SGK1_RAT
ID SGK1_RAT Reviewed; 430 AA.
AC Q06226;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Serine/threonine-protein kinase Sgk1;
DE EC=2.7.11.1;
DE AltName: Full=Serum/glucocorticoid-regulated kinase 1;
GN Name=Sgk1; Synonyms=Sgk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer 344;
RX PubMed=8455596; DOI=10.1128/mcb.13.4.2031-2040.1993;
RA Webster M.K., Goya L., Ge Y., Maiyar A.C., Firestone G.L.;
RT "Characterization of sgk, a novel member of the serine/threonine protein
RT kinase gene family which is transcriptionally induced by glucocorticoids
RT and serum.";
RL Mol. Cell. Biol. 13:2031-2040(1993).
RN [2]
RP INDUCTION BY CNS INJURY.
RX PubMed=7854047; DOI=10.1016/0169-328x(94)90090-6;
RA Imaizumi K., Tsuda M., Wanaka A., Tohyama M., Takagi T.;
RT "Differential expression of sgk mRNA, a member of the Ser/Thr protein
RT kinase gene family, in rat brain after CNS injury.";
RL Brain Res. Mol. Brain Res. 26:189-196(1994).
RN [3]
RP INDUCTION BY FSH.
RX PubMed=7740159; DOI=10.1016/b978-0-12-571150-0.50014-7;
RA Richards J.S., Fitzpatrick S.L., Clemens J.W., Morris J.K., Alliston T.,
RA Sirois J.;
RT "Ovarian cell differentiation: a cascade of multiple hormones, cellular
RT signals, and regulated genes.";
RL Recent Prog. Horm. Res. 50:223-254(1995).
RN [4]
RP INDUCTION BY P53.
RC TISSUE=Mammary epithelium;
RX PubMed=8647846; DOI=10.1074/jbc.271.21.12414;
RA Maiyar A.C., Huang A.J., Phu P.T., Cha H.H., Firestone G.L.;
RT "p53 stimulates promoter activity of the sgk. serum/glucocorticoid-
RT inducible serine/threonine protein kinase gene in rodent mammary epithelial
RT cells.";
RL J. Biol. Chem. 271:12414-12422(1996).
RN [5]
RP PHOSPHORYLATION AT THR-256.
RX PubMed=10357815; DOI=10.1093/emboj/18.11.3024;
RA Park J., Leong M.L., Buse P., Maiyar A.C., Firestone G.L., Hemmings B.A.;
RT "Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-
RT kinase-stimulated signaling pathway.";
RL EMBO J. 18:3024-3033(1999).
RN [6]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=10051674; DOI=10.1073/pnas.96.5.2514;
RA Chen S.-Y., Bhargava A., Mastroberardino L., Meijer O.C., Wang J., Buse P.,
RA Firestone G.L., Verrey F., Pearce D.;
RT "Epithelial sodium channel regulated by aldosterone-induced protein sgk.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2514-2519(1999).
RN [7]
RP FUNCTION IN REGULATION OF SLC1A6/EAAT4.
RX PubMed=15504348; DOI=10.1016/j.bbrc.2004.09.193;
RA Boehmer C., Philippin M., Rajamanickam J., Mack A., Broer S., Palmada M.,
RA Lang F.;
RT "Stimulation of the EAAT4 glutamate transporter by SGK protein kinase
RT isoforms and PKB.";
RL Biochem. Biophys. Res. Commun. 324:1242-1248(2004).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF MAPT/TAU, AND INTERACTION WITH MAPT/TAU.
RX PubMed=16982696; DOI=10.1128/mcb.01017-06;
RA Yang Y.C., Lin C.H., Lee E.H.;
RT "Serum- and glucocorticoid-inducible kinase 1 (SGK1) increases neurite
RT formation through microtubule depolymerization by SGK1 and by SGK1
RT phosphorylation of tau.";
RL Mol. Cell. Biol. 26:8357-8370(2006).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF MAPK1/ERK2, AND INTERACTION WITH MAPK3/ERK1;
RP MAPK1/ERK2; MAP2K1/MEK1 AND MAP2K2/MEK2.
RX PubMed=19447520; DOI=10.1016/j.jhep.2009.02.027;
RA Won M., Park K.A., Byun H.S., Kim Y.R., Choi B.L., Hong J.H., Park J.,
RA Seok J.H., Lee Y.H., Cho C.H., Song I.S., Kim Y.K., Shen H.M., Hur G.M.;
RT "Protein kinase SGK1 enhances MEK/ERK complex formation through the
RT phosphorylation of ERK2: implication for the positive regulatory role of
RT SGK1 on the ERK function during liver regeneration.";
RL J. Hepatol. 51:67-76(2009).
CC -!- FUNCTION: Serine/threonine-protein kinase which is involved in the
CC regulation of a wide variety of ion channels, membrane transporters,
CC cellular enzymes, transcription factors, neuronal excitability, cell
CC growth, proliferation, survival, migration and apoptosis. Plays an
CC important role in cellular stress response. Contributes to regulation
CC of renal Na(+) retention, renal K(+) elimination, salt appetite,
CC gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient
CC transport, insulin-dependent salt sensitivity of blood pressure, salt
CC sensitivity of peripheral glucose uptake, cardiac repolarization and
CC memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A
CC and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and
CC KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels:
CC BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2
CC /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid
CC transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine
CC transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1,
CC Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate
CC receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3,
CC SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and
CC SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase,
CC and transcription factors: CTNNB1 and nuclear factor NF-kappa-B.
CC Stimulates sodium transport into epithelial cells by enhancing the
CC stability and expression of SCNN1A/ENAC. This is achieved by
CC phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its
CC interaction with 14-3-3 proteins, thereby preventing it from binding to
CC SCNN1A/ENAC and targeting it for degradation. Regulates store-operated
CC Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates
CC KCNJ1/ROMK1 directly via its phosphorylation or indirectly via
CC increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and
CC activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates
CC SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65
CC and promotes its localization to the nucleus. Phosphorylates FBXW7 and
CC plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1
CC resulting in its relocalization from the nucleus to the cytoplasm.
CC Phosphorylates FOXO3, promoting its exit from the nucleus and
CC interference with FOXO3-dependent transcription. Phosphorylates BRAF
CC and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates
CC SLC9A3/NHE3 in response to dexamethasone, resulting in its activation
CC and increased localization at the cell membrane. Phosphorylates CREB1.
CC Necessary for vascular remodeling during angiogenesis (By similarity).
CC Phosphorylates MAPT/TAU and mediates microtubule depolymerization and
CC neurite formation in hippocampal neurons. Phosphorylates MAPK1/ERK2 and
CC activates it by enhancing its interaction with MAP2K1/MEK1 and
CC MAP2K2/MEK2. May also play an important role in the development of
CC particular groups of neurons in the postnatal brain. {ECO:0000250,
CC ECO:0000269|PubMed:15504348, ECO:0000269|PubMed:16982696,
CC ECO:0000269|PubMed:19447520}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- ACTIVITY REGULATION: Two specific sites, one in the kinase domain (Thr-
CC 256) and the other in the C-terminal regulatory region (Ser-421), need
CC to be phosphorylated for its full activation. Phosphorylation at Ser-
CC 396 and Ser-400 are also essential for its activity. Activated by WNK1,
CC WNK2, WNK3 and WNK4 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Forms a trimeric complex with
CC FBXW7 and NOTCH1. Interacts with MAPK3/ERK1, MAPK1/ERK2, MAP2K1/MEK1,
CC MAP2K2/MEK2, NEDD4, NEDD4L, MAPK7, CREB1, SLC9A3R2/NHERF2 and
CC KCNJ1/ROMK1. Associates with the mammalian target of rapamycin complex
CC 2 (mTORC2) via an interaction with MAPKAP1/SIN1 (By similarity).
CC Interacts with MAPT/TAU. {ECO:0000250, ECO:0000269|PubMed:16982696,
CC ECO:0000269|PubMed:19447520}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Endoplasmic reticulum membrane {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Mitochondrion {ECO:0000250}. Note=The subcellular
CC localization is controlled by the cell cycle, as well as by exposure to
CC specific hormones and environmental stress stimuli. In proliferating
CC cells, it shuttles between the nucleus and cytoplasm in synchrony with
CC the cell cycle, and in serum/growth factor-stimulated cells it resides
CC in the nucleus. In contrast, after exposure to environmental stress or
CC treatment with glucocorticoids, it is detected in the cytoplasm and
CC with certain stress conditions is associated with the mitochondria. In
CC osmoregulation through the epithelial sodium channel, it can be
CC localized to the cytoplasmic surface of the cell membrane. Nuclear,
CC upon phosphorylation (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in most tissues with highest levels in
CC the ovary, thymus and lung. In the kidney, expressed within glomeruli
CC of the cortex, at low levels in outer medulla and moderate levels in
CC inner medulla and papilla. {ECO:0000269|PubMed:10051674}.
CC -!- INDUCTION: Up-regulated by aldosterone in distal nephron (tubules) of
CC the kidney. By dexamethasone and serum. By tumor suppressor p53 in
CC mammary epithelial tumor cells. By FSH in granulosa cells. By injury to
CC the central nervous system. {ECO:0000269|PubMed:10051674,
CC ECO:0000269|PubMed:7740159, ECO:0000269|PubMed:7854047,
CC ECO:0000269|PubMed:8647846}.
CC -!- PTM: Regulated by phosphorylation. Activated by phosphorylation on Ser-
CC 421 by mTORC2, transforming it into a substrate for PDPK1 which
CC phosphorylates it on Thr-256. Phosphorylation on Ser-396 and Ser-400
CC are also essential for its activity. Phosphorylation on Ser-78 by MAPK7
CC is required for growth factor-induced cell cycle progression (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by NEDD4L; which promotes proteasomal degradation.
CC Ubiquitinated by SYVN1 at the endoplasmic reticulum; which promotes
CC rapid proteasomal degradation and maintains a high turnover rate in
CC resting cells (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; L01624; AAA42137.1; -; mRNA.
DR PIR; A48094; A48094.
DR AlphaFoldDB; Q06226; -.
DR SMR; Q06226; -.
DR IntAct; Q06226; 1.
DR MINT; Q06226; -.
DR STRING; 10116.ENSRNOP00000057871; -.
DR iPTMnet; Q06226; -.
DR PhosphoSitePlus; Q06226; -.
DR PaxDb; Q06226; -.
DR RGD; 3668; Sgk1.
DR eggNOG; KOG0598; Eukaryota.
DR InParanoid; Q06226; -.
DR PhylomeDB; Q06226; -.
DR BRENDA; 2.7.11.1; 5301.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR Reactome; R-RNO-6804757; Regulation of TP53 Degradation.
DR Reactome; R-RNO-9031628; NGF-stimulated transcription.
DR PRO; PR:Q06226; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043423; F:3-phosphoinositide-dependent protein kinase binding; IPI:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0015459; F:potassium channel regulator activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:RGD.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; ISO:RGD.
DR GO; GO:0048156; F:tau protein binding; IPI:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:1904045; P:cellular response to aldosterone; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IMP:MGI.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IDA:RGD.
DR GO; GO:0043402; P:glucocorticoid mediated signaling pathway; IMP:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007616; P:long-term memory; IMP:RGD.
DR GO; GO:0007019; P:microtubule depolymerization; IDA:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0031115; P:negative regulation of microtubule polymerization; IDA:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; IDA:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:RGD.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:RGD.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IMP:RGD.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:RGD.
DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI.
DR GO; GO:0008542; P:visual learning; IMP:RGD.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Apoptosis; ATP-binding; Cell membrane; Cytoplasm; Disulfide bond;
KW Endoplasmic reticulum; Kinase; Membrane; Mitochondrion; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transferase;
KW Ubl conjugation.
FT CHAIN 1..430
FT /note="Serine/threonine-protein kinase Sgk1"
FT /id="PRO_0000086645"
FT DOMAIN 98..354
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 355..430
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..60
FT /note="Necessary for localization to the mitochondria"
FT /evidence="ECO:0000250"
FT REGION 66..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 131..141
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT ACT_SITE 222
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 104..112
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 127
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00141"
FT MOD_RES 78
FT /note="Phosphoserine; by MAPK7"
FT /evidence="ECO:0000250|UniProtKB:O00141"
FT MOD_RES 256
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000269|PubMed:10357815"
FT MOD_RES 368
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O00141"
FT MOD_RES 396
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00141"
FT MOD_RES 400
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00141"
FT MOD_RES 421
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00141"
FT DISULFID 193
FT /note="Interchain (with C-258)"
FT /evidence="ECO:0000250"
FT DISULFID 258
FT /note="Interchain (with C-193)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 430 AA; 48927 MW; 0D5845B04156F26D CRC64;
MTVKTEAARS TLTYSRMRGM VAILIAFMKQ RRMGLNDFIQ KLANNSYACK HPEVQSYLKI
SQPQEPELMN ANPSPPPSPS QQINLGPSSN PHAKPSDFHF LKVIGKGSFG KVLLARHKAE
EAFYAVKVLQ KKAILKKKEE KHIMSERNVL LKNVKHPFLV GLHFSFQTAD KLYFVLDYIN
GGELFYHLQR ERCFLEPRAR FYAAEIASAL GYLHSLNIVY RDLKPENILL DSQGHIVLTD
FGLCKENIEH NGTTSTFCGT PEYLAPEVLH KQPYDRTVDW WCLGAVLYEM LYGLPPFYSR
NTAEMYDNIL NKPLQLKNIT NSARHLLEGL LQKDRTKRLG AKDDFMEIKS HIFFSLINWD
DLINKKITPP FNPNVSGPSD LRHFDPEFTE EPVPSSIGRS PDSILVTASV KEAAEAFLGF
SYAPPMDSFL
