Serine/threonine-protein kinase Sgk1

UniProt O00141 Organism Homo sapiens Gene SGK, SGK1 EC 2.7.11.1

Also known as: SGK, SGK1

Function

Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1.

Classification

Family (Pfam): PF00069 Pkinase, PF00433 Pkinase_C
InterPro: AGC-kinase_C, Kinase-like_dom_sf, Pkinase_C, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
Functional cluster: Serine/Threonine Protein Kinases

Experimental structures · PDB · 4

2R5T X-ray 1.90A
3HDM X-ray 2.60A
3HDN X-ray 3.10A
7PUE X-ray 2.51A

A predicted model is available from AlphaFold.

Gene Ontology · 31

Neighborhood · nearest proteins

Nearest neighbours of Serine/threonine-protein kinase Sgk1: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Serine/threonine-protein kinase Sgk3 19 shared papers
Serine/threonine-protein kinase Sgk2 9 shared papers
E3 ubiquitin-protein ligase NEDD4-like 5 shared papers
Amyloid beta precursor protein binding family B member 1 1 shared papers
Mitogen-activated protein kinase kinase kinase 3 1 shared papers
Solute carrier family 2, facilitated glucose transporter member 4 1 shared papers
Sodium/hydrogen exchanger 3 1 shared papers
Mitogen-activated protein kinase 7 1 shared papers
Serine/threonine-protein kinase Sgk1 2 shared papers
Serine/threonine-protein kinase Sgk2 2 shared papers
Forkhead box protein O3 1 shared papers
Cyclic AMP-responsive element-binding protein 1 1 shared papers

Literature · 59 cited papers

WNK1 is a chloride-stimulated scaffold that regulates mTORC2 activity and ion transport. J. Cell Sci. · 2022
Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+ exchanger NHE3 by glucocorticoids. Mol. Biol. Cell · 2011
Second AKT: the rise of SGK in cancer signalling. Growth Factors · 2010
Interaction of serum- and glucocorticoid regulated kinase 1 (SGK1) with the WW-domains of Nedd4-2 is required for epithelial sodium channel regulation. PLoS ONE · 2010
Significance of SGK1 in the regulation of neuronal function. J. Physiol. (Lond.) · 2010
The serum and glucocorticoid inducible kinases SGK1-3 stimulate the neutral amino acid transporter SLC6A19. Cell. Physiol. Biochem. · 2010
mTOR complex-2 activates ENaC by phosphorylating SGK1. J. Am. Soc. Nephrol. · 2010
Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
Sgk1 activates MDM2-dependent p53 degradation and affects cell proliferation, survival, and differentiation. J. Mol. Med. · 2009
Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration. J. Hepatol. · 2009
Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
Regulation of a third conserved phosphorylation site in SGK1. J. Biol. Chem. · 2009
… and 47 more in the literature graph

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