date: '2026-09-20' scope: Full-gene TreeGrafter re-review of six substrate/lineage exemplars; all source annotations, descriptions, core functions and authored NEW assertions assessed. genes: - gene: HETGA/Cgas gene_file: genes/HETGA/Cgas/Cgas-ai-review.yaml status: awaiting_adjudication scope: full_gene outcome: changed annotation_count: 14 final_annotation_count: 14 annotations: - original_index: 0 term_id: GO:0002218 term_label: activation of innate immune response evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: UNDECIDED action: ACCEPT outcome: changed rationale: The curated ancestral cGAS inference is supported by the intact catalytic triad, zinc thumb and nucleotide-binding machinery in A0AAX6RS70 and mammalian cGAMP-STING experiments. PMID:41066557 establishes reversal of the nuclear homologous-recombination phenotype, not loss of innate immune signaling. Prolonged chromatin retention could affect signaling quantitatively, but is not evidence that this inherited function is absent. Acceptance remains an evolutionary inference; naked-mole-rat immune-output assays have not been located. propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_TRANSFER comment: Supports the ancestral cGAS signaling function; no target-specific evidence of loss of this function was found. - source_id: UniProtKB:Q8N884 source_label: human CGAS source_status: SUPPORTS_TRANSFER comment: Supports the ancestral cGAS signaling function; no target-specific evidence of loss of this function was found. - source_id: MGI:MGI:2442261 source_label: mouse Cgas source_status: SUPPORTS_TRANSFER comment: Supports the ancestral cGAS signaling function; no target-specific evidence of loss of this function was found. residue_claims_not_applicable: The established cGAS catalytic and DNA-binding machinery is conserved; quantitative compartmental regulation has not demonstrated loss of this inherited pathway role. - original_index: 1 term_id: GO:0002230 term_label: positive regulation of defense response to virus by host evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: UNDECIDED action: ACCEPT outcome: changed rationale: The curated ancestral cGAS inference is supported by the intact catalytic triad, zinc thumb and nucleotide-binding machinery in A0AAX6RS70 and mammalian cGAMP-STING experiments. PMID:41066557 establishes reversal of the nuclear homologous-recombination phenotype, not loss of innate immune signaling. Prolonged chromatin retention could affect signaling quantitatively, but is not evidence that this inherited function is absent. Acceptance remains an evolutionary inference; naked-mole-rat immune-output assays have not been located. propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_TRANSFER comment: Supports the ancestral cGAS signaling function; no target-specific evidence of loss of this function was found. residue_claims_not_applicable: The established cGAS catalytic and DNA-binding machinery is conserved; quantitative compartmental regulation has not demonstrated loss of this inherited pathway role. - original_index: 2 term_id: GO:0003682 term_label: chromatin binding evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: 'This is the one molecular function for which there is explicit naked-mole-rat evidence. The primary study reports that the four species-specific substitutions make cGAS retain chromatin longer after DNA damage, and refers to the resulting state as prolonged chromatin binding. The structural basis is also intact: the arginine anchor by which cGAS docks onto the nucleosome acidic patch (human R255) is conserved as R287 in A0AAX6RS70. Rather than being weakened by the naked-mole-rat divergence, chromatin binding is enhanced by it, so this term is not merely retained but is core.' propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_TRANSFER comment: Node assertion independently confirmed in the target species by PMID:41066557, which is the strongest possible outcome for a propagated term. residue_claims: - claim_type: RETAINED role: nucleosome acidic-patch arginine anchor method: MSA comment: 'Human R255 is the arginine that docks cGAS onto the nucleosome acidic patch. Its retention in the naked-mole-rat protein is consistent with the reported chromatin retention, and refutes any suggestion that chromatin binding was lost in this lineage. It carries a second implication worth recording: R255E in human releases over 100-fold more basal cGAMP, so this residue is also the switch that keeps chromatin-bound cGAS catalytically restrained, and its conservation means the naked-mole-rat protein retains that restraint while spending longer in the restrained state. Correspondence from an ad hoc global alignment (Cgas-bioinformatics/align_cgas.py), so no shared alignment release is pinned.' anchor: accession: UniProtKB:Q8N884 position: 255 residue: R sequence_version: 2 target: accession: UniProtKB:A0AAX6RS70 position: 287 residue: R sequence_version: 1 - original_index: 3 term_id: GO:0003690 term_label: double-stranded DNA binding evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: ACCEPT action: ACCEPT outcome: changed rationale: cGAS reads B-form double-stranded DNA through a zinc thumb and a set of basic DNA-binding surfaces. Residue transfer from human cGAS shows the zinc thumb intact (H390/C396/C397/C404 to H422/C428/C429/C436) and the C-terminal DNA-binding region 384-407 at 62.5% identity, i.e. ordinary orthologue-level conservation with no disruption. The only substitutions among human single-residue annotations that touch DNA are K187 and L195, which UniProt annotates as tuning preference for curved long DNA and which lie in the fast-evolving disordered N-terminal arm; those affect substrate preference at most, not the capacity to bind dsDNA. The native chromatin phenotype is compatible with a DNA-binding protein but, by itself, does not distinguish contacts with DNA from contacts with histones. Nothing about the species-specific C-terminal divergence bears on this. propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_TRANSFER residue_claims: - claim_type: RETAINED role: zinc thumb, first cysteine of the Zn(2+)-coordinating pair that reads B-form dsDNA method: MSA comment: Checked because a degraded zinc thumb would be the expected signature if dsDNA reading had been lost in this lineage. All four Zn(2+) ligands (H390, C396, C397, C404 in human) are present; C396 is recorded here as the representative site. Correspondence from an ad hoc global alignment, so no alignment release is pinned. anchor: accession: UniProtKB:Q8N884 position: 396 residue: C sequence_version: 2 target: accession: UniProtKB:A0AAX6RS70 position: 428 residue: C sequence_version: 1 - original_index: 4 term_id: GO:0005634 term_label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: The entire naked-mole-rat phenotype is a nuclear one — retention on chromatin after DNA damage, promotion of the FANCI-RAD50 interaction, and RAD50 recruitment to damage sites. A protein cannot do that without a nuclear pool. This is therefore not merely a propagated localization but one corroborated by the species-specific evidence, and it is the compartment in which the core naked-mole-rat activity takes place. propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_TRANSFER comment: Node assertion corroborated in the target species by PMID:41066557. - original_index: 5 term_id: GO:0005829 term_label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: 'Cytosolic localization is the best-established property of cGAS in mammals, and the Euteleostomi node carries it on experimental grounding from both human CGAS and mouse Cgas. Nothing in the naked-mole-rat work excludes a cytosolic pool: what changes in this species is how long the protein stays on chromatin once damage occurs, which shifts the balance between compartments rather than abolishing one of them. The commentary on the primary paper likewise still describes the protein as a cytosolic sensor. A localization claim is a weaker assertion than the functional output that normally accompanies it, and it survives here even though that output is left UNDECIDED — the caveat about the size of the cytosolic pool belongs on the DNA-sensing process terms, not on the existence of the compartment.' propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_TRANSFER - original_index: 6 term_id: GO:0006974 term_label: DNA damage response evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: 'The propagated term is confirmed in the target species. cGAS in the naked mole-rat changes its behaviour specifically upon DNA damage — it is retained on chromatin instead of being extracted — and that change feeds directly into repair-factor recruitment. The term is broad, but here breadth is appropriate: it is the correct parent for both the chromatin-retention step and the downstream recruitment step, and the more specific claim is captured separately by the proposed GO:1905168 row.' propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_TRANSFER comment: Seeded by UniProtKB:Q8N884 alone at this node; the assertion is nevertheless independently confirmed in the naked mole-rat by PMID:41066557. - original_index: 7 term_id: GO:0032481 term_label: positive regulation of type I interferon production evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: UNDECIDED action: ACCEPT outcome: changed rationale: The curated ancestral cGAS inference is supported by the intact catalytic triad, zinc thumb and nucleotide-binding machinery in A0AAX6RS70 and mammalian cGAMP-STING experiments. PMID:41066557 establishes reversal of the nuclear homologous-recombination phenotype, not loss of innate immune signaling. Prolonged chromatin retention could affect signaling quantitatively, but is not evidence that this inherited function is absent. Acceptance remains an evolutionary inference; naked-mole-rat immune-output assays have not been located. propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_TRANSFER comment: Supports the ancestral cGAS signaling function; no target-specific evidence of loss of this function was found. residue_claims_not_applicable: The established cGAS catalytic and DNA-binding machinery is conserved; quantitative compartmental regulation has not demonstrated loss of this inherited pathway role. - original_index: 8 term_id: GO:0035861 term_label: site of double-strand break evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: The naked-mole-rat abstract does not use the phrase "site of double-strand break", so the direct localization claim is one step beyond what it literally states. But it does say that cGAS is retained on chromatin specifically upon DNA damage and that this facilitates RAD50 recruitment to damage sites — RAD50 being an MRN subunit whose recruitment defines the double-strand break site — and the human orthologue is experimentally documented at double-strand breaks, which is what seeds the node. The species-specific change is to the duration of that residence, not to whether it happens. Accepting is therefore the reading most consistent with the evidence, with the caveat recorded that the naked-mole-rat localization has not been imaged directly. propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_TRANSFER comment: 'Seeded at this node by UniProtKB:Q8N884 alone. Donor count is not the issue: the question is whether the naked mole rat still goes to damage sites, and the species-specific evidence indicates it does so for longer, not less.' - original_index: 9 term_id: GO:0038001 term_label: paracrine signaling evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: KEEP_AS_NON_CORE action: ACCEPT outcome: changed rationale: GO:0038001 specifies transmission through intercellular fluid. Primary PMID:33768207 establishes export of freely soluble cGAMP and effects on recipient immune cells; this is the relevant paracrine comparator, whereas the gap-junction route in PMID:24077100 alone would not meet that definition. cGAS performs direct work by synthesizing the signal even though other proteins export or import it. Conserved synthesis and the ancestral annotation support transfer to naked-mole-rat cGAS, with species-specific route and output still unmeasured. propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_TRANSFER comment: Node grounding is fine; the term is simply a contextual consequence rather than a core activity. - original_index: 10 term_id: GO:0061501 term_label: 2',3'-cyclic GMP-AMP synthase activity evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: 'This term comes from a different and much deeper node than the rest of the set — PTN000838114 at taxon:6072 (Eumetazoa), seeded by eight members spanning fly cGLRs, zebrafish, mouse and human — and the naked mole rat is well inside it. Since no naked-mole-rat enzymology exists, the propagation was checked against sequence rather than accepted on trust: the catalytic Mg(2+) triad (human E225/D227/D319) transfers intact to E257/D259/D351, the zinc thumb is complete, and the ATP, GTP and cGAMP contacts are conserved. There is no pseudoenzyme signature. Critically, the four residues responsible for the naked mole-rat''s altered DNA-repair behaviour all lie in the C-terminal Mab-21-like HhH/H2TH-like domain (437-541), downstream of the zinc thumb and far from the active site, so the functional divergence documented in this species is regulatory and does not touch catalysis. The remaining honest gap is that conserved machinery establishes capability rather than measured activity, which is recorded as a knowledge gap and an experiment rather than by downgrading the call.' propagation_review: root_cause: NO_FAILURE_CORE source_entities: - source_id: PANTHER:PTN000838114 source_label: Eumetazoan mab-21 nucleotidyltransferase node (PTHR10656) source_status: SUPPORTS_TRANSFER comment: IBD at taxon:6072 with eight seeds across fly, coral, zebrafish, mouse and human; a much deeper placement than the Euteleostomi node carrying the other twelve terms. residue_claims: - claim_type: RETAINED role: catalytic Mg(2+) ligand and 2',3'-cGAMP contact method: MSA comment: The central residue of the cGAS nucleotidyltransferase triad (E225/D227/D319 in human). Recorded explicitly because this is the residue whose loss would justify a pseudoenzyme call; it is present, so no such argument is available. Correspondence from an ad hoc global alignment (Cgas-bioinformatics/align_cgas.py), so no alignment release is pinned. anchor: accession: UniProtKB:Q8N884 position: 227 residue: D sequence_version: 2 target: accession: UniProtKB:A0AAX6RS70 position: 259 residue: D sequence_version: 1 - claim_type: RETAINED role: catalytic Mg(2+) ligand and ATP contact method: MSA comment: Second member of the same triad, checked independently so the conclusion does not rest on a single position. anchor: accession: UniProtKB:Q8N884 position: 225 residue: E sequence_version: 2 target: accession: UniProtKB:A0AAX6RS70 position: 257 residue: E sequence_version: 1 - claim_type: RETAINED role: catalytic Mg(2+) ligand, GTP and 2',3'-cGAMP contact method: MSA comment: Third member of the catalytic triad, likewise intact. anchor: accession: UniProtKB:Q8N884 position: 319 residue: D sequence_version: 2 target: accession: UniProtKB:A0AAX6RS70 position: 351 residue: D sequence_version: 1 - original_index: 11 term_id: GO:0071360 term_label: cellular response to exogenous dsRNA evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: UNDECIDED action: UNDECIDED outcome: changed rationale: QuickGO currently defines GO:0071360 as cellular response to exogenous dsRNA and lists four positive mouse experimental annotations feeding the cGAS ancestral node. However, the inspected full text of PMID:23258413 reports that poly(I:C) did not stimulate purified cGAS, and PMID:24077100 centers on DNA-triggered cGAMP transfer. The other two cited studies concern dsDNA-dependent N-terminal activation and are abstract-only here. Direct RNA sensing is not required for an indirect cellular-response annotation, so these observations do not justify removal. The unresolved question is whether the complete donor evidence supports an indirect dsRNA response or a DNA/RNA term mismatch; absence of a naked-mole-rat assay is not the reason for uncertainty. propagation_review: root_cause: UNRESOLVED source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: UNRESOLVED comment: Positive mouse experimental source rows are present, but their support for dsRNA rather than dsDNA response requires full-text adjudication. - source_id: MGI:MGI:2442261 source_label: mouse Cgas source_status: UNRESOLVED comment: Positive mouse experimental source rows are present, but their support for dsRNA rather than dsDNA response requires full-text adjudication. residue_claims_not_applicable: This is uncertainty about the stimulus and biological-process evidence in the donor studies, not catalytic residue loss. - original_index: 12 term_id: GO:2000042 term_label: negative regulation of double-strand break repair via homologous recombination evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: REMOVE action: REMOVE outcome: confirmed rationale: 'This is the one propagated term with direct, species-specific evidence against it. The primary study states that naked-mole-rat cGAS lacks the suppressive function that the human and mouse orthologs have in homologous recombination repair, and attributes the difference to four amino acids fixed during evolution. The replacement activity runs in the opposite direction: prolonged chromatin retention strengthens the FANCI-RAD50 interaction and promotes RAD50 recruitment to damage sites, potentiating homologous recombination. The propagation is not defective at its source. PTN002579681 sits at taxon:117571 (Euteleostomi) and its seeds — mouse Cgas and human CGAS — genuinely do suppress homologous recombination, so the PAINT curator encoded a real and well-supported property of the species that had been examined. What fails is the assumption that the property is conserved across the whole clade. The naked mole rat is inside that clade and does the opposite, which is exactly the target-specific evidence of functional divergence needed to challenge a node placement — as distinct from an objection based on how many donors seeded it. Retaining a negative-regulation term alongside the positive one would assert both directions at once, so this row is removed rather than modified, and the correct activity is asserted separately as GO:1905168.' propagation_review: root_cause: PROPAGATION_BAD failure_modes: - REGULATORY_SIGN_INVERSION - FUNCTIONAL_DIVERGENCE source_entities: - source_id: PANTHER:PTN002579681 source_label: Euteleostomi cGAS node (PTHR10656) source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET comment: The IBD is correct for the clade members that were tested; it is the extension to the naked mole rat that fails, because this lineage inverted the sign of the regulation. - source_id: UniProtKB:Q8N884 source_label: human CGAS source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET comment: Nuclear human cGAS genuinely suppresses homologous recombination; PMID:41066557 uses it as the explicit contrast to the naked-mole-rat protein. - source_id: MGI:MGI:2442261 source_label: mouse Cgas source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET comment: Same as human; named as a contrasting ortholog in the primary study. residue_claims: - claim_type: SUBSTITUTED role: C-terminal regulatory position; one of the four residues reported to distinguish naked-mole-rat from human and mouse cGAS in homologous recombination repair method: MSA comment: 'The abstract states that four amino acids changed but does not name them; secondary coverage names S463D, E511K, Y527L, T530K without stating the numbering frame. The frame was resolved here from sequence: read in naked-mole-rat numbering the wild-type residues are exactly S463, E511, Y527 and T530, and the aligned human residues are D431, K479, L495 and K498, so the reported series is a humanising one. E511 is recorded as the representative position. The residue identities and the correspondence are verified; the functional attribution to these specific positions rests on the secondary summary and is therefore corroborated rather than proven. Correspondence from an ad hoc global alignment (Cgas-bioinformatics/align_cgas.py), so no alignment release is pinned.' anchor: accession: UniProtKB:Q8N884 position: 479 residue: K sequence_version: 2 target: accession: UniProtKB:A0AAX6RS70 position: 511 residue: E sequence_version: 1 - original_index: 13 term_id: GO:1905168 term_label: positive regulation of double-strand break repair via homologous recombination evidence_type: IMP original_reference_id: PMID:41066557 negated: false previous_action: NEW action: NEW outcome: confirmed rationale: 'The primary study reports a positive, mechanistically specified role for cGAS in homologous recombination in this species: prolonged chromatin binding strengthens the FANCI-RAD50 interaction and facilitates RAD50 recruitment to damage sites, thereby potentiating homologous recombination repair. The conclusion is drawn from an engineered four-residue substitution series that shifts the naked-mole-rat protein toward the human and mouse behaviour, which is why IMP is the appropriate evidence code. GO:1905168 was chosen deliberately over the two neighbouring options. The gene product is not itself performing recombination, so GO:0000724 double-strand break repair via homologous recombination would overstate the role; and the effect is specific to the homologous-recombination pathway rather than to repair in general, so the broader GO:2000781 positive regulation of double-strand break repair would understate it. The identifier was confirmed against QuickGO rather than written from memory. No accompanying ageing or lifespan term is proposed. The abstract does support an anti-ageing role, but reduced senescence and extended lifespan here are indirect, downstream consequences of improved repair, and NEW is explicitly not for indirect or pleiotropic effects.' changes: - Restored conserved innate immune activation, antiviral defense and type-I interferon roles; HR sign reversal does not establish loss of cGAMP-STING signaling. - Restored paracrine signaling because cGAS synthesizes the transferred signal. - Retained negative-HR rejection and direct positive-HR authored NEW; made immune core/description consistent. - Reframed dsRNA uncertainty around actual donor stimulus evidence after inspecting full primary PMID:23258413/24077100 and live QuickGO mouse positive rows, not absence of a naked-mole-rat assay. - Integrated Falcon/Affinage mechanism and limitations and primary mammalian evidence; corrected claim that every nucleotide contact is identical. - 'Final ontology check: GO:0038001 requires transmission through intercellular fluid. Gap-junction transfer alone (PMID:24077100) is insufficient; added primary PMID:33768207 demonstrating freely soluble extracellular cGAMP export and recipient immune effects, supporting the accepted paracrine role through signal synthesis.' action_change_count: 4 evidence: existing_adjudications: - genes/HETGA/Cgas/Cgas-deep-research-falcon.md - genes/HETGA/Cgas/Cgas-deep-research-affinage-human-ortholog.md primary_references: - PMID:41066557 - PMID:23258413 - PMID:24077100 - PMID:28214358 - PMID:28363908 - PMID:33768207 notes_file: genes/HETGA/Cgas/Cgas-notes.md limits: Provider findings are used with target/comparator and full-text limitations stated in the reviews; no duplicate external adjudication launched by this agent. context_references: - PMID:41066590 - PMID:41935903 - PMID:41198971 - PMID:29340215 - PMID:34199458 adjudication: state: requested owner: root go_terms: - GO:0071360 question: Do all four mouse donor studies support an indirect cellular response to exogenous dsRNA, or is a dsDNA response mapped to the wrong term? Direct RNA-sensing failure alone does not refute indirect BP participation. primary_access: 23258413 and PMID:24077100 full text inspected;28214358 and PMID:28363908 abstract-only. Native HR paper PMID:41066557 abstract inspected; Science full text HTTP403. report: null source_rows_preserved: true source_annotation_count: 13 validation: command: just validate HETGA Cgas result: passed warnings: [] warning_disposition: Warnings suggesting new annotations are not treated as instructions to create redundant assertions; core synthesis is retained without extra NEW rows. history_record: history/genes/HETGA/Cgas/2026-09-21T015121Z-codex-787f1f.yaml history_validation: passed new_assertion_review: added_in_this_session: 0 preexisting_retained: - GO:1905168 source_annotations_removed: 0 ancestor_check: QuickGO is_a/part_of check found no accepted ancestor of the three retained authored NEW terms; none introduces a redundant parent/child of an accepted existing assertion. - gene: DESRO/K9IFT7 gene_file: genes/DESRO/K9IFT7/K9IFT7-ai-review.yaml status: awaiting_adjudication scope: full_gene outcome: changed annotation_count: 8 final_annotation_count: 8 annotations: - original_index: 0 term_id: GO:0002227 term_label: innate immune response in mucosa evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: The beta-defensin fold and conserved secretory architecture support an inherited innate effector function. The target transcript was obtained from salivary gland and the native vampirome study reports defensin-family expression in accessory glands, consistent with an oral mucosal context. No lineage-specific loss is established; lack of a purified bat assay does not itself make the inherited term too specific. - original_index: 1 term_id: GO:0005615 term_label: extracellular space evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: ACCEPT action: ACCEPT outcome: changed rationale: The 1–23 signal peptide and UniProt secretion assignment support the extracellular mature peptide. Extracellular region and extracellular space are compatible; a broad parent is not an erroneous location. - original_index: 2 term_id: GO:0031731 term_label: CCR6 chemokine receptor binding evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: UNDECIDED action: UNDECIDED outcome: changed rationale: The record mixes a tentative CCR6-ligand statement with imported sperm-related functions. The Falcon report does not test K9IFT7 binding, reconstruct the relevant defensin orthology, or evaluate conservation of the receptor-interaction surface. This is an unresolved specific interaction inference, not a conclusion that bat proteins must have a new direct assay. Root has been asked to adjudicate exact K9IFT7/JAA44743.1 placement and donor experiments. - original_index: 3 term_id: GO:0050829 term_label: defense response to Gram-negative bacterium evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: The secreted beta-defensin 1-like architecture supports the ancestral antimicrobial-spectrum inference, and no target-specific loss of this defense role is established. Human beta-defensin 1 activity can depend strongly on redox conditions, so this term does not assert equal potency against every bacterial species or in every environment. Exact K9IFT7 MICs remain unmeasured. - original_index: 4 term_id: GO:0050830 term_label: defense response to Gram-positive bacterium evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: The secreted beta-defensin 1-like architecture supports the ancestral antimicrobial-spectrum inference, and no target-specific loss of this defense role is established. Human beta-defensin 1 activity can depend strongly on redox conditions, so this term does not assert equal potency against every bacterial species or in every environment. Exact K9IFT7 MICs remain unmeasured. - original_index: 5 term_id: GO:0005576 term_label: extracellular region evidence_type: IEA original_reference_id: GO_REF:0000120 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: The 1–23 signal peptide and UniProt secretion assignment support the extracellular mature peptide. Extracellular region and extracellular space are compatible; a broad parent is not an erroneous location. - original_index: 6 term_id: GO:0006952 term_label: defense response evidence_type: IEA original_reference_id: GO_REF:0000120 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: This is a secreted beta-defensin 1-like peptide from salivary gland. Conserved antimicrobial family function supports defense response and defense response to bacterium; the broader label remains biologically correct. - original_index: 7 term_id: GO:0042742 term_label: defense response to bacterium evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: ACCEPT action: ACCEPT outcome: changed rationale: This is a secreted beta-defensin 1-like peptide from salivary gland. Conserved antimicrobial family function supports defense response and defense response to bacterium; the broader label remains biologically correct. changes: - Restored mucosal innate defense, Gram-positive/negative defense, extracellular region and broad defense response. - Added missing project-independent description/core, native salivary-gland provenance, primary PMID:23411029 and comparative redox-dependent hBD1 evidence PMID:21248850. - Read existing Falcon fully, distinguishing unrelated DEFB105/DEFB107 copy numbers from target evidence. CCR6 remains unresolved for specific orthology/interaction reasons. action_change_count: 5 evidence: existing_adjudications: - genes/DESRO/K9IFT7/K9IFT7-deep-research-falcon.md primary_references: - PMID:23411029 - PMID:21248850 notes_file: genes/DESRO/K9IFT7/K9IFT7-notes.md limits: Provider findings are used with target/comparator and full-text limitations stated in the reviews; no duplicate external adjudication launched by this agent. adjudication: state: requested owner: root go_terms: - GO:0031731 question: Does exact K9IFT7/JAA44743.1 support retained CCR6 binding through defensin orthology, receptor-interaction determinants and donor experiments? report: null source_rows_preserved: true source_annotation_count: 8 validation: command: just validate DESRO K9IFT7 result: passed warnings: [] warning_disposition: Warnings suggesting new annotations are not treated as instructions to create redundant assertions; core synthesis is retained without extra NEW rows. history_record: history/genes/DESRO/K9IFT7/2026-09-21T015123Z-codex-4a5829.yaml history_validation: passed new_assertion_review: added_in_this_session: 0 preexisting_retained: [] source_annotations_removed: 0 ancestor_check: QuickGO is_a/part_of check found no accepted ancestor of the three retained authored NEW terms; none introduces a redundant parent/child of an accepted existing assertion. - gene: DESRO/K9IMD0 gene_file: genes/DESRO/K9IMD0/K9IMD0-ai-review.yaml status: awaiting_adjudication scope: full_gene outcome: changed annotation_count: 27 final_annotation_count: 27 annotations: - original_index: 0 term_id: GO:0005769 term_label: early endosome evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: REMOVE action: UNDECIDED outcome: changed rationale: Secreted lactotransferrin can associate with cell-surface receptors and enter endosomal pathways. A signal peptide and extracellular anticoagulant role do not refute plasma-membrane or endosomal association. The present report does not resolve conservation of the specific trafficking interaction in K9IMD0; retain uncertainty pending the focused lactotransferrin adjudication. - original_index: 1 term_id: GO:0005886 term_label: plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: REMOVE action: UNDECIDED outcome: changed rationale: Secreted lactotransferrin can associate with cell-surface receptors and enter endosomal pathways. A signal peptide and extracellular anticoagulant role do not refute plasma-membrane or endosomal association. The present report does not resolve conservation of the specific trafficking interaction in K9IMD0; retain uncertainty pending the focused lactotransferrin adjudication. - original_index: 2 term_id: GO:0019731 term_label: antibacterial humoral response evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: MARK_AS_OVER_ANNOTATED action: ACCEPT outcome: changed rationale: K9IMD0 retains the bilobed transferrin scaffold and annotated iron-binding sites; the salivary proteome places lactotransferrin among antimicrobial components. Conserved iron sequestration and lactotransferrin-family antimicrobial mechanisms support the inherited defense role. Anticoagulant activity does not demonstrate loss of this ancestral function, and the evidence does not justify calling a true broad immune term an over-annotation. This remains comparative inference rather than a purified bat bactericidal assay. - original_index: 3 term_id: GO:0035821 term_label: modulation of process of another organism evidence_type: IEA original_reference_id: GO_REF:0000108 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: Native draculin inhibits prey coagulation factors and the 2013 proteomic/transcriptomic study maps the draculin scaffold to lactotransferrin. Modulation of another organism, negative regulation of an organismal process, and toxin activity are compatible with a salivary factor evolved to disrupt prey hemostasis. A narrower coagulation term does not invalidate them, and a BP term is not an appropriate replacement for an MF toxin assertion. Sequence-to-activity mapping remains explicitly qualified because recombinant confirmation is lacking. - original_index: 4 term_id: GO:0055037 term_label: recycling endosome evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: REMOVE action: UNDECIDED outcome: changed rationale: Secreted lactotransferrin can associate with cell-surface receptors and enter endosomal pathways. A signal peptide and extracellular anticoagulant role do not refute plasma-membrane or endosomal association. The present report does not resolve conservation of the specific trafficking interaction in K9IMD0; retain uncertainty pending the focused lactotransferrin adjudication. - original_index: 5 term_id: GO:0001503 term_label: ossification evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: REMOVE action: UNDECIDED outcome: changed rationale: Lactotransferrin can affect osteoblast and osteoclast behavior in other mammals, but the report does not establish which receptor-dependent functions K9IMD0 retains. Absence of ossification measurements in a saliva-focused paper is not evidence of loss. Keep this specific physiological transfer unresolved pending the focused review. - original_index: 6 term_id: GO:0002376 term_label: immune system process evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: MARK_AS_OVER_ANNOTATED action: ACCEPT outcome: changed rationale: K9IMD0 retains the bilobed transferrin scaffold and annotated iron-binding sites; the salivary proteome places lactotransferrin among antimicrobial components. Conserved iron sequestration and lactotransferrin-family antimicrobial mechanisms support the inherited defense role. Anticoagulant activity does not demonstrate loss of this ancestral function, and the evidence does not justify calling a true broad immune term an over-annotation. This remains comparative inference rather than a purified bat bactericidal assay. - original_index: 7 term_id: GO:0005576 term_label: extracellular region evidence_type: IEA original_reference_id: GO_REF:0000120 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: Saliva isolation indicates a secreted/extracellular protein [PMID:7740503]. - original_index: 8 term_id: GO:0005615 term_label: extracellular space evidence_type: IEA original_reference_id: GO_REF:0000120 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: Experimental purification from saliva supports extracellular space localization [PMID:7740503]. - original_index: 9 term_id: GO:0006508 term_label: proteolysis evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: MARK_AS_OVER_ANNOTATED action: UNDECIDED outcome: changed rationale: The target record contains conserved lactotransferrin protease annotations transferred from human LTF, and the Falcon report describes family proteolysis while noting no target assay. Inhibition of prey coagulation proteases does not preclude the protein having its own hydrolytic activity. Assess the proposed catalytic determinants and donor experiments before either accepting or rejecting these nested catalytic/process terms. - original_index: 10 term_id: GO:0006811 term_label: monoatomic ion transport evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: REMOVE action: UNDECIDED outcome: changed rationale: The protein retains the transferrin iron-binding architecture and family-level receptor-mediated uptake provides a plausible transport mechanism. The previous anticoagulant-only rationale did not establish loss. Binding alone, however, does not resolve which physiological iron-transport steps are retained in this bat sequence, so the focused report will assess the inherited claim. - original_index: 11 term_id: GO:0006826 term_label: iron ion transport evidence_type: IEA original_reference_id: GO_REF:0000120 negated: false previous_action: MARK_AS_OVER_ANNOTATED action: UNDECIDED outcome: changed rationale: The protein retains the transferrin iron-binding architecture and family-level receptor-mediated uptake provides a plausible transport mechanism. The previous anticoagulant-only rationale did not establish loss. Binding alone, however, does not resolve which physiological iron-transport steps are retained in this bat sequence, so the focused report will assess the inherited claim. - original_index: 12 term_id: GO:0008233 term_label: peptidase activity evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: MARK_AS_OVER_ANNOTATED action: UNDECIDED outcome: changed rationale: The target record contains conserved lactotransferrin protease annotations transferred from human LTF, and the Falcon report describes family proteolysis while noting no target assay. Inhibition of prey coagulation proteases does not preclude the protein having its own hydrolytic activity. Assess the proposed catalytic determinants and donor experiments before either accepting or rejecting these nested catalytic/process terms. - original_index: 13 term_id: GO:0008236 term_label: serine-type peptidase activity evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: MARK_AS_OVER_ANNOTATED action: UNDECIDED outcome: changed rationale: The target record contains conserved lactotransferrin protease annotations transferred from human LTF, and the Falcon report describes family proteolysis while noting no target assay. Inhibition of prey coagulation proteases does not preclude the protein having its own hydrolytic activity. Assess the proposed catalytic determinants and donor experiments before either accepting or rejecting these nested catalytic/process terms. - original_index: 14 term_id: GO:0016787 term_label: hydrolase activity evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: MARK_AS_OVER_ANNOTATED action: UNDECIDED outcome: changed rationale: The target record contains conserved lactotransferrin protease annotations transferred from human LTF, and the Falcon report describes family proteolysis while noting no target assay. Inhibition of prey coagulation proteases does not preclude the protein having its own hydrolytic activity. Assess the proposed catalytic determinants and donor experiments before either accepting or rejecting these nested catalytic/process terms. - original_index: 15 term_id: GO:0042742 term_label: defense response to bacterium evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: MARK_AS_OVER_ANNOTATED action: ACCEPT outcome: changed rationale: K9IMD0 retains the bilobed transferrin scaffold and annotated iron-binding sites; the salivary proteome places lactotransferrin among antimicrobial components. Conserved iron sequestration and lactotransferrin-family antimicrobial mechanisms support the inherited defense role. Anticoagulant activity does not demonstrate loss of this ancestral function, and the evidence does not justify calling a true broad immune term an over-annotation. This remains comparative inference rather than a purified bat bactericidal assay. - original_index: 16 term_id: GO:0046872 term_label: metal ion binding evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: MARK_AS_OVER_ANNOTATED action: ACCEPT outcome: changed rationale: The full-length sequence contains two transferrin domains and multiple annotated Fe(3+) ligand sites. The inherited metal-binding inference is supported independently of the proposed anticoagulant specialization; no demonstrated loss of the binding sites was found. - original_index: 17 term_id: GO:0051241 term_label: negative regulation of multicellular organismal process evidence_type: IEA original_reference_id: GO_REF:0000117 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: Native draculin inhibits prey coagulation factors and the 2013 proteomic/transcriptomic study maps the draculin scaffold to lactotransferrin. Modulation of another organism, negative regulation of an organismal process, and toxin activity are compatible with a salivary factor evolved to disrupt prey hemostasis. A narrower coagulation term does not invalidate them, and a BP term is not an appropriate replacement for an MF toxin assertion. Sequence-to-activity mapping remains explicitly qualified because recombinant confirmation is lacking. - original_index: 18 term_id: GO:0090729 term_label: toxin activity evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: Native draculin inhibits prey coagulation factors and the 2013 proteomic/transcriptomic study maps the draculin scaffold to lactotransferrin. Modulation of another organism, negative regulation of an organismal process, and toxin activity are compatible with a salivary factor evolved to disrupt prey hemostasis. A narrower coagulation term does not invalidate them, and a BP term is not an appropriate replacement for an MF toxin assertion. Sequence-to-activity mapping remains explicitly qualified because recombinant confirmation is lacking. - original_index: 19 term_id: GO:0004867 term_label: serine-type endopeptidase inhibitor activity evidence_type: IDA original_reference_id: PMID:10556567 negated: false previous_action: NEW action: NEW outcome: changed rationale: GOA lacks the specific serine protease inhibitor activity, but biochemical studies show direct inhibition of FXa/IXa [PMID:7740503; PMID:10556567]. The assignment follows the curated native draculin evidence and 2013 sequence/proteomic mapping; recombinant K9IMD0 confirmation is still lacking (PMID:23411029), so a focused mapping review is pending. - original_index: 20 term_id: GO:0005615 term_label: extracellular space evidence_type: IDA original_reference_id: PMID:10556567 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: The study describes draculin as a factor in vampire bat saliva, supporting extracellular localization [PMID:10556567]. - original_index: 21 term_id: GO:0005615 term_label: extracellular space evidence_type: IDA original_reference_id: PMID:23748026 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: The proteomic/transcriptomic study discusses vampire bat oral secretions and draculin, consistent with extracellular secretion [PMID:23748026]. - original_index: 22 term_id: GO:0005615 term_label: extracellular space evidence_type: IDA original_reference_id: PMID:7740503 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: Isolation from saliva indicates a secreted extracellular protein [PMID:7740503]. - original_index: 23 term_id: GO:0005615 term_label: extracellular space evidence_type: IDA original_reference_id: PMID:9795244 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: The study explicitly describes draculin as isolated from saliva, consistent with extracellular space [PMID:9795244]. - original_index: 24 term_id: GO:0030195 term_label: negative regulation of blood coagulation evidence_type: IDA original_reference_id: PMID:10556567 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: Direct biochemical evidence shows draculin inhibits FXa, consistent with anticoagulant activity [PMID:10556567]. - original_index: 25 term_id: GO:0030195 term_label: negative regulation of blood coagulation evidence_type: IDA original_reference_id: PMID:7740503 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: Experimental data show inhibition of IXa/Xa by draculin [PMID:7740503]. - original_index: 26 term_id: GO:0030195 term_label: negative regulation of blood coagulation evidence_type: IDA original_reference_id: PMID:9795244 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: The study states draculin is a natural anticoagulant that inhibits IXa/Xa [PMID:9795244]. changes: - Restored conserved metal binding and antimicrobial/immune roles; anticoagulant specialization alone is not a loss mechanism. - Changed unsupported membrane/endosomal, iron-transport, proteolysis/hydrolase and ossification exclusions to UNDECIDED. - Restored broad other-organism modulation, negative-organismal regulation and toxin activity; removed cross-aspect MF-to-BP replacement. - Integrated substantive Falcon findings and primary PMID:23411029 mapping caveat. Existing native secretion/coagulation IDAs and authored inhibitor NEW remain supported by the curated native assays plus 2013 scaffold mapping, explicitly awaiting exact recombinant sequence/activity confirmation. - Updated description/core to include conserved lactotransferrin biology and qualify the exact anticoagulant mapping. action_change_count: 17 evidence: existing_adjudications: - genes/DESRO/K9IMD0/K9IMD0-deep-research-falcon.md primary_references: - PMID:10556567 - PMID:23748026 - PMID:7740503 - PMID:9795244 - PMID:23411029 notes_file: genes/DESRO/K9IMD0/K9IMD0-notes.md limits: Provider findings are used with target/comparator and full-text limitations stated in the reviews; no duplicate external adjudication launched by this agent. adjudication: state: requested owner: root go_terms: - GO:0005769 - GO:0005886 - GO:0055037 - GO:0001503 - GO:0006508 - GO:0006811 - GO:0006826 - GO:0008233 - GO:0008236 - GO:0016787 question: Which ancestral lactotransferrin iron-handling, protease, receptor-trafficking and physiological roles are retained in exact K9IMD0, and how securely does native draculin anticoagulant activity map to this sequence? report: null source_rows_preserved: true source_annotation_count: 26 validation: command: just validate DESRO K9IMD0 result: passed warnings: [] warning_disposition: Warnings suggesting new annotations are not treated as instructions to create redundant assertions; core synthesis is retained without extra NEW rows. history_record: history/genes/DESRO/K9IMD0/2026-09-21T015124Z-codex-27f3d9.yaml history_validation: passed new_assertion_review: added_in_this_session: 0 preexisting_retained: - GO:0004867 source_annotations_removed: 0 ancestor_check: QuickGO is_a/part_of check found no accepted ancestor of the three retained authored NEW terms; none introduces a redundant parent/child of an accepted existing assertion. - gene: PSEPK/moeB gene_file: genes/PSEPK/moeB/moeB-ai-review.yaml status: reviewed scope: full_gene outcome: changed annotation_count: 8 final_annotation_count: 8 annotations: - original_index: 0 term_id: GO:0003824 term_label: catalytic activity evidence_type: IEA original_reference_id: GO_REF:0000117 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: ATP-dependent transfer of AMP to the terminal carboxylate of MoaD is catalytic nucleotidyl transfer. The specific molybdopterin-synthase adenylyltransferase term is already retained, and its broad catalytic ancestors remain correct. OpenScientist supports the classical MoeB architecture and conserved mechanism while explicitly noting that Q88PW3 has not been assayed. - original_index: 1 term_id: GO:0004792 term_label: thiosulfate-cyanide sulfurtransferase activity evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: REMOVE action: REMOVE outcome: changed rationale: MoeB activates MoaD by ATP-dependent adenylylation; it does not use thiosulfate or cyanide in the assigned reaction. The 251-aa target lacks the C-terminal rhodanese domain found in multifunctional MoeB/MoeZ-family fusions; this is an architecture and reaction mismatch, not merely absence of a target assay. - original_index: 2 term_id: GO:0005737 term_label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: MARK_AS_OVER_ANNOTATED action: ACCEPT outcome: changed rationale: MoeB operates with soluble MoaD in the cytoplasmic molybdenum-cofactor pathway. Cytoplasm and cytosol are compatible core localizations; redundancy does not establish over-annotation. - original_index: 3 term_id: GO:0005829 term_label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: KEEP_AS_NON_CORE action: ACCEPT outcome: changed rationale: MoeB operates with soluble MoaD in the cytoplasmic molybdenum-cofactor pathway. Cytoplasm and cytosol are compatible core localizations; redundancy does not establish over-annotation. - original_index: 4 term_id: GO:0008146 term_label: sulfotransferase activity evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: REMOVE action: REMOVE outcome: changed rationale: MoeB adenylates MoaD; sulfur loading is a separate reaction supplied by a sulfur-donor system. Sulfotransferases transfer sulfate groups; the shared sulfur-pathway context does not confer that chemistry on the MoaD adenylase. - original_index: 5 term_id: GO:0008641 term_label: ubiquitin-like modifier activating enzyme activity evidence_type: IEA original_reference_id: GO_REF:0000002 negated: false previous_action: REMOVE action: REMOVE outcome: changed rationale: The live GO:0008641 definition requires ATP-dependent formation of a high-energy thiolester bond. Q88PW3 is supported only as the enzyme that adenylates the C-terminal carboxylate of the MoaD sulfur carrier; that acyl-adenylate step does not itself perform the E1 thiolester chemistry specified by the term. - original_index: 6 term_id: GO:0016779 term_label: nucleotidyltransferase activity evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: ATP-dependent transfer of AMP to the terminal carboxylate of MoaD is catalytic nucleotidyl transfer. The specific molybdopterin-synthase adenylyltransferase term is already retained, and its broad catalytic ancestors remain correct. OpenScientist supports the classical MoeB architecture and conserved mechanism while explicitly noting that Q88PW3 has not been assayed. - original_index: 7 term_id: GO:0061605 term_label: molybdopterin-synthase adenylyltransferase activity evidence_type: IEA original_reference_id: GO_REF:0000120 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: UniProt supplies the MoaD C-terminal adenylylation reaction and EC 2.7.7.80. changes: - Restored broad catalytic and nucleotidyltransferase activities plus cytoplasm/cytosol as core. - Retained rhodanese/sulfotransferase/E1-thioester rejection based on chemistry, live GO definition and target non-fused domain architecture. - Incorporated complete existing OpenScientist mechanism, reported orthology, lack of target assay and primary PMID:11713534/17223713 comparative evidence. action_change_count: 4 evidence: existing_adjudications: - genes/PSEPK/moeB/moeB-deep-research-openscientist.md primary_references: - PMID:11713534 - PMID:17223713 notes_file: genes/PSEPK/moeB/moeB-notes.md limits: Provider findings are used with target/comparator and full-text limitations stated in the reviews; no duplicate external adjudication launched by this agent. adjudication: state: not_needed source_rows_preserved: true source_annotation_count: 8 validation: command: just validate PSEPK moeB result: passed warnings: - '⚠ [WARNING] at core_functions[0].directly_involved_in[0] : Process term GO:0006777 (Mo-molybdopterin cofactor biosynthetic process) is not reflected in existing_annotations block (Suggestion: Consider adding this term to existing_annotations with action: NEW if it''s a novel annotation)' warning_disposition: Warnings suggesting new annotations are not treated as instructions to create redundant assertions; core synthesis is retained without extra NEW rows. history_record: history/genes/PSEPK/moeB/2026-09-21T015125Z-codex-d437d1.yaml history_validation: passed new_assertion_review: added_in_this_session: 0 preexisting_retained: [] source_annotations_removed: 0 ancestor_check: QuickGO is_a/part_of check found no accepted ancestor of the three retained authored NEW terms; none introduces a redundant parent/child of an accepted existing assertion. - gene: PSEPK/pvdD gene_file: genes/PSEPK/pvdD/pvdD-ai-review.yaml status: awaiting_adjudication scope: full_gene outcome: changed annotation_count: 10 final_annotation_count: 10 annotations: - original_index: 0 term_id: GO:0003824 term_label: catalytic activity evidence_type: IEA original_reference_id: GO_REF:0000002 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: PvdD directly catalyzes amino-acid activation and peptide assembly. A broad catalytic ancestor remains valid even when a specific NRPS term is available. - original_index: 1 term_id: GO:0005737 term_label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: Pyoverdine precursor assembly occurs in the cytoplasm. Cytoplasm and cytosol are compatible; their overlap does not refute either localization. - original_index: 2 term_id: GO:0005829 term_label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: ACCEPT action: ACCEPT outcome: confirmed rationale: Cytosol is the correct localization. Falcon deep research confirms PvdD-mediated peptide assembly occurs in the cytoplasm before precursor export across the inner membrane and periplasmic maturation. - original_index: 3 term_id: GO:0009239 term_label: enterobactin biosynthetic process evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: MODIFY action: MODIFY outcome: confirmed rationale: The enterobactin process is an over-transfer error. Falcon deep research confirms PvdD is the pyoverdine NRPS in KT2440 and that a pvdD mutant does not produce pyoverdine, so the correct process is pyoverdine biosynthesis, not enterobactin. - original_index: 4 term_id: GO:0009366 term_label: enterobactin synthetase complex evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: REMOVE action: REMOVE outcome: changed rationale: The target PP_4219 genetic evidence and modular NRPS architecture establish a pyoverdine biosynthetic enzyme, not an enterobactin synthetase subunit. The shared nonribosomal assembly chemistry is insufficient for this specific complex assignment. The exact P. aeruginosa PvdL/PvdI/PvdJ/PvdD assembly composition is comparative, not established for this target. - original_index: 5 term_id: GO:0031177 term_label: phosphopantetheine binding evidence_type: IEA original_reference_id: GO_REF:0000120 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: Q88F79 contains three phosphopantetheine-bearing carrier domains. This specific cofactor-binding term is supported and need not be discarded because carrier activity describes the integrated role more fully. The carrier-activity term remains in the core synthesis. - original_index: 6 term_id: GO:0043041 term_label: amino acid activation for nonribosomal peptide biosynthetic process evidence_type: IEA original_reference_id: GO_REF:0000120 negated: false previous_action: KEEP_AS_NON_CORE action: ACCEPT outcome: changed rationale: Its adenylation domains directly activate monomers for the nonribosomal assembly reaction. A mechanistic subprocess of the defining activity is core, not incidental. - original_index: 7 term_id: GO:0044550 term_label: secondary metabolite biosynthetic process evidence_type: IEA original_reference_id: GO_REF:0000120 negated: false previous_action: MODIFY action: ACCEPT outcome: changed rationale: Pyoverdine is a secondary metabolite and PvdD directly builds its peptide scaffold. The broad process is valid; a siderophore-specific term does not contradict it. - original_index: 8 term_id: GO:0047527 term_label: 2,3-dihydroxybenzoate-serine ligase activity evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: MODIFY action: MODIFY outcome: changed rationale: The target is a pyoverdine NRPS with target PP_4219 genetic and domain support; DHB-serine ligation is the distinct enterobactin chemistry. Keep the NRPS amino-acid-ligation replacement without assigning the threonine-rich substrate map of P. aeruginosa PvdD to this three-module KT2440 protein. - original_index: 9 term_id: GO:0072330 term_label: monocarboxylic acid biosynthetic process evidence_type: IEA original_reference_id: GO_REF:0000117 negated: false previous_action: REMOVE action: UNDECIDED outcome: changed rationale: The former removal only contrasted pyoverdine with enterobactin, which does not answer whether a biosynthetic product is a monocarboxylic acid. KT2440 makes several pyoverdine variants with distinct cyclization and acyl side chains. GO:0072330 requires production of an organic acid containing one carboxyl group; the specific structures, rather than their siderophore name, must settle the claim. An independent structural check is pending. changes: - Restored catalytic activity, cytoplasm, phosphopantetheine binding, core amino-acid activation and secondary-metabolite biosynthesis. - Preserved substrate/complex-specific enterobactin corrections, removed unverified P. aeruginosa module-residue assignments from target rationale. - Changed monocarboxylic-acid biosynthesis REMOVE to UNDECIDED pending actual free-carboxyl count and ontology interpretation. - Read entire Falcon, distinguished target mutant evidence from comparator imaging/module specificity. Added primary PMID:25895945 KT2440 structures; did not misattribute new P. taiwanensis structures in PMID:28631237. action_change_count: 6 evidence: existing_adjudications: - genes/PSEPK/pvdD/pvdD-deep-research-falcon.md primary_references: - PMID:12700264 - PMID:19459056 - PMID:28631237 - PMID:31451546 - PMID:25895945 notes_file: genes/PSEPK/pvdD/pvdD-notes.md limits: Provider findings are used with target/comparator and full-text limitations stated in the reviews; no duplicate external adjudication launched by this agent. adjudication: state: requested owner: root go_terms: - GO:0072330 question: Do the actual KT2440 PVD1/2/3 structures include a monocarboxylic acid whose biosynthesis PvdD participates in? Count free carboxyls with cyclization and acyl side chains and check GO/ChEBI scope. independent_check: Root confirmed cyclic hydroxyAsp-Dab wording in PMID:31451546 and structural variants in PMID:25895945; molecular figure download challenged, so no definitive free-carboxyl count claimed. report: null source_rows_preserved: true source_annotation_count: 10 validation: command: just validate PSEPK pvdD result: passed warnings: - '⚠ [WARNING] at core_functions[0].molecular_function : Core function term GO:1904091 (non-ribosomal peptide synthetase activity) is not reflected in existing_annotations block (Suggestion: Consider adding this term to existing_annotations with action: NEW if it''s a novel annotation)' - '⚠ [WARNING] at core_functions[0].directly_involved_in[1] : Process term GO:0019290 (siderophore biosynthetic process) is not reflected in existing_annotations block (Suggestion: Consider adding this term to existing_annotations with action: NEW if it''s a novel annotation)' - '⚠ [WARNING] at core_functions[1].molecular_function : Core function term GO:0140414 (phosphopantetheine-dependent carrier activity) is not reflected in existing_annotations block (Suggestion: Consider adding this term to existing_annotations with action: NEW if it''s a novel annotation)' warning_disposition: Warnings suggesting new annotations are not treated as instructions to create redundant assertions; core synthesis is retained without extra NEW rows. history_record: history/genes/PSEPK/pvdD/2026-09-21T015127Z-codex-126cbb.yaml history_validation: passed new_assertion_review: added_in_this_session: 0 preexisting_retained: [] source_annotations_removed: 0 ancestor_check: QuickGO is_a/part_of check found no accepted ancestor of the three retained authored NEW terms; none introduces a redundant parent/child of an accepted existing assertion. - gene: METEA/mdcD gene_file: genes/METEA/mdcD/mdcD-ai-review.yaml status: reviewed scope: full_gene outcome: changed annotation_count: 9 final_annotation_count: 9 annotations: - original_index: 0 term_id: GO:0003989 term_label: acetyl-CoA carboxylase activity evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: REMOVE action: REMOVE outcome: changed rationale: The target has the MdcD-specific family assignment and neighboring mdcA/C/E genes. Its inferred reaction is decarboxylation of specialized ACP-bound malonyl substrate; it is not the ATP/biotin-dependent acetyl-CoA-to-malonyl-CoA reaction. Shared carboxyltransferase-fold ancestry does not establish retained substrate or pathway identity. - original_index: 1 term_id: GO:0006633 term_label: fatty acid biosynthetic process evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: REMOVE action: REMOVE outcome: changed rationale: MdcD acts in the malonate-degradation complex with a specialized MdcC carrier. It does not provide the malonyl-CoA-building reaction of acetyl-CoA carboxylase. The distinct substrate-carrier and target neighborhood, rather than simple absence of a native assay, argue against this inherited pathway assignment. - original_index: 2 term_id: GO:2001295 term_label: malonyl-CoA biosynthetic process evidence_type: IEA original_reference_id: GO_REF:0000118 negated: false previous_action: REMOVE action: REMOVE outcome: changed rationale: The characterized homologous complex decarboxylates malonyl groups on specialized MdcC and regenerates acetyl-MdcC. It does not synthesize malonyl-CoA. The target MdcD-specific family and mdcA/C/E neighborhood support that pathway distinction. - original_index: 3 term_id: GO:0004658 term_label: propionyl-CoA carboxylase activity evidence_type: IEA original_reference_id: GO_REF:0000003 negated: false previous_action: REMOVE action: REMOVE outcome: changed rationale: The source EC6.4.1.3 mapping conflicts with the MdcD-specific family and malonate-decarboxylase gene neighborhood. The inferred ACP-bound decarboxylation does not carboxylate propionyl-CoA to methylmalonyl-CoA. No source EC field is rewritten. - original_index: 4 term_id: GO:0005975 term_label: carbohydrate metabolic process evidence_type: IEA original_reference_id: GO_REF:0000002 negated: false previous_action: KEEP_AS_NON_CORE action: REMOVE outcome: changed rationale: The prior KEEP_AS_NON_CORE rationale cited only the possibility that acetate feeds central carbon metabolism. Malonate is a dicarboxylic acid and MdcD directly decarboxylates its ACP-bound derivative; no carbohydrate-processing step performed by MdcD is established. A downstream metabolite connection is insufficient for involvement in GO:0005975 as defined. This is a pathway-scope distinction, not rejection for breadth. - original_index: 5 term_id: GO:0016740 term_label: transferase activity evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: REMOVE action: REMOVE outcome: changed rationale: The actual MdcD-MdcE reaction releases CO2 without transferring the carboxyl group to an acceptor. MdcA supplies the separate ACP-transferase step. A homologous carboxyltransferase fold and membership in a complex containing a transferase do not confer transferase activity on MdcD. - original_index: 6 term_id: GO:0016831 term_label: carboxy-lyase activity evidence_type: IEA original_reference_id: GO_REF:0000002 negated: false previous_action: ACCEPT action: ACCEPT outcome: changed rationale: The target-specific family and gene neighborhood support MdcD identity, while primary homolog structures place decarboxylation at the MdcD-MdcE interface. A broad but correct catalytic class is appropriate; the function is executed together with MdcE. - original_index: 7 term_id: GO:0016874 term_label: ligase activity evidence_type: IEA original_reference_id: GO_REF:0000043 negated: false previous_action: REMOVE action: REMOVE outcome: changed rationale: The inferred MdcD-MdcE reaction is a biotin-independent decarboxylation, not energy-dependent joining of substrates. The target is a catalytic component of the malonate-degradation complex; related ACC/PCC ligase chemistry is not retained merely because of shared fold. - original_index: 8 term_id: GO:0090410 term_label: malonate catabolic process evidence_type: ISS original_reference_id: file:METEA/mdcD/mdcD-deep-research-falcon.md negated: false previous_action: NEW action: NEW outcome: changed rationale: The MdcD-specific family assignment and independently checked mdcA/C/D/E neighborhood in AM1 support transfer of the experimentally characterized bacterial malonate-degradation role. MdcD contributes the decarboxylation step itself, so this is participation rather than merely necessity or downstream metabolic association. The evidence remains ISS; no AM1 assay is claimed. changes: - Confirmed specific ACC/PCC/ligase/transferase and fatty-acid/malonyl-CoA mismatches against primary PMID:28757619, MdcD-specific domains and newly checked target neighboring genes. - 'Changed carbohydrate metabolism KEEP_AS_NON_CORE to REMOVE: downstream acetate assimilation does not establish carbohydrate-pathway participation by MdcD.' - Retained authored malonate-catabolism NEW as ISS with independent target mdcA/C/D/E neighborhood and primary comparator evidence; no native assay claimed. - Corrected description and core complex contribution; removed invented target 35% identity, overbroad knockout interpretation and wrong EC4.1.1.89 claim. Integrated Falcon substantive mechanism/caveats. action_change_count: 1 evidence: existing_adjudications: - genes/METEA/mdcD/mdcD-deep-research-falcon.md primary_references: - PMID:19440302 - PMID:28757619 notes_file: genes/METEA/mdcD/mdcD-notes.md limits: Provider findings are used with target/comparator and full-text limitations stated in the reviews; no duplicate external adjudication launched by this agent. adjudication: state: not_needed source_rows_preserved: true source_annotation_count: 8 validation: command: just validate METEA mdcD result: passed warnings: [] warning_disposition: Warnings suggesting new annotations are not treated as instructions to create redundant assertions; core synthesis is retained without extra NEW rows. history_record: history/genes/METEA/mdcD/2026-09-21T015128Z-codex-f256d5.yaml history_validation: passed new_assertion_review: added_in_this_session: 0 preexisting_retained: - GO:0090410 source_annotations_removed: 0 ancestor_check: QuickGO is_a/part_of check found no accepted ancestor of the three retained authored NEW terms; none introduces a redundant parent/child of an accepted existing assertion.