Ank2 (Ankyrin 2) is the neuronal ankyrin of Drosophila. The locus encodes many products, from short ankyrin-repeat proteins to the giant Ank2-L and Ank2-XL isoforms. The giant isoforms are membrane-cytoskeleton adaptors in motoneuron axons and presynaptic terminals: they link the L1-family adhesion molecule Neuroglian to the spectrin cytoskeleton and, through their extended C-terminal regions, bind and organise presynaptic microtubules, which maintains neuromuscular junction stability. The product described here, Ank2-PE (697 aa), consists of an isoform-specific histidine-rich N terminus followed by the first 13 of the ankyrin repeats shared with the giant isoforms and a short unique C-terminal tail. It has none of the giant-isoform sequence beyond the N-terminal part of the repeat domain. It has been detected at the plasma membrane by organelle proteomics, but its own binding partners and neuronal role have not been determined.
IMP PMID:18439405 A presynaptic giant ankyrin stabilizes the NMJ through regul...
MARK AS OVER ANNOTATED
Summary: True of the Ank2 gene (giant isoforms), but an over-annotation of the 697-residue Ank2-PE product, which lacks the microtubule-binding region.
Reason: Ank2 mutants show disorganised presynaptic microtubules, and Pielage et al. 2008 map the stabilising and microtubule-organising activity of Ank2-L to its extended C-terminal domain, which binds synaptic microtubules directly. The annotation is a gene-level FlyBase assertion carried on every Ank2 product accession. Q3KN55 contains only giant-isoform residues 9-517 (13 of the 21 ANK repeats) and nothing C-terminal to them, so it lacks the region to which this activity has been mapped. The claim is correct for the locus and should be kept on the canonical/giant products, but attributing microtubule cytoskeleton organisation to this short product over-annotates it. This is not a statement that the curator chose the wrong gene.
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.
MARK AS OVER ANNOTATED
Summary: True of the Ank2 gene (giant isoforms), but an over-annotation of the 697-residue Ank2-PE product, which lacks the microtubule-binding region.
Reason: Ank2 mutants show disorganised presynaptic microtubules, and Pielage et al. 2008 map the stabilising and microtubule-organising activity of Ank2-L to its extended C-terminal domain, which binds synaptic microtubules directly. The annotation is a gene-level FlyBase assertion carried on every Ank2 product accession. Q3KN55 contains only giant-isoform residues 9-517 (13 of the 21 ANK repeats) and nothing C-terminal to them, so it lacks the region to which this activity has been mapped. The claim is correct for the locus and should be kept on the canonical/giant products, but attributing microtubule cytoskeleton organisation to this short product over-annotates it. This is not a statement that the curator chose the wrong gene.
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.
IPI PMID:37061542 Next-generation large-scale binary protein interaction netwo...
REMOVE
Summary: Generic protein binding (Tramtrack, from a large-scale binary interaction screen) is uninformative.
Reason: The IPI row records a binary interaction with the transcriptional repressor Tramtrack (P17789) from the genome-scale Drosophila yeast two-hybrid network; UniProt/IntAct record four experiments for Q3KN55. Under the protein-binding policy the bare GO:0005515 term is removed because it carries no functional information. Removal does not mean the interaction was not observed. No more specific molecular function can be derived from it: a cytoplasmic membrane-associated ankyrin-repeat product and a nuclear BTB-zinc-finger repressor have no established shared process.
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. Re-review (2026-10-20): the LOPIT assignment is a FlyBase gene-level row on every Ank2 accession; Q3KN55 retains the N-terminal 13 ANK repeats shared with the membrane-associated giant isoforms, so a cytoplasmic-face plasma-membrane location is compatible with its sequence, and the broad term is as precise as the proteomic evidence allows.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
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.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
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.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
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.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
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.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
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.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
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.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
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.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
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. Re-review (2026-10-20): FlyBase makes this annotation to the Ank2 gene and UniProt/GOA carry it on every Ank2 product accession (the same row is on the canonical M9MRX4 and on Ank2-L Q7KU92), so it is a gene-level claim that is not in doubt for the locus. Q3KN55 shares only giant-isoform residues 9-517 (13 of 21 ANK repeats) and no experiment identifies the short PE product, so its own participation stays UNDECIDED; the gene-level claim belongs on the canonical-product review.
Residues 159-667 of Q3KN55 are identical to residues 9-517 of both the UniProt gene-centric canonical Ank2 product M9MRX4
file:DROME/Ank2/Ank2-deep-research-falcon.md
Assignment to the specific Q3KN55/RE55168p sequence is less certain because the accession was not used to identify experimental constructs in the retrieved papers.
GO:1900074 negative regulation of neuromuscular synaptic transmission
IMP PMID:22153373 Glial-derived prodegenerative signaling in the Drosophila ne...
REMOVE
Summary: Contradicted by the cited full text: loss of ank2 lowers evoked EPSPs, secondary to NMJ degeneration.
Reason: The full text of Keller et al. 2011 is available. It reports that ank2 mutants have reduced average EPSP amplitudes and attributes the reduction to the severe degeneration of the presynaptic terminal in these mutants, which eiger loss suppresses. A loss-of-function decrease in transmission is the opposite of what "negative regulation of neuromuscular synaptic transmission" asserts, and the effect is an indirect consequence of terminal loss rather than regulation of transmission. A sign-corrected replacement (positive regulation) is not proposed, because the reduced transmission follows from degeneration, which the neuron cellular homeostasis row already covers. The same gene-level row is on every Ank2 product accession; the problem is the claim itself, not the isoform.
The occurrence of severely degenerated NMJs in ank2 mutants (Figures 2E and 2F) correlates well with the number of recordings that show large defects in EPSP amplitude compared to wild-type
Core Functions
Short Ank2-PE product made of an isoform-specific N terminus and the N-terminal 13 ankyrin repeats shared with the giant Ank2 membrane-cytoskeleton adaptors; associated with the plasma membrane by organelle proteomics. No molecular function has been established for this product, and it lacks the giant-isoform regions responsible for microtubule organisation and synapse stabilisation.
Here, we apply LOPIT, a mass-spectrometry based technique that simultaneously maps proteins to specific subcellular compartments, to Drosophila embryos.
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?
Suggested Experiments
Experiment: Express epitope-tagged Ank2-PE in motoneurons of ank2 mutants and test its localisation (axon, presynaptic membrane, soma) and binding to Neuroglian, and whether it rescues any ank2 phenotype; complement with isoform-specific CRISPR deletion of the PE first exon.
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. Extracellular localization is refuted for this product, which has no signal peptide. Exocytosis remains unverified for this exact isoform; gene-level synaptic evidence and donor labels cannot resolve it.
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, and a PubMed search of Drosophila Ank2 found no exocytosis or secretion study, so neither correctness nor biological refutation is justified. The term is absent from the GOA of both Q3KN55 and the sibling Ank2 product M9MRX4.
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: Residence in the extracellular region requires a route out of the cell, normally an N-terminal signal peptide, and the 697-residue Ank2-PE product scored here has none. Its N terminus begins MAQFVTHIQPTLMEASQGHVPHHH and continues as a histidine-rich, disordered, low-complexity segment (MobiDB-lite disordered region 17-112) with no hydrophobic core, and the record carries no signal peptide or transmembrane feature. Q3KN55 consists of that unique N terminus, the first 13 ankyrin repeats shared with the giant isoforms, and a short tail, none of which supplies a secretion signal. The model's donor is the secreted spider toxin Q9XZC0, whose compartment cannot be transferred through shared ankyrin repeats. Characterized Ank2 isoforms are intracellular membrane-cytoskeleton adaptors, and the Ank2 ankyrin-repeat domain that Ank2-PE retains is described as part of an intracellular linker to transmembrane partners. Neither Q3KN55 nor the sibling Ank2 product M9MRX4 carries an extracellular term in GOA.
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."
PMID:31475145: "The positioning and stability of CAMs at the plasma membrane is coordinated by intracellular linker molecules like Ankyrins that provide an association to the cellular cytoskeleton"
Ankyrin 2 (Ank2) encodes a cytoskeletal binding protein required for proper function of the product of &bgr;-Spec via direct interaction. It contributes to the regulation of short-term memory, sound perception, microtubule cytoskeleton and neuromuscular junction development and synapsis.