Switch #: SWTI000668

Switch type: Binary

Switch subtype: Physicochemical compatibility

Description:
The GSK3-beta binding site at S12 in Estrogen receptor beta (ESR2) is primed by (most likely) RAC-alpha serine/threonine-protein kinase (AKT1). This enhances the binding of SUMO-conjugating enzyme UBC9 (UBE2I) at the adjacent Sumoylation site. This site is also primed at S6 (most likely) by AKT1. The addition of SUMO at K4 stabilises ESR2 as it prevents the ubiquitination at K4 (see switch details)

Participants:
(1) Estrogen receptor beta (ESR2)
(2) Glycogen synthase kinase-3 beta (GSK3B)
(3) SUMO-conjugating enzyme UBC9 (UBE2I)

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 ESR2 - GSK3B

Interfaces
(1) MOD_GSK3_1 motif (₅NSPSSLNS₁₂) in Estrogen receptor beta (ESR2)
(2) Protein kinase domain _(56-340) in Glycogen synthase kinase-3 beta (GSK3B)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₁₂ on Estrogen receptor beta (ESR2)) of the Estrogen receptor beta (ESR2) MOD_GSK3_1 motif - Glycogen synthase kinase-3 beta (GSK3B) Protein kinase domain interaction

2Interaction #2 ESR2 - UBE2I

Interfaces
(3) ELM:MOD_SUMO_PHOS motif (₄KNSP₇) in Estrogen receptor beta (ESR2)
(4) Ubiquitin-conjugating enzyme _(8-152) in SUMO-conjugating enzyme UBC9 (UBE2I)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₆ on Estrogen receptor beta (ESR2)) of the Estrogen receptor beta (ESR2) MOD_SUMO_PHOS motif - SUMO-conjugating enzyme UBC9 (UBE2I) Ubiquitin-conjugating enzyme interaction

(1) Identification of estrogen receptor β as a SUMO-1 target reveals a novel phosphorylated sumoylation motif and regulation by glycogen synthase kinase 3β.
Picard et al. Mol. Cell. Biol. (2012)

Other switches involving participants
Glycogen synthase kinase-3 beta (GSK3B) - 18 more (view)
Estrogen receptor beta (ESR2) - 2 more (view)
SUMO-conjugating enzyme UBC9 (UBE2I) - 8 more (view)

Other switches involving interfaces
Protein kinase domain - 35 more (view)
MOD_GSK3_1 - 18 more (view)
Ubiquitin-conjugating enzyme - 8 more (view)
ELM:MOD_SUMO_PHOS - 1 more (view)