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Protein

Serine/threonine-protein kinase Sgk3

Gene

Sgk3

Organism
Mus musculus (Mouse)
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, cell growth, proliferation, survival and migration. Up-regulates Na+ channels: SCNN1A/ENAC and SCN5A, K+ channels: KCNA3/KV1.3, KCNE1, KCNQ1 and KCNH2/HERG, epithelial Ca2+ channels: TRPV5 and TRPV6, chloride channel: BSND, creatine transporter: SLC6A8, Na+/dicarboxylate cotransporter: SLC13A2/NADC1, Na+-dependent phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters: SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1, SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na+/H+ exchanger: SLC9A3/NHE3, and the Na+/K+ ATPase. Plays a role in the regulation of renal tubular phosphate transport and bone density. Phosphorylates NEDD4L and GSK3B. Positively regulates ER transcription activity through phosphorylation of FLII. Negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Two specific sites, one in the kinase domain (Thr-320) and the other in the C-terminal regulatory region (Ser-486), need to be phosphorylated for its full activation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei191ATPPROSITE-ProRule annotation1
Active sitei286Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi168 – 176ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase Sgk3 (EC:2.7.11.1)
Alternative name(s):
Cytokine-independent survival kinase
Serum/glucocorticoid-regulated kinase 3
Serum/glucocorticoid-regulated kinase-like
Gene namesi
Name:Sgk3
Synonyms:Cisk, Sgkl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2182368. Sgk3.

Subcellular locationi

  • Cytoplasmic vesicle 1 Publication
  • Early endosome 1 Publication
  • Recycling endosome By similarity

  • Note: Endosomal localization is a prerequisite for complete kinase activity. It is essential for its colocalization with the kinase responsible for phosphorylating Ser-486 thus allowing PDPK1 phosphorylation of Thr-320 resulting in complete activation of SGK3. Colocalizes with SLC9A3/NHE3 in the recycling endosomes (By similarity). Localized in vesicle-like structures and in the early endosome.By similarity

GO - Cellular componenti

  • cytoplasmic, membrane-bounded vesicle Source: MGI
  • early endosome Source: UniProtKB-SubCell
  • recycling endosome Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi90R → A: Diminishes binding to phosphoinositides. 1 Publication1
Mutagenesisi191K → A: No activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866501 – 496Serine/threonine-protein kinase Sgk3Add BLAST496

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei126PhosphoserineCombined sources1
Modified residuei129PhosphoserineCombined sources1
Modified residuei138PhosphoserineBy similarity1
Modified residuei142PhosphoserineBy similarity1
Modified residuei320Phosphothreonine; by PDPK1By similarity1
Modified residuei461PhosphoserineBy similarity1
Modified residuei465PhosphoserineBy similarity1
Modified residuei486PhosphoserineBy similarity1

Post-translational modificationi

Activated by phosphorylation on Ser-486 by an unknown kinase (may be mTORC2 but not confirmed), transforming it into a substrate for PDPK1 which then phosphorylates it on Thr-320.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9ERE3.
MaxQBiQ9ERE3.
PaxDbiQ9ERE3.
PRIDEiQ9ERE3.

PTM databases

iPTMnetiQ9ERE3.
PhosphoSitePlusiQ9ERE3.

Expressioni

Tissue specificityi

Widely expressed, predominantly in the heart, spleen and 7-day embryo.

Gene expression databases

BgeeiENSMUSG00000025915.
CleanExiMM_SGK3.
ExpressionAtlasiQ9ERE3. baseline and differential.
GenevisibleiQ9ERE3. MM.

Interactioni

Subunit structurei

Interacts with GSK3B and FLII. Interacts with PDPK1 in a phosphorylation-dependent manner.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000095437.

Structurei

Secondary structure

1496
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi15 – 26Combined sources12
Beta strandi29 – 40Combined sources12
Beta strandi43 – 50Combined sources8
Helixi51 – 64Combined sources14
Helixi66 – 68Combined sources3
Helixi84 – 101Combined sources18
Helixi105 – 108Combined sources4
Helixi111 – 116Combined sources6
Turni117 – 120Combined sources4
Helixi122 – 124Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XTEX-ray1.60A7-160[»]
1XTNX-ray2.20A/B7-126[»]
ProteinModelPortaliQ9ERE3.
SMRiQ9ERE3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9ERE3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 124PXPROSITE-ProRule annotationAdd BLAST113
Domaini162 – 419Protein kinasePROSITE-ProRule annotationAdd BLAST258
Domaini420 – 496AGC-kinase C-terminalAdd BLAST77

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi195 – 205Nuclear localization signalBy similarityAdd BLAST11

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 PX (phox homology) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
KOG2101. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00860000133668.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ9ERE3.
KOiK13304.
OMAiFTEEMVP.
OrthoDBiEOG091G06FF.
PhylomeDBiQ9ERE3.
TreeFamiTF320906.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR001683. Phox.
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.
PF00787. PX. 1 hit.
[Graphical view]
SMARTiSM00312. PX. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
SSF64268. SSF64268. 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.
PS50195. PX. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9ERE3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRDCIMDYK ESCPSVSIPS SDEHREKKKR FTVYKVLVSV GRSEWFVFRR
60 70 80 90 100
YAEFDKLYNS LKKQFPAMAL KIPAKRIFGD NFDPDFIKQR RAGLNEFIQN
110 120 130 140 150
LVRYPELYNH PDVRAFLQMD SPRHQSDPSE DEDERSTSKP HSTSRNINLG
160 170 180 190 200
PTGNPHAKPT DFDFLKVIGK GSFGKVLLAK RKLDGKFYAV KVLQKKIVLN
210 220 230 240 250
RKEQKHIMAE RNVLLKNVKH PFLVGLHYSF QTTEKLYFVL DFVNGGELFF
260 270 280 290 300
HLQRERSFPE PRARFYAAEI ASALGYLHSI KIVYRDLKPE NILLDSMGHV
310 320 330 340 350
VLTDFGLCKE GIAISDTTTT FCGTPEYLAP EVIRKQPYDN TVDWWCLGAV
360 370 380 390 400
LYEMLYGLPP FYCRDVAEMY DNILHKPLNL RPGVSLTAWS ILEELLEKNR
410 420 430 440 450
QNRLGAKEDF LEIQNHPFFE SLSWTDLVQK KIPPPFNPNV AGPDDIRNFD
460 470 480 490
AVFTEETVPY SVCVSSDYSI VNASVLEADD AFVGFSYAPP SEDLFL
Length:496
Mass (Da):57,145
Last modified:March 1, 2001 - v1
Checksum:i4B7D2804A5948BAD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti114R → G in BAC27349 (PubMed:16141072).Curated1
Sequence conflicti204Q → P in BAC27349 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF312007 mRNA. Translation: AAG34115.1.
AK030314 mRNA. Translation: BAC26895.1.
AK031133 mRNA. Translation: BAC27269.1.
AK031328 mRNA. Translation: BAC27349.1.
AK146561 mRNA. Translation: BAE27261.1.
AK151181 mRNA. Translation: BAE30182.1.
AK171120 mRNA. Translation: BAE42262.1.
AK171186 mRNA. Translation: BAE42298.1.
AK171959 mRNA. Translation: BAE42748.1.
AK172323 mRNA. Translation: BAE42945.1.
CCDSiCCDS14816.1.
RefSeqiNP_001032848.1. NM_001037759.1.
NP_573483.1. NM_133220.2.
NP_808215.2. NM_177547.3.
UniGeneiMm.336410.

Genome annotation databases

EnsembliENSMUST00000097826; ENSMUSP00000095437; ENSMUSG00000025915.
ENSMUST00000166384; ENSMUSP00000130078; ENSMUSG00000025915.
ENSMUST00000168907; ENSMUSP00000126861; ENSMUSG00000025915.
ENSMUST00000171265; ENSMUSP00000127462; ENSMUSG00000025915.
GeneIDi170755.
KEGGimmu:170755.
UCSCiuc007agu.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF312007 mRNA. Translation: AAG34115.1.
AK030314 mRNA. Translation: BAC26895.1.
AK031133 mRNA. Translation: BAC27269.1.
AK031328 mRNA. Translation: BAC27349.1.
AK146561 mRNA. Translation: BAE27261.1.
AK151181 mRNA. Translation: BAE30182.1.
AK171120 mRNA. Translation: BAE42262.1.
AK171186 mRNA. Translation: BAE42298.1.
AK171959 mRNA. Translation: BAE42748.1.
AK172323 mRNA. Translation: BAE42945.1.
CCDSiCCDS14816.1.
RefSeqiNP_001032848.1. NM_001037759.1.
NP_573483.1. NM_133220.2.
NP_808215.2. NM_177547.3.
UniGeneiMm.336410.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XTEX-ray1.60A7-160[»]
1XTNX-ray2.20A/B7-126[»]
ProteinModelPortaliQ9ERE3.
SMRiQ9ERE3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000095437.

PTM databases

iPTMnetiQ9ERE3.
PhosphoSitePlusiQ9ERE3.

Proteomic databases

EPDiQ9ERE3.
MaxQBiQ9ERE3.
PaxDbiQ9ERE3.
PRIDEiQ9ERE3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000097826; ENSMUSP00000095437; ENSMUSG00000025915.
ENSMUST00000166384; ENSMUSP00000130078; ENSMUSG00000025915.
ENSMUST00000168907; ENSMUSP00000126861; ENSMUSG00000025915.
ENSMUST00000171265; ENSMUSP00000127462; ENSMUSG00000025915.
GeneIDi170755.
KEGGimmu:170755.
UCSCiuc007agu.1. mouse.

Organism-specific databases

CTDi23678.
MGIiMGI:2182368. Sgk3.

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
KOG2101. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00860000133668.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ9ERE3.
KOiK13304.
OMAiFTEEMVP.
OrthoDBiEOG091G06FF.
PhylomeDBiQ9ERE3.
TreeFamiTF320906.

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.

Miscellaneous databases

EvolutionaryTraceiQ9ERE3.
PROiQ9ERE3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025915.
CleanExiMM_SGK3.
ExpressionAtlasiQ9ERE3. baseline and differential.
GenevisibleiQ9ERE3. MM.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR001683. Phox.
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.
PF00787. PX. 1 hit.
[Graphical view]
SMARTiSM00312. PX. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
SSF64268. SSF64268. 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.
PS50195. PX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSGK3_MOUSE
AccessioniPrimary (citable) accession number: Q9ERE3
Secondary accession number(s): Q3UAY2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 22, 2003
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 145 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. 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.