Cadmus (cdm; also Imp13, CG7212) is the Drosophila importin-13, a 971-residue member of the importin-beta (karyopherin-beta) superfamily built from HEAT repeats with an N-terminal importin-beta/Ran-binding region. It is a bidirectional nucleocytoplasmic transport receptor: it binds cargo in the cytoplasm and carries it through nuclear pores, with RanGTP binding in the nucleus releasing import cargo. In Drosophila it forms a ring-like structure that encircles the exon junction complex core heterodimer Mago-Y14 for nuclear import; by orthology with vertebrate importin-13 it is also expected to export selected proteins such as eIF1A. The tagged protein is found in and around nuclei of neurons and muscles. Cadmus is essential for viability, and mutants show defective photoreceptor responses and, at the larval neuromuscular junction, a muscle-dependent homeostatic increase in presynaptic transmitter release.
Existing Annotations Review
GO Term
Evidence
Action
Reason
GO:0005049 nuclear export signal receptor activity
IBA GO_REF:0000033
ACCEPT
Summary: Importin-13 subfamily receptor that also carries export cargo; inherited via PANTHER SF33 / PAINT.
Reason: Cadmus is in PANTHER subfamily PTHR12363:SF33 (IMPORTIN-13) together with human IPO13, which exports eIF1A from the nucleus in a RanGTP-coupled manner; the PAINT node PTN000270925 places this activity on the importin-13 lineage. There is no Drosophila-specific export assay, so the claim rests on subfamily inheritance rather than a fly experiment. The PTHR12363 family review records the family-wide distribution of this term as unresolved because the transportin-3 branch differs, but the fly protein sits in the importin-13 branch with the experimentally characterised exporter. Accepted as part of the bidirectional transport receptor function; note that Imp13 export is atypical (eIF1A binding is only indirectly Ran-regulated), so the term should be read as export receptor activity rather than leucine-rich NES recognition.
Summary: Cadmus is detected in and around neuronal and muscle nuclei, consistent with its nucleocytoplasmic shuttling cycle.
Reason: A tagged rescuing genomic construct shows Imp13 in and around nuclei (perinuclear in larval brain, nuclear in muscle). The nuclear site of RanGTP-triggered Mago-Y14 release (structural work) makes nucleus a genuine site of action for an import receptor. All three rows (IEA, two NAS) assert the same claim and are accepted consistently.
NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle.
ACCEPT
Summary: Cadmus is detected in and around neuronal and muscle nuclei, consistent with its nucleocytoplasmic shuttling cycle.
Reason: A tagged rescuing genomic construct shows Imp13 in and around nuclei (perinuclear in larval brain, nuclear in muscle). The nuclear site of RanGTP-triggered Mago-Y14 release (structural work) makes nucleus a genuine site of action for an import receptor. All three rows (IEA, two NAS) assert the same claim and are accepted consistently.
NAS PMID:20122403 Nuclear import mechanism of the EJC component Mago-Y14 revea...
ACCEPT
Summary: Cadmus is detected in and around neuronal and muscle nuclei, consistent with its nucleocytoplasmic shuttling cycle.
Reason: A tagged rescuing genomic construct shows Imp13 in and around nuclei (perinuclear in larval brain, nuclear in muscle). The nuclear site of RanGTP-triggered Mago-Y14 release (structural work) makes nucleus a genuine site of action for an import receptor. All three rows (IEA, two NAS) assert the same claim and are accepted consistently.
Summary: Pore/envelope-associated transit of a shuttling karyopherin; perinuclear localization observed in fly.
Reason: Karyopherins of the importin-beta superfamily act at the nuclear envelope while translocating through nuclear pore complexes; the PAINT assignment to the importin-13 node is consistent with the perinuclear signal seen for the fly genomic-tagged protein. It is not an integral envelope membrane protein, but is_active_in nuclear envelope is the conventional location for these receptors.
Summary: Cadmus imports the Mago-Y14 heterodimer into the nucleus.
Reason: The Drosophila Imp13-Mago-Y14 crystal structure directly demonstrates fly Imp13 as an import receptor for an EJC cargo, and the human ortholog in the same PANTHER subfamily imports UBC9 and Y14. Protein import into nucleus is the core process. IBA and IEA rows assert the same claim and are accepted together.
The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface.
Summary: Cadmus imports the Mago-Y14 heterodimer into the nucleus.
Reason: The Drosophila Imp13-Mago-Y14 crystal structure directly demonstrates fly Imp13 as an import receptor for an EJC cargo, and the human ortholog in the same PANTHER subfamily imports UBC9 and Y14. Protein import into nucleus is the core process. IBA and IEA rows assert the same claim and are accepted together.
The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface.
Summary: Correct but general; the specific processes are protein import into and export from the nucleus.
Reason: Intracellular protein transport is true but uninformative for a karyopherin. The InterPro importin-beta N-terminal domain mapping is refined by the fly structural evidence for nuclear import of Mago-Y14 and by importin-13 subfamily export of eIF1A. Both specific descendants are listed, matching terms the review already carries.
The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface.
IMP PMID:14504225 A genetic screen for synaptic transmission mutants mapping t...
KEEP AS NON CORE
Summary: Mutant ERG transmission defects are a supported but indirect consequence of loss of a nuclear transport receptor.
Reason: Clonal loss of cdm/imp13 abolishes ERG on/off transients and genomic rescue restores them, so the genetic requirement is solid. However the photoreceptors also have reduced phototransduction responses, indicating broad cellular dysfunction rather than a direct role in the transmission machinery. The source screen is abstract-only here, so the curated IMP is retained as non-core rather than downgraded further.
Summary: Ran (small GTPase) binding drives cargo release in the importin-13 cycle.
Reason: The human IPO13-RanGTP structure (same PANTHER subfamily as fly Cadmus) shows RanGTP displaces Mago-Y14 by steric hindrance; RanGTP binding is the defining regulatory interaction of importin-beta family receptors. The more specific Ran GTPase binding term has been merged into this term, so it is already as specific as GO allows.
IMP PMID:14504225 A genetic screen for synaptic transmission mutants mapping t...
KEEP AS NON CORE
Summary: Phototaxis defect is an organismal consequence of photoreceptor dysfunction in mutants.
Reason: The behavioural screen phenotype is supported by the later demonstration that imp13 is required in photoreceptors for phototransduction and transmission. A nuclear transport receptor does not perform any step of phototaxis; this is a downstream organismal phenotype, kept as non-core because the curated source (abstract-only in cache) cannot be fully inspected.
every aspect of the eye phenotype is rescued by the genomic transgene
GO:0042564 NLS-dependent protein nuclear import complex
IPI PMID:20122403 Nuclear import mechanism of the EJC component Mago-Y14 revea...
ACCEPT
Summary: Cadmus forms a nuclear import complex with its cargo Mago-Y14.
Reason: The Drosophila Imp13-Mago-Y14 complex was crystallised, directly establishing a receptor-cargo import complex. Mago-Y14 is recognised via a folded surface rather than a classical linear NLS, but GO uses this complex term for importin-cargo import complexes generally. IPI and NAS rows are accepted consistently.
The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface.
GO:0042564 NLS-dependent protein nuclear import complex
NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle.
ACCEPT
Summary: Cadmus forms a nuclear import complex with its cargo Mago-Y14.
Reason: The Drosophila Imp13-Mago-Y14 complex was crystallised, directly establishing a receptor-cargo import complex. Mago-Y14 is recognised via a folded surface rather than a classical linear NLS, but GO uses this complex term for importin-cargo import complexes generally. IPI and NAS rows are accepted consistently.
The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface.
GO:0043243 positive regulation of protein-containing complex disassembly
NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle.
MARK AS OVER ANNOTATED
Summary: Cargo release is disassembly of Cadmus's own transport complex, triggered by RanGTP, not regulation of disassembly of other complexes.
Reason: The NAS derives from a general review of the import cycle (abstract-only). In the importin-13 cycle RanGTP binding releases Mago-Y14 by steric hindrance, and eIF1A release in the cytoplasm is triggered by import-cargo loading; in both cases the receptor is a component of the complex being dismantled, with Ran or the competing cargo as the effector. Describing the receptor as positively regulating complex disassembly over-reads this mechanism, and there is no evidence that Cadmus disassembles the EJC on mRNA.
Summary: Inferred from a process annotation; the rescuing tagged protein is nuclear in muscle and not at the synapse.
Reason: This IEA is a logical transfer from neuron-neuron synaptic transmission. The functional genomic-tagged protein is detected in muscle nuclei but not at the NMJ; synaptic signal appears only on overexpression. The location is therefore not supported at endogenous levels.
Imp13 expression only in the muscle nuclei but not at the synapse
GO:0050804 modulation of chemical synaptic transmission
IMP PMID:19403829 Importin 13 regulates neurotransmitter release at the Drosop...
MARK AS OVER ANNOTATED
Summary: The NMJ release phenotype is a homeostatic response to muscle defects, which the authors describe as indirect.
Reason: In imp13 mutants quantal content is increased at low Ca2+, and muscle (not neuronal) expression rescues it; the authors conclude the increased release is a synaptic homeostatic response to muscular defects and that imp13 "might be indirectly linked" to homeostasis. A nuclear transport receptor acting in muscle does not itself modulate chemical synaptic transmission; the annotation records necessity, not participation. Retained as over-annotation rather than removed because the phenotype is real and curator-assigned.
NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle.
MODIFY
Summary: Nuclear export is correct for the importin-13 subfamily but the cargo is protein; use protein export from nucleus.
Reason: Imp13 exports the protein eIF1A (human ortholog in the same PANTHER subfamily SF33), and Cadmus carries the corresponding IBA export receptor activity. The supported export is of protein cargo, so the specific descendant protein export from nucleus is preferred. No fly-specific export assay exists; this rests on subfamily inheritance.
NAS PMID:20122403 Nuclear import mechanism of the EJC component Mago-Y14 revea...
MODIFY
Summary: Import into nucleus is correct but general; the cargo is protein (Mago-Y14).
Reason: The fly Imp13-Mago-Y14 structure establishes protein import; protein import into nucleus, already carried by the gene, is the appropriate specific descendant.
The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface.
GO:0061608 nuclear import signal receptor activity
IBA GO_REF:0000033
ACCEPT
Summary: Cadmus is an import receptor that binds Mago-Y14 cargo for nuclear import.
Reason: Directly supported in fly by the Imp13-Mago-Y14 structure and inherited across PANTHER SF33 (human IPO13 imports UBC9 and Y14). This is the core molecular function. The cargo is recognised through a folded surface rather than a linear NLS, which the GO term definition (cargo-binding receptor activity) accommodates.
The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface.
mediates import of the RBM8 (Y14) protein, and is therefore referred to as importin 13 (Imp13)
Core Functions
Nuclear import receptor that binds folded protein cargo such as the Mago-Y14 heterodimer and carries it into the nucleus, where RanGTP binding releases it.
The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface.
Q: Which Drosophila nuclear export cargoes, if any, does Cadmus carry (e.g. eIF1A), and is export activity conserved in the fly importin-13?
Q: Which nuclear import cargo(es) of Cadmus in muscle underlie the homeostatic increase in presynaptic release seen in mutants?
Suggested Experiments
Experiment: Test nuclear export of Drosophila eIF1A by Cadmus in S2 cells (permeabilised-cell export assay or RNAi with eIF1A localization readout).
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.
LSP — Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Nucleocytoplasmic transport is supported by the direct fly Imp13-Mago-Y14 import complex and the conserved bidirectional importin-13 cycle. It is broader than the existing protein-import and export annotations.
Supporting Evidence:
PMID:20122403: "The heterodimer is imported back into the nucleus by Importin 13 (Imp13), a member of the karyopherin-beta family of transport factors. We have elucidated the structural basis of the Mago-Y14 nuclear import cycle. The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface."
PMID:11447110: "Imp13 also shows export activity towards the translation initiation factor eIF1A"
LSP — Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Cadmus directly carries Mago-Y14 in nuclear import. Intracellular protein transport is correct but less specific than the supported nuclear-import annotation already in GOA.
Supporting Evidence:
PMID:20122403: "The heterodimer is imported back into the nucleus by Importin 13 (Imp13), a member of the karyopherin-beta family of transport factors. We have elucidated the structural basis of the Mago-Y14 nuclear import cycle. The 3.35 A structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface."
cadmus (cdm) encodes a member of the importin beta family of nucleocytoplasmic cargo shuttling proteins. It functions at the neuromuscular junction to maintain normal subsynaptic reticulum structure and presynaptic probability of release.