HOG1 (YLR113W, UniProt P32485) curation notes

2026-09-24 initial review

Identity and activation

• Hog1 is the terminal MAPK of the high-osmolarity glycerol (HOG) pathway; Pbs2 is its MAPKK.
  PMID:7681220
  PMID:7681220
• Activation-loop TGY: Pbs2 phosphorylates Thr174/Tyr176.
  [file:yeast/HOG1/HOG1-deep-research-falcon.md "Pbs2 is the immediate upstream MAPK kinase and phosphorylates Hog1 at Thr174 and Tyr176."]
• Upstream: Sln1-Ypd1-Ssk1 phosphorelay -> Ssk2/Ssk22 and the Sho1 branch (Ste11) converge on Pbs2 (deep research, section 2). This is the grounding for modules/scer_hog1_cascade.yaml, where Hog1 is the MAPK tier (GO:0004707).

Kinase activity / direct substrates (all with in vitro kinase assays)

• Rck2 (Ser519) PMID:10805732
• Sko1 PMID:11230135
• Smp1 PMID:12482976
• Sic1 PMID:15448699
• Hsl1 PMID:16688223
• Ubp3 S695 PMID:21743437
• Mrc1 PMID:23178807
• Net1 PMID:32265285
• Dot1 PMID:38270553
• Rgc2/Fps1 channel closure. PMID:24298058

Localization

• Cytoplasmic at rest, transient nuclear accumulation on activation. PMID:10817757
• Ptp2 (nuclear) and Ptp3 (cytoplasmic) tether/anchor Hog1. PMID:10817757
• Recruited to chromatin at stress promoters via Hot1 and other TFs. PMID:12743037

Transcriptional output

• Hog1 anchored at promoters recruits Pol II. PMID:12743037
• lncRNA / CDC28 induction via chromatin association. PMID:24508389
• Hot1 was found as a two-hybrid partner, but the biochemical interaction could not be confirmed in that paper. PMID:10409737

Cell-cycle control (non-core, osmostress-coupled)

• G1 (Sic1), S (Mrc1: PMID:23178807), G2 (Hsl1), mitotic exit (Net1: PMID:32265285).

Other

• Calmodulin binding: single study, abstract only. PMID:27421986
• Autophagy: hog1 deletion makes starvation-induced autophagy osmosensitive (addendum, abstract only). PMID:16874103

Curation decisions (summary)

• Protein binding rows: MODIFY to protein kinase binding (GO:0019901) for kinase partners (Rck2, Hsl1, Ste7); MODIFY to RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629) for Hot1; REMOVE for Sic1, Ubp3 and Mrc1 (enzyme-substrate contacts that are better captured by the kinase activity and the downstream process annotations; removing the rows does not mean the interactions are false).
• Core: MAP kinase activity in the osmosensory signaling pathway / stress-activated MAPK cascade / cellular hyperosmotic response (cytoplasm, nucleus); MAP kinase activity driving positive regulation of Pol II transcription at osmostress genes (nucleus, chromatin).
• GO:0000161 "osmosensory signaling MAPK cascade" is obsolete (checked with runoak), so it was not used.

2026-10-11 fungal PAINT re-review

• Re-fetched yeast/HOG1; the 60 GOA rows were still in sync with the existing review and validation passed before PAINT edits.
• PTHR24055 PAINT currently uses the broad MAPK-family PANTHER:PTN000622075 for generic Ser/Thr kinase activity, nucleus and cytoplasm, and the fungal HOG/Sty1 PANTHER:PTN001172058 for osmosensory signaling pathway, cellular response to oxidative stress, and stress-activated MAPK cascade. These six IBAs remain biologically correct for budding yeast Hog1. The broad node is safe for kinase/nucleocytoplasmic calls because Hog1 is an intact MAPK with direct cytoplasmic and nuclear substrates, and the fungal HOG/Sty1 node matches the HOG cascade; the oxidative-stress process remains non-core because peroxide/organic-acid activation is contextual relative to the central hyperosmotic response. The peroxide support was rechecked from a UniProt-cited primary paper. PMID:15177185
• A fresh PubMed sweep found and cached the 2013 Rgc2/Fps1 mechanism paper, resolving the initial-review caveat above. Hog1 is recruited to the Fps1 N-terminal cytoplasmic domain and phosphorylates Rgc2 to close the glycerol channel. PMID:24298058
• Newer full-text HOG literature extends the non-osmotic and SHO1-gating picture but does not overturn the core PAINT calls: acetic-acid stress granules scaffold Hog1 with its upstream kinase Pbs2 PMID:40067148, and the SHO1 branch has three osmotic gates, including control over Pbs2-to-Hog1 phosphorylation PMID:42256267. A 2024 flocculation paper also links HOG signaling to FLO-gene expression and flocculation, but its abstract does not justify any new core GO term. PMID:38648231
• Attempted just deep-research yeast HOG1 --provider falcon --fallback perplexity-lite, but no Falcon or Perplexity provider credentials were available in this run. The existing Falcon research file plus cached primary literature were sufficient for this targeted PAINT re-review.