SSK1 (YLR006C, UniProt Q07084) curation notes

Identity

• Osmolarity two-component system protein SSK1; 712 aa; C-terminal CheY-like receiver
  (Response_reg, PF00072) domain at 505-647 with phospho-acceptor Asp554
  [file:yeast/SSK1/SSK1-uniprot.txt "DOMAIN 505..647"].
• Non-enzymatic response regulator: [file:yeast/SSK1/SSK1-deep-research-falcon.md
  "Ssk1 itself does not catalyze phosphorylation of Ssk2."]

Phosphorelay (receiver function)

• Sln1-Ypd1-Ssk1 multistep phosphorelay: PMID:8808622; PMID:8808622
• Original identification as a two-component system controlling the osmosensing MAPK
  cascade: PMID:8183345
• Logic is derepression: phosphorylated Ssk1 is inactive, unphosphorylated Ssk1 active.
  Phosphorylation-site or Ypd1-binding mutants are hyperactive PMID:18573873.
• Ypd1-binding surface is the receiver alpha1 helix / beta1-alpha1 loop (E510, N512, I514,
  I518) PMID:18573873.

Output: activation of the Ssk2/Ssk22 MAP3Ks

• PMID:9482735; PMID:9482735 -> direct activator of a protein
  kinase (GO:0030295) and MAP3K binding (GO:0031435).
• UniProt: [file:yeast/SSK1/SSK1-uniprot.txt "SUBUNIT: Interacts with SSK2, SSK22 and
  YPD1."]
• Two-step model: Ssk1 binding relieves autoinhibition, Ssk2 then autophosphorylates and
  becomes Ssk1-independent (PMID:9482735 abstract).

Self-inhibition / dimer

• PMID:18573873; PMID:18573873. Model: Ssk1~P/Ssk1-OH heterodimers are
  inactive; only Ssk1-OH/Ssk1-OH dimers efficiently activate Ssk2. This explains why the
  SGD term "regulation of p38MAPK cascade" (not only positive regulation) fits.
• Homodimerization (GO:0042803) is experimentally supported (gel filtration, co-precipitation)
  but SGD curated this paper without adding it; left as a suggested question, not NEW.

Turnover

• Unphosphorylated Ssk1 is degraded by Ubc7-dependent ubiquitin-proteasome system
  (Sato et al. 2003, PMID:12944490 per UniProt; not cached) [file:yeast/SSK1/SSK1-deep-research-falcon.md
  "Loss of UBC7 impairs Ssk1 degradation and delays Hog1 dephosphorylation, indicating
  that Ssk1 turnover contributes to pathway shutoff after osmoadaptation."]. Horie 2008
  did not detect significant degradation over their time course, and argues degradation
  is a slow (hour-scale) down-regulation mechanism.

Localization

• Cytoplasm PMID:14665464; GFP signal weak, nuclear presence not excluded.

Peripheral phenotypes

• Low-pH (pH 3.0) actin depolarization depends on the Sln1 branch of HOG
  PMID:19633059. Abstract-only cache; SGD curator (full text) attributed IMP to SSK1. Ssk1 acts
  as the upstream signalling input; the actin effect is executed by Hog1 and polarisome
  proteins. Kept as non-core.

Protein-binding (GO:0005515) rows

• Partners: SSK2 (P53599), SSK22 (P25390) -- both MAP3Ks -> MODIFY to GO:0031435.
• Partner YPD1 (Q07688; PCA PMID:18467557, Y2H PMID:18719252) is the phosphodonor Hpt
  protein; its binding is part of the response regulator activity already captured by
  GO:0000156. No informative binding MF exists for Hpt binding -> REMOVE (interaction is
  real and well-established, removal only drops the uninformative term).

GO-CAM

• No SSK1 entry in gocams/index.tsv. Module modules/scer_hog1_cascade.yaml uses
  GO:0000156 for the Ssk1 tier.