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> O00141 B7UUP7 B7UUP8 B7UUP9 B7Z5B2 E1P583

Q5TCN2 Q5TCN3 Q5TCN4 Q5VY65 Q9UN56 SGK1_HUMAN Serine/threonine-protein kinase
Sgk1 2.7.11.1 Serum/glucocorticoid-regulated kinase 1 SGK1 SGK Homo sapiens
Human Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia
Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae Homo Cloning
and characterization of a putative human serine/threonine protein kinase
transcriptionally modified during anisotonic and isotonic alterations of cell
volume.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1) Genomic organization and
chromosomal localization of the human SGK protein kinase gene.NUCLEOTIDE SEQUENCE
[GENOMIC DNA] ALTERNATIVE SPLICING (ISOFORM 1) An evolutionarily conserved N-
terminal Sgk1 variant with enhanced stability and improved function.NUCLEOTIDE
SEQUENCE [MRNA] (ISOFORM 2) FUNCTION ALTERNATIVE PROMOTER USAGE INDUCTION
SUBCELLULAR LOCATION TISSUE SPECIFICITY Brain Transcriptional variants of
serum/glucocorticoid regulated kinase 1 show differential localisation and
regulation.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 5) ALTERNATIVE PROMOTER
USAGE Glioblastoma Hippocampus Skin A catalogue of genes in the human dermal
papilla cells as identified by expressed sequence tags.NUCLEOTIDE SEQUENCE [LARGE
SCALE MRNA] (ISOFORM 1) Hair follicle dermal papilla Complete sequencing and
characterization of 21,243 full-length human cDNAs.NUCLEOTIDE SEQUENCE [LARGE SCALE
MRNA] (ISOFORMS 2 AND 3) Brain The DNA sequence and analysis of human
chromosome 6.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] The status, quality, and expansion
of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).NUCLEOTIDE
SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1) Cervix Characterization of the
structure and regulation of two novel isoforms of serum- and glucocorticoid-induced
protein kinase.TISSUE SPECIFICITY Activation of serum- and glucocorticoid-
regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase
is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and
PDK2.PHOSPHORYLATION AT THR-256 AND SER-422 MUTAGENESIS OF THR-256 AND SER-422
Brain Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK
in diabetic nephropathy.CHARACTERIZATION BMK1 mediates growth factor-induced cell
proliferation through direct cellular activation of serum and glucocorticoid-
inducible kinase.PHOSPHORYLATION AT SER-78 BY MAPK7 INTERACTION WITH MAPK7
Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by cyclic AMP
and insulin.PHOSPHORYLATION AT THR-369 BY PKA Serum- and glucocorticoid-inducible
kinase SGK phosphorylates and negatively regulates B-Raf.FUNCTION IN
PHOSPHORYLATION OF BRAF Protein kinase SGK mediates survival signals by
phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a).FUNCTION Serum
and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the
epithelial Na+ channel.INTERACTION WITH NEDD4 AND NEDD4L MUTAGENESIS OF LYS-127;
TYR-298 AND SER-422 FUNCTION Activation of Na+/K+-ATPase by the serum and
glucocorticoid-dependent kinase isoforms.FUNCTION IN REGULATION OF NA(+)/K(+)
ATPASE K(+) channel activation by all three isoforms of serum- and
glucocorticoid-dependent protein kinase SGK.FUNCTION Molecular requirements for
the regulation of the renal outer medullary K(+) channel ROMK1 by the serum- and
glucocorticoid-inducible kinase SGK1.FUNCTION INTERACTION WITH SLC9A3R2/NHERF2 AND
KCNJ1/ROMK1 Serum and glucocorticoid inducible kinases in the regulation of the
cardiac sodium channel SCN5A.FUNCTION IN REGULATION OF SCN5A Inhibition of
mitogen-activated kinase kinase kinase 3 activity through phosphorylation by the
serum- and glucocorticoid-induced kinase 1.FUNCTION IN PHOSPHORYLATION OF
MAP3K3/MEKK3 Regulation of the glutamate transporter EAAT1 by the ubiquitin
ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3
and protein kinase B.FUNCTION IN REGULATION OF KCNA3/KV1.3 MUTAGENESIS OF LYS-127
AND SER-422 Importin-alpha mediates the regulated nuclear targeting of serum- and
glucocorticoid-inducible protein kinase (Sgk) by recognition of a nuclear
localization signal in the kinase central domain.NUCLEAR LOCALIZATION SIGNAL
Regulation of KCNE1-dependent K(+) current by the serum and glucocorticoid-
inducible kinase (SGK) isoforms.FUNCTION IN REGULATION OF KCNE1 AND KCNQ1
Regulation of intestinal phosphate cotransporter NaPi IIb by ubiquitin ligase
Nedd4-2 and by serum- and glucocorticoid-dependent kinase 1.FUNCTION IN REGULATION
OF SLC34A2/NAPI-2B FUNCTION IN PHOSPHORYLATION OF NEDD4L Stimulation of renal Na+
dicarboxylate cotransporter 1 by Na+/H+ exchanger regulating factor 2, serum and
glucocorticoid inducible kinase isoforms, and protein kinase B.FUNCTION IN
REGULATION OF SLC13A2/NADC1 Regulation of the epithelial Ca2+ channel TRPV5 by
the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase
isoforms SGK1 and SGK3 expressed in Xenopus oocytes.FUNCTION IN REGULATION OF TRPV5
A novel pathway of epithelial sodium channel activation involves a serum- and
glucocorticoid-inducible kinase consensus motif in the C terminus of the channel's
alpha-subunit.FUNCTION Regulation of the voltage gated K+ channel Kv1.3 by the
ubiquitin ligase Nedd4-2 and the serum and glucocorticoid inducible kinase
SGK1.FUNCTION MUTAGENESIS OF LYS-127 AND SER-422 Regulation of CLC-Ka/barttin by
the ubiquitin ligase Nedd4-2 and the serum- and glucocorticoid-dependent
kinases.FUNCTION IN REGULATION OF BSND Activation of NHE3 by dexamethasone
requires phosphorylation of NHE3 at Ser663 by SGK1.FUNCTION IN PHOSPHORYLATION OF
SLC9A3/NHE3 The serine/threonine kinases SGK1, 3 and PKB stimulate the amino acid
transporter ASCT2.FUNCTION IN REGULATION OF SLC1A5/ASCT2 Regulation of the
excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent
kinases SGK1 and SGK3.FUNCTION IN REGULATION OF SLC1A7/EAAT5 Stimulation of the
creatine transporter SLC6A8 by the protein kinases SGK1 and SGK3.FUNCTION IN
REGULATION OF SLC6A8 Serum/glucocorticoid-inducible kinase can phosphorylate the
cyclic AMP response element binding protein, CREB.FUNCTION IN PHOSPHORYLATION OF
CREB1 INTERACTION WITH CREB1 Nedd4-2 phosphorylation induces serum and
glucocorticoid-regulated kinase (SGK) ubiquitination and degradation.UBIQUITINATION
SGK1 kinase upregulates GLUT1 activity and plasma membrane expression.FUNCTION IN
REGULATION OF SLC2A1/GLUT1 Serum- and glucocorticoid-inducible kinase 1 (SGK1)
increases neurite formation through microtubule depolymerization by SGK1 and by
SGK1 phosphorylation of tau.FUNCTION IN PHOSPHORYLATION OF MAPT/TAU INTERACTION
WITH MAPT/TAU Subcellular location of serum- and glucocorticoid-induced kinase-1
in renal and mammary epithelial cells.SUBCELLULAR LOCATION Role of SGK1 kinase in
regulating glucose transport via glucose transporter GLUT4.FUNCTION IN
PHOSPHORYLATION OF SLC2A4/GLUT4 Regulation of the epithelial calcium channel
TRPV6 by the serum and glucocorticoid-inducible kinase isoforms SGK1 and
SGK3.FUNCTION IN REGULATION OF TRPV6 Regulation Fe65 localization to the nucleus
by SGK1 phosphorylation of its Ser566 residue.FUNCTION IN PHOSPHORYLATION OF
APBB1/FE65 mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and
activation of serum- and glucocorticoid-induced protein kinase 1
(SGK1).PHOSPHORYLATION AT SER-422 BY MTORC2 Kinase-selective enrichment enables
quantitative phosphoproteomics of the kinome across the cell cycle.PHOSPHORYLATION
[LARGE SCALE ANALYSIS] AT SER-74; SER-397 AND SER-401 IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS] Cervix carcinoma A brain-specific SGK1
splice isoform regulates expression of ASIC1 in neurons.ALTERNATIVE PROMOTER USAGE
(ISOFORMS 2 AND 3) Regulation of a third conserved phosphorylation site in
SGK1.PHOSPHORYLATION AT SER-397 AND SER-401 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.FUNCTION IN
PHOSPHORYLATION OF MAPK1/ERK2 INTERACTION WITH MAPK3/ERK1; MAPK1/ERK2; MAP2K1/MEK1
AND MAP2K2/MEK2 Sgk1 activates MDM2-dependent p53 degradation and affects cell
proliferation, survival, and differentiation.FUNCTION IN PHOSPHORYLATION OF MDM2
Large-scale proteomics analysis of the human kinome.PHOSPHORYLATION [LARGE SCALE
ANALYSIS] AT SER-74; SER-397 AND SER-401 IDENTIFICATION BY MASS SPECTROMETRY [LARGE
SCALE ANALYSIS] The serum and glucocorticoid inducible kinases SGK1-3 stimulate
the neutral amino acid transporter SLC6A19.FUNCTION IN REGULATION OF SLC6A19 mTOR
complex-2 activates ENaC by phosphorylating SGK1.PHOSPHORYLATION AT SER-422 BY
MTORC2 INTERACTION WITH MTORC2 Interaction of serum- and glucocorticoid regulated
kinase 1 (SGK1) with the WW-domains of Nedd4-2 is required for epithelial sodium
channel regulation.FUNCTION Quantitative phosphoproteomics reveals widespread
full phosphorylation site occupancy during mitosis.PHOSPHORYLATION [LARGE SCALE
ANALYSIS] AT SER-397 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
Cervix carcinoma Serum- and glucocorticoid-induced kinase 3 in recycling
endosomes mediates acute activation of Na+/H+ exchanger NHE3 by
glucocorticoids.FUNCTION IN REGULATION OF SLC9A3/NHE3 SUBCELLULAR LOCATION
Stimulus-dependent regulation of serum and glucocorticoid inducible protein kinase
(SGK) transcription, subcellular localization and enzymatic activity.REVIEW Sgk
kinases and their role in epithelial transport.REVIEW Second AKT: the rise of SGK
in cancer
signalling.REVIEW ON FUNCTION Significance of SGK1 in the regulation of neuronal
function.REVIEW ON FUNCTION Crystal structure of the kinase domain of serum and
glucocorticoid-regulated kinase 1 in complex with AMP PNP.X-RAY CRYSTALLOGRAPHY
(1.90 ANGSTROMS) OF 60-431 SUBUNIT DISULFIDE BOND Patterns of somatic mutation in
human cancer genomes.VARIANTS [LARGE SCALE ANALYSIS] ILE-219 AND VAL-342
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.
ATP + a protein = ADP + a phosphoprotein. 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.
Homodimer; disulfide-linked. Forms a trimeric complex with FBXW7 and NOTCH1.
Interacts with MAPK3/ERK1, MAPK1/ERK2, MAP2K1/MEK1, MAP2K2/MEK2, NEDD4, NEDD4L,
MAPT/TAU, MAPK7, CREB1, SLC9A3R2/NHERF2 and KCNJ1/ROMK1. Associates with the
mammalian target of rapamycin complex 2 (mTORC2) via an interaction with
MAPKAP1/SIN1. Cytoplasm Nucleus Endoplasmic reticulum membrane Cell
membrane Mitochondrion 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
O00141-1 1 O00141-2 2 Sgk1.1 Sgk1_v2 Produced by alternative promoter usage.
O00141-3 3 Sgk1.2 Produced by alternative promoter usage. O00141-4 4 Produced
by alternative splicing of isoform 1. O00141-5 5 Produced by alternative
promoter usage. Expressed in most tissues with highest levels in the pancreas,
followed by placenta, kidney and lung. Isoform 2 is strongly expressed in brain and
pancreas, weaker in heart, placenta, lung, liver and skeletal muscle. Induced by
a very large spectrum of stimuli distinct from glucocorticoids and serum. These
include aldosterone, cell shrinkage, cell swelling, TGF-beta, ischemic injury of
the brain, neuronal excitotoxicity memory consolidation, chronic viral hepatitis,
DNA-damaging agents, vitamin D3 psychophysiological stress, iron, glucose, EDN1,
CSF2, fibroblast growth factor, platelet-derived growth factor, phorbolesters,
follicle-stimulating hormone, sorbitol, heat shock, oxidative stress, UV
irradiation, and p53/TP53. Many of these stimuli are highly cell-specific, as is
the case, for example for aldosterone, which has been found to stimulate its
expression only in cells derived from aldosterone-responsive epithelia. Isoform 2
is not induced by glucocorticoids but by excessive extracellular glucose and by
TGFB1, in cultured cells. Isoform 2 subcellular localization at the cell membrane
and resistance to proteasomal degradation is mediated by the sequences within the
first 120 amino acids. Regulated by phosphorylation. Activated by phosphorylation
on Ser-422 by mTORC2, transforming it into a substrate for PDPK1 which
phosphorylates it on Thr-256. Phosphorylation on Ser-397 and Ser-401 are also
essential for its activity. Phosphorylation on Ser-78 by MAPK7 is required for
growth factor-induced cell cycle progression. 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. Belongs to
the protein kinase superfamily. AGC Ser/Thr protein kinase family. Contains 1
AGC-kinase C-terminal domain. Contains 1 protein kinase domain.
3D-structure Alternative promoter usage Alternative splicing Apoptosis ATP-binding
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
MTVKTEAAKGTLTYSRMRGMVAILI
MVNKDMNGFPVKKCSAFQFFKKRVRRWIKSPMVSVDKHQSPSLKYTGSSMVHIPPGEPDFESSLCQTCLGEHAFQRGVLPQEN
ESCSWETQSGCEVREPCNHANILTKPDPRTFWTNDDP MTVKTEAAKGTLTYSRMRGMVAILI
MGEMQGALARARLESLLRPRHKKRAEAQKRSESFLLSGL MTVKTEAAKGTLTYSRMRGMVAILI
MKPSKRFFISPPSST MTVKTEAAKGTLTYSRMRGMVAILI
MSSQSSSLSEACSREAYSSHNWALPPASRSNPQPAYPWATRRMKEEAIKPPLK V I A V K M
T A T D T E Y A S A S D Q E K R E G I
V P R D E
MTVKTEAAKGTLTYSRMRGMVAILIAFMKQRRMGLNDFIQKIANNSYACKHPEVQSILKI
SQPQEPELMNANPSPPPSPSQQINLGPSSNPHAKPSDFHFLKVIGKGSFGKVLLARHKAE
EVFYAVKVLQKKAILKKKEEKHIMSERNVLLKNVKHPFLVGLHFSFQTADKLYFVLDYIN
GGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTD
FGLCKENIEHNSTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSR
NTAEMYDNILNKPLQLKPNITNSARHLLEGLLQKDRTKRLGAKDDFMEIKSHVFFSLINW
DDLINKKITPPFNPNVSGPNDLRHFDPEFTEEPVPNSIGKSPDSVLVTASVKEAAEAFLG FSYAPPTDSFL
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