Ank2 encodes a diverse set of neuronal ankyrin proteins. Its giant isoforms stabilize presynaptic terminals by organizing the membrane-associated cytoskeleton and synaptic microtubules. Q3KN55 corresponds specifically to the 697-residue Ank2-PE isoform, with a low-complexity N terminus followed by ankyrin repeats. It does not contain the extended C-terminal region responsible for the well-characterized microtubule-organizing activity of Ank2-L. The physiological partners, localization and independent role of this short isoform remain incompletely established.
IMP PMID:18439405 A presynaptic giant ankyrin stabilizes the NMJ through regul...
UNDECIDED
Summary: Microtubule cytoskeleton organization is not resolved for the short Ank2-PE isoform.
Reason: Q3KN55 is the 697-residue Ank2-PE polypeptide, whereas the decisive synaptic studies characterize giant Ank2 isoforms. The gene-level experimental annotation is credible, but the available evidence does not establish that this short product independently executes the same role. This is an unresolved isoform transfer, not evidence that the FlyBase curator annotated the wrong gene. The paper explicitly maps stabilization and microtubule organization to the extended C terminus of Ank2-L, absent from the selected ankyrin-repeat-only architecture; full text is unavailable in the publication cache, so additional experiments on Ank2-PE cannot be excluded.
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.
IMP PMID:18439406 Drosophila ankyrin 2 is required for synaptic stability.
UNDECIDED
Summary: Microtubule cytoskeleton organization is not resolved for the short Ank2-PE isoform.
Reason: Q3KN55 is the 697-residue Ank2-PE polypeptide, whereas the decisive synaptic studies characterize giant Ank2 isoforms. The gene-level experimental annotation is credible, but the available evidence does not establish that this short product independently executes the same role. This is an unresolved isoform transfer, not evidence that the FlyBase curator annotated the wrong gene. The accessible abstract specifies two giant isoforms. Their localization to the presynaptic membrane cytoskeleton supports the gene-level biology; it does not resolve localization of Ank2-PE, and the full text was not accessible.
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.
IPI PMID:37061542 Next-generation large-scale binary protein interaction netwo...
KEEP AS NON CORE
Summary: A binary interaction with Tramtrack is recorded, without an established physiological activity.
Reason: The IPI annotation and UniProt IntAct record identify binding to Tramtrack (P17789), with four experiments recorded for Q3KN55. Retain the measured interaction as non-core; generic protein binding neither establishes an evolved molecular function nor justifies a transcriptional or synaptic role for this isoform. The large-scale interaction paper provides assay context, but its main text does not identify the Ank2 construct, so the exact ORF remains a follow-up question.
HDA PMID:19317464 Mapping organelle proteins and protein complexes in Drosophi...
ACCEPT
Summary: Retain the experimental plasma-membrane association.
Reason: The HDA row records plasma-membrane association from LOPIT proteomics in Drosophila embryos. This broad location is compatible with the retained ankyrin-repeat interaction module and the membrane-associated cellular ankyrin family; it does not require the giant isoformsβ extended microtubule-binding tail. Defer to the curated experimental protein assignment rather than reject a plausible observation because the cached abstract lacks the peptide table. Isoform-discriminating peptides remain worth checking, and this membrane association does not establish secretion, extracellular exposure or localization to a particular presynaptic nanodomain.
Here, we apply LOPIT, a mass-spectrometry based technique that simultaneously maps proteins to specific subcellular compartments, to Drosophila embryos.
IMP PMID:18439405 A presynaptic giant ankyrin stabilizes the NMJ through regul...
UNDECIDED
Summary: Neuromuscular junction development is not resolved for the short Ank2-PE isoform.
Reason: Q3KN55 is the 697-residue Ank2-PE polypeptide, whereas the decisive synaptic studies characterize giant Ank2 isoforms. The gene-level experimental annotation is credible, but the available evidence does not establish that this short product independently executes the same role. This is an unresolved isoform transfer, not evidence that the FlyBase curator annotated the wrong gene. The paper explicitly maps stabilization and microtubule organization to the extended C terminus of Ank2-L, absent from the selected ankyrin-repeat-only architecture; full text is unavailable in the publication cache, so additional experiments on Ank2-PE cannot be excluded.
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.
IMP PMID:18439406 Drosophila ankyrin 2 is required for synaptic stability.
UNDECIDED
Summary: Neuromuscular junction development is not resolved for the short Ank2-PE isoform.
Reason: Q3KN55 is the 697-residue Ank2-PE polypeptide, whereas the decisive synaptic studies characterize giant Ank2 isoforms. The gene-level experimental annotation is credible, but the available evidence does not establish that this short product independently executes the same role. This is an unresolved isoform transfer, not evidence that the FlyBase curator annotated the wrong gene. The accessible abstract specifies two giant isoforms. Their localization to the presynaptic membrane cytoskeleton supports the gene-level biology; it does not resolve localization of Ank2-PE, and the full text was not accessible.
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.
IMP PMID:22939627 Drosophila auditory organ genes and genetic hearing defects.
UNDECIDED
Summary: Sensory perception of sound is not resolved for the short Ank2-PE isoform.
Reason: The FlyBase IMP annotation places Ank2 in auditory function, consistent with a neuronal cytoskeletal protein. The accessible abstract reports a broad hearing screen without resolving Ank2 isoforms or identifying the Ank2 perturbation. Full-text and supplementary allele/construct information are needed to assess this exact short product; the absence of Ank2 from the abstract is not evidence against the curator.
IMP PMID:23390136 Homozygous and heterozygous disruptions of ANK3: at the cros...
UNDECIDED
Summary: Short-term memory is not resolved for the short Ank2-PE isoform.
Reason: The study explicitly includes a Drosophila knockdown model despite its human ANK3-focused title, so the annotation is not dismissed as a species or gene-name mistake. Memory effects support an Ank2 gene-level neuronal phenotype. The accessible abstract does not resolve the depleted isoforms; the effect on the 697-residue Ank2-PE product requires the full construct/isoform evidence.
IDA PMID:18439406 Drosophila ankyrin 2 is required for synaptic stability.
UNDECIDED
Summary: Neuromuscular junction is not resolved for the short Ank2-PE isoform.
Reason: Q3KN55 is the 697-residue Ank2-PE polypeptide, whereas the decisive synaptic studies characterize giant Ank2 isoforms. The gene-level experimental annotation is credible, but the available evidence does not establish that this short product independently executes the same role. This is an unresolved isoform transfer, not evidence that the FlyBase curator annotated the wrong gene. The accessible abstract specifies two giant isoforms. Their localization to the presynaptic membrane cytoskeleton supports the gene-level biology; it does not resolve localization of Ank2-PE, and the full text was not accessible. Full-text domain-deletion experiments in PMID:31475145 show that presynaptic targeting depends on specific ankyrin-repeat subdomains, so a generic repeat match does not alone resolve this fine localization for the short product.
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.
IDA PMID:18439406 Drosophila ankyrin 2 is required for synaptic stability.
UNDECIDED
Summary: Presynaptic periactive zone is not resolved for the short Ank2-PE isoform.
Reason: Q3KN55 is the 697-residue Ank2-PE polypeptide, whereas the decisive synaptic studies characterize giant Ank2 isoforms. The gene-level experimental annotation is credible, but the available evidence does not establish that this short product independently executes the same role. This is an unresolved isoform transfer, not evidence that the FlyBase curator annotated the wrong gene. The accessible abstract specifies two giant isoforms. Their localization to the presynaptic membrane cytoskeleton supports the gene-level biology; it does not resolve localization of Ank2-PE, and the full text was not accessible. Full-text domain-deletion experiments in PMID:31475145 show that presynaptic targeting depends on specific ankyrin-repeat subdomains, so a generic repeat match does not alone resolve this fine localization for the short product.
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.
IDA PMID:18439405 A presynaptic giant ankyrin stabilizes the NMJ through regul...
UNDECIDED
Summary: Presynaptic membrane is not resolved for the short Ank2-PE isoform.
Reason: Q3KN55 is the 697-residue Ank2-PE polypeptide, whereas the decisive synaptic studies characterize giant Ank2 isoforms. The gene-level experimental annotation is credible, but the available evidence does not establish that this short product independently executes the same role. This is an unresolved isoform transfer, not evidence that the FlyBase curator annotated the wrong gene. The paper explicitly maps stabilization and microtubule organization to the extended C terminus of Ank2-L, absent from the selected ankyrin-repeat-only architecture; full text is unavailable in the publication cache, so additional experiments on Ank2-PE cannot be excluded. Full-text domain-deletion experiments in PMID:31475145 show that presynaptic targeting depends on specific ankyrin-repeat subdomains, so a generic repeat match does not alone resolve this fine localization for the short product.
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.
IDA PMID:18439406 Drosophila ankyrin 2 is required for synaptic stability.
UNDECIDED
Summary: Presynaptic membrane is not resolved for the short Ank2-PE isoform.
Reason: Q3KN55 is the 697-residue Ank2-PE polypeptide, whereas the decisive synaptic studies characterize giant Ank2 isoforms. The gene-level experimental annotation is credible, but the available evidence does not establish that this short product independently executes the same role. This is an unresolved isoform transfer, not evidence that the FlyBase curator annotated the wrong gene. The accessible abstract specifies two giant isoforms. Their localization to the presynaptic membrane cytoskeleton supports the gene-level biology; it does not resolve localization of Ank2-PE, and the full text was not accessible. Full-text domain-deletion experiments in PMID:31475145 show that presynaptic targeting depends on specific ankyrin-repeat subdomains, so a generic repeat match does not alone resolve this fine localization for the short product.
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.
IDA PMID:18439405 A presynaptic giant ankyrin stabilizes the NMJ through regul...
UNDECIDED
Summary: Terminal bouton is not resolved for the short Ank2-PE isoform.
Reason: Q3KN55 is the 697-residue Ank2-PE polypeptide, whereas the decisive synaptic studies characterize giant Ank2 isoforms. The gene-level experimental annotation is credible, but the available evidence does not establish that this short product independently executes the same role. This is an unresolved isoform transfer, not evidence that the FlyBase curator annotated the wrong gene. The paper explicitly maps stabilization and microtubule organization to the extended C terminus of Ank2-L, absent from the selected ankyrin-repeat-only architecture; full text is unavailable in the publication cache, so additional experiments on Ank2-PE cannot be excluded. Full-text domain-deletion experiments in PMID:31475145 show that presynaptic targeting depends on specific ankyrin-repeat subdomains, so a generic repeat match does not alone resolve this fine localization for the short product.
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.
We show that specific subdomains control synaptic but not axonal localization of Ank2-L.
GO:0045887 positive regulation of synaptic assembly at neuromuscular junction
IMP PMID:23390136 Homozygous and heterozygous disruptions of ANK3: at the cros...
UNDECIDED
Summary: Positive regulation of synaptic assembly at neuromuscular junction is not resolved for the short Ank2-PE isoform.
Reason: The study explicitly includes a Drosophila knockdown model despite its human ANK3-focused title, so the annotation is not dismissed as a species or gene-name mistake. Memory effects support an Ank2 gene-level neuronal phenotype. The accessible abstract does not resolve the depleted isoforms or the neuromuscular-junction synapse-assembly assay; the effect on the 697-residue Ank2-PE product requires the full construct/isoform evidence.
IMP PMID:16920632 Control of axonal sprouting and dendrite branching by the Nr...
UNDECIDED
Summary: Axon extension is not resolved for the short Ank2-PE isoform.
Reason: The paper reports an intracellular Nrg-Ank mechanism in neuronal morphogenesis and suppression of abnormal axonal sprouting. The cached abstract does not resolve the Ank construct or distinguish the short Ank2-PE protein from other ankyrins. The full text is needed before judging the GOA axon-extension assertion for this product; no wrong-gene or wrong-paralog claim follows from this limited access.
IGI PMID:22153373 Glial-derived prodegenerative signaling in the Drosophila ne...
UNDECIDED
Summary: Neuron cellular homeostasis is not resolved for the short Ank2-PE isoform.
Reason: The full-text study directly tests ank2 mutants and shows severe NMJ degeneration with genetic suppression by eiger loss, supporting the neuronal-homeostasis role of the Ank2 locus. It uses the ank2^2001 mutant from the giant-Ank2 study rather than a selective perturbation of Ank2-PE. The gene-level interaction therefore does not settle the contribution of the selected short isoform.
As reported previously, mutations in ank2 cause severe NMJ degeneration leading to complete elimination of the presynaptic nerve terminal at many NMJs
GO:1900074 negative regulation of neuromuscular synaptic transmission
IMP PMID:22153373 Glial-derived prodegenerative signaling in the Drosophila ne...
UNDECIDED
Summary: Negative regulation of neuromuscular synaptic transmission is not resolved for the short Ank2-PE isoform.
Reason: The full text shows reduced evoked EPSP amplitudes after ank2 loss and recovery when eiger is also removed. This supports maintenance of synaptic integrity and transmission, but does not by itself establish an evolved function of negatively regulating transmission. The genetic background and short-isoform contribution also remain unresolved. The physiological direction and annotation rationale require closer curator/figure-level review before retaining this negative-regulation term as core or proposing removal.
Q: Which localization, interaction and neuronal phenotypes have been measured specifically for Ank2-PE (Q3KN55; FBpp0292239), rather than the giant Ank2 isoforms?
Q: Do the LOPIT peptides and the Tramtrack interaction-screen ORF distinguish the 697-residue Ank2-PE product from other Ank2 proteins?
Q: What evidence supports the negative direction of the neuromuscular-transmission annotation in the ank2/eiger experiment?
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
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.
Review rationale: 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.
Review rationale: 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.
PMID:18439405: "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."
PMID:22153373: "Next, we confirmed that the loss of ank2 results in impaired average EPSP amplitudes"
Review rationale: 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.
PMID:18439406: "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."