Moleskin evidence notes

Q9VSD6 is the native 1049-residue PA product of FBgn0026252 (AAF50487/NP_524780), the sole current protein. DIM-7, D-Importin-7 and Moleskin refer to this locus. FlyBase.

PMID:11262240(https://pubmed.ncbi.nlm.nih.gov/11262240/) establishes activated ERK nuclear import by mutation, association and rescue. PMID:17699602(https://pubmed.ncbi.nlm.nih.gov/17699602/) connects cortical DIM-7/integrin localization with import. The abstract's perinuclear ring is ERK cargo under import blockade, so that particular sentence is not used as direct localization evidence for Moleskin itself.

PMID:23885126(https://pmc.ncbi.nlm.nih.gov/articles/PMC3771954/) is cached with full text and identifies an additional snRNP pathway: Moleskin associates with snurportin and U1/U2/U4-containing snRNPs, localizes to Cajal bodies, and is required for normal snRNP/coilin/SMN distribution. Co-immunoprecipitation supports physical association with the RNP cargo, not necessarily direct contact with naked RNA. These RNA-specific binding rows are retained as non-core features of cargo association, while the nuclear-import receptor is the core activity.

PMID:16540506(https://pmc.ncbi.nlm.nih.gov/articles/PMC1994332/) full text differentiates ommatidial rotation from chirality and larval proliferation from later apoptotic loss. Pupal msk-null cells show activated caspase despite the negative early-larval apoptosis result. The survival annotation is retained in the documented stage. The wing/eye phenotype papers PMID:16308331 and PMID:17110483 remain partly abstract-only after full-text retrieval attempts; their curated cell-type annotations are biologically consistent with the verified ERK-import mechanism and are not overturned because of incomplete cache access.

The high-throughput localization paper PMID:25294944 is cached with full text but its main prose does not name msk. The nuclear/cytosolic calls are independently supported by direct target studies, so the survey annotations are accepted without pretending to have independently inspected a supplementary target row.

ProtNLM intracellular protein transport is LSP relative to specific nuclear import. The developmental phenotype set remains non-core to distinguish the transport receptor's biochemical role from its varied signaling consequences.

Falcon completed successfully in 456.68 seconds. Its additional cargo leads were checked against cached primary full texts: PMID:17785517(https://pubmed.ncbi.nlm.nih.gov/17785517/) identifies Msk in a fly RNAi screen for nuclear import of phosphorylated Mad; PMID:35246520(https://pmc.ncbi.nlm.nih.gov/articles/PMC8897400/) shows cytoplasmic Yorkie accumulation after Msk depletion in wing discs, including two RNAi lines and growth rescue. These support a broader cargo repertoire. The mammalian dominant-cargo hierarchy is not automatically asserted for fly; the direct fly conclusion is Msk-dependent Yorkie nuclear accumulation. The Falcon synthesis omits the verified snRNP/Cajal-body pathway, which remains part of the review.

2026-10-20 — Full re-review, independent of the ProtNLM2 predictions

Identity: Q9VSD6 is the full-length 1049-aa CG7935/FBgn0026252 product (EMBL AAF50487), the single annotated protein of the locus, with the importin-beta N-terminal (IPR001494, PF03810 IBN_N), XPO2/Cse1 central (PF08506) and IPO7/11-like TPR (PF25758) regions. It is the canonical product, not a fragment, isoform or alternative model (the UniProt entry is unreviewed/TrEMBL only because no Swiss-Prot entry exists for fly Msk).

Evolutionary placement: UniProt and the frozen PANTHER inventory put Msk in PTHR10997:SF18 "D-IMPORTIN 7_RANBP7" together with yeast Nmd5 (P46970), Arabidopsis SAD2 (F4IRR2), S. pombe SPCC550.11 (O59809) and Dictyostelium Q55CX9. Vertebrate importin-7 (human O95373, mouse Q9EPL8) is in SF27 "IMPORTIN-7" and importin-8 in SF26, so the vertebrate IPO7/IPO8 pair sits in separate, presumably post-duplication, subfamilies. The fly-vertebrate functional relationship is supported experimentally by cross-species rescue: Xenopus importin-7 restores dpERK nuclear import in DIM-7-depleted S2 cells PMID:17699602. All IBA rows come from PTN000108134, the PTHR10997 root node (it also carries exportin-2, importin-9, importin-11 donors); nuclear import signal receptor activity and protein import into nucleus are inherited from that node and Msk is one of the experimental donors for GO:0006606 and GO:0005829. Nothing subfamily-specific was transferred from vertebrate IPO7. PANTHER family review interpro/panther/PTHR10997/PTHR10997-review.yaml lists Msk as the SF18 representative; no disagreement on subfamily placement, though that review does not mention that human/mouse IPO7 are in SF27, not SF18.

Changes made in this re-review:
- U1/U2/U4 snRNA binding (IDA, PMID:23885126): KEEP_AS_NON_CORE -> MARK_AS_OVER_ANNOTATED. Full text shows snRNAs co-precipitating with GFP-Msk from lysate ("GFP-Msk also coprecipitated with U1, U2, and U4 snRNAs"), and the Msk-dSNUP association is Ran- and RNA-dependent; this is snRNP cargo association, not demonstrated RNA binding by Msk.
- Cajal body organization (IMP) and Cajal body (IDA): ACCEPT -> KEEP_AS_NON_CORE. Necessity for normal Cajal bodies follows from defective snRNP import; Msk does not build the body.
- negative regulation of neuron apoptotic process (IMP, PMID:16540506): KEEP_AS_NON_CORE -> MARK_AS_OVER_ANNOTATED. Full text: larval clones lack activated Caspase-3 and p35 does not rescue clone size; only pupal survivors die with caspase. This is a viability consequence, not apoptosis regulation, and neurons are not specifically shown.
- perinuclear region of cytoplasm (IDA, PMID:17699602): ACCEPT -> UNDECIDED. Abstract-only (Europe PMC full text for PMC1995703 not retrievable on 2026-10-20); the only perinuclear statement in the abstract concerns ERK cargo.
- small GTPase binding (IEA): kept ACCEPT. I considered MODIFY to "Ran GTPase binding" (GO:0008536) but OLS reports GO:0008536 as obsolete, so small GTPase binding is the current term for the RanGTP interaction.
- All other rows (nucleus, cytosol, cytoplasm, nucleoplasm, nuclear envelope, cell cortex, protein import into nucleus, nuclear import signal receptor activity, intracellular protein transport MODIFY, and the wing/eye developmental IMP/IGI rows as non-core) were re-examined and left as they were.
- Considered but not added: NEW GO:0061015 snRNA import into nucleus (FlyBase captured the same data as protein import into nucleus); raised as a suggested question instead.

Relative for next review: yeast NMD5 (P46970), the best-characterized member of the same PANTHER subfamily SF18; no review exists in genes/yeast. Human IPO7 (O95373) is the better-studied vertebrate relative but lies in a different subfamily (SF27). No module in modules/ includes msk; related Drosophila modules that could use it as an import step are dmel_bmp_signaling.yaml, dmel_hippo_signaling.yaml, dmel_smn_complex.yaml and erk_cascade.yaml.