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Protein: SGK1_HUMAN

Serine/threonine-protein kinase Sgk1

FUNCTION: Protein kinase that plays an important role in cellular stress response. Activates certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability and renal sodium excretion. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Mediates cell survival signals, phosphorylates and negatively regulates pro-apoptotic FOXO3A. Phosphorylates NEDD4L, which leads to its inactivation and to the subsequent activation of various channels and transporters such as ENaC, KCNA3/Kv1.3 or EAAT1. Isoform 2 exhibited a greater effect on cell plasma membrane expression of ENaC and Na(+) transport than isoform 1. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. more...

ENZYME REGULATION: Two specific sites, one in the kinase domain (Thr-256) and the other in the C-terminal regulatory region (Ser- 422), need to be phosphorylated for its full activation.

SUBUNIT: Interacts with NEDD4 and NEDD4L.

SUBCELLULAR LOCATION: Isoform 2: Cell membrane.

SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Endoplasmic reticulum. Note=Nuclear, upon phosphorylation.

ALTERNATIVE PRODUCTS: Event=Alternative promoter usage, Alternative splicing; Named isoforms=5; Name=1; IsoId=O00141-1; Sequence=Displayed; Name=2; Synonyms=Sgk1.1, Sgk1_v2; IsoId=O00141-2; Sequence=VSP_037784; Note=Produced by alternative promoter usage; Name=3; Synonyms=Sgk1.2; IsoId=O00141-3; Sequence=VSP_037785; Note=Produced by alternative promoter usage; Name=4; IsoId=O00141-4; Sequence=VSP_037786; Note=Produced by alternative splicing of isoform 1; Name=5; IsoId=O00141-5; Sequence=VSP_037787; Note=Produced by alternative promoter usage;

TISSUE SPECIFICITY: Expressed in most tissues with highest levels in the pancreas, followed by placenta, kidney and lung. Isoform 2 is strongly expressed in brain and pancreas, weaker in heart, placenta, lung, liver and skeletal muscle.

INDUCTION: Isoform 1 is induced by serum and/or glucocorticoids. Isoform 2 is not induced by glucocorticoids. By excessive extracellular glucose and by TGFB1, in cultured cells.

DOMAIN: Isoform 2 subcellular localization at the plasma membrane is mediated by the sequences within the first 120 amino acids.

PTM: Regulated by phosphorylation. Phosphoinositide 3-kinase (PI3- kinase) pathway promotes phosphorylation at Ser-422 which in turn increases the phosphorylation of Thr-256 by PDPK1.

PTM: Ubiquitinated by NEDD4L; which promotes proteasomal degradation. Ubiquitinated by SYVN1 at the endoplasmic reticulum; which promotes rapid proteasomal degradation and maintains a high turnover rate in resting cells. Isoform 2 shows enhanced stability. Isoform 2 resistance to proteasomal degradation is mediated by the sequences within the first 120-amino acid.

SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.

SIMILARITY: Contains 1 AGC-kinase C-terminal domain.

SIMILARITY: Contains 1 protein kinase domain.

GENE SYNONYMS: SGK.

COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.

 

Organism:

  • Homo sapiens

Gene Symbol:

  • SGK1

Synonyms:

  • Serum/glucocorticoid-regulated kinase 1
  • 2.7.11.1

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