SKIP (Drosophila melanogaster) manual literature review

No deep-research API was available, so this review was done manually from PubMed
searches and cached full texts. Searches: "SKIP3 Shal Drosophila", "(CG31163 OR
"Shal K+ channel interacting protein" OR SKIP3) AND Drosophila", "SKIP Shal
Tsunoda S[Author]". Only two Drosophila papers study SKIP (FBgn0051163, CG31163). Hits on
human "SKIP3" (TRIB3, PMID:12743605, PMID:21896644) concern an unrelated tribbles-family
kinase-like protein and were excluded.

Gene and protein

• SKIP (Shal K+ channel interacting protein), CG31163, chromosome 3R (94A). The locus
  encodes several products. UniProt A0A0B4K6C1 (1034 aa, NP_001247234.1) is a long
  isoform with an N-terminal SAM domain (7-66), an SH3 domain (727-788), a second SAM
  domain (819-879) and several disordered regions (UniProt FT lines, PROSITE/MobiDB-lite
  evidence). It belongs to the SASH1/SAMSN1 (SAM and SH3 domain) family, PANTHER
  PTHR12301:SF8.
• Diao et al. described three products: SKIP1 (CG31163-PB/PC, 952 aa; SAM1 + SH3 + SAM2),
  SKIP2 (CG31163-PA, 778 aa; SH3 + SAM2) and SKIP3 (SAM1 + 61-residue tail)
  PMID:19463952.
• The authors proposed an adaptor/scaffold role from the domain content alone
  PMID:19463952. SAM1-SAM1, SAM1-SAM2 and SAM2-SAM2 interactions were not detected in Y2H
  PMID:19463952.

Shal (Kv4) channel interaction and regulation (SKIP3 isoform)

• SKIP3 was isolated in a Y2H screen with the Shal1 C-terminus and confirmed by GST
  pulldown PMID:19463952. The interaction was specific relative to Shaker, Shaw and Shab C-termini.
• Shal binding needs the eight C-terminal residues unique to SKIP3 PMID:19463952.
• My isoform comparison (file:DROME/SKIP/SKIP-bioinformatics/RESULTS.md) identifies the
  128-aa UniProt product A0A0B4KH49 as SKIP3. Its unique C-terminal octapeptide is absent
  from A0A0B4K6C1, so the Shal-binding data do not apply to the product reviewed here.
• In Sf9 cells SKIP3 did not change Shal currents PMID:19463952. In embryonic neurons homozygous for Df(3R)Exel6190, a deficiency removing SKIP
  and about 17 other genes, more neurons had very fast-inactivating Shal currents, and
  myc-SKIP3 expression reversed this PMID:19463952.
• Localization: myc-tagged SKIP1 and SKIP3, expressed with elav-GAL4, are found in neuronal
  cell bodies and in puncta along processes PMID:19463952. SKIP1/3 transcripts are expressed in the embryonic CNS and PNS.

Olfactory behaviour (gene level)

• In a gene-trap screen, line BG00076 (pGT insertion in the SKIP 5' UTR) had reduced
  olfactory trap responses. Precise excision restored behaviour, and SKIP transcript was
  reduced about five-fold PMID:22530061.
• Electroantennograms were normal, so the defect does not lie in primary odorant
  transduction. The authors suggest it may act centrally or in synaptic transmission
  PMID:22530061. Which isoforms the insertion affects is not known.

Gaps

• No molecular activity has been shown for the long SAM-SH3-SAM isoforms, including
  A0A0B4K6C1. No partners of SAM1, SH3 or SAM2 are known.
• No single-gene null allele was used in the electrophysiology. The deficiency removes 18
  genes, but the defect was rescued by SKIP3.