SGK1
entrez
6446
canonical
uniprot
O00141
canonical
ensembl
ENSG00000118515
resolver
ensp
ENSP00000237305
resolver
ensp
ENSP00000356832
resolver
ensp
ENSP00000396242
resolver
ensp
ENSP00000434302
resolver
ensp
ENSP00000434450
resolver
enst
ENST00000475719
resolver
genesymbol
SGK1
resolver
genesymbol_syn
SGK
resolver
hgnc
HGNC:10810
resolver
uniprot
B7UUP7
resolver
uniprot
B7UUP8
resolver
uniprot
B7UUP9
resolver
uniprot
B7Z325
resolver
uniprot
B7Z5B2
resolver
uniprot
E1P583
resolver
uniprot
E9PR89
resolver
uniprot
Q5TCN2
resolver
uniprot
Q5TCN3
resolver
uniprot
Q5TCN4
resolver
uniprot
Q5VY65
resolver
uniprot
Q9UN56
resolver
uniprot_entry
B7Z325_HUMAN
resolver
uniprot_entry
E9PR89_HUMAN
resolver
uniprot_entry
SGK1_HUMAN
resolver
uniprot_sec
B7UUP7
resolver
uniprot_sec
B7UUP8
resolver
uniprot_sec
B7UUP9
resolver
uniprot_sec
B7Z5B2
resolver
uniprot_sec
E1P583
resolver
uniprot_sec
Q5TCN2
resolver
uniprot_sec
Q5TCN3
resolver
uniprot_sec
Q5TCN4
resolver
uniprot_sec
Q5VY65
resolver
uniprot_sec
Q9UN56
resolver
activity_regulation
ACTIVITY 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 (PubMed:10191262). Phosphorylation at Ser-397 and Ser-401 are also essential for its activity (PubMed:19068477). Activated by WNK1, WNK2, WNK3 and WNK4; which promote phosphorylation by mTORC2 (PubMed:36373794). {ECO:0000269|PubMed:10191262, ECO:0000269|PubMed:19068477, ECO:0000269|PubMed:36373794}.
uniprot
proteins
amino_acid_sequence
MTVKTEAAKGTLTYSRMRGMVAILIAFMKQRRMGLNDFIQKIANNSYACKHPEVQSILKISQPQEPELMNANPSPPPSPSQQINLGPSSNPHAKPSDFHFLKVIGKGSFGKVLLARHKAEEVFYAVKVLQKKAILKKKEEKHIMSERNVLLKNVKHPFLVGLHFSFQTADKLYFVLDYINGGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKENIEHNSTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKPLQLKPNITNSARHLLEGLLQKDRTKRLGAKDDFMEIKSHVFFSLINWDDLINKKITPPFNPNVSGPNDLRHFDPEFTEEPVPNSIGKSPDSVLVTASVKEAAEAFLGFSYAPPTDSFL
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 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. {ECO:0000269|PubMed:11154281, ECO:0000269|PubMed:11410590, ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12397388, ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12634932, ECO:0000269|PubMed:12650886, ECO:0000269|PubMed:12761204, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:14623317, ECO:0000269|PubMed:14706641, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15044175, ECO:0000269|PubMed:15234985, ECO:0000269|PubMed:15319523, ECO:0000269|PubMed:15496163, ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:15737648, ECO:0000269|PubMed:15845389, ECO:0000269|PubMed:15888551, ECO:0000269|PubMed:16036218, ECO:0000269|PubMed:16443776, ECO:0000269|PubMed:16982696, ECO:0000269|PubMed:17382906, ECO:0000269|PubMed:18005662, ECO:0000269|PubMed:18304449, ECO:0000269|PubMed:18753299, ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:19756449, ECO:0000269|PubMed:20511718, ECO:0000269|PubMed:20730100, ECO:0000269|PubMed:21865597}.
uniprot
proteins
mass_dalton
48942
uniprot
proteins
mutagenesis
MUTAGEN 127; /note="K->M: Abolishes enzymatic activity."; /evidence="ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001"; MUTAGEN 256; /note="T->A: Low activity."; /evidence="ECO:0000269|PubMed:10191262"; MUTAGEN 256; /note="T->D: Low activity."; /evidence="ECO:0000269|PubMed:10191262"; MUTAGEN 256; /note="T->E: Low activity."; /evidence="ECO:0000269|PubMed:10191262"; MUTAGEN 298; /note="Y->A: Abolishes interaction with NEDD4 and NEDD4L."; /evidence="ECO:0000269|PubMed:11696533"; MUTAGEN 422; /note="S->A: Low activity."; /evidence="ECO:0000269|PubMed:10191262, ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001"; MUTAGEN 422; /note="S->D: 10-fold activation."; /evidence="ECO:0000269|PubMed:10191262, ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001
uniprot
proteins
post_translational_modification
PTM: Regulated by phosphorylation (PubMed:10191262, PubMed:11096081, PubMed:18925875, PubMed:20338997, PubMed:36373794). Activated by phosphorylation on Ser-422 by mTORC2, transforming it into a substrate for PDPK1 which phosphorylates it on Thr-256 (PubMed:10191262, PubMed:18925875, PubMed:20338997, PubMed:36373794). Phosphorylation on Ser-397 and Ser-401 are also essential for its activity (PubMed:19068477). Phosphorylation on Ser-78 by MAPK7 is required for growth factor-induced cell cycle progression (PubMed:11254654). {ECO:0000269|PubMed:10191262, ECO:0000269|PubMed:11096081, ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:19068477, ECO:0000269|PubMed:20338997, ECO:0000269|PubMed:36373794}.; 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. {ECO:0000269|PubMed:15576372}.
uniprot
proteins
protein_family
AGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10191262
uniprot
proteins
pubmed
10548550
uniprot
proteins
pubmed
10884438
uniprot
proteins
pubmed
11096081
uniprot
proteins
pubmed
11154281
uniprot
proteins
pubmed
11254654
uniprot
proteins
pubmed
11410590
uniprot
proteins
pubmed
11696533
uniprot
proteins
pubmed
12397388
uniprot
proteins
pubmed
12590200
uniprot
proteins
pubmed
12631736
uniprot
proteins
pubmed
12634932
uniprot
proteins
pubmed
12649597
uniprot
proteins
pubmed
12650886
uniprot
proteins
pubmed
12761204
uniprot
proteins
pubmed
12911626
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14623317
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14706641
uniprot
proteins
pubmed
15040001
uniprot
proteins
pubmed
15044175
uniprot
proteins
pubmed
15234985
uniprot
proteins
pubmed
15319523
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15496163
uniprot
proteins
pubmed
15576372
uniprot
proteins
pubmed
15733869
uniprot
proteins
pubmed
15737648
uniprot
proteins
pubmed
15845389
uniprot
proteins
pubmed
15888551
uniprot
proteins
pubmed
16036218
uniprot
proteins
pubmed
16443776
uniprot
proteins
pubmed
16460280
uniprot
proteins
pubmed
16982696
uniprot
proteins
pubmed
17202226
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17382906
uniprot
proteins
pubmed
17965184
uniprot
proteins
pubmed
18005662
uniprot
proteins
pubmed
18304449
uniprot
proteins
pubmed
18334630
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18753299
uniprot
proteins
pubmed
18925875
uniprot
proteins
pubmed
19068477
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19447520
uniprot
proteins
pubmed
19756449
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20338997
uniprot
proteins
pubmed
20511718
uniprot
proteins
pubmed
20530112
uniprot
proteins
pubmed
20730100
uniprot
proteins
pubmed
20919962
uniprot
proteins
pubmed
21865597
uniprot
proteins
pubmed
36373794
uniprot
proteins
pubmed
9114008
uniprot
proteins
pubmed
9722955
uniprot
proteins
sequence_length
431
uniprot
proteins
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.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane.
uniprot
proteins