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.