Q06226
uniprot
Q06226
canonical
activity_regulation
ACTIVITY REGULATION: Two specific sites, one in the kinase domain (Thr-256) and the other in the C-terminal regulatory region (Ser-421), need to be phosphorylated for its full activation (PubMed:16006511). Phosphorylation at Ser-396 and Ser-400 are also essential for its activity (By similarity). Activated by WNK1, WNK2, WNK3 and WNK4 (PubMed:16006511). {ECO:0000250|UniProtKB:O00141, ECO:0000269|PubMed:16006511}.
uniprot
proteins
amino_acid_sequence
MTVKTEAARSTLTYSRMRGMVAILIAFMKQRRMGLNDFIQKLANNSYACKHPEVQSYLKISQPQEPELMNANPSPPPSPSQQINLGPSSNPHAKPSDFHFLKVIGKGSFGKVLLARHKAEEAFYAVKVLQKKAILKKKEEKHIMSERNVLLKNVKHPFLVGLHFSFQTADKLYFVLDYINGGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKENIEHNGTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKPLQLKNITNSARHLLEGLLQKDRTKRLGAKDDFMEIKSHIFFSLINWDDLINKKITPPFNPNVSGPSDLRHFDPEFTEEPVPSSIGRSPDSILVTASVKEAAEAFLGFSYAPPMDSFL
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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 SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. 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 (By similarity). Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. May also play an important role in the development of particular groups of neurons in the postnatal brain. {ECO:0000250, ECO:0000269|PubMed:15504348, ECO:0000269|PubMed:16982696, ECO:0000269|PubMed:19447520}.
uniprot
proteins
mass_dalton
48927
uniprot
proteins
mutagenesis
MUTAGEN 78; /note="S->A: Does not affect SGK1 activation."; /evidence="ECO:0000269|PubMed:16006511"; MUTAGEN 256; /note="T->A: Decreased activation of SGK1."; /evidence="ECO:0000269|PubMed:16006511"; MUTAGEN 256; /note="T->D: Mimics phosphorylation; leading to basal activity."; /evidence="ECO:0000269|PubMed:16006511"; MUTAGEN 421; /note="S->A: Decreased activation of SGK1."; /evidence="ECO:0000269|PubMed:16006511"; MUTAGEN 421; /note="S->D: Mimics phosphorylation; leading to basal activity."; /evidence="ECO:0000269|PubMed:16006511
uniprot
proteins
post_translational_modification
PTM: Regulated by phosphorylation. Activated by phosphorylation on Ser-421 by mTORC2, transforming it into a substrate for PDPK1 which phosphorylates it on Thr-256 (PubMed:16006511). Phosphorylation on Ser-396 and Ser-400 are also essential for its activity (By similarity). Phosphorylation on Ser-78 by MAPK7 is required for growth factor-induced cell cycle progression (PubMed:16006511). {ECO:0000250|UniProtKB:O00141, ECO:0000269|PubMed:16006511}.; 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 (By similarity). {ECO:0000250}.
uniprot
proteins
protein_family
AGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10051674
uniprot
proteins
pubmed
10357815
uniprot
proteins
pubmed
15504348
uniprot
proteins
pubmed
16006511
uniprot
proteins
pubmed
16982696
uniprot
proteins
pubmed
19447520
uniprot
proteins
pubmed
7740159
uniprot
proteins
pubmed
7854047
uniprot
proteins
pubmed
8455596
uniprot
proteins
pubmed
8647846
uniprot
proteins
sequence_length
430
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Endoplasmic reticulum membrane {ECO:0000250}. Cell membrane {ECO:0000250}. Mitochondrion {ECO:0000250}. Note=The subcellular localization is controlled by the cell cycle, as well as by exposure to specific hormones and environmental stress stimuli. In proliferating cells, it shuttles between the nucleus and cytoplasm in synchrony with the cell cycle, and in serum/growth factor-stimulated cells it resides in the nucleus. In contrast, after exposure to environmental stress or treatment with glucocorticoids, it is detected in the cytoplasm and with certain stress conditions is associated with the mitochondria. In osmoregulation through the epithelial sodium channel, it can be localized to the cytoplasmic surface of the cell membrane. Nuclear, upon phosphorylation (By similarity). {ECO:0000250}.
uniprot
proteins