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Protein

Serine/threonine-protein kinase Sgk1

Gene

Sgk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 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.10 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Activity regulationi

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 WNK4.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei127ATPPROSITE-ProRule annotation1
Active sitei222Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi104 – 112ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Stress response
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 3474
ReactomeiR-MMU-2672351 Stimuli-sensing channels
R-MMU-6804757 Regulation of TP53 Degradation

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1340062 Sgk1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3988610

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866431 – 431Serine/threonine-protein kinase Sgk1Add BLAST431

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei74PhosphoserineBy similarity1
Modified residuei78Phosphoserine; by MAPK7By similarity1
Disulfide bondi193Interchain (with C-258)By similarity
Modified residuei256Phosphothreonine; by PDPK1By similarity1
Disulfide bondi258Interchain (with C-193)By similarity
Modified residuei369Phosphothreonine; by PKABy similarity1
Modified residuei397PhosphoserineBy similarity1
Modified residuei401PhosphoserineBy similarity1
Modified residuei422PhosphoserineBy similarity1

Post-translational modificationi

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 (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

PaxDbiQ9WVC6
PRIDEiQ9WVC6

PTM databases

iPTMnetiQ9WVC6
PhosphoSitePlusiQ9WVC6

Expressioni

Inductioni

Up-regulated by tumor suppressor p53 in mammary epithelial tumor cells.

Gene expression databases

BgeeiENSMUSG00000019970 Expressed in 334 organ(s), highest expression level in cumulus cell
CleanExiMM_SGK1
ExpressionAtlasiQ9WVC6 baseline and differential
GenevisibleiQ9WVC6 MM

Interactioni

Subunit structurei

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

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203197, 5 interactors
DIPiDIP-48845N
IntActiQ9WVC6, 5 interactors
STRINGi10090.ENSMUSP00000114074

Chemistry databases

BindingDBiQ9WVC6

Structurei

3D structure databases

ProteinModelPortaliQ9WVC6
SMRiQ9WVC6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini98 – 355Protein kinasePROSITE-ProRule annotationAdd BLAST258
Domaini356 – 431AGC-kinase C-terminalAdd BLAST76

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 60Necessary for localization to the mitochondriaBy similarityAdd BLAST60

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi131 – 141Nuclear localization signalBy similarityAdd BLAST11

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi131 – 141Glu/Lys-richAdd BLAST11

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00920000148938
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiQ9WVC6
KOiK13302
OMAiEVKEPCN
OrthoDBiEOG091G06FF
PhylomeDBiQ9WVC6
TreeFamiTF320906

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
SMARTiView protein in SMART
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9WVC6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MTVKAEAARS TLTYSRMRGM VAILIAFMKQ RRMGLNDFIQ KIASNTYACK
60 70 80 90 100
HAEVQSILKM SHPQEPELMN ANPSPPPSPS QQINLGPSSN PHAKPSDFHF
110 120 130 140 150
LKVIGKGSFG KVLLARHKAE EVFYAVKVLQ 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 NKPLQLKPNI TNSARHLLEG LLQKDRTKRL GAKDDFMEIK
360 370 380 390 400
SHIFFSLINW DDLINKKITP PFNPNVSGPS DLRHFDPEFT EEPVPSSIGR
410 420 430
SPDSILVTAS VKEAAEAFLG FSYAPPVDSF L
Length:431
Mass (Da):48,928
Last modified:November 1, 1999 - v1
Checksum:i6DF5B8464A4C2754
GO
Isoform 2 (identifier: Q9WVC6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: MTVKAEAARSTLTYSRMRGMVAILI → MVNKDMNGFP...PRTFWTNDDA

Show »
Length:524
Mass (Da):59,571
Checksum:i5AB3CBA333DA87D1
GO
Isoform 3 (identifier: Q9WVC6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: MTVKAEAARSTLTYSRMRGMVAILI → MGEMQGALARARLESLLRPRHKKRAEAQKRSESVLLSGL

Show »
Length:445
Mass (Da):50,533
Checksum:i275D16D8FD41AEEC
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9Q1B0E9Q1B0_MOUSE
Non-specific serine/threonine prote...
Sgk1
417Annotation score:
E9Q8C1E9Q8C1_MOUSE
Non-specific serine/threonine prote...
Sgk1
404Annotation score:
D3YV51D3YV51_MOUSE
Serine/threonine-protein kinase Sgk...
Sgk1
266Annotation score:
D3Z0E8D3Z0E8_MOUSE
Serine/threonine-protein kinase Sgk...
Sgk1
82Annotation score:
D3YXA3D3YXA3_MOUSE
Serine/threonine-protein kinase Sgk...
Sgk1
89Annotation score:
F6RKM6F6RKM6_MOUSE
Serine/threonine-protein kinase Sgk...
Sgk1
90Annotation score:

Sequence cautioni

The sequence AAH70401 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti87P → L in BAE26849 (PubMed:16141072).Curated1
Sequence conflicti347M → V in BAE26849 (PubMed:16141072).Curated1
Sequence conflicti347M → V in BAE26871 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0377881 – 25MTVKA…VAILI → MVNKDMNGFPVKKCSAFQFF KKRVRRWIKSPMVSVDKHQS PNLKYTGPAGVHLPPGESDF EAMCQSCLGDHAFQRGMLPP EESCSWEIQPGCEVKEQCNH ANILTKPDPRTFWTNDDA in isoform 2. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_0377891 – 25MTVKA…VAILI → MGEMQGALARARLESLLRPR HKKRAEAQKRSESVLLSGL in isoform 3. 1 PublicationAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF139638 mRNA Translation: AAD43302.1
AF205855 mRNA Translation: AAF19429.1
AK132234 mRNA Translation: BAE21048.1
AK146037 mRNA Translation: BAE26849.1
AK146062 mRNA Translation: BAE26871.1
AK159131 mRNA Translation: BAE34843.1
AK167364 mRNA Translation: BAE39461.1
CH466562 Genomic DNA Translation: EDL03408.1
BC005720 mRNA Translation: AAH05720.1
BC070401 mRNA Translation: AAH70401.1 Different initiation.
CCDSiCCDS23726.1 [Q9WVC6-1]
CCDS48515.1 [Q9WVC6-2]
CCDS48517.1 [Q9WVC6-3]
RefSeqiNP_001155317.2, NM_001161845.2 [Q9WVC6-2]
NP_001155319.1, NM_001161847.2
NP_001155320.1, NM_001161848.2
NP_001155321.1, NM_001161849.2
NP_001155322.1, NM_001161850.2 [Q9WVC6-3]
NP_035491.1, NM_011361.3 [Q9WVC6-1]
UniGeneiMm.28405

Genome annotation databases

EnsembliENSMUST00000020145; ENSMUSP00000020145; ENSMUSG00000019970 [Q9WVC6-1]
ENSMUST00000092673; ENSMUSP00000090343; ENSMUSG00000019970 [Q9WVC6-3]
ENSMUST00000120509; ENSMUSP00000114074; ENSMUSG00000019970 [Q9WVC6-2]
GeneIDi20393
KEGGimmu:20393
UCSCiuc007eov.2 mouse [Q9WVC6-2]
uc007eow.2 mouse [Q9WVC6-3]
uc007eox.2 mouse [Q9WVC6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF139638 mRNA Translation: AAD43302.1
AF205855 mRNA Translation: AAF19429.1
AK132234 mRNA Translation: BAE21048.1
AK146037 mRNA Translation: BAE26849.1
AK146062 mRNA Translation: BAE26871.1
AK159131 mRNA Translation: BAE34843.1
AK167364 mRNA Translation: BAE39461.1
CH466562 Genomic DNA Translation: EDL03408.1
BC005720 mRNA Translation: AAH05720.1
BC070401 mRNA Translation: AAH70401.1 Different initiation.
CCDSiCCDS23726.1 [Q9WVC6-1]
CCDS48515.1 [Q9WVC6-2]
CCDS48517.1 [Q9WVC6-3]
RefSeqiNP_001155317.2, NM_001161845.2 [Q9WVC6-2]
NP_001155319.1, NM_001161847.2
NP_001155320.1, NM_001161848.2
NP_001155321.1, NM_001161849.2
NP_001155322.1, NM_001161850.2 [Q9WVC6-3]
NP_035491.1, NM_011361.3 [Q9WVC6-1]
UniGeneiMm.28405

3D structure databases

ProteinModelPortaliQ9WVC6
SMRiQ9WVC6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203197, 5 interactors
DIPiDIP-48845N
IntActiQ9WVC6, 5 interactors
STRINGi10090.ENSMUSP00000114074

Chemistry databases

BindingDBiQ9WVC6
ChEMBLiCHEMBL3988610

PTM databases

iPTMnetiQ9WVC6
PhosphoSitePlusiQ9WVC6

Proteomic databases

PaxDbiQ9WVC6
PRIDEiQ9WVC6

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020145; ENSMUSP00000020145; ENSMUSG00000019970 [Q9WVC6-1]
ENSMUST00000092673; ENSMUSP00000090343; ENSMUSG00000019970 [Q9WVC6-3]
ENSMUST00000120509; ENSMUSP00000114074; ENSMUSG00000019970 [Q9WVC6-2]
GeneIDi20393
KEGGimmu:20393
UCSCiuc007eov.2 mouse [Q9WVC6-2]
uc007eow.2 mouse [Q9WVC6-3]
uc007eox.2 mouse [Q9WVC6-1]

Organism-specific databases

CTDi6446
MGIiMGI:1340062 Sgk1

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00920000148938
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiQ9WVC6
KOiK13302
OMAiEVKEPCN
OrthoDBiEOG091G06FF
PhylomeDBiQ9WVC6
TreeFamiTF320906

Enzyme and pathway databases

BRENDAi2.7.11.1 3474
ReactomeiR-MMU-2672351 Stimuli-sensing channels
R-MMU-6804757 Regulation of TP53 Degradation

Miscellaneous databases

PROiPR:Q9WVC6
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000019970 Expressed in 334 organ(s), highest expression level in cumulus cell
CleanExiMM_SGK1
ExpressionAtlasiQ9WVC6 baseline and differential
GenevisibleiQ9WVC6 MM

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
SMARTiView protein in SMART
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSGK1_MOUSE
AccessioniPrimary (citable) accession number: Q9WVC6
Secondary accession number(s): Q3TJN4
, Q3UKD0, Q3UKF2, Q3V1V1, Q6NS85
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 1, 1999
Last modified: September 12, 2018
This is version 155 of the entry and version 1 of the sequence. See 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
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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