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Switch #:
SWTI000323
Switch type:
Specificity
Switch subtype:
Domain hiding

Description:
Phosphorylation of Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) by Serine/threonine-protein kinase Sgk1 (SGK1) induces binding to 14-3-3 protein eta (YWHAH). This inhibits (whether allosterically or sterically is not known) interactions of NEDD4L via its WW domains with the PY motif in Amiloride-sensitive sodium channel subunit gamma (SCNN1G) (ENaC). As a result, ENaC does not get degraded and ENaC-mediated Na+ currents increase.

Participants:
(1) Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)
(2) 14-3-3 protein eta (YWHAH)
(3) Amiloride-sensitive sodium channel subunit gamma (SCNN1G)

Interactions
Interaction #1 NEDD4L - YWHAH

Is mutually exclusive with Interaction #2 SCNN1G - NEDD4L

Interfaces
(1) LIG_14-3-3_1 motif (465RSLSSP470) in Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)
(2) 14-3-3 protein (4-241) in 14-3-3 protein eta (YWHAH)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S468 on Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)) of the Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) LIG_14-3-3_1 motif - 14-3-3 protein eta (YWHAH) 14-3-3 protein interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S468: Serine/threonine-protein kinase Sgk1 (SGK1)

Interaction #2 SCNN1G - NEDD4L

Is mutually exclusive with Interaction #1 NEDD4L - YWHAH

Interfaces
(3) LIG_WW_1 motif (624PPKY627) in Amiloride-sensitive sodium channel subunit gamma (SCNN1G)
(4) WW domain (235-264) and (407-436) and (519-548) and (570-599) in Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)

Interaction Regulation
Effector binding Abrogation (14-3-3 protein eta (YWHAH)) of the Amiloride-sensitive sodium channel subunit gamma (SCNN1G) LIG_WW_1 motif - Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) WW domain interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S468: Serine/threonine-protein kinase Sgk1 (SGK1)

Context
Switch localisation
ELM curated: nucleus, cytosol, internal side of plasma membrane, integral membrane protein, integral plasma membrane protein


Switch pathways
Inferred: Aldosterone-regulated sodium reabsorption
References

(1) 14-3-3 Mediates phosphorylation-dependent inhibition of the interaction between the ubiquitin E3 ligase Nedd4-2 and epithelial Na+ channels.
Nagaki et al. Biochemistry (2006)

See also

Other switches involving participants
14-3-3 protein eta (YWHAH) - 1 more (view)

Other switches involving interfaces
WW domain - 105 more (view)
14-3-3 protein - 38 more (view)
LIG_14-3-3_1 - 13 more (view)
LIG_WW_1 - 17 more (view)




Choose visualisation: NEDD4L SCNN1G



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