FUS3 (YBL016W, P16892) curation notes

Identity

• Mating-pheromone-response MAP kinase of S. cerevisiae; CMGC Ser/Thr kinase, TEY activation loop (Thr180/Tyr182), EC 2.7.11.24 [file:yeast/FUS3/FUS3-uniprot.txt "Dually phosphorylated on Thr-180 and Tyr-182 by STE7 in response"].
• Paralog: KSS1 (partially redundant; filamentation MAPK). Reviewed in parallel in genes/yeast/KSS1/ — binding-term choices kept consistent (Ste7 -> GO:0031434, Ste11 -> GO:0031435, Kss1-Fus3 and Bck2 rows removed).

Activation (MAPK tier of Ste11 -> Ste7 -> Fus3 on Ste5)

• Thr180/Tyr182 phosphorylation required, STE11/STE7-dependent, not autocatalytic PMID:1628831.
• Ste7 is a dual-specificity kinase that activates Fus3 in vitro PMID:8384702.
• Reconstituted cascade Ste11 -> Ste7 -> Fus3 PMID:8159759.
• High-affinity Ste7 docking PMID:8668180.
• Ste5 scaffold: two-hybrid binding with Ste11/Ste7/Fus3 [PMID:7851759, PMID:8062390]; Ste5-VWA/ms domain catalytically unlocks Fus3 for Ste7 PMID:19303851.
• Ste5 FBD allosterically triggers Fus3 autophosphorylation (monophosphorylated Fus3), promoting Ste5 phosphorylation and dampening output (negative feedback) PMID:16424299.
• Fus3 activity is highest in 350-500 kDa Ste5 complex PMID:10233162.

Substrates/outputs

• In vitro kinase assay: STE12 and FAR1 candidates PMID:8334305.
• Dig1/Dig2 (Rst1/Rst2) are Fus3 substrates/partners that repress Ste12 PMID:9094309.
• Fus2 S84 phosphorylation drives Fus2 nuclear export (cell fusion) PMID:22588722.
• Gpa1-Fus3 binding contributes to mating polarity-site guidance, but the 2025 Robertson et al. analysis argues the effect is not explained by Fus3 phosphorylation of Ste4, Ste18, Far1 or Bni1 [PMID:40833811 "binding of Gpa1 to Fus3 contributes to polarity site guidance by pheromone"; PMID:40833811 "phosphorylation of Ste4, Ste18, Far1, and Bni1 by Fus3 does not account"].
• Tec1 T273 phosphorylation -> SCF-dependent degradation -> signaling specificity PMID:15620357; second site T276 needed for Cdc4 binding PMID:19897738.
• Limits Kss1 activation PMID:11583629.
• Kinase-independent inhibition of invasion crosstalk PMID:9393860.

Invasive growth

• Fus3 is a NEGATIVE regulator of haploid invasive growth PMID:10652102; fus3 deletion causes erroneous invasive growth PMID:15620357. So GO:0001403 (positive process) annotations are MODIFIED to GO:2000218.

Ty1

• Fus3 suppresses Ty1 transposition post-translationally, requiring basal activation PMID:9566871. Kept non-core under GO:0010526 (regulation-of-transposition terms are obsolete).

Localization

• Nucleus and cytoplasm, shuttles; mating projection tips PMID:11781566.
• Gradient of active Fus3 emanating from shmoo tip PMID:17952059.
• Nuclear shift during filamentous growth PMID:18417610.
• UniProt "Periplasm" (-> GO:0042597) is an erroneous mapping (cites PMID:11781566 which shows projection tips). Removed.
• Mitochondrion from organelle proteomics only; stress granule from Jain 2016 core proteome — non-core/over-annotated.

Interaction rows with doubtful sources

• PMID:23267104 (Meier et al., Streptococcus pneumoniae interactome) supports a Fus3-Tim12 IPI; the cached text has no yeast content. Removed as uninformative protein binding; not asserting the interaction is false.
• A7TJH8 is Vanderwaltozyma polyspora Ste5 (xeno interaction, PMID:23953117 evolution study).