Cadmus is Drosophila importin-13, a Ran-regulated karyopherin that shuttles protein cargo between cytoplasm and nucleus. It recognizes the Mago-Y14 heterodimer through a conserved folded interaction surface. Cadmus is expressed in and around neuronal and muscle nuclei and supports synaptic homeostasis, including postsynaptic control of presynaptic transmitter release.
Existing Annotations Review
GO Term
Evidence
Action
Reason
GO:0005049 nuclear export signal receptor activity
IBA GO_REF:0000033
ACCEPT
Summary: Cadmus is the bidirectional importin-13 transport receptor.
Reason: Cadmus is the bidirectional importin-13 transport receptor. Fly Imp13 is structurally characterized with its import cargo Mago-Y14, while mammalian Imp13 directly exports eIF1A; the conserved importin-13 mechanism and curated phylogenetic assignment support nuclear export without claiming a fly eIF1A assay.
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.
Summary: The nuclear-envelope annotation captures the pore-associated transport step of a shuttling karyopherin.
Reason: The nuclear-envelope annotation captures the pore-associated transport step of a shuttling karyopherin. Fly Imp13 is observed in perinuclear structures, and its conserved import cycle requires nuclear pore passage; it is not an integral nuclear-envelope membrane protein.
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.
Summary: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import.
Reason: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import. The Drosophila Imp13-Mago-Y14 structure directly establishes the import complex; recognition involves a folded cargo surface rather than requiring a classical linear NLS.
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.
Summary: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import.
Reason: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import. The Drosophila Imp13-Mago-Y14 structure directly establishes the import complex; recognition involves a folded cargo surface rather than requiring a classical linear NLS.
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.
Summary: Intracellular protein transport is correct but broader than the characterized importin-13 nuclear import pathway.
Reason: Intracellular protein transport is correct but broader than the characterized importin-13 nuclear import pathway. Mago-Y14 is a direct fly cargo; protein import into nucleus is the more informative process.
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.
IMP PMID:14504225 A genetic screen for synaptic transmission mutants mapping t...
KEEP AS NON CORE
Summary: Cadmus loss perturbs visual-system transmission and synaptic homeostasis.
Reason: Cadmus loss perturbs visual-system transmission and synaptic homeostasis. Mutant and genomic-rescue experiments connect CG7212/imp13 to the original visual screen; at the NMJ the protein acts in muscle to alter presynaptic release. These are supported organismal consequences of a nuclear transport receptor rather than a transmitter receptor or direct vesicle-release factor.
Summary: Ran binding controls cargo release in the importin-13 transport cycle.
Reason: Ran binding controls cargo release in the importin-13 transport cycle. The human Imp13-RanGTP structure and conserved fly cargo-binding structure support this mechanistic interaction; the term does not imply indiscriminate binding to all small GTPases.
IMP PMID:14504225 A genetic screen for synaptic transmission mutants mapping t...
KEEP AS NON CORE
Summary: Cadmus loss perturbs visual-system transmission and synaptic homeostasis.
Reason: Cadmus loss perturbs visual-system transmission and synaptic homeostasis. Mutant and genomic-rescue experiments connect CG7212/imp13 to the original visual screen; at the NMJ the protein acts in muscle to alter presynaptic release. These are supported organismal consequences of a nuclear transport receptor rather than a transmitter receptor or direct vesicle-release factor.
imp13 is required in the muscles to control presynaptic release.
GO:0042564 NLS-dependent protein nuclear import complex
IPI PMID:20122403 Nuclear import mechanism of the EJC component Mago-Y14 revea...
ACCEPT
Summary: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import.
Reason: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import. The Drosophila Imp13-Mago-Y14 structure directly establishes the import complex; recognition involves a folded cargo surface rather than requiring a classical linear NLS.
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.
GO:0042564 NLS-dependent protein nuclear import complex
NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle.
ACCEPT
Summary: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import.
Reason: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import. The Drosophila Imp13-Mago-Y14 structure directly establishes the import complex; recognition involves a folded cargo surface rather than requiring a classical linear NLS.
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.
GO:0043243 positive regulation of protein-containing complex disassembly
NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle.
ACCEPT
Summary: Cargo release entails disassembly of the receptor-cargo transport complex.
Reason: Cargo release entails disassembly of the receptor-cargo transport complex. Structural comparison explains RanGTP-dependent release of Mago-Y14 from importin-13; this is not disassembly of the mature exon junction complex on mRNA.
Summary: Synaptic function does not establish endogenous residence at the synapse.
Reason: Synaptic function does not establish endogenous residence at the synapse. The rescuing genomic tagged protein was detected in muscle nuclei but not at the NMJ synapse; synaptic fluorescence occurred under overexpression. Thus the logical process-to-location transfer is stronger than the localization evidence.
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...
KEEP AS NON CORE
Summary: Cadmus loss perturbs visual-system transmission and synaptic homeostasis.
Reason: Cadmus loss perturbs visual-system transmission and synaptic homeostasis. Mutant and genomic-rescue experiments connect CG7212/imp13 to the original visual screen; at the NMJ the protein acts in muscle to alter presynaptic release. These are supported organismal consequences of a nuclear transport receptor rather than a transmitter receptor or direct vesicle-release factor.
NAS PMID:17287812 Molecular mechanism of the nuclear protein import cycle.
ACCEPT
Summary: Cadmus is the bidirectional importin-13 transport receptor.
Reason: Cadmus is the bidirectional importin-13 transport receptor. Fly Imp13 is structurally characterized with its import cargo Mago-Y14, while mammalian Imp13 directly exports eIF1A; the conserved importin-13 mechanism and curated phylogenetic assignment support nuclear export without claiming a fly eIF1A assay.
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.
NAS PMID:20122403 Nuclear import mechanism of the EJC component Mago-Y14 revea...
ACCEPT
Summary: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import.
Reason: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import. The Drosophila Imp13-Mago-Y14 structure directly establishes the import complex; recognition involves a folded cargo surface rather than requiring a classical linear NLS.
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.
GO:0061608 nuclear import signal receptor activity
IBA GO_REF:0000033
ACCEPT
Summary: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import.
Reason: Cadmus binds the Mago-Y14 cargo and mediates its nuclear import. The Drosophila Imp13-Mago-Y14 structure directly establishes the import complex; recognition involves a folded cargo surface rather than requiring a classical linear NLS.
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.
Core Functions
Recognizes protein cargo for nuclear import through the nuclear pore.
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.
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."