Switch #: SWTI000282

Switch type: Specificity

Switch subtype: Altered binding specificity

Description:
Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 1 (FGD1), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD1 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD1 for degradation.

Participants:
(1) FYVE, RhoGEF and PH domain-containing protein 1 (FGD1)
(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 FGD1 - GSK3B

Is mutually exclusive with Interaction #2 FGD1 - BTRC

Interfaces
(1) MOD_GSK3_1 motif (₂₈₀NRDSGIDS₂₈₇) in FYVE, RhoGEF and PH domain-containing protein 1 (FGD1)
(2) Protein kinase domain _(56-340) in Glycogen synthase kinase-3 beta (GSK3B)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₂₈₇ on FYVE, RhoGEF and PH domain-containing protein 1 (FGD1)) of the FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) MOD_GSK3_1 motif - Glycogen synthase kinase-3 beta (GSK3B) Protein kinase domain interaction

2Interaction #2 FGD1 - BTRC

Requires Interaction #1 FGD1 - GSK3B
Is mutually exclusive with Interaction #1 FGD1 - GSK3B

Interfaces
(3) DEG_SCF_TRCP1_1 motif (₂₈₂DSGIDS₂₈₇) in FYVE, RhoGEF and PH domain-containing protein 1 (FGD1)
(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 S₂₈₃ and S₂₈₇ on FYVE, RhoGEF and PH domain-containing protein 1 (FGD1)) of the FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) 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: S₂₈₃: Glycogen synthase kinase-3 beta (GSK3B)

(1) The FWD1/beta-TrCP-mediated degradation pathway establishes a 'turning off switch' of a Cdc42 guanine nucleotide exchange factor, FGD1.
Hayakawa et al. Genes Cells (2005)

Other switches involving participants
Glycogen synthase kinase-3 beta (GSK3B) - 18 more (view)
F-box/WD repeat-containing protein 1A (BTRC) - 17 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_TRCP1_1 - 17 more (view)