Moleskin (DIM-7) is the Drosophila importin-7 nuclear transport receptor, a soluble importin-beta-family karyopherin with an N-terminal Ran-binding importin-beta domain. It mediates nuclear accumulation of activated ERK, phosphorylated Mad and Yorkie, and participates in snurportin-associated import of spliceosomal snRNPs, including delivery to Cajal bodies. Regulated cortical and nucleocytoplasmic distribution links signaling to tissue growth and differentiation, while its snRNP-transport role supports nuclear RNA-processing machinery. Moleskin also has a cytoplasmic role in the embryonic musculature. It becomes enriched at muscle attachment sites in an integrin-dependent manner, acts in the muscle upstream of the Elmo-Mbc-Rac module, and signals to tendon cells through the EGFR ligand Vein, so msk mutant embryos fail to form stable muscle-tendon attachments.
IDA PMID:11262240 Nuclear import of activated D-ERK by DIM-7, an importin fami...
ACCEPT
Summary: Moleskin shuttles between cytoplasm and nucleus in its import cycle.
Reason: Moleskin shuttles between cytoplasm and nucleus in its import cycle. Direct fly studies establish nuclear localization, cytoplasmic cargo association and nuclear Cajal-body residence, independently supporting the subcellular assignments also recorded in the protein-trap survey.
Summary: Moleskin shuttles between cytoplasm and nucleus in its import cycle.
Reason: Moleskin shuttles between cytoplasm and nucleus in its import cycle. Direct fly studies establish nuclear localization, cytoplasmic cargo association and nuclear Cajal-body residence, independently supporting the subcellular assignments also recorded in the protein-trap survey.
Summary: The nuclear-envelope assignment represents nuclear-pore passage by an importin-family receptor.
Reason: The nuclear-envelope assignment represents nuclear-pore passage by an importin-family receptor. Direct cargo-import experiments support this conserved transport-cycle location without implying an integral membrane protein.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg...
ACCEPT
Summary: Moleskin shuttles between cytoplasm and nucleus in its import cycle.
Reason: Moleskin shuttles between cytoplasm and nucleus in its import cycle. Direct fly studies establish nuclear localization, cytoplasmic cargo association and nuclear Cajal-body residence, independently supporting the subcellular assignments also recorded in the protein-trap survey.
IDA PMID:23885126 Identification and characterization of Drosophila Snurportin...
ACCEPT
Summary: Moleskin shuttles between cytoplasm and nucleus in its import cycle.
Reason: Moleskin shuttles between cytoplasm and nucleus in its import cycle. Direct fly studies establish nuclear localization, cytoplasmic cargo association and nuclear Cajal-body residence, independently supporting the subcellular assignments also recorded in the protein-trap survey.
Summary: Moleskin shuttles between cytoplasm and nucleus in its import cycle.
Reason: Moleskin shuttles between cytoplasm and nucleus in its import cycle. Direct fly studies establish nuclear localization, cytoplasmic cargo association and nuclear Cajal-body residence, independently supporting the subcellular assignments also recorded in the protein-trap survey.
HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg...
ACCEPT
Summary: Moleskin shuttles between cytoplasm and nucleus in its import cycle.
Reason: Moleskin shuttles between cytoplasm and nucleus in its import cycle. Direct fly studies establish nuclear localization, cytoplasmic cargo association and nuclear Cajal-body residence, independently supporting the subcellular assignments also recorded in the protein-trap survey.
Summary: Moleskin shuttles between cytoplasm and nucleus in its import cycle.
Reason: Moleskin shuttles between cytoplasm and nucleus in its import cycle. Direct fly studies establish nuclear localization, cytoplasmic cargo association and nuclear Cajal-body residence, independently supporting the subcellular assignments also recorded in the protein-trap survey.
IDA PMID:11262240 Nuclear import of activated D-ERK by DIM-7, an importin fami...
ACCEPT
Summary: Moleskin shuttles between cytoplasm and nucleus in its import cycle.
Reason: Moleskin shuttles between cytoplasm and nucleus in its import cycle. Direct fly studies establish nuclear localization, cytoplasmic cargo association and nuclear Cajal-body residence, independently supporting the subcellular assignments also recorded in the protein-trap survey.
IDA PMID:11262240 Nuclear import of activated D-ERK by DIM-7, an importin fami...
KEEP AS NON CORE
Summary: Moleskin has a regulated cortical pool associated with integrin-dependent ERK import.
Reason: Moleskin has a regulated cortical pool associated with integrin-dependent ERK import. DIM-7 and integrins localize to peripheral actin-containing regions; this is a documented regulatory location rather than the primary endpoint of imported cargo.
IDA PMID:17699602 Nuclear localization of the ERK MAP kinase mediated by Droso...
KEEP AS NON CORE
Summary: Moleskin has a regulated cortical pool associated with integrin-dependent ERK import.
Reason: Moleskin has a regulated cortical pool associated with integrin-dependent ERK import. DIM-7 and integrins localize to peripheral actin-containing regions; this is a documented regulatory location rather than the primary endpoint of imported cargo.
Summary: Moleskin is importin-7 and a receptor for nuclear import of activated D-ERK and snRNP cargo.
Reason: Moleskin is importin-7 and a receptor for nuclear import of activated D-ERK and snRNP cargo. Target mutations reduce nuclear D-ERK and wild-type Msk rescues import; independent snRNP association and cytoplasmic accumulation in mutants establish a second import pathway. Its molecular role is cargo transport across the nuclear pore.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
IDA PMID:11262240 Nuclear import of activated D-ERK by DIM-7, an importin fami...
ACCEPT
Summary: Moleskin is importin-7 and a receptor for nuclear import of activated D-ERK and snRNP cargo.
Reason: Moleskin is importin-7 and a receptor for nuclear import of activated D-ERK and snRNP cargo. Target mutations reduce nuclear D-ERK and wild-type Msk rescues import; independent snRNP association and cytoplasmic accumulation in mutants establish a second import pathway. Its molecular role is cargo transport across the nuclear pore.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
IMP PMID:23885126 Identification and characterization of Drosophila Snurportin...
ACCEPT
Summary: Moleskin is importin-7 and a receptor for nuclear import of activated D-ERK and snRNP cargo.
Reason: Moleskin is importin-7 and a receptor for nuclear import of activated D-ERK and snRNP cargo. Target mutations reduce nuclear D-ERK and wild-type Msk rescues import; independent snRNP association and cytoplasmic accumulation in mutants establish a second import pathway. Its molecular role is cargo transport across the nuclear pore.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
Summary: The intracellular protein-transport annotation is correct but broad.
Reason: The intracellular protein-transport annotation is correct but broad. Loss-and-rescue experiments establish protein import into the nucleus as the specific transport process executed by Moleskin.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
IMP PMID:16308331 MAP kinase subcellular localization controls both pattern an...
KEEP AS NON CORE
Summary: Moleskin-dependent MAPK nuclear access affects wing patterning and the differentiation/proliferation choice.
Reason: Moleskin-dependent MAPK nuclear access affects wing patterning and the differentiation/proliferation choice. The curated mutant annotations are consistent with the wing study and the independently established ERK-import mechanism; these developmental outcomes do not define a separate molecular function.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
IMP PMID:16308331 MAP kinase subcellular localization controls both pattern an...
KEEP AS NON CORE
Summary: Moleskin-dependent MAPK nuclear access affects wing patterning and the differentiation/proliferation choice.
Reason: Moleskin-dependent MAPK nuclear access affects wing patterning and the differentiation/proliferation choice. The curated mutant annotations are consistent with the wing study and the independently established ERK-import mechanism; these developmental outcomes do not define a separate molecular function.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
IMP PMID:16308331 MAP kinase subcellular localization controls both pattern an...
KEEP AS NON CORE
Summary: Moleskin-dependent MAPK nuclear access affects wing patterning and the differentiation/proliferation choice.
Reason: Moleskin-dependent MAPK nuclear access affects wing patterning and the differentiation/proliferation choice. The curated mutant annotations are consistent with the wing study and the independently established ERK-import mechanism; these developmental outcomes do not define a separate molecular function.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
IDA PMID:23885126 Identification and characterization of Drosophila Snurportin...
KEEP AS NON CORE
Summary: Moleskin is detected in nuclear Cajal bodies, a destination of the snRNP cargo it imports.
Reason: Full-text re-review of PMID:23885126 confirms that Msk localizes to Cajal bodies and associates with snurportin and Sm-class snRNPs. Cajal-body residence is a genuine but peripheral location for a soluble import receptor whose core sites of action are the cytosol, the nuclear pore and the nucleoplasm, so it is kept as non-core rather than as a core location.
IMP PMID:16540506 smoothened and thickveins regulate Moleskin/Importin 7-media...
KEEP AS NON CORE
Summary: Moleskin is required for normal ommatidial rotation through regulated MAPK signaling.
Reason: Moleskin is required for normal ommatidial rotation through regulated MAPK signaling. The primary study distinguishes this phenotype from chirality and from steps where redundant transport appears sufficient.
IMP PMID:23885126 Identification and characterization of Drosophila Snurportin...
KEEP AS NON CORE
Summary: Moleskin is required for normal Cajal bodies, most plausibly because it imports the snRNP cargo that these bodies receive.
Reason: msk-null larvae lose coilin and SMN signals and accumulate trimethylguanosine-capped RNA in the cytoplasm (PMID:23885126). This establishes necessity, and the data point to a cargo-import defect upstream of Cajal-body assembly rather than Msk building or organizing the body itself. The curated IMP is retained but as a non-core downstream consequence of the import-receptor activity.
IDA PMID:23885126 Identification and characterization of Drosophila Snurportin...
MARK AS OVER ANNOTATED
Summary: The assay detected U snRNAs co-precipitating with GFP-Msk from S2 cytoplasmic lysate, i.e. association with assembled snRNP/snurportin cargo, not binding of Msk to the RNA.
Reason: In PMID:23885126 (full text) U1, U2 and U4 snRNAs co-immunoprecipitate with GFP-Msk and with GFP-dSNUP, and the Msk-dSNUP interaction is Ran- and RNA-dependent. Co-precipitation from lysate cannot distinguish direct RNA contact from association via snurportin or Sm proteins, and importin-beta-type receptors recognize cargo through protein adaptors (snurportin binds the TMG cap). The data support snRNP cargo association by an import receptor; an snRNA-binding molecular function for Msk is an over-interpretation.
IDA PMID:23885126 Identification and characterization of Drosophila Snurportin...
MARK AS OVER ANNOTATED
Summary: The assay detected U snRNAs co-precipitating with GFP-Msk from S2 cytoplasmic lysate, i.e. association with assembled snRNP/snurportin cargo, not binding of Msk to the RNA.
Reason: In PMID:23885126 (full text) U1, U2 and U4 snRNAs co-immunoprecipitate with GFP-Msk and with GFP-dSNUP, and the Msk-dSNUP interaction is Ran- and RNA-dependent. Co-precipitation from lysate cannot distinguish direct RNA contact from association via snurportin or Sm proteins, and importin-beta-type receptors recognize cargo through protein adaptors (snurportin binds the TMG cap). The data support snRNP cargo association by an import receptor; an snRNA-binding molecular function for Msk is an over-interpretation.
IDA PMID:23885126 Identification and characterization of Drosophila Snurportin...
MARK AS OVER ANNOTATED
Summary: The assay detected U snRNAs co-precipitating with GFP-Msk from S2 cytoplasmic lysate, i.e. association with assembled snRNP/snurportin cargo, not binding of Msk to the RNA.
Reason: In PMID:23885126 (full text) U1, U2 and U4 snRNAs co-immunoprecipitate with GFP-Msk and with GFP-dSNUP, and the Msk-dSNUP interaction is Ran- and RNA-dependent. Co-precipitation from lysate cannot distinguish direct RNA contact from association via snurportin or Sm proteins, and importin-beta-type receptors recognize cargo through protein adaptors (snurportin binds the TMG cap). The data support snRNP cargo association by an import receptor; an snRNA-binding molecular function for Msk is an over-interpretation.
Summary: The importin-7 transport cycle uses the conserved Ran GTPase interaction for directionality and cargo release.
Reason: The importin-7 transport cycle uses the conserved Ran GTPase interaction for directionality and cargo release. Moleskin is the experimentally identified fly importin-7 and functions in nuclear import; this term captures the conserved receptor-Ran interaction, not binding to arbitrary small GTPases.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
IMP PMID:16308331 MAP kinase subcellular localization controls both pattern an...
KEEP AS NON CORE
Summary: Moleskin-dependent MAPK nuclear access affects wing patterning and the differentiation/proliferation choice.
Reason: Moleskin-dependent MAPK nuclear access affects wing patterning and the differentiation/proliferation choice. The curated mutant annotations are consistent with the wing study and the independently established ERK-import mechanism; these developmental outcomes do not define a separate molecular function.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
IMP PMID:17110483 A genetic screen in Drosophila for genes interacting with se...
KEEP AS NON CORE
Summary: Moleskin contributes to compound-eye differentiation through nuclear transport of developmental signaling factors.
Reason: Moleskin contributes to compound-eye differentiation through nuclear transport of developmental signaling factors. msk mutant eyes have multiple cell-type defects, including an R8-to-R2,5 fate switch, supporting the developmental annotation set. These are phenotypic consequences of the import receptor rather than distinct biochemical activities.
IMP PMID:17110483 A genetic screen in Drosophila for genes interacting with se...
KEEP AS NON CORE
Summary: Moleskin contributes to compound-eye differentiation through nuclear transport of developmental signaling factors.
Reason: Moleskin contributes to compound-eye differentiation through nuclear transport of developmental signaling factors. msk mutant eyes have multiple cell-type defects, including an R8-to-R2,5 fate switch, supporting the developmental annotation set. These are phenotypic consequences of the import receptor rather than distinct biochemical activities.
msk eyes demonstrate reductions in the number of R8 photoreceptors due to an R8 to R2,5 fate switch
GO:0043524 negative regulation of neuron apoptotic process
IMP PMID:16540506 smoothened and thickveins regulate Moleskin/Importin 7-media...
MARK AS OVER ANNOTATED
Summary: msk-null eye clones are lost, but the data show a cell-viability consequence of losing a general import receptor rather than regulation of neuronal apoptosis.
Reason: In PMID:16540506 (full text) larval msk clones are small but do not stain for activated Caspase-3, and p35 expression does not rescue clone size; only msk-null cells that persist to the pupal stage die with caspase activation. Neither observation shows Msk acting in the control of apoptosis, nor that the dying cells are neurons specifically. Late death of import-deficient cells is a pleiotropic downstream outcome of loss of nuclear import, so the regulatory process term over-states the evidence.
IMP PMID:17110483 A genetic screen in Drosophila for genes interacting with se...
KEEP AS NON CORE
Summary: Moleskin contributes to compound-eye differentiation through nuclear transport of developmental signaling factors.
Reason: Moleskin contributes to compound-eye differentiation through nuclear transport of developmental signaling factors. msk mutant eyes have multiple cell-type defects, including an R8-to-R2,5 fate switch, supporting the developmental annotation set. These are phenotypic consequences of the import receptor rather than distinct biochemical activities.
IDA PMID:17699602 Nuclear localization of the ERK MAP kinase mediated by Droso...
UNDECIDED
Summary: The only perinuclear observation visible in the cached abstract is of ERK cargo, not of DIM-7/Msk.
Reason: PMID:17699602 is abstract-only in the cache, and Europe PMC returned no full text on retrieval (2026-10-20). The abstract reports that ERK accumulates in a perinuclear ring when DIM-7 is depleted, and places DIM-7 itself at the cortex. The curator may have seen perinuclear DIM-7 staining in a figure, which is plausible for an import receptor, but this cannot be verified here, so the row is left undecided rather than accepted or removed.
IGI PMID:17110483 A genetic screen in Drosophila for genes interacting with se...
KEEP AS NON CORE
Summary: Moleskin contributes to compound-eye differentiation through nuclear transport of developmental signaling factors.
Reason: Moleskin contributes to compound-eye differentiation through nuclear transport of developmental signaling factors. msk mutant eyes have multiple cell-type defects, including an R8-to-R2,5 fate switch, supporting the developmental annotation set. These are phenotypic consequences of the import receptor rather than distinct biochemical activities.
IMP PMID:17110483 A genetic screen in Drosophila for genes interacting with se...
KEEP AS NON CORE
Summary: Moleskin contributes to compound-eye differentiation through nuclear transport of developmental signaling factors.
Reason: Moleskin contributes to compound-eye differentiation through nuclear transport of developmental signaling factors. msk mutant eyes have multiple cell-type defects, including an R8-to-R2,5 fate switch, supporting the developmental annotation set. These are phenotypic consequences of the import receptor rather than distinct biochemical activities.
msk eyes demonstrate reductions in the number of R8 photoreceptors due to an R8 to R2,5 fate switch
GO:0061608 nuclear import signal receptor activity
IBA GO_REF:0000033
ACCEPT
Summary: Moleskin is importin-7 and a receptor for nuclear import of activated D-ERK and snRNP cargo.
Reason: Moleskin is importin-7 and a receptor for nuclear import of activated D-ERK and snRNP cargo. Target mutations reduce nuclear D-ERK and wild-type Msk rescues import; independent snRNP association and cytoplasmic accumulation in mutants establish a second import pathway. Its molecular role is cargo transport across the nuclear pore.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7.
dpERK nuclear import can be restored in DIM-7-deficient cells by Xenopus Importin-7, demonstrating that ERK import is an evolutionarily conserved function of this protein.
Q: PANTHER places Moleskin in PTHR10997:SF18 with yeast Nmd5, Arabidopsis SAD2 and fission-yeast SPCC550.11, while vertebrate importin-7 (SF27) and importin-8 (SF26) form separate subfamilies. Is Msk the single pre-duplication ortholog of both vertebrate IPO7 and IPO8, and are any IPO8-specific cargoes (for example Argonaute or SRP19) imported by Msk in flies?
Q: FlyBase captured the snRNP import defect of msk mutants as protein import into nucleus. Would GO:0061015 snRNA import into nucleus be the more appropriate process term for a receptor that imports snurportin-bound TMG-capped snRNPs, or is the RNP cargo better described as protein import?
Suggested Experiments
Experiment: Test direct binding of recombinant Msk to purified dSNUP, Sm core particles and naked U snRNAs in the presence of RanGTP or RanGDP, to determine whether Msk contacts the RNA or only the protein adaptors of snRNP cargo.
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: Intracellular protein transport is directly supported by the loss of activated ERK nuclear import in moleskin mutants and rescue by wild-type DIM-7. A second primary study identifies Moleskin association with snurportin/snRNP cargo and an snRNP-import defect. The existing protein import into nucleus annotation is more specific than the predicted general intracellular transport.
Supporting Evidence:
PMID:11262240: "Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7."
PMID:23885126: "the importin-7 orthologue Moleskin (Msk) physically associates with both dSNUP and spliceosomal snRNPs and localizes to nuclear Cajal bodies."
moleskin (msk) encodes an importin that contributes to protein import into the nucleus. It is involved in eye development, muscle attachment and wing cell fate specification.