A decomposition of the Saccharomyces cerevisiae high-osmolarity glycerol (HOG) MAP kinase cascade, the osmostress-activated fungal realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay). High external osmolarity is sensed by two upstream branches - the Sln1 two-component phosphorelay (which derepresses the MAP3Ks Ssk2/Ssk22) and the Sho1 branch (which routes through Ste11) - both converging on the single MAP2K Pbs2, which dually phosphorylates the MAPK Hog1 on its TGY activation-loop motif. Active Hog1 translocates to the nucleus and activates transcription factors (Hot1, Msn2/Msn4, Sko1) that induce glycerol-biosynthesis and stress-response genes restoring osmotic balance. The kinase relay - Ssk2/Ssk22 -> Pbs2 -> Hog1 - is declared as an inner bundle that `conforms_to` mapk_relay, while the osmosensing input and the Hog1 transcriptional output are this cascade's free extensions around the conforming core. Grounded in GO:0007231 (osmosensory signaling pathway).
This module is the Saccharomyces cerevisiae HOG-pathway realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay), and embeds two nested conforming bundles: the inner `sln1_phosphorelay` node bundles the Sln1 -> Ypd1 -> Ssk1 tiers and conforms to MODULE:two_component_relay, and the inner `hog1_relay` node bundles the Ssk2/Ssk22 -> Pbs2 -> Hog1 tiers and conforms to mapk_relay. The downstream Hog1 transcriptional output is this cascade's free extension around the conforming cores. Representative UniProt members (Sln1 P39928, Ypd1 Q07688, Ssk1 Q07084, Ssk2 P53599, Pbs2 P08018, Hog1 P32485) were verified against UniProt. No matching UniProt-seed PAINT IBD rows were found in the local interpro/panther cache for these S. cerevisiae exemplars, so this species-specific cascade is not assigned a PTN ancestry anchor in this pass.
All recommended fields populated.
✗ none found
No MODULE:scer_hog1_cascade deep-research report alongside the module YAML.
1 leaf node(s) with no concrete protein grounding:
✓ every declared conforms_to bundle matches its template motif.
0 complete review(s) · 0 with deep research · 6 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| Pbs2 P08018 | ✗ | — | — |
| Hog1 P32485 | ✗ | — | — |
| Sln1 P39928 | ✗ | — | — |
| Ssk2 P53599 | ✗ | — | — |
| Ssk1 Q07084 | ✗ | — | — |
| Ypd1 Q07688 | ✗ | — | — |
High external osmolarity is sensed by the Sln1 two-component phosphorelay: the sensor histidine kinase Sln1 transfers a phosphoryl group through the Hpt intermediate Ypd1 to the response regulator Ssk1. Under high osmolarity Sln1 is inactivated, so Ssk1 accumulates unphosphorylated and activates the Ssk2/Ssk22 MAP3K tier (a derepression logic). A parallel Sho1 branch (via Ste11) also feeds Pbs2. This bundle is an instance of the generic two-component phosphorelay.
The osmosensor histidine kinase Sln1 autophosphorylates and feeds the relay.
Senses osmolarity and initiates the phosphorelay.
The Hpt intermediate Ypd1 shuttles the phosphoryl group from Sln1 to Ssk1.
Relays the phosphoryl group from Sln1 to Ssk1.
The response regulator Ssk1 receives the phosphoryl group; its unphosphorylated (high-osmolarity) form activates the Ssk2/Ssk22 MAP3K tier.
Couples the phosphorelay state to the Ssk2/Ssk22 MAP3K tier.
The three-tier kinase relay of the HOG cascade: the MAP3K Ssk2 (with paralog Ssk22) phosphorylates the MAP2K Pbs2, which dually phosphorylates the MAPK Hog1 on its TGY activation-loop motif.
The MAP3K Ssk2 (and its paralog Ssk22), derepressed by the Sln1 phosphorelay, phosphorylates and activates Pbs2.
Top kinase tier; activates Pbs2.
The dual-specificity MAP2K Pbs2, which also scaffolds the pathway, phosphorylates Hog1 on both threonine and tyrosine of its TGY motif.
Middle kinase tier; dual-specificity activation of Hog1.
Dually phosphorylated Hog1 becomes an active proline-directed serine/threonine kinase and translocates to the nucleus to act on osmostress substrates.
Effector kinase transducing the osmostress signal to substrates.
Nuclear Hog1 activates transcription factors (Hot1, Msn2/Msn4, Sko1) that induce glycerol-biosynthesis (e.g. GPD1) and general stress-response genes, restoring osmotic balance; Hog1 also has cytoplasmic targets controlling cell-cycle and translation.
Converts Hog1 activity into the osmostress gene program.