides direct anti-ELP2 cytoplasmic staining. Independent target-specific HPA evidence now resolves a supported main cytosolic pool, matching GO:0005829, which excludes organelles while allowing protein complexes. This refinement combines sources; it does not claim that the historical assay or the SL mapping itself resolved cytosol. The additional nuclear pool remains compatible.

Proposed replacements: cytosol

Summary: Refine the supported cytoplasmic location to cytosol.

Reason: The literal SL-0086→GO:0005737 mapping faithfully reproduces the broader UniProt location. Independent target-specific HPA evidence now resolves a supported main cytosolic pool, matching GO:0005829, which excludes organelles while allowing protein complexes. This refinement combines sources; it does not claim that the historical assay or the SL mapping itself resolved cytosol. The additional nuclear pool remains compatible.

Proposed replacements: cytosol

Summary: Refine the supported cytoplasmic location to cytosol.

Reason: PMID11714725 reports cytoplasmic Elongator using ELP1/ELP3 localization; independent PMID11818576 directly stains ELP2. Independent target-specific HPA evidence now resolves a supported main cytosolic pool, matching GO:0005829, which excludes organelles while allowing protein complexes. This refinement combines sources; it does not claim that the historical assay or the SL mapping itself resolved cytosol. The additional nuclear pool remains compatible.

Proposed replacements: cytosol

Summary: Cytosol is the supported main HPA location of human ELP2.

Reason: Current HPA target-specific XML identifies cytosol as the main compartment with supported reliability. HPA002996 and CAB020835 provide cytosolic observations across human cell lines, while nuclear localization is additional. This matches the major cellular pool of the Elongator subunit; it is not an exclusivity or splice-product-specific claim.

Summary: Historical human Elongator experiments support a transcription-regulatory context.

Reason: PMID11714725 reports polymerase/early-elongation-complex association and histone acetylation, rather than the chromatin-transcription stimulation assay previously attributed to it here. In PMID11818576, purified Elongator restored acetyl-CoA-dependent transcription from chromatin in Elongator-depleted nuclear extract, although it did not stimulate the fully defined reconstituted system (Functional Analysis; Fig. 5; Discussion). This is positive complex-level evidence in a particular biochemical context. PMID27847465 supports the predominant tRNA-modification role and explains how translation defects can cause transcription phenotypes in cells; it also leaves distinct transcription functions open. That account does not by itself explain away acute cell-free add-back. Retain the imported TAS as non-core, without assigning independent transcriptional catalysis to ELP2 or generalizing the assay to its principal cellular function.

Summary: ELP2 has a supported complex-level transcription-elongation context.

Reason: PMID11714725 associates human Elongator with RNA polymerase II and early elongation complexes. PMID11818576 reports positive chromatin-transcription rescue in depleted nuclear extract, but a negative result in a fully defined reconstituted system; its Discussion also leaves a possible initiation contribution unresolved. Thus the evidence supports a historical transcription-associated complex context without isolating an ELP2-dependent elongation step. PMID27847465 favors a primary tRNA-modification role and explains some whole-cell transcription phenotypes as secondary effects, while retaining the possibility of additional transcription functions. Retain the source-specific TAS as non-core because of the early-elongation association and positive extract assay; do not treat it as a demonstration of autonomous ELP2 RNA-chain extension or a universal cellular elongation role.

Summary: Elongator-mediated tRNA modification provides a translational-regulation context.

Reason: PMID22854966 discusses translational fidelity through tRNA modification in its introduction and directly identifies human ELP2 within the six-subunit complex. Its perturbation experiments chiefly target ELP1, ELP3, ELP5 and ELP6, so they are not a direct ELP2-specific translation assay. The imported NAS claim is biologically consistent with the conserved complex function summarized in PMID27847465. Retain the broader translation-regulatory consequence as non-core, with the more informative tRNA-modification process already represented.

Summary: The historical transcription-associated Elongator complex is supported.

Reason: PMID11714725 identifies ELP2 within human Elongator and shows association of the complex with RNA polymerase II and early elongation complexes. PMID11818576 adds positive chromatin-transcription rescue in depleted nuclear extract, despite failure to stimulate the fully defined system. Together these support a bounded historical transcription-complex context, rather than membership inferred solely from a transcription phenotype. GO:0008023 requires a complex affecting polymerase-II elongation and is a separate assertion from the tRNA-modification complex GO:0033588; the exact transcriptional step remains less secure than the biochemical association. PMID27847465 describes tRNA modification as predominant and secondary effects as an explanation for some cellular phenotypes, but explicitly leaves distinct transcription functions open. Retain the experimental complex annotation as non-core on the positive biochemical evidence, without making it the identity of all cytosolic Elongator or an established core ELP2 function.

Summary: The mouse experimental donor supports contextual protein-kinase binding.

Reason: The literal Q91WG4 donor has an MGI IDA GO:0019901 annotation to PMID10954736. That original uses murine StIP1, endogenous M1-cell JAK1/JAK2/TYK2 co-immunoprecipitation and mapped GST-StIP1 pull-downs; recombinant JAK1 corroboration is stated as data not shown. The human sequence comparison is not a human ELP2 binding assay. Retain the orthology-based binding context as non-core. The study did not recover a stable STAT3–StIP1–JAK1 ternary complex, so no signaling-scaffold function or equivalence of current human splice products is inferred. Failure to recover a ternary complex does not negate the positive binary kinase-association experiments; antibody species specificity likewise does not contradict the mouse donor assay. These limits restrict human extrapolation and mechanism, rather than establishing that the imported orthology-based binding assertion is over-annotated.

Summary: Phylogeny and direct human evidence support conserved Elongator membership.

Reason: The literal IBD for GO:0033588 lies at opisthokont node PTN000521836 on the ancestry of human leaf PTN002543553 in PTHR44111. Its three donor identities exactly match the imported row; current donor records retain experimental grounding, including human PMID22854966. The displayed human sequence matches the family MSA exactly. No loss record occurs on the inspected target path. Human ELP2 as its own experimental donor is legitimate, not circular evidence.

Summary: Human ELP2 is identified in purified six-subunit Elongator.

Reason: PMID22854966 purified Elongator from the cleared cytoplasmic fraction of HEK293 cells expressing C-terminally FLAG-tagged ELP4, with an untagged-cell control, and identified ELP2 among the six co-eluting subunits by mass spectrometry. This directly supports complex membership despite the paper focusing on ELP5/ELP6. No isolated ELP2 catalytic activity or sequence-resolved natural splice product is established by this purification.

Summary: The ELP2-specific InterPro mapping correctly identifies Elongator membership.

Reason: IPR037289 explicitly maps to GO:0033588 and its actual target match spans human ELP2 residues5–823. The mapping is independently consistent with human six-subunit purification and ELP2-dependent ELP1/ELP3 assembly evidence. Accept the family-based complex annotation without converting the WD40 architecture into an autonomous enzyme assignment.

Summary: Association experiments support ELP2 as part of human Elongator.

Reason: The ELP4-FLAG affinity purification in PMID22854966 recovers ELP2 together with the other Elongator subunits from human cells. This supports the imported part_of complex assertion. It does not identify which subunit pair forms a purified direct interface, and the later ELP5 interaction-mapping experiments should not be reassigned to ELP2.