Switch #: SWTI000278

Switch type: Specificity

Switch subtype: Altered binding specificity

Description:
Phosphorylation of Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) at S384 by CDK2 primes CCNE1 for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B) at T380, which creates a recognition site for F box proteins of the SCF ubiquitin ligase complex (F-box/WD repeat-containing protein 7 (FBXW7)) that target CCNE1 for degradation.

Participants:
(1) Isoform E-S of G1/S-specific cyclin-E1 (CCNE1)
(2) Glycogen synthase kinase-3 beta (GSK3B)
(3) F-box/WD repeat-containing protein 7 (FBXW7)

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 CCNE1 - GSK3B

Is mutually exclusive with Interaction #2 CCNE1 - FBXW7

Interfaces
(1) MOD_GSK3_1 motif (₃₇₇GLLTPPQS₃₈₄) in Isoform E-S of G1/S-specific cyclin-E1 (CCNE1)
(2) Protein kinase domain _(56-340) in Glycogen synthase kinase-3 beta (GSK3B)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₃₈₄ on Isoform E-S of G1/S-specific cyclin-E1 (CCNE1)) of the Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) MOD_GSK3_1 motif - Glycogen synthase kinase-3 beta (GSK3B) Protein kinase domain interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S₃₈₄: Cyclin-dependent kinase 2 (CDK2)

2Interaction #2 CCNE1 - FBXW7

Requires Interaction #1 CCNE1 - GSK3B
Is mutually exclusive with Interaction #1 CCNE1 - GSK3B

Interfaces
(3) DEG_SCF_FBW7_1 motif (₃₇₈LLTPPQS₃₈₄) in Isoform E-S of G1/S-specific cyclin-E1 (CCNE1)
(4) WD domain, G-beta repeat _(371-407) and _(411-447) and _(451-487) and _(491-527) and _(531-567) and _(571-607) and _(611-650) in F-box/WD repeat-containing protein 7 (FBXW7)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of T₃₈₀ and S₃₈₄ on Isoform E-S of G1/S-specific cyclin-E1 (CCNE1)) of the Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) DEG_SCF_FBW7_1 motif - F-box/WD repeat-containing protein 7 (FBXW7) WD domain, G-beta repeat interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: T₃₈₀: Glycogen synthase kinase-3 beta (GSK3B); S₃₈₄: Cyclin-dependent kinase 2 (CDK2)

(1) Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation.
Welcker et al. Mol. Cell (2003)

Other switches involving participants
Glycogen synthase kinase-3 beta (GSK3B) - 18 more (view)
F-box/WD repeat-containing protein 7 (FBXW7) - 8 more (view)

Other switches involving interfaces
Protein kinase domain - 35 more (view)
MOD_GSK3_1 - 18 more (view)
WD domain, G-beta repeat - 36 more (view)
DEG_SCF_FBW7_1 - 4 more (view)