STE7 (YDL159W, UniProt P06784) curation notes

Identity

Ste7, 515 aa, protein kinase domain 191-466; STE Ser/Thr kinase family, MAP kinase kinase subfamily
(UniProt). PANTHER PTHR48013:SF9 (MAP2K family). Activation-loop Ser359/Thr363 phosphorylated; S359A
and T363A are inactive [file:yeast/STE7/STE7-uniprot.txt, MUTAGEN features citing PMID:8131746].

Dual-specificity kinase that phosphorylates Fus3 on its activation-loop Thr/Tyr and activates it
PMID:8384702.
In vitro reconstituted cascade: Ste11 -> Ste7 -> Fus3 PMID:8159759; Ste11-dependent phosphosite required for Ste7 activity PMID:8159759.
Pheromone activates Ste7 independently of Fus3/Kss1; Ste7 activation precedes MAPK modification
PMID:8455599.
High-affinity docking of Kss1 and Fus3 to Ste7 (Kd ~5 nM), independent of catalytic core; Hog1, Mpk1
and Erk2 do not bind; docking-region deletions reduce signaling PMID:8668180.
Substrate selectivity: Kss1 is intrinsically a good Ste7 substrate, Fus3 a poor one; the Ste5
minimal-scaffold (VWA) domain binds Ste7 tightly and "unlocks" Fus3 (~5000-fold kcat increase)
PMID:19303851. Conserved across Fus3 orthologs PMID:23953117.
Reciprocal feedback: Fus3/Kss1 phosphorylate Ste7 (hyperphosphorylation) [PMID:8455599,
PMID:15456892]; feedback phosphorylation does not attenuate Ste7 kinase activity PMID:15456892.
GO: GO:0004708 MAP kinase kinase activity (is_a GO:0004712 protein Ser/Thr/Tyr kinase activity).
Rhea-based IEAs for Tyr kinase (true: Tyr of TEY/TXY motif) and Ser kinase (no evidence of physiological
Ser phosphorylation; treated as over-annotation from the EC 2.7.12.2 reaction set).

Pheromone response MAPK cascade (Ste20-Ste11-Ste7-Fus3/Kss1 on the Ste5 scaffold) [PMID:8455599,
PMID:8668180, PMID:8062390, PMID:7851759].
Filamentous/invasive growth pathway: Ste7 -> Kss1, Ste5-independent PMID:9363895;
haploid invasive growth and diploid pseudohyphal growth require STE7 [PMID:8001818, PMID:8643578].
Constitutive Ste7 activates Kss1 but not Fus3 in vivo, driving invasion but not mating PMID:15456892.
Glycosylation-defect response: a Sho1 -> Ste20/Ste50 -> Ste11 -> Ste7 -> Kss1 -> Ste12 pathway activates
FUS1 and contributes to cell wall integrity PMID:10880465. GO:0000196 "cell integrity MAPK cascade"
is defined as the Slt2-containing cascade; Ste7 is not a tier of that cascade, so the annotation is a
term mismatch (MODIFY to generic MAPK cascade).

Predominantly cytoplasmic; localizes to mating projection tips in pheromone-treated cells
PMID:11781566; Fus3-activating kinases partitioned to shmoo tip PMID:17952059.

Kss1/Fus3: direct high-affinity docking (PMID:8668180) plus Y2H/AP-MS -> MODIFY to GO:0051019
mitogen-activated protein kinase binding.
Ste5: scaffold binding (PMID:8062390, PMID:7851759, PMID:9311911, PMID:19303851) -> MODIFY to
GO:0097110 scaffold protein binding.
Hog1 (AP-MS, PMID:20489023): Bardwell 1996 found no detectable Hog1-Ste7 association in vitro; Hog1 is
activated by Pbs2 not Ste7 -> REMOVE (uninformative; not asserting the co-purification is false).
Cdc14 (AP-MS, PMID:20489023): no functional consequence for Ste7 established in cached text -> REMOVE.

Pheromone-dependent Ste7 polyubiquitination regulated by Ubp3 (Wang & Dohlman 2002, JBC) [cited via
file:yeast/STE7/STE7-deep-research-falcon.md; not fetched].