Snail (Sp-sna, Q6UCK0) — curation notes

Identity

• UniProt Q6UCK0 (TrEMBL, "Zinc-finger transcription factor", gene name Snail), 341 aa, five
  C-terminal C2H2 zinc fingers (residues 199-341), N-terminal region with a SNAG-like basic
  stretch; "Belongs to the snail C2H2-type zinc-finger protein family" (UniProt SIMILARITY, ARBA).
  EMBL AY372519 / AAQ74988.1, RefSeq NP_999825.1, GeneID 378469. The sequence was a direct
  submission (Materna S.C., Davidson E.H., Aug-2003); there is no RX PubMed= line in the
  UniProt record. The accompanying publication is the genome-wide C2H2 survey
  PMID:16997293
  (abstract only; the abstract does not name snail individually).
• PANTHER PTHR24388:SF54 ("PROTEIN ESCARGOT" subfamily); the IBA rows are seeded from the PAINT
  nodes PTN002810938 and PTN001227002; the WITH/FROM lists include human SNAI1 (O95863) and SNAI2
  (O43623), several Drosophila (FBgn) and mouse (MGI) Snail/Scratch-family genes, zebrafish and worm
  members.
• Community alias in the Davidson/McClay GRN literature: snail, Sp-sna (S. purpuratus),
  Lv-snail / LvSnail2 (Lytechinus variegatus).

What the gene product is

Snail-family zinc-finger transcriptional repressor. Snail proteins across animals repress
E-cadherin transcription and drive the de-adhesion step of epithelial-mesenchymal transition
(EMT) PMID:24598159.

Place in the sea urchin GRN (mostly Lytechinus variegatus data)

Important organism caveat: the functional work on sea urchin Snail was done in Lytechinus
variegatus, not S. purpuratus. Wu & McClay 2007 (Development; abstract only cached) is the
primary paper PMID:17287249; the abstract itself does not state the species, but Shashikant et al. 2018 and Saunders & McClay 2014 both state it was L. variegatus PMID:30264451.

Findings in L. variegatus:
- Required in micromeres for PMC ingression PMID:17287249.
- Represses cadherin transcription and is needed for cadherin endocytosis
PMID:17287249.
- GRN position: downstream of Pmar1 and Alx1, upstream of PMC-expressed genes
PMID:17287249.
- Timing: expressed just before EMT and switched off in PMCs shortly after ingression
[PMID:18495103 "Snail is expressed just prior to EMT, and is necessary, shortly after its expression, for PMC ingression ( Wu and McClay, 2007 )"; "unlike snail expression , which disappears from PMCs shortly after ingression ( Wu and McClay, 2007 )"].
- Twist and snail both depend on Alx1, but a Twist->snail link is not established
PMID:18495103. Lvtwist is downregulated in Sna morphants only at MB stage PMID:18495103.
- Saunders & McClay 2014 (full text cached): snail is one of the 13 pre-EMT TFs required for EMT
PMID:24598159. Snail knockdown specifically blocks the de-adhesion sub-circuit while the other four cell-state changes still occur PMID:24598159; alx1, twist and snail form the de-adhesion sub-circuit PMID:24598159. Snail is NOT required for apical constriction PMID:24598159. In the Lv GRN snail also feeds erg PMID:24598159. The MASO used is called LvSnail2 PMID:24598159.
- Hardin & Illingworth 2006 (L. variegatus, abstract only): a snail homologue is also expressed
transiently in subsets of non-skeletogenic (secondary) mesenchyme and in the ciliated band, and
this expression is lost in radialized embryos PMID:16958110.

S. purpuratus-specific evidence (sparse and conflicting)

Shashikant et al. 2018 (review, full text) summarise the situation
PMID:30264451:
- Oliveri et al. 2008 considered Sp-snail irrelevant to early PMC specification because it is
expressed at very low levels until gastrulation PMID:30264451. (The cached text of PMID:18413610 does not itself mention snail.)
- Barsi et al. 2014 found Sp-sna enriched in PMCs at mesenchyme blastula; Rafiq et al. 2014 did
not, and found Sp-sna up in Alx1 morphants, opposite to Lv PMID:30264451. (The cached text of PMID:24604781 and the abstract of PMID:24496631 do not name snail; the statements are taken from the review.)
- Saunders & McClay note snail/twist are in the Lv model but not the S. purpuratus GRN model
PMID:24598159.

Curation decisions

• All six GOA rows are electronic (4 IBA, 2 IEA) and are sign-neutral TF / nucleus terms; all
  consistent with a Snail-family zinc-finger repressor. ACCEPT all.
• NEW rows kept minimal and flagged ISS (ortholog in L. variegatus): GO:0001227 (repressor
  activity; cadherin repression) and GO:0001837 (EMT; Snail executes the de-adhesion step via
  cadherin repression and is required for PMC ingression). Comparator check via QuickGO: human
  SNAI1 (O95863) carries GO:0001227 (IBA), GO:0001837 and GO:0010718 (ISS), GO:0000122 (ISS);
  Drosophila sna (P08044) carries GO:0000122 (IDA). So the EMT/repressor terms are the convention
  for Snail-family proteins that repress cadherin, not a gap in curation.
• Participation test: Snail is the repressor that directly silences the cadherin gene, i.e. it
  performs the de-adhesion step of EMT rather than merely being required upstream.
• No S. purpuratus perturbation data exist; the Sp-specific expression data are conflicting, so no
  NEW row is given an S. purpuratus IMP/IEP code. gocams/index.tsv has no entry for Q6UCK0.
• GO:0000122 is not added as a separate NEW row (descendant of the existing GO:0006355 row; the
  sign is captured by GO:0001227).