Serine/threonine-protein kinase Sgk1

Details

Name
Serine/threonine-protein kinase Sgk1
Synonyms
  • 2.7.11.1
  • Serum/glucocorticoid-regulated kinase 1
  • SGK
Gene Name
SGK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007831|Serine/threonine-protein kinase Sgk1
MTVKTEAAKGTLTYSRMRGMVAILIAFMKQRRMGLNDFIQKIANNSYACKHPEVQSILKI
SQPQEPELMNANPSPPPSPSQQINLGPSSNPHAKPSDFHFLKVIGKGSFGKVLLARHKAE
EVFYAVKVLQKKAILKKKEEKHIMSERNVLLKNVKHPFLVGLHFSFQTADKLYFVLDYIN
GGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTD
FGLCKENIEHNSTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSR
NTAEMYDNILNKPLQLKPNITNSARHLLEGLLQKDRTKRLGAKDDFMEIKSHVFFSLINW
DDLINKKITPPFNPNVSGPNDLRHFDPEFTEEPVPNSIGKSPDSVLVTASVKEAAEAFLG
FSYAPPTDSFL
Number of residues
431
Molecular Weight
48941.96
Theoretical pI
8.81
GO Classification
Functions
ATP binding / calcium channel regulator activity / chloride channel regulator activity / potassium channel regulator activity / protein serine/threonine kinase activity / protein serine/threonine/tyrosine kinase activity / sodium channel regulator activity
Processes
apoptotic process / cellular response to DNA damage stimulus / cellular sodium ion homeostasis / intracellular signal transduction / ion transmembrane transport / long-term memory / neuron projection morphogenesis / peptidyl-serine phosphorylation / 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 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
Components
cytoplasm / cytosol / endoplasmic reticulum membrane / mitochondrion / nucleoplasm / plasma membrane
General Function
Sodium channel regulator activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021373|Serine/threonine-protein kinase Sgk1 (SGK1)
ATGGTAAACAAAGACATGAATGGATTCCCAGTCAAGAAATGCTCAGCCTTCCAATTTTTT
AAGAAGCGGGTACGAAGGTGGATCAAGAGCCCAATGGTCAGTGTGGACAAGCATCAGAGT
CCCAGCCTGAAGTACACCGGCTCCTCCATGGTGCACATCCCTCCAGGGGAGCCAGACTTC
GAGTCTTCCTTGTGTCAAACATGCCTGGGTGAACATGCTTTCCAAAGAGGGGTTCTCCCT
CAGGAGAACGAGTCATGTTCATGGGAAACTCAATCTGGGTGTGAAGTGAGAGAGCCATGT
AATCATGCCAACATCCTGACCAAGCCCGATCCAAGAACCTTCTGGACTAATGATGATCCA
GCTTTCATGAAGCAGAGGAGGATGGGTCTGAACGACTTTATTCAGAAGATTGCCAATAAC
TCCTATGCATGCAAACACCCTGAAGTTCAGTCCATCTTGAAGATCTCCCAACCTCAGGAG
CCTGAGCTTATGAATGCCAACCCTTCTCCTCCACCAAGTCCTTCTCAGCAAATCAACCTT
GGCCCGTCGTCCAATCCTCATGCTAAACCATCTGACTTTCACTTCTTGAAAGTGATCGGA
AAGGGCAGTTTTGGAAAGGTTCTTCTAGCAAGACACAAGGCAGAAGAAGTGTTCTATGCA
GTCAAAGTTTTACAGAAGAAAGCAATCCTGAAAAAGAAAGAGGAGAAGCATATTATGTCG
GAGCGGAATGTTCTGTTGAAGAATGTGAAGCACCCTTTCCTGGTGGGCCTTCACTTCTCT
TTCCAGACTGCTGACAAATTGTACTTTGTCCTAGACTACATTAATGGTGGAGAGTTGTTC
TACCATCTCCAGAGGGAACGCTGCTTCCTGGAACCACGGGCTCGTTTCTATGCTGCTGAA
ATAGCCAGTGCCTTGGGCTACCTGCATTCACTGAACATCGTTTATAGAGACTTAAAACCA
GAGAATATTTTGCTAGATTCACAGGGACACATTGTCCTTACTGACTTCGGACTCTGCAAG
GAGAACATTGAACACAACAGCACAACATCCACCTTCTGTGGCACGCCGGAGTATCTCGCA
CCTGAGGTGCTTCATAAGCAGCCTTATGACAGGACTGTGGACTGGTGGTGCCTGGGAGCT
GTCTTGTATGAGATGCTGTATGGCCTGCCGCCTTTTTATAGCCGAAACACAGCTGAAATG
TACGACAACATTCTGAACAAGCCTCTCCAGCTGAAACCAAATATTACAAATTCCGCAAGA
CACCTCCTGGAGGGCCTCCTGCAGAAGGACAGGACAAAGCGGCTCGGGGCCAAGGATGAC
TTCATGGAGATTAAGAGTCATGTCTTCTTCTCCTTAATTAACTGGGATGATCTCATTAAT
AAGAAGATTACTCCCCCTTTTAACCCAAATGTGAGTGGGCCCAACGACCTACGGCACTTT
GACCCCGAGTTTACCGAAGAGCCTGTCCCCAACTCCATTGGCAAGTCCCCTGACAGCGTC
CTCGTCACAGCCAGCGTCAAGGAAGCTGCCGAGGCTTTCCTAGGCTTTTCCTATGCGCCT
CCCACGGACTCTTTCCTCTGA
Chromosome Location
6
Locus
6q23
External Identifiers
ResourceLink
UniProtKB IDO00141
UniProtKB Entry NameSGK1_HUMAN
GenBank Protein ID1834511
GenBank Gene IDY10032
HGNC IDHGNC:10810
General References
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  32. Shojaiefard M, Christie DL, Lang F: Stimulation of the creatine transporter SLC6A8 by the protein kinases SGK1 and SGK3. Biochem Biophys Res Commun. 2005 Sep 2;334(3):742-6. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03247Flavin mononucleotideapproved, investigationalunknownDetails
DB07837[4-(5-naphthalen-2-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl]acetic acidexperimentalunknownDetails
DB081914-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acidexperimentalunknownDetails