id: Q3KN55 gene_symbol: Ank2 taxon: id: NCBITaxon:7227 label: Drosophila melanogaster status: COMPLETE description: The selected protein is the short neuronal Ank2-PE isoform. Toxin activity is contradicted by its cellular ankyrin identity and the distinct multidomain mechanism of the indicated latrotoxin donor. Exocytosis and extracellular localization remain unverified for this exact isoform; gene-level synaptic evidence and donor labels cannot resolve either claim. source_documents: - genes/DROME/Ank2/Ank2-protnlm-source.json - genes/DROME/Ank2/Ank2-uniprot.txt - genes/DROME/Ank2/Ank2-PE-flybase-source.txt - genes/DROME/Ank2/Q9XZC0-uniprot-source.txt - genes/DROME/Ank2/P16157-uniprot-source.txt predictions: - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 source_reference_id: file:DROME/Ank2/Ank2-protnlm-source.json predicted_term: id: GO:0090729 label: toxin activity predicted_term_type: GO_MF review: assessment: NPI error_type: DOMAIN_ARCHITECTURE_MISMATCH confidence_score: 0 summary: Q3KN55 is the native short Ank2-PE product of the Drosophila neuronal ankyrin locus, not a latrotoxin. The prediction metadata identify alpha-latrocrustotoxin Q9XZC0 as the phmmer donor (model score 0.49; phmmer score 293.2). The experimentally determined latrotoxin structure requires a central membrane-insertion domain in addition to ankyrin-like repeats; generic repeat similarity does not transfer its evolved inter-organism toxic function to the fly cellular ankyrin. The target record instead shows a low-complexity N terminus and ankyrin repeats, with no evidence for the toxin-specific architecture or venom role. This is a biologically incompatible functional transfer, not a demonstrated paralog relationship or a FlyBase annotation error. No equivalent toxin term occurs in the target GOA. supported_by: - reference_id: file:DROME/Ank2/Ank2-uniprot.txt supporting_text: ID Q3KN55_DROME Unreviewed; 697 AA. - reference_id: file:DROME/Ank2/Ank2-PE-flybase-source.txt supporting_text: CG42734-PE - reference_id: PMID:34845192 supporting_text: A C-terminal domain of ankyrin-like repeats shields a central membrane insertion domain of six parallel α-helices. - reference_id: file:DROME/Ank2/Ank2-uniprot.txt supporting_text: FT REGION 17..112 - reference_id: file:DROME/Ank2/Ank2-uniprot.txt supporting_text: FT REPEAT 193..225 - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 source_reference_id: file:DROME/Ank2/Ank2-protnlm-source.json predicted_term: id: GO:0006887 label: exocytosis predicted_term_type: GO_BP review: assessment: UNC confidence_score: 1 summary: Ank2-dependent synaptic stability and neurotransmission make a role in vesicle release conceivable, but they do not establish exocytosis by the exact 697-residue Ank2-PE isoform. The principal experiments characterize giant Ank2 isoforms and their extended C-terminal microtubule-organizing region. The API metadata indicate human ankyrin-1 P16157 as the donor for this claim (model score 0.53; phmmer score 889.4), rather than the latrotoxin donor used for the toxin claim. Donor exocytosis annotation and synaptic phenotypes are insufficient to resolve transfer across these distinct proteins and isoforms. An Ank2-PE-specific secretion assay or supported interaction with the vesicle-fusion apparatus is missing, so neither correctness nor biological refutation is justified; the term is absent from target GOA. supported_by: - reference_id: file:DROME/Ank2/Ank2-uniprot.txt supporting_text: ID Q3KN55_DROME Unreviewed; 697 AA. - reference_id: file:DROME/Ank2/Ank2-PE-flybase-source.txt supporting_text: CG42734-PE - reference_id: PMID:18439405 supporting_text: The stabilizing functions of Ank2-L can be mapped to the extended C-terminal domain that we demonstrate can directly bind and organize synaptic microtubules. - reference_id: PMID:22153373 supporting_text: Next, we confirmed that the loss of ank2 results in impaired average EPSP amplitudes - reference_id: file:DROME/Ank2/P16157-uniprot-source.txt supporting_text: DR GO; GO:0006887; P:exocytosis; NAS:UniProtKB. - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 source_reference_id: file:DROME/Ank2/Ank2-protnlm-source.json predicted_term: id: GO:0005576 label: extracellular region predicted_term_type: GO_CC review: assessment: UNC confidence_score: 1 summary: The cellular ankyrin identity and intracellular scaffold biology of characterized Ank2 isoforms argue against a secreted extracellular protein. The model instead points to the secreted spider toxin Q9XZC0 (model score 0.54; phmmer score 293.2); its compartment cannot be transferred through shared ankyrin repeats. However, the available localization studies concern giant Ank2 isoforms or an unresolved proteomics protein group, and the 697-residue Ank2-PE product lacks direct isoform-specific localization data. The sequence record has no annotated signal peptide, but absence of a signal annotation alone is not a complete localization test. Extracellular residence therefore remains unsupported rather than experimentally refuted for this exact product; no equivalent target GOA term exists. supported_by: - reference_id: file:DROME/Ank2/Ank2-uniprot.txt supporting_text: ID Q3KN55_DROME Unreviewed; 697 AA. - reference_id: file:DROME/Ank2/Ank2-PE-flybase-source.txt supporting_text: CG42734-PE - reference_id: PMID:18439406 supporting_text: we recovered mutations in Drosophila ankyrin 2 (ank2) affecting two giant Ank2 isoforms that are specifically expressed in the nervous system and associate with the presynaptic membrane cytoskeleton. - reference_id: file:DROME/Ank2/Q9XZC0-uniprot-source.txt supporting_text: 'CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:10234443}. Target' references: - id: PMID:18439405 title: A presynaptic giant ankyrin stabilizes the NMJ through regulation of presynaptic microtubules and transsynaptic cell adhesion. full_text_unavailable: true - id: PMID:18439406 title: Drosophila ankyrin 2 is required for synaptic stability. full_text_unavailable: true - id: PMID:22153373 title: Glial-derived prodegenerative signaling in the Drosophila neuromuscular system. full_text_unavailable: false - id: PMID:34845192 title: Molecular architecture of black widow spider neurotoxins. - id: file:DROME/Ank2/Ank2-PE-flybase-source.txt title: 'FlyBase FBpp0292239: Dmel Ank2-PE polypeptide report' - id: file:DROME/Ank2/Ank2-protnlm-source.json title: ProtNLM2 original Q3KN55 prediction and evidence metadata - id: file:DROME/Ank2/Ank2-uniprot.txt title: 'UniProtKB Q3KN55: 697-residue Ank2-PE sequence and features' - id: file:DROME/Ank2/P16157-uniprot-source.txt title: 'UniProtKB P16157: human ankyrin-1 donor' - id: file:DROME/Ank2/Q9XZC0-uniprot-source.txt title: 'UniProtKB Q9XZC0: alpha-latrocrustotoxin donor'