Switch #:
SWTI000283
Switch type:
Specificity
Switch subtype:
Altered binding specificity

Description:
Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation.

Participants:
(1) FYVE, RhoGEF and PH domain-containing protein 3 (FGD3)
(2) Glycogen synthase kinase-3 beta (GSK3B)
(3) F-box/WD repeat-containing protein 1A (BTRC)

Interactions
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 FGD3 - GSK3B

Is mutually exclusive with

Interfaces
(1) MOD_GSK3_1 motif (77GIDSPSSS84) in FYVE, RhoGEF and PH domain-containing protein 3 (FGD3)
(2) Protein kinase domain (56-340) in Glycogen synthase kinase-3 beta (GSK3B)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S84 on FYVE, RhoGEF and PH domain-containing protein 3 (FGD3)) of the FYVE, RhoGEF and PH domain-containing protein 3 (FGD3) MOD_GSK3_1 motif - Glycogen synthase kinase-3 beta (GSK3B) Protein kinase domain interaction

2Interaction #2 FGD3 - GSK3B

Requires Interaction #1 FGD3 - GSK3B
Is mutually exclusive with

Interfaces
(3) MOD_GSK3_1 motif (73NRDSGIDS80) in FYVE, RhoGEF and PH domain-containing protein 3 (FGD3)
(4) Protein kinase domain (56-340) in Glycogen synthase kinase-3 beta (GSK3B)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S80 on FYVE, RhoGEF and PH domain-containing protein 3 (FGD3)) of the FYVE, RhoGEF and PH domain-containing protein 3 (FGD3) MOD_GSK3_1 motif - Glycogen synthase kinase-3 beta (GSK3B) Protein kinase domain interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S80: Glycogen synthase kinase-3 beta (GSK3B)

3Interaction #3 FGD3 - BTRC

Requires Interaction #2 FGD3 - GSK3B
Is mutually exclusive with

Interfaces
(5) DEG_SCF_TRCP1_1 motif (75DSGIDS80) in FYVE, RhoGEF and PH domain-containing protein 3 (FGD3)
(6) 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 S76 and S80 on FYVE, RhoGEF and PH domain-containing protein 3 (FGD3)) of the FYVE, RhoGEF and PH domain-containing protein 3 (FGD3) 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: S76: Glycogen synthase kinase-3 beta (GSK3B); S80: Glycogen synthase kinase-3 beta (GSK3B)

Context
Switch localisation
ELM curated: cytosol, nucleus, nucleoplasm, Chromosome
Inferred: cytosol, nucleus


Switch pathways
Inferred: Wnt signaling pathway, Hedgehog signaling pathway
References

(1) Novel insights into FGD3, a putative GEF for Cdc42, that undergoes SCF(FWD1/beta-TrCP)-mediated proteasomal degradation analogous to that of its homologue FGD1 but regulates cell morphology and motility differently from FGD1.
Hayakawa et al. Genes Cells (2008)




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