SKIP

Gene Description

SKIP (Shal K+ channel interacting protein, CG31163) is a neuronal Drosophila gene of the SAM- and SH3-domain (SASH1/SAMSN1) adaptor family. It encodes several isoforms built from an N-terminal SAM domain, an SH3 domain and a second, C-terminal SAM domain in different combinations. A0A0B4K6C1 is a long 1034-residue isoform carrying all three domains, separated by disordered regions, and has no predicted transmembrane segment. The short isoform SKIP3, which consists of the first SAM domain plus a tail ending in eight unique residues, binds the cytoplasmic C terminus of the Kv4-family channel Shal through that octapeptide. In embryonic neurons SKIP3 increases the share of Shal channels with slower fast inactivation. Long isoforms such as this one lack the Shal-binding octapeptide, and no partner or activity is known for them. When expressed in neurons, tagged SKIP proteins are cytoplasmic and are found in cell bodies and in puncta along neurites. SKIP is expressed throughout the embryonic central and peripheral nervous system and in adult antennae. A gene-trap insertion in the SKIP 5' UTR reduces olfactory-driven trap behaviour, and precise excision reverts this, but electroantennogram responses are normal.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: Electronic cytoplasm annotation derived from an ARBA rule (UniProt subcellular-location line). It agrees with direct imaging of tagged SKIP isoforms in neurons and with the soluble adaptor architecture of the protein. Reason: The ARBA source is not used as support. Independently, myc-tagged SKIP1 (a long isoform with the same SAM1-SH3-SAM2 architecture as A0A0B4K6C1) and SKIP3 were imaged in the soma and in puncta along processes of cultured Drosophila neurons. The authors propose that SKIP3 may recruit cytosolic regulators. A0A0B4K6C1 has no predicted transmembrane helix or signal peptide, and its annotated features are SAM and SH3 protein-interaction domains and disordered regions. Cytoplasm is the most specific location supported for the whole protein. It is kept at this level, and the neuronal cell body term is added as a NEW row. Supporting Evidence: PMID:19463952 We found that myc-SKIP3 and myc-SKIP1 are localized to neuronal cell bodies and in puncta along neuronal processes (Fig. 3)
GO:0007608 sensory perception of smell	IMP PMID:22530061 A screen for genes expressed in the olfactory organs of Dros...	KEEP AS NON CORE	Summary: FlyBase IMP from an olfactory gene-trap screen. Line BG00076, carrying a pGT insertion in the SKIP 5' UTR, shows reduced olfactory trap responses in both sexes. Precise excision reverts the defect, and SKIP transcript is reduced about five-fold. Reason: The full text was read. The genetics are sound (two independent precise excisions restore behaviour, and transcript levels are reduced), so the annotation is supported at the gene level and is kept. It is non-core. The assay measures olfactory-driven trap behaviour, and electroantennograms are normal, so primary odorant transduction is unaffected. The authors suggest a central or synaptic role. The insertion lowers SKIP transcript but is not mapped to particular isoforms, and the SKIP products that bind Shal (SKIP3) differ from this long isoform. The annotation records a phenotype-level requirement and does not identify which part of olfactory perception SKIP performs. Supporting Evidence: PMID:22530061 For BG00076 we found that precise excision of the pGT element in two independent excision lines rescued the olfactory response in both females and males (Figure 4A and 4B), confirming that the olfactory behaviour defect is due to the pGT element insertion. PMID:22530061 There was no effect on the EAG, but a limited set of odours was tested, and in addition if the gene is involved in synaptic transmission then we would not expect to see a primary EAG defect. file:DROME/SKIP/SKIP-deep-research-manual.md Which isoforms the insertion affects is not known.
GO:0043025 neuronal cell body	IDA PMID:19463952 Fast inactivation of Shal (K(v)4) K+ channels is regulated b...	NEW	Summary: Proposed location. In elav-GAL4 primary neuronal cultures, myc-tagged long isoform SKIP1 and short isoform SKIP3 localize to neuronal cell bodies and to puncta along processes. Reason: This is direct imaging of a tagged protein. The authors repeated it in a SKIP-deficient background to address overexpression artefacts. SKIP1 (Q8SZS0) shares the SAM1-SH3-SAM2 architecture of A0A0B4K6C1 and is identical to it over the N-terminal SAM1 region. The localization therefore applies to the long isoforms, not only to the Shal-binding SKIP3. The punctate signal along processes has no assigned compartment, so no neuron projection sub-compartment term is proposed. Supporting Evidence: PMID:19463952 We found that myc-SKIP3 and myc-SKIP1 are localized to neuronal cell bodies and in puncta along neuronal processes (Fig. 3) file:DROME/SKIP/SKIP-bioinformatics/RESULTS.md A0A0B4K6C1 is a long isoform like SKIP1

Core Functions

Cytoplasmic multi-domain adaptor of neurons. The long SAM1-SH3-SAM2 isoform A0A0B4K6C1 has no demonstrated molecular activity or binding partner. Its SAM and SH3 domains suggest a scaffolding role, but SKIP SAM domains do not self-associate, and the Shal K+ channel-binding octapeptide that underlies the known function of the short isoform SKIP3 is absent from it. No molecular function term is asserted for this product.

Cellular Locations:

neuronal cell body

Supporting Evidence:

PMID:19463952
We found that myc-SKIP3 and myc-SKIP1 are localized to neuronal cell bodies and in puncta along neuronal processes (Fig. 3)
PMID:19463952
Given that SAM and SH3 domains have been shown to mediate protein-protein interactions, SKIP proteins are likely to function as a family of adaptor or scaffolding proteins.
file:DROME/SKIP/SKIP-bioinformatics/RESULTS.md
Shal binding and Shal-inactivation regulation demonstrated for SKIP3 cannot be transferred to it.

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Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Manual

📚 Additional Documentation

Notes

Bioinformatics Results

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