Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Serine/threonine-protein kinase Sgk1

Gene

Sgk1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 Ca2+ 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.By similarity3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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. Phosphorylation at Ser-396 and Ser-400 are also essential for its activity. Activated by WNK1, WNK2, WNK3 and WNK4 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei127 – 1271ATPPROSITE-ProRule annotation
Active sitei222 – 2221Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi104 – 1129ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • 3-phosphoinositide-dependent protein kinase binding Source: RGD
  • ATP binding Source: UniProtKB-KW
  • calcium channel regulator activity Source: GO_Central
  • chloride channel regulator activity Source: GO_Central
  • cofactor binding Source: RGD
  • potassium channel regulator activity Source: GO_Central
  • protein serine/threonine kinase activity Source: RGD
  • sodium channel regulator activity Source: GO_Central
  • tau protein binding Source: RGD

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cellular response to insulin stimulus Source: MGI
  • cellular sodium ion homeostasis Source: RGD
  • glucocorticoid mediated signaling pathway Source: RGD
  • intracellular signal transduction Source: GO_Central
  • long-term memory Source: RGD
  • microtubule depolymerization Source: RGD
  • negative regulation of apoptotic process Source: RGD
  • negative regulation of microtubule polymerization Source: RGD
  • neuron projection morphogenesis Source: RGD
  • peptidyl-serine phosphorylation Source: RGD
  • positive regulation of cell growth Source: RGD
  • positive regulation of dendrite morphogenesis Source: RGD
  • positive regulation of sodium ion transport Source: MGI
  • positive regulation of transporter activity Source: GO_Central
  • protein phosphorylation Source: RGD
  • regulation of cell cycle Source: RGD
  • regulation of cell proliferation Source: GO_Central
  • regulation of protein localization Source: MGI
  • visual learning Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Stress response

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase Sgk1 (EC:2.7.11.1)
Alternative name(s):
Serum/glucocorticoid-regulated kinase 1
Gene namesi
Name:Sgk1
Synonyms:Sgk
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3668. Sgk1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • Endoplasmic reticulum membrane By similarity
  • Cell membrane By similarity
  • Mitochondrion By similarity

  • 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).By similarity

GO - Cellular componenti

  • cytoplasm Source: RGD
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • mitochondrion Source: UniProtKB-SubCell
  • neuron projection Source: RGD
  • nucleus Source: RGD
  • perinuclear region of cytoplasm Source: RGD
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 430430Serine/threonine-protein kinase Sgk1PRO_0000086645Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei74 – 741PhosphoserineBy similarity
Modified residuei78 – 781Phosphoserine; by MAPK7By similarity
Disulfide bondi193 – 193Interchain (with C-258)By similarity
Modified residuei256 – 2561Phosphothreonine; by PDPK11 Publication
Disulfide bondi258 – 258Interchain (with C-193)By similarity
Modified residuei368 – 3681Phosphothreonine; by PKABy similarity
Modified residuei396 – 3961PhosphoserineBy similarity
Modified residuei400 – 4001PhosphoserineBy similarity
Modified residuei421 – 4211PhosphoserineBy similarity

Post-translational modificationi

Regulated by phosphorylation. Activated by phosphorylation on Ser-421 by mTORC2, transforming it into a substrate for PDPK1 which phosphorylates it on Thr-256. Phosphorylation on Ser-396 and Ser-400 are also essential for its activity. Phosphorylation on Ser-78 by MAPK7 is required for growth factor-induced cell cycle progression (By similarity).By similarity
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).By similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ06226.
PRIDEiQ06226.

PTM databases

iPTMnetiQ06226.
PhosphoSiteiQ06226.

Expressioni

Tissue specificityi

Expressed in most tissues with highest levels in the ovary, thymus and lung. In the kidney, expressed within glomeruli of the cortex, at low levels in outer medulla and moderate levels in inner medulla and papilla.1 Publication

Inductioni

Up-regulated by aldosterone in distal nephron (tubules) of the kidney. By dexamethasone and serum. By tumor suppressor p53 in mammary epithelial tumor cells. By FSH in granulosa cells. By injury to the central nervous system.4 Publications

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Forms a trimeric complex with FBXW7 and NOTCH1. Interacts with MAPK3/ERK1, MAPK1/ERK2, MAP2K1/MEK1, MAP2K2/MEK2, NEDD4, NEDD4L, MAPK7, CREB1, SLC9A3R2/NHERF2 and KCNJ1/ROMK1. Associates with the mammalian target of rapamycin complex 2 (mTORC2) via an interaction with MAPKAP1/SIN1 (By similarity). Interacts with MAPT/TAU.By similarity2 Publications

GO - Molecular functioni

  • 3-phosphoinositide-dependent protein kinase binding Source: RGD
  • tau protein binding Source: RGD

Protein-protein interaction databases

IntActiQ06226. 1 interaction.
MINTiMINT-5114766.
STRINGi10116.ENSRNOP00000057871.

Structurei

3D structure databases

ProteinModelPortaliQ06226.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini98 – 354257Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini355 – 43076AGC-kinase C-terminalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6060Necessary for localization to the mitochondriaBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi131 – 14111Nuclear localization signalBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi131 – 14111Glu/Lys-richAdd
BLAST

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
HOVERGENiHBG108317.
InParanoidiQ06226.
PhylomeDBiQ06226.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q06226-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTVKTEAARS TLTYSRMRGM VAILIAFMKQ RRMGLNDFIQ KLANNSYACK
60 70 80 90 100
HPEVQSYLKI SQPQEPELMN ANPSPPPSPS QQINLGPSSN PHAKPSDFHF
110 120 130 140 150
LKVIGKGSFG KVLLARHKAE EAFYAVKVLQ KKAILKKKEE KHIMSERNVL
160 170 180 190 200
LKNVKHPFLV GLHFSFQTAD KLYFVLDYIN GGELFYHLQR ERCFLEPRAR
210 220 230 240 250
FYAAEIASAL GYLHSLNIVY RDLKPENILL DSQGHIVLTD FGLCKENIEH
260 270 280 290 300
NGTTSTFCGT PEYLAPEVLH KQPYDRTVDW WCLGAVLYEM LYGLPPFYSR
310 320 330 340 350
NTAEMYDNIL NKPLQLKNIT NSARHLLEGL LQKDRTKRLG AKDDFMEIKS
360 370 380 390 400
HIFFSLINWD DLINKKITPP FNPNVSGPSD LRHFDPEFTE EPVPSSIGRS
410 420 430
PDSILVTASV KEAAEAFLGF SYAPPMDSFL
Length:430
Mass (Da):48,927
Last modified:February 1, 1995 - v1
Checksum:i0D5845B04156F26D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L01624 mRNA. Translation: AAA42137.1.
PIRiA48094.
UniGeneiRn.4636.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L01624 mRNA. Translation: AAA42137.1.
PIRiA48094.
UniGeneiRn.4636.

3D structure databases

ProteinModelPortaliQ06226.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ06226. 1 interaction.
MINTiMINT-5114766.
STRINGi10116.ENSRNOP00000057871.

PTM databases

iPTMnetiQ06226.
PhosphoSiteiQ06226.

Proteomic databases

PaxDbiQ06226.
PRIDEiQ06226.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

RGDi3668. Sgk1.

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
HOVERGENiHBG108317.
InParanoidiQ06226.
PhylomeDBiQ06226.

Enzyme and pathway databases

BRENDAi2.7.11.1. 5301.

Miscellaneous databases

PROiQ06226.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum."
    Webster M.K., Goya L., Ge Y., Maiyar A.C., Firestone G.L.
    Mol. Cell. Biol. 13:2031-2040(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Fischer 344.
  2. "Differential expression of sgk mRNA, a member of the Ser/Thr protein kinase gene family, in rat brain after CNS injury."
    Imaizumi K., Tsuda M., Wanaka A., Tohyama M., Takagi T.
    Brain Res. Mol. Brain Res. 26:189-196(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY CNS INJURY.
  3. "Ovarian cell differentiation: a cascade of multiple hormones, cellular signals, and regulated genes."
    Richards J.S., Fitzpatrick S.L., Clemens J.W., Morris J.K., Alliston T., Sirois J.
    Recent Prog. Horm. Res. 50:223-254(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY FSH.
  4. "p53 stimulates promoter activity of the sgk. serum/glucocorticoid-inducible serine/threonine protein kinase gene in rodent mammary epithelial cells."
    Maiyar A.C., Huang A.J., Phu P.T., Cha H.H., Firestone G.L.
    J. Biol. Chem. 271:12414-12422(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY P53.
    Tissue: Mammary epithelium.
  5. "Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway."
    Park J., Leong M.L., Buse P., Maiyar A.C., Firestone G.L., Hemmings B.A.
    EMBO J. 18:3024-3033(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-256.
  6. Cited for: INDUCTION, TISSUE SPECIFICITY.
  7. "Stimulation of the EAAT4 glutamate transporter by SGK protein kinase isoforms and PKB."
    Boehmer C., Philippin M., Rajamanickam J., Mack A., Broer S., Palmada M., Lang F.
    Biochem. Biophys. Res. Commun. 324:1242-1248(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN REGULATION OF SLC1A6/EAAT4.
  8. "Serum- and glucocorticoid-inducible kinase 1 (SGK1) increases neurite formation through microtubule depolymerization by SGK1 and by SGK1 phosphorylation of tau."
    Yang Y.C., Lin C.H., Lee E.H.
    Mol. Cell. Biol. 26:8357-8370(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF MAPT/TAU, INTERACTION WITH MAPT/TAU.
  9. "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."
    Won M., Park K.A., Byun H.S., Kim Y.R., Choi B.L., Hong J.H., Park J., Seok J.H., Lee Y.H., Cho C.H., Song I.S., Kim Y.K., Shen H.M., Hur G.M.
    J. Hepatol. 51:67-76(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF MAPK1/ERK2, INTERACTION WITH MAPK3/ERK1; MAPK1/ERK2; MAP2K1/MEK1 AND MAP2K2/MEK2.

Entry informationi

Entry nameiSGK1_RAT
AccessioniPrimary (citable) accession number: Q06226
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 6, 2016
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.