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Names & Taxonomy

Uniprot ID:: O00141
Entry Name:: SGK1_HUMAN
Status:: reviewed
Protein Names:: Serine/threonine-protein kinase Sgk1 (EC 2.7.11.1) (Serum/glucocorticoid-regulated kinase 1)
Gene Names:: SGK1 SGK
Gene Names Primary:: SGK1
Organism:: Homo sapiens (Human)

Structure

Length:: 431
Sequence:: MTVKTEAAKGTLTYSRMRGMVAILIAFMKQRRMGLNDFIQKIANNSYACKHPEVQSILKISQPQEPELMNANPSPPPSPSQQINLGPSSNPHAKPSDFHFLKVIGKGSFGKVLLARHKAEEVFYAVKVLQKKAILKKKEEKHIMSERNVLLKNVKHPFLVGLHFSFQTADKLYFVLDYINGGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKENIEHNSTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKPLQLKPNITNSARHLLEGLLQKDRTKRLGAKDDFMEIKSHVFFSLINWDDLINKKITPPFNPNVSGPNDLRHFDPEFTEEPVPNSIGKSPDSVLVTASVKEAAEAFLGFSYAPPTDSFL
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cytoplasm. Nucleus. Endoplasmic reticulum membrane. Cell membrane. Mitochondrion. 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.; Isoform 2: Cell membrane.

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 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.
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:: 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. Phosphorylation at Ser-397 and Ser-401 are also essential for its activity. Activated by WNK1, WNK2, WNK3 and WNK4.
Active Site:: ACT_SITE 222 222 Proton acceptor.
Gene Ontology Go:: cytoplasm
cytosol
endoplasmic reticulum membrane
mitochondrion
neuron projection
nucleoplasm
nucleus
perinuclear region of cytoplasm
plasma membrane
ATP binding
calcium channel regulator activity
chloride channel regulator activity
cofactor binding
potassium channel regulator activity
protein serine/threonine kinase activity
protein serine/threonine/tyrosine kinase activity
sodium channel regulator activity
apoptotic process
cellular response to DNA damage stimulus
cellular sodium ion homeostasis
glucocorticoid mediated signaling pathway
intracellular signal transduction
ion transmembrane transport
long-term memory
microtubule depolymerization
negative regulation of apoptotic process
negative regulation of microtubule polymerization
neuron projection morphogenesis
peptidyl-serine phosphorylation
positive regulation of cell growth
positive regulation of dendrite morphogenesis
positive regulation of sodium ion transport
positive regulation of transporter activity
protein phosphorylation
regulation of apoptotic process
regulation of blood pressure
regulation of catalytic activity
regulation of cell cycle
regulation of cell growth
regulation of cell migration
regulation of cell proliferation
regulation of gastric acid secretion
regulation of sequence-specific DNA binding transcription factor activity
renal sodium ion absorption
response to stress
sodium ion transport
transmembrane transport
visual learning
Gene Ontology Biological Process:: apoptotic process
cellular response to DNA damage stimulus
cellular sodium ion homeostasis
glucocorticoid mediated signaling pathway
intracellular signal transduction
ion transmembrane transport
long-term memory
microtubule depolymerization
negative regulation of apoptotic process
negative regulation of microtubule polymerization
neuron projection morphogenesis
peptidyl-serine phosphorylation
positive regulation of cell growth
positive regulation of dendrite morphogenesis
positive regulation of sodium ion transport
positive regulation of transporter activity
protein phosphorylation
regulation of apoptotic process
regulation of blood pressure
regulation of catalytic activity
regulation of cell cycle
regulation of cell growth
regulation of cell migration
regulation of cell proliferation
regulation of gastric acid secretion
regulation of sequence-specific DNA binding transcription factor activity
renal sodium ion absorption
response to stress
sodium ion transport
transmembrane transport
visual learning
Gene Ontology Molecular Function:: ATP binding
calcium channel regulator activity
chloride channel regulator activity
cofactor binding
potassium channel regulator activity
protein serine/threonine/tyrosine kinase activity
protein serine/threonine kinase activity
sodium channel regulator activity
Gene Ontology Cellular Component:: cytoplasm
cytosol
endoplasmic reticulum membrane
mitochondrion
neuron projection
nucleoplasm
nucleus
perinuclear region of cytoplasm
plasma membrane
Keywords:: 3D-structure
ATP-binding
Alternative promoter usage
Alternative splicing
Apoptosis
Cell membrane
Complete proteome
Cytoplasm
Disulfide bond
Endoplasmic reticulum
Kinase
Membrane
Mitochondrion
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Stress response
Transferase
Ubl conjugation

Names & Taxonomy

Structure

Subcellular location

Function

Publication