Switch #: SWTI000297

Switch type: Specificity

Switch subtype: Altered binding specificity

Description:
Phosphorylation of Zinc finger protein SNAI1 (SNAI1) at S100 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of S96 by GSK3B targets Zinc finger protein SNAI1 (SNAI1) to the SCF ubiquitin ligase complexes F-box/WD repeat-containing protein 1A (BTRC), which marks it for degradation.

Participants:
(1) Zinc finger protein SNAI1 (SNAI1)
(2) Glycogen synthase kinase-3 beta (GSK3B)
(3) F-box/WD repeat-containing protein 1A (BTRC)

This is a sequential switch. The interactions in this switch take place in a defined order. The order is defined by numbers to the left of each interaction. More than one interaction can occur in each step, these interactions occur independently but are necessary for future step

1Interaction #1 SNAI1 - GSK3B

Is mutually exclusive with Interaction #2 SNAI1 - BTRC

Interfaces
(1) MOD_GSK3_1 motif (₉₃DEDSGKGS₁₀₀) in Zinc finger protein SNAI1 (SNAI1)
(2) Protein kinase domain _(56-340) in Glycogen synthase kinase-3 beta (GSK3B)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₁₀₀ on Zinc finger protein SNAI1 (SNAI1)) of the Zinc finger protein SNAI1 (SNAI1) MOD_GSK3_1 motif - Glycogen synthase kinase-3 beta (GSK3B) Protein kinase domain interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S₁₀₀ : Glycogen synthase kinase-3 beta (GSK3B).

2Interaction #2 SNAI1 - BTRC

Requires Interaction #1 SNAI1 - GSK3B
Is mutually exclusive with Interaction #1 SNAI1 - GSK3B

Interfaces
(3) DEG_SCF_TRCP1_1 motif (₉₅DSGKGS₁₀₀) in Zinc finger protein SNAI1 (SNAI1)
(4) WD domain, G-beta repeat _(297-329) and _(333-369) and _(373-409) and _(416-452) and _(456-492) and _(496-532) and _(545-581) in F-box/WD repeat-containing protein 1A (BTRC)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₉₆ and S₁₀₀ on Zinc finger protein SNAI1 (SNAI1)) of the Zinc finger protein SNAI1 (SNAI1) DEG_SCF_TRCP1_1 motif - F-box/WD repeat-containing protein 1A (BTRC) WD domain, G-beta repeat interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S₉₆: Glycogen synthase kinase-3 beta (GSK3B)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S₉₆ : Glycogen synthase kinase-3 beta (GSK3B). S₁₀₀ : Glycogen synthase kinase-3 beta (GSK3B).

(1) The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation.
Viñas-Castells et al. J. Biol. Chem. (2010)

(2) Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition.
Zhou et al. Nat. Cell Biol. (2004)